Truvada

Nucleoside and Nucleotide Reverse Transcriptase Inhibitor (NRTI) Combinations

For storage information, see specific product information within the How Supplied section.
Data are available from the manufacturer which describe stability of Truvada tablets when stored in the recommended container system and exposed to temperatures and relative humidity (RH) that are inconsistent with the FDA-approved prescribing information. These storage conditions and corresponding acceptable storage durations are described below.
-20 degrees C (-4 degrees F) stored in original sealed bottle: 14 days
5 degrees C (41 degrees F) stored in original sealed bottle: 2 months
40 degrees C (104 degrees F) with 75% RH stored in original sealed bottle: 6 months
50 degrees C (122 degrees F) stored in original sealed bottle: 3 days
25 degrees C (77 degrees F) with 60% RH stored in original bottle WITHOUT induction seal: 6 weeks
30 degrees C (86 degrees F) with 75% RH stored in original bottle WITHOUT induction seal: 6 weeks
Acceptable storage durations solely relate to the stability of the tablets relative to the specific storage conditions; they do not endorse use beyond the expiration date as stated on the original packaging.
The decision to store tablets in a manner outside the FDA-approved prescribing information is at the discretion of the healthcare provider.

Oral Administration

May be administered with or without food.
Tablets must be swallowed whole.

Severe

bone fractures / Delayed / 1.3-1.3
lactic acidosis / Delayed / Incidence not known
diabetes insipidus / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
Fanconi syndrome / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
hepatic decompensation / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
hepatitis B exacerbation / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

hypercholesterolemia / Delayed / 22.0-22.0
depression / Delayed / 9.0-9.0
hyperamylasemia / Delayed / 8.0-8.0
hypertriglyceridemia / Delayed / 4.0-4.0
elevated hepatic enzymes / Delayed / 1.0-3.0
hyperbilirubinemia / Delayed / 0-3.0
hematuria / Delayed / 3.0-3.0
hypoglycemia / Early / 0-3.0
hyperglycemia / Delayed / 2.0-3.0
neutropenia / Delayed / 3.0-3.0
glycosuria / Early / 0-1.0
hepatomegaly / Delayed / Incidence not known
steatosis / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
osteomalacia / Delayed / Incidence not known
osteoporosis / Delayed / Incidence not known
myopathy / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
neuritis / Delayed / Incidence not known
dyspnea / Early / Incidence not known

Mild

nausea / Early / 9.0-9.0
diarrhea / Early / 9.0-9.0
fatigue / Early / 9.0-9.0
sinusitis / Delayed / 8.0-8.0
infection / Delayed / 5.0-8.0
dizziness / Early / 8.0-8.0
rash / Early / 7.0-7.0
headache / Early / 6.0-6.0
pharyngitis / Delayed / 5.0-5.0
insomnia / Early / 5.0-5.0
abdominal pain / Early / 4.0-4.0
weight loss / Delayed / 3.0-3.0
vomiting / Early / 2.0-2.0
abnormal dreams / Early / 10.0
pruritus / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
skin discoloration / Delayed / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
vesicular rash / Delayed / Incidence not known
polyuria / Early / Incidence not known
flatulence / Early / Incidence not known
dyspepsia / Early / Incidence not known
anorexia / Delayed / Incidence not known
rhinitis / Early / Incidence not known
cough / Delayed / Incidence not known
fever / Early / Incidence not known
anxiety / Delayed / Incidence not known
weakness / Early / Incidence not known
back pain / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
paresthesias / Delayed / Incidence not known
asthenia / Delayed / Incidence not known

Hepatitis B and HIV coinfection, hepatitis B exacerbation

Emtricitabine; tenofovir disoproxil fumarate (DF) is not indicated for the treatment of patients with hepatitis B and HIV coinfection, although both drugs can be used together off-label for the treatment of hepatitis B virus (HBV) infection.[34362] It should be noted that only the individual tablet formulations have been studied in HBV; the combination tablet has not been studied. Perform HBV screening in all patients prior to initiating therapy with emtricitabine; tenofovir DF to assure appropriate treatment. Patients who are coinfected with HIV and HBV should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. When considering discontinuation of emtricitabine; tenofovir DF, it is important to note that some patients with HBV infection have experienced severe acute hepatitis B exacerbation, including reports of liver decompensation and liver failure, after stopping treatment. All patients who discontinue emtricitabine; tenofovir DF should have transaminase concentrations monitored every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. If appropriate, resumption of anti-hepatitis B treatment may be required. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [29746] [34362] [46638]

HIV serum status

Due to the potential for the development of drug resistance, the use of emtricitabine; tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (PrEP) is contraindicated in individuals with positive or unknown HIV serum status. Confirm a negative HIV test immediately prior to initiating prophylaxis, at least every 3 months during therapy (prior to authorizing prescription refills), and when discontinuing PrEP. If symptoms consistent with acute HIV infection develop after a potential exposure, discontinue prophylactic therapy and reconfirm HIV status.[29746] In addition to HIV screening, all recipients of HIV PrEP should undergo testing for a sexually transmitted infection (STI) before initiating therapy and approximately every 4 to 12 months thereafter, depending on specific population and/or STI.

