TRIUMEQ

Integrase Strand Transfer Inhibitor (INSTI) and Nucleoside and Nucleotide Reverse Transcriptase Inhibitor (NRTI) Combinations

 
Screen for HLA-B*5701 before initiating treatment to reduce the risk of hypersensitivity reaction. HLA-B*5701-positive patients MUST not receive abacavir.
 
Hazardous Drugs Classification
Abacavir is classified as a hazardous drug.
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.

Oral Administration

Available as 2 dosage forms:
Triumeq oral tablet (600 mg abacavir, 50 mg dolutegravir, 300 mg lamivudine)
Triumeq PD tablet for oral suspension (60 mg abacavir, 5 mg dolutegravir, 30 mg lamivudine)
Triumeq and Triumeq PD cannot be interchanged on a mg-per-mg basis because of differing pharmacokinetic profiles of the dolutegravir component. If a pediatric patient switches from Triumeq PD to Triumeq, the dosage must be adjusted. Incorrect dosing of a given formulation may result in loss of therapeutic effect, development of resistance, or adverse reactions.

Oral Solid Formulations

Tablet (Triumeq)
Administer with or without food.
DO NOT chew, cut, or crush the tablets.
Administer at least 2 hours before or 6 hours after taking cation-containing antacids or laxatives (i.e., magnesium, aluminum), sucralfate, oral calcium supplements, oral iron supplements, or buffered medications. Alternatively, may administer oral calcium and iron supplements concurrently if administered with food.[57813]

Oral Liquid Formulations

Tablet for oral suspension (Triumeq PD)
DO NOT swallow the tablets whole. DO NOT chew, cut, or crush the tablets.
Fully disperse the tablets for oral suspension in 20 mL of drinking water (if using 4, 5, or 6 tablets) or 15 mL of drinking water (if using 3 tablets) in the supplied cup.
Swirl the suspension so that no lumps remain.
Once fully dispersed, administer the oral suspension within 30 minutes of mixing.
For those unable to use the supplied cup, an appropriately-sized syringe may be used to administer the oral suspension.
Administer with or without food.
Administer at least 2 hours before or 6 hours after taking cation-containing antacids or laxatives (i.e., magnesium, aluminum), sucralfate, oral calcium supplements, oral iron supplements, or buffered medications. Alternatively, may administer oral calcium and iron supplements concurrently if administered with food.[57813]

Severe

suicidal ideation / Delayed / 0-2.0
seizures / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
hepatitis B exacerbation / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
lactic acidosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
myocardial infarction / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known

Moderate

neutropenia / Delayed / 3.0-4.0
elevated hepatic enzymes / Delayed / 1.0-3.0
hyperglycemia / Delayed / 2.0-2.0
hypertriglyceridemia / Delayed / 0-2.0
depression / Delayed / 1.0-1.0
peripheral neuropathy / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
splenomegaly / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
steatosis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
lymphopenia / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known
oral ulceration / Delayed / Incidence not known

Mild

insomnia / Early / 3.0-3.0
headache / Early / 2.0-2.0
fatigue / Early / 2.0-2.0
lethargy / Early / 0-2.0
anorexia / Delayed / 0-2.0
vomiting / Early