Truvada

Rx

Combination product of a nucleotide and a nucleoside reverse transcriptase inhibitor
Used in combination with other antiretroviral agents for the treatment of HIV infection, and in combination with safe sex practices for HIV pre-exposure prophylaxis in adults and adolescents without HIV weighing more than 35 kg
Black Box warning for severe, acute exacerbations of hepatitis B virus (HBV) in patients with HBV who have discontinued emtricitabine; tenofovir disoproxil fumarate

For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
NOTE: Children must be able to swallow whole tablets in order to use emtricitabine; tenofovir DF fixed-dose combination tablets.
Oral dosage Adults

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily.

Children and Adolescents weighing 35 kg or more

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily.

Children and Adolescents weighing 28 to 34 kg

1 tablet (emtricitabine 167 mg; tenofovir DF 250 mg) PO once daily.

Children weighing 22 to 27 kg

1 tablet (emtricitabine 133 mg; tenofovir DF 200 mg) PO once daily.

Children weighing 17 to 21 kg

1 tablet (emtricitabine 100 mg; tenofovir DF 150 mg) PO once daily.

For human immunodeficiency virus (HIV) prophylaxis. For HIV prophylaxis† after occupational exposure to HIV. Oral dosage Adults

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily, in combination with a third antiretroviral agent, is a preferred regimen for HIV post-exposure prophylaxis (PEP). According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however, if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. The recommended third antiretroviral agent to be administered in combination with emtricitabine; tenofovir DF varies among published guidelines and includes one of the following: raltegravir, dolutegravir, lopinavir; ritonavir, or atazanavir boosted with ritonavir. Additionally, emtricitabine; tenofovir may be used as part of alternative regimens in combination with other antiretroviral agents. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

For HIV pre-exposure prophylaxis (PrEP) in high-risk patients without HIV to reduce the risk of sexually acquired HIV-1 and to reduce HIV acquisition risk in injection drug users†. Oral dosage Adults

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily as part of a comprehensive HIV prevention program.[29746]

Adolescents weighing 35 kg or more

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily as part of a comprehensive HIV prevention program.[29746]

For HIV prophylaxis† after nonoccupational exposure to HIV, including sexual assault.
NOTE: Higher risk exposures for which prophylaxis is recommended include exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood when the source is known to be HIV-positive. Exposures to a source patient with unknown HIV status should be assessed on a case-by-case basis.
Oral dosage

NOTE: Children must be able to swallow whole tablets to use emtricitabine; tenofovir DF fixed-dose combination tablets.

Adults

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily plus raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults. Emtricitabine; tenofovir DF in combination with darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Adolescents weighing 35 kg or more

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily plus raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Emtricitabine; tenofovir DF in combination with darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Adolescents weighing 28 to 34 kg

1 tablet (emtricitabine 167 mg; tenofovir DF 250 mg) PO once daily plus raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents. Emtricitabine; tenofovir DF in combination with darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Children weighing 35 kg or more

1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO once daily plus raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Emtricitabine; tenofovir DF in combination with lopinavir/ritonavir or darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Children weighing 28 to 34 kg

1 tablet (emtricitabine 167 mg; tenofovir DF 250 mg) PO once daily plus raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Emtricitabine; tenofovir DF in combination with lopinavir/ritonavir or darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Children weighing 22 to 27 kg

1 tablet (emtricitabine 133 mg; tenofovir DF 200 mg) PO once daily plus raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Emtricitabine; tenofovir DF in combination with lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

Children weighing 17 to 21 kg

1 tablet (emtricitabine 100 mg; tenofovir DF 150 mg) PO once daily plus raltegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. Emtricitabine; tenofovir DF in combination with lopinavir/ritonavir or darunavir/ritonavir (children 3 years and older) is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

For HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM)-intermittent 2-1-1 regimen†.
NOTE: Although not an FDA-approved regimen for emtricitabine; tenofovir DF, efficacy of the on-demand, 2-1-1 intermittent regimen for HIV PrEP has been established in 2 clinical studies for MSM (double-blind, randomized study and subsequent open-label study). In the double-blind, randomized study (n = 400), during a median follow-up of 9.3 months, a total of 2 HIV-1 infections occurred in the emtricitabine; tenofovir DF group (incidence 0.91 per 100 person-years) compared with 14 infections in the placebo group (incidence 6.6 per 100 person-years) for a relative reduction in the emtricitabine; tenofovir DF group of 86% (95% CI: 40% to 98%; p = 0.002). In the open-label extension study (n = 361; median follow-up 18.3 months), HIV incidence was 0.19 per 100 person-years (95% CI: 0.01 to 1.08) in the emtricitabine; tenofovir DF group compared with 6.6 per 100 person-years (95% CI: 3.6 to 11.05) in the placebo group during the randomized phase of the study, indicating a relative reduction of 97% (95% CI: 81% to 100%) in the incidence of HIV with on-demand PrEP.
Oral dosage Adults

2 tablets (emtricitabine 400 mg; tenofovir DF 600 mg) PO in the 2 to 24 hours before sex (closer to 24 hours preferred), followed by 1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO 24 hours after the initial two-tablet dose, followed by 1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO 48 hours after the initial two-tablet dose. Based on the timing of subsequent sexual events, MSM should be instructed to take additional doses as follows: If sex occurs on the consecutive day after completing the 2-1-1 doses, take 1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO daily until 48 hours after the last sexual event. If a gap of less than 7 days occurs between the last tablet and the next sexual event, resume 1 tablet (emtricitabine 200 mg; tenofovir DF 300 mg) PO daily. If a gap of 7 days or more occurs between the last tablet and next sexual event, start again with 2 tablets (emtricitabine 400 mg; tenofovir DF 600 mg).

Hepatic Impairment

The safety and efficacy of emtricitabine; tenofovir disoproxil fumarate have not been established in patients with decompensated hepatic disease.

Renal Impairment

NOTE: Use of emtricitabine; tenofovir disoproxil fumarate (DF) for pre-exposure prophylaxis is not recommended in patients with CrCl < 60 mL/min. For the treatment of HIV in adults with renal impairment, the following dosage adjustment are recommended (no data are available to make dose recommendations for pediatric patients with renal impairment):
CrCl >= 50 mL/min: No dosage adjustment needed.
CrCl 30—49 mL/min: 1 tablet (emtricitabine 200 mg and tenofovir DF 300 mg) PO every 48 hours.
CrCl < 30 mL/min: Not recommended.
 
Intermittent hemodialysis
It is recommended that patients requiring hemodialysis not receive emtricitabine; tenofovir DF.

Abacavir; Dolutegravir; Lamivudine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Abacavir; Lamivudine, 3TC: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Abrocitinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with abrocitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Moderate) Coadministration of acalabrutinib and tenofovir disoproxil fumerate may increase may increase the absorption and plasma concentration of tenofovir disoproxil fumerate. Monitor patients for tenofovir-related adverse reactions and discontinue use in patients who experience an adverse reaction. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Tenofovir disoproxil fumerate is a BCRP substrate.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Aspirin: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Acetaminophen; Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Acyclovir: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Adagrasib: (Moderate) Coadministration of tenofovir disoproxil fumarate with adagrasib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and adagrasib is a P-gp inhibitor.
Adefovir: (Major) Avoid coadministration of tenofovir disoproxil fumarate with adefovir. Both tenofovir and adefovir are primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration may increase concentrations of both drugs resulting in additive nephrotoxicity. Additionally, in the treatment of chronic hepatitis B, tenofovir should not be administered in combination with adefovir to avoid multi-drug resistance. If coadministration is necessary, patients should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein. (Moderate) Patients who are concurrently taking adefovir with emtricitabine are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Amikacin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aminoglycosides: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aminosalicylate sodium, Aminosalicylic acid: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Amiodarone: (Moderate) Coadministration of tenofovir disoproxil fumarate with amiodarone may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and amiodarone is a P-gp inhibitor.
Amlodipine; Celecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Amphotericin B lipid complex (ABLC): (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Amphotericin B liposomal (LAmB): (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Amphotericin B: (Minor) Additive nephrotoxicity can also occur if amphotericin B is given concomitantly with tenofovir. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Butalbital; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Caffeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Carisoprodol: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Dipyridamole: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Omeprazole: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Aspirin, ASA; Oxycodone: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Atazanavir: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Atazanavir; Cobicistat: (Moderate) Tenofovir decreases atazanavir AUC and Cmin. If atazanavir and tenofovir, PMPA are to be coadministered, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg once per day with food in patients >= 40 kg; atazanavir should not be coadministered with tenofovir without ritonavir. Data are insufficient to recommend atazanavir dosing in children < 40 kg who are also receiving concomitant tenofovir. In three post-marketing clinical trials, atazanavir AUC and Cmin were decreased by approximately 25% and 23 to 40%, respectively, when atazanavir was coadministered with tenofovir, PMPA as compared to atazanavir alone. Coadministration of atazanavir and tenofovir without ritonavir could lead to loss or lack of virologic response and possible resistance to atazanavir. In addition, atazanavir appears to increase tenofovir plasma concentrations, which could lead to adverse effects associated with tenofovir, including renal disorders. Increased tenofovir concentrations have been noted in the following combination regimens: tenofovir with ritonavir 'boosted' atazanavir; tenofovir, atazanavir, and lopinavir; ritonavir. Patients who receive tenofovir with atazanavir and any form/dose of ritonavir should be monitored for tenofovir-associated adverse events, with tenofovir being discontinued in patients who develop such adverse events. Although there are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir, the clinical significance of an interaction is suspected to be insignificant. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food.
Bacitracin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as bacitracin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Berotralstat: (Moderate) Coadministration of tenofovir disoproxil fumarate with berotralstat may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and berotralstat is a P-gp inhibitor.
Bismuth Subsalicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Brigatinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with brigatinib is necessary. Tenofovir disoproxil fumarate is a substrate of P-glycoprotein (P-gp) and BCRP. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters.
Bupivacaine; Meloxicam: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Cabozantinib: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Cannabidiol: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with capmatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) and BCRP substrate and capmatinib is a P-gp and BCRP inhibitor.
Carboplatin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Carvedilol: (Moderate) Increased concentrations of tenofovir may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and tenofovir is a P-gp substrate.
Celecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Celecoxib; Tramadol: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Choline Salicylate; Magnesium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Cidofovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Cisplatin: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Clindamycin: (Moderate) Concomitant use of tenofovir and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
Colistimethate, Colistin, Polymyxin E: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Colistin: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as colistimethate sodium. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Conivaptan: (Moderate) Use caution when administering conivaptan and tenofovir concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as tenofovir, PMPA, can increase tenofovir exposure leading to increased or prolonged therapeutic effects and adverse events.
Cyclosporine: (Major) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, such as cyclosporine, should be carefully monitored for changes in serum creatinine and phosphorus.
Darolutamide: (Moderate) Caution is advised with the coadministration of darolutamide and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and darolutamide is a BCRP inhibitor.
Darunavir: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Darunavir; Cobicistat: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Pharmacokinetic parameters (AUC, Cmax, Cmin) of tenofovir, PMPA are elevated when administered in combination with darunavir and ritonavir. The clinical significance of this interaction has not been established, and dosage adjustments are not recommended. Monitor the patients closely for tenofovir-related adverse events.
Dextromethorphan; Quinidine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Dichlorphenamide: (Major) Use of dichlorphenamide and tenofovir disoproxil fumarate is not recommended because of increased tenofovir exposure and a risk of tenofovir-related adverse effects. Monitor closely for signs of drug toxicity if coadministration cannot be avoided. For example, it is important to monitor renal and hepatic function for all patients during treatment with tenofovir, as the drug may cause hepatotoxicity or nephrotoxicity. Increased tenofovir exposure is possible. Tenofovir is a sensitive OAT1 substrate. Dichlorphenamide inhibits OAT1.
Diclofenac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diclofenac; Misoprostol: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Didanosine, ddI: (Major) HIV guidelines recommend against concurrent use of tenofovir, PMPA and didanosine; however, these medications can be used together, if necessary, in patients with a creatinine clearance 60 mL/min or more if the didanosine dose is reduced; decrease the didanosine dose to 250 mg in patients weighing 60 kg or more and to 200 mg in patients weighing 25 to 59 kg. Concurrent administration of tenofovir, PMPA and didanosine, ddI increases the concentration of both didanosine and its active metabolite (dideoxyadenosine 5-triphosphate) which may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. In addition, this combination has been associated with CD4 cell count decline despite viral suppression, high rates of early virologic failure, and rapid selection of resistance mutations. The mechanism of the interaction is not known, but the interaction occurs with both buffered and non-buffered didanosine formulations. When coadministered, tenofovir and didanosine EC may be taken under fasted conditions or with a light meal (under 400 kcal, containing 20% or less fat); coadministration of didanosine buffered tablet formulation with tenofovir should be under fasted conditions. Coadministration of tenofovir and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine therapy should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
Diflunisal: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diphenhydramine; Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Diphenhydramine; Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Dofetilide: (Major) Dofetilide should be co-administered with tenofovir, PMPA with caution since both drugs are actively secreted via cationic secretion and could compete for common renal tubular transport systems. This results in a possible increase in plasma concentrations of either drug. Increased concentrations of dofetilide may increase the risk for side effects including proarrhythmia. Careful patient monitoring and dose adjustment of dofetilide is recommended. (Moderate) Use caution when administering dofetilide concurrently with emtricitabine as both drugs are actively secreted via cationic secretion and could compete for common renal tubular transport systems. This results in a possible increase in plasma concentrations of either drug. Increased concentrations of dofetilide may increase the risk for side effects including proarrhythmia.
Dolutegravir; Lamivudine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Dronedarone: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as dronedarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elacestrant: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Eliglustat: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect.
Enasidenib: (Moderate) Coadministration of tenofovir disoproxil fumarate with enasidenib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and enasidenib is a P-gp and BCRP inhibitor.
Encorafenib: (Moderate) Coadministration of tenofovir disoproxil fumarate with encorafenib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and encorafenib is a BCRP inhibitor.
Erythromycin: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Ethiodized Oil: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Etodolac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Etravirine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as etravirine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Fenoprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Flurbiprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Foscarnet: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as foscarnet. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and foscarnet are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir is administered in combination with nephrotoxic agents, such as foscarnet. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir, and/or the co-administered drug. Drugs that decrease renal function may increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Fostamatinib: (Moderate) Monitor for tenofovir toxicities that may require tenofovir disoproxil dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP or P-gp substrate may increase the concentration of the BCRP or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a BCRP inhibitor; tenofovir disoproxil is a substrate for BCRP and P-gp. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%.
Futibatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with futibatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and futibatinib is a P-gp and BCRP inhibitor.
Ganciclovir: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Gentamicin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Gilteritinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with gilteritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a substrate of P-gp and BCRP and gilteritinib is a P-gp and BCRP inhibitor.
Grapefruit juice: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as grapefruit juice. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Hydrocodone; Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Ibuprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acut

e renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Famotidine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Oxycodone: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ibuprofen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Indomethacin: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Interferons: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Iodixanol: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Iohexol: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Iomeprol: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Iopamidol: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Iopromide: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Ioversol: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Isosulfan Blue: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Istradefylline: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with istradefylline is necessary as concurrent use may increase tenofovir exposure. Tenofovir is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as itraconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ketoconazole: (Moderate) Monitor for an increase in tenofovir-related adverse effects if coadministration with ketoconazole is necessary. Concurrent use may increase tenofovir exposure. Tenofovir disoproxil fumarate is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Ketoprofen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Ketorolac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Lamivudine, 3TC: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lapatinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with lapatinib is necessary. Tenofovir is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. Increased plasma concentrations of tenofovir may occur.
Lasmiditan: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Closely monitor for tenofovir-associated adverse reactions if ledipasvir is administered with tenofovir disoproxil fumarate. In addition, because safety has not been established, avoid use of ledipasvir in combination with HIV regimens that contain tenofovir disoproxil fumarate and HIV protease inhibitors boosted with ritonavir. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate. If coadministration is deemed necessary, closely monitor for tenofovir adverse effects. Plasma concentrations of tenofovir may increase when administered with ledipasvir. Tenofovir is a substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); ledipasvir is an inhibitor of both P-gp and BCRP.
Leniolisib: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Levoketoconazole: (Moderate) Monitor for an increase in tenofovir-related adverse effects if coadministration with ketoconazole is necessary. Concurrent use may increase tenofovir exposure. Tenofovir disoproxil fumarate is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lonafarnib: (Moderate) Coadministration of tenofovir disoproxil fumarate with lonafarnib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and lonafarnib is a P-gp inhibitor.
Lopinavir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Minor) There are varying results in reports of an interaction between tenofovir and lopinavir; ritonavir. In one report, the concurrent administration of tenofovir with lopinavir; ritonavir increased tenofovir Cmax 31%, AUC 34%, and Cmin 29%, with slight (15%) decreases in lopinavir Cmax and AUC; the alterations may be a food effect rather than a drug-drug interaction. In another report, lopinavir; ritonavir (400 mg; 100 mg PO twice daily for 14 days) increased the tenofovir (300 mg/day PO) Cmin 51% and AUC 32%, with no effect seen on lopinavir; ritonavir pharmacokinetics. While the clinical significance of this interaction is unknown, and is suspected to be insignificant, patients receiving lopinavir; ritonavir with tenofovir should be monitored for tenofovir-associated adverse events.
Lumacaftor; Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Magnesium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Maribavir: (Moderate) Coadministration of tenofovir disoproxil fumarate with maribavir may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and maribavir is a P-gp and BCRP inhibitor.
Meclofenamate Sodium: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Mefenamic Acid: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Mefloquine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Meloxicam: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Methenamine; Sodium Salicylate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Methotrexate: (Major) Avoid concomitant use of methotrexate with tenofovir disoproxil fumarate due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Tenofovir disoproxil fumarate and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with tenofovir disoproxil fumarate may result in decreased renal function as well as increased methotrexate plasma concentrations.
Midostaurin: (Moderate) Coadministration of tenofovir disoproxil fumarate with midostaurin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitapivat: (Moderate) Coadministration of tenofovir disoproxil fumarate with mitapivat may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and mitapivat is a P-gp inhibitor.
Nabumetone: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen; Esomeprazole: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Naproxen; Pseudoephedrine: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Nelfinavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as nelfinavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Neratinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with neratinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Non-Ionic Contrast Media: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Nonsteroidal antiinflammatory drugs: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Orlistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with tenofovir, PMPA. Loss of virological control has been reported in HIV-infected patients taking orlistat with tenofovir disoproxil fumarate and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued. (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Osimertinib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Oteseconazole: (Moderate) Coadministration of tenofovir disoproxil fumarate with oteseconazole may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
Oxaprozin: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Pacritinib: (Moderate) Concomitant use of tenofovir disoproxil fumarate with pacritinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Pamidronate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Paromomycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Piroxicam: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Pirtobrutinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with pirtobrutinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and pirtobrutinib is a P-gp and BCRP inhibitor.
Plazomicin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Polymyxin B: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as polymyxin B. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Posaconazole: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Pretomanid: (Moderate) Coadministration of tenofovir disoproxil fumarate with pretomanid may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and pretomanid is a P-gp and BCRP inhibitor.
Probenecid: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Probenecid; Colchicine: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Propafenone: (Moderate) Coadministration of tenofovir disoproxil fumarate with propafenone may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and propafenone is a P-gp inhibitor.
Quinidine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ranolazine: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ranolazine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Regorafenib: (Moderate) Use caution if coadministration of regorafenib with tenofovir, PMPA is necessary, and monitor for an increase in tenofovir-related adverse reactions. Tenofovir is a BCRP substrate and regorafenib is a BCRP inhibitor. Regorafenib-mediated BCRP inhibition may increase exposure to tenofovir.
Ribavirin: (Moderate) Use emtricitabine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies.
Ritonavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate, concurrently with inhibitors of P-gp and BCRP, such as ritonavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Rolapitant: (Moderate) Use caution if tenofovir, PMPA and rolapitant are used concurrently, and monitor for tenofovir-related adverse effects. Tenofovir is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, respectively, on day 8 after rolapitant administration. When rolapitant was administered with digoxin, a P-gp substrate, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Salicylates: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Salsalate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Saquinavir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as saquinavir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Selpercatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with selpercatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Coadministration of tenofovir disoproxil fumarate with taurursodiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and taurursodiol is a P-gp and BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir with tenofovir disoproxil fumarate. Taking these medications together may increase tenofovir plasma concentrations, potentially increasing the risk for adverse events. Tenofovir disoproxil fumarate is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Voxilaprevir is a BCRP inhibitor. (Moderate) Monitor patients for tenofovir-associated adverse reactions, such as renal toxicity, in patients receiving regimens containing tenofovir disoproxil fumarate and velpatasvir due to potential increases in tenofovir serum concentrations. When administered concurrently with velpatasvir, the peak concentration (Cmax), systemic exposure (AUC), and the trough concentration (Cmin) of tenofovir increased by 44%, 40%, and 84%, respectively. Tenofovir is a substrate of the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) transporters, while velpatasvir inhibits both BCRP and P-gp. Consider use of tenofovir alafenamide in place of tenofovir disoproxil fumarate.
Sorafenib: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with sorafenib is necessary. Tenofovir is a P-glycoprotein (P-gp) substrate and sorafenib inhibits P-gp in vitro. Sorafenib may increase the concentrations of concomitantly administered drugs that are P-gp substrates.
Sotorasib: (Moderate) Coadministration of tenofovir disoproxil fumarate with sotorasib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and sotorasib is a P-gp and BCRP inhibitor.
Sparsentan: (Moderate) Coadministration of tenofovir disoproxil fumarate with sparsentan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp and BCRP substrate and sparsentan is a P-gp and BCRP inhibitor.
Streptomycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Sulindac: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Sumatriptan; Naproxen: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Tacrolimus: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, including tacrolimus. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered with tacrolimus. Consider the potential for drug interaction prior to and during concurrent use of these medications. Medications that decrease renal function, such as tacrolimus, may increase concentrations of emtricitabine; as emtricitabine is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion.
Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tedizolid: (Moderate) Coadministration of tenofovir disoproxil fumarate with tedizolid may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and tedizolid is a BCRP inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in tenofovir disoproxil fumarate-related adverse reactions if coadministration with temsirolimus is necessary. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use may lead to increased concentrations of tenofovir disoproxil fumarate.
Tepotinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with tepotinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tezacaftor; Ivacaftor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ivacaftor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Ticagrelor: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with tenofovir, results in decreased tipranavir concentrations. The clinical significance of this interaction has not been established, and no recommendations for tenofovir dosage adjustments are available.
Tobramycin: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Tolmetin: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Trandolapril; Verapamil: (Moderate) Coadministration of tenofovir disoproxil fumarate with verapamil may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and verapamil is a P-gp inhibitor.
Trospium: (Minor) Both trospium and tenofovir are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or tenofovir due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or tenofovir, PMPA is recommended.
Tucatinib: (Moderate) Coadministration of tenofovir disoproxil fumarate with tucatinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor.
Valacyclovir: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as valacyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein. (Moderate) Monitor for valacyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase valacyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as valacyclovir and emtricitabine, may increase the risk of adverse reactions.
Valdecoxib: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions.
Valganciclovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as valganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and valganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Minor) Since tenofovir is primarily eliminated by the kidneys, concurrent administration of tenofovir disoproxil with valganciclovir may increase serum concentrations of tenofovir via competition for renal tubular secretion.
Vancomycin: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
Vemurafenib: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as vemurafenib. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Verapamil: (Moderate) Coadministration of tenofovir disoproxil fumarate with verapamil may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and verapamil is a P-gp inhibitor.
Voclosporin: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as clarithromycin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Zoledronic Acid: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as zoledronic acid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Zonisamide: (Minor) Caution is advised when administering tenofovir disoproxil fumarate concurrently with zonisamide, as coadministration may result in elevated tenofovir plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as zonisamide, may increase absorption of tenofovir, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions.

Emtricitabine, Tenofovir/Emtricitabine, Tenofovir Disoproxil Fumarate/Truvada Oral Tab: 100-150mg, 133-200mg, 167-250mg, 200-300mg

Adults

200 mg/day emtricitabine and 300 mg/day tenofovir DF PO is FDA-approved maximum; however, intermittent doses of 400 mg/day emtricitabine and 600 mg/day tenofovir DF PO have been used off-label for HIV pre-exposure prophylaxis.

Geriatric

200 mg/day emtricitabine and 300 mg/day tenofovir DF PO is FDA-approved maximum; however, intermittent doses of 400 mg/day emtricitabine and 600 mg/day tenofovir DF PO have been used off-label for HIV pre-exposure prophylaxis.

Adolescents

weight 35 kg or more: 200 mg/day emtricitabine and 300 mg/day tenofovir DF PO.
weight 28 to 34 kg: 167 mg/day emtricitabine and 250 mg/day tenofovir DF PO.

Children

weight 35 kg or more: 200 mg/day emtricitabine and 300 mg/day tenofovir DF PO.
weight 28 to 34 kg: 167 mg/day emtricitabine and 250 mg/day tenofovir DF PO.
weight 22 to 27 kg: 133 mg/day emtricitabine and 200 mg/day tenofovir DF PO.
weight 17 to 21 kg: 100 mg/day emtricitabine and 150 mg/day tenofovir DF PO.
weight less than 17 kg: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

In combination studies evaluating the in vitro antiviral activity of emtricitabine and tenofovir disoproxil fumarate together, no antagonism was observed.
 
Emtricitabine: Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) by competing with the natural substrate deoxycytidine 5'-triphosphate for incorporation into nascent viral DNA, resulting in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, epsilon, and mitochondrial DNA polymerase-gamma.
The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in lymphoblastoid cell lines, the MAGI-CCR5 cell line, and peripheral blood mononuclear cells (PBMC). The 50% effective concentration (EC50) values for emtricitabine were in the range of 1.3 to 640 nanomolar. Emtricitabine displayed antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 7 to 75 nanomolar) and showed strain-specific activity against HIV-2 (EC50 values ranged from 7 to 1,500 nanomolar in PBMCs and MAGI cells).
Emtricitabine-resistant isolates of HIV-1 have been selected in cell culture and in vivo. Genotypic analysis of these isolates showed that the reduced susceptibility to emtricitabine was associated with a valine or isoleucine (M184V/I) substitution in the HIV-1 RT. People with the M184V/I mutation are cross-resistant to lamivudine, but retain susceptibility to didanosine, stavudine, tenofovir, and zidovudine, and to non-nucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 isolates containing the K65R substitution, selected in vivo by abacavir, didanosine, and tenofovir, demonstrated reduced susceptibility to inhibition by emtricitabine. Viruses harboring substitutions conferring reduced susceptibility to zidovudine and stavudine (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E) or didanosine (L74V) remained susceptible to emtricitabine. HIV-1 containing the K103N substitution associated with resistance to NNRTIs was susceptible to emtricitabine.
 
Tenofovir disoproxil fumarate: Tenofovir inhibits viral reverse transcriptase and acts as a DNA chain terminator. Tenofovir disoproxil fumarate (tenofovir DF) is an acyclic nucleoside phosphonate (nucleotide) diester analog of adenosine monophosphate. Tenofovir DF requires initial diester hydrolysis for conversion to tenofovir. Tenofovir is then taken up by cells and undergoes phosphorylation to form tenofovir diphosphate (PMPApp). Tenofovir diphosphate competitively inhibits RNA- and DNA-directed reverse transcriptase. Tenofovir diphosphate competes with the natural substrate deoxyadenosine 5'-triphosphate (dATP) and, since it lacks a 3' hydroxyl group, causes premature DNA termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta, and mitochondrial DNA polymerase-gamma.
The IC50 (50% inhibitory concentration) of tenofovir against HIV-1 in vitro is 40 to 8,500 nanomolar. Induction of antiretroviral resistance to acyclic phosphonomethylether nucleosides like tenofovir in vitro is difficult, possibly because of their similarity to the natural substrate (dATP). HIV isolates with reduced susceptibility to tenofovir have been selected in vitro. These viruses expressed the K65R mutation in reverse transcriptase and showed a 3- to 4- fold reduction in susceptibility to tenofovir. During clinical trials, 3% of tenofovir-treated patients developed the K65R mutation. Despite the development of resistance to NRTIs, HIV isolates from patients after 24 or 48 weeks of tenofovir treatment showed no significant changes in tenofovir susceptibility unless the K65R mutation was present. Tenofovir shows minor to moderate synergy with didanosine and nelfinavir, and strong synergy with zidovudine, amprenavir and all non-nucleoside reverse transcriptase inhibitors (NNRTIs) tested.

Emtricitabine; tenofovir disoproxil fumarate tablets are administered orally. The steady state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate are unaffected when administered together, compared to each agent being administered alone.
Emtricitabine: When given at a dose of 200 mg once daily, the plasma half-life is approximately 10 hours and the metabolite, emtricitabine-triphosphate, has an intracellular half-life of approximately 39 hours. Emtricitabine exhibits low plasma protein binding (less than 4%), and protein-binding is independent of plasma concentration. At peak plasma concentrations, the mean plasma to blood drug concentration ratio is approximately 1 and the mean semen to plasma drug concentration ratio is approximately 4. Metabolism occurs via oxidation to 3'-sulfoxide diastereomer (approximately 9% of dose) and via conjugation with glucuronic acid to 2'-O-glucuronide (approximately 4% of dose). Emtricitabine is excreted renally. The renal clearance is greater than the estimated creatinine clearance; elimination is presumed to be by both glomerular filtration and active tubular secretion, suggesting there may be competition for elimination with other compounds that are also renally eliminated.
Tenofovir disoproxil fumarate: Due to the presence of a phosphonate group, tenofovir disoproxil fumarate (DF) is negatively charged at neutral pH, which limits its bioavailability. Following absorption, tenofovir DF is rapidly converted to tenofovir. Protein binding is negligible. Intracellularly, tenofovir undergoes phosphorylation to its active metabolite, tenofovir diphosphate (PMPApp). Tenofovir and tenofovir diphosphate have a prolonged intracellular half-life (15 to 50 hours). In vitro studies indicate that neither tenofovir DF nor tenofovir are substrates of cytochrome P450 enzymes. Tenofovir is eliminated by a combination of glomerular filtration and active renal tubular secretion; there may be competition for elimination with other compounds that are also renally eliminated.
 
Affected transporters: P-gp, BCRP
Tenofovir DF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Administration with inhibitors of these transporters may result in increased absorption of tenofovir.

Oral Route

In fasting, healthy subjects, one emtricitabine; tenofovir disoproxil fumarate (Truvada) tablet was found to be bioequivalent to the coadministration of 1 emtricitabine (Emtriva) capsule (200 mg) plus 1 tenofovir disoproxil fumarate (Viread) tablet (300 mg). The administration of emtricitabine; tenofovir disoproxil fumarate with food affects the pharmacokinetic parameters of tenofovir, but not emtricitabine. The AUC and Cmax of tenofovir increase approximately 35% and 15%, respectively, when emtricitabine; tenofovir disoproxil fumarate is administered with food.
Emtricitabine: Emtricitabine is rapidly and extensively absorbed, with a mean absolute bioavailability of 93% and peak plasma concentrations occurring at 1 to 2 hours post-dose. The AUC and Cmax increase in proportion to oral dosage over the range of 25 to 200 mg.
Tenofovir disoproxil fumarate: Oral bioavailability of tenofovir from tenofovir disoproxil fumarate (DF) 300 mg is 25% in the fasted state. After multiple oral doses of tenofovir DF (300 mg once daily), 32 +/- 10% of the administered dose is recovered in urine over 24 hours. Following a single, orally administered dose, the terminal elimination half-life of tenofovir is approximately 17 hours. Comparatively, during clinical trials, after IV administration of tenofovir, 70% to 80% of the dose is recovered in the urine as unchanged drug within 72 hours.

Pregnancy

Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend the use of emtricitabine; tenofovir disoproxil fumarate (DF) as a preferred 2-NRTI backbone in patients with HIV who are pregnant or trying to conceive. In addition, guidelines recommend emtricitabine; tenofovir DF as pre-exposure prophylaxis in patients who are at risk of HIV acquisition during periconception, pregnancy, and postpartum periods. Healthcare providers are advised to counsel patients about the benefits of pre-exposure prophylaxis on reducing maternal HIV acquisition and perinatal HIV transmission, and about potential risks to the mother, fetus, and infant during periconception, pregnancy and postpartum use of the drug. Available data from the Antiretroviral Pregnancy Registry, which includes first trimester exposures to emtricitabine (more than 4,225 exposures) and tenofovir DF (more than 4,655 exposures), have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When exposure occurred in the first trimester, the prevalence of defects was 2.7% (95% CI: 2.2 to 3.2) for emtricitabine and 2.5% (95% CI: 2 to 3) for tenofovir DF. Available data regarding use of emtricitabine; tenofovir DF as pre-exposure prophylaxis suggest that the benefits outweigh any potential toxicity. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for the development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to emtricitabine; tenofovir alafenamide; registry information can be obtained at www.apregistry.com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). The Department of Health and Human Services (HHS) recommends the use of emtricitabine; tenofovir DF during breast-feeding as pre-exposure prophylaxis in mothers who are at risk of HIV acquisition. Mothers should be counseled about the benefits of pre-exposure prophylaxis on reducing maternal HIV acquisition and postnatal HIV transmission, and about potential risks. Limited data suggest small amounts of emtricitabine and tenofovir DF are excreted into breast milk. One study estimated the exposure to emtricitabine in exclusively breast-fed infants at approximately 2% of the recommended infant dose. In this same study, tenofovir DF exposure in exclusively breast-fed infants was found to be equivalent to approximately 4.2 micrograms per day. In a short-term study of emtricitabine; tenofovir DF use as pre-exposure prophylaxis in breast-feeding women without HIV, the estimated infant dose from breast milk and plasma concentrations were 12,500-fold (tenofovir) and more than 200-fold (emtricitabine) lower, respectively, than the therapeutic doses for infants. Other antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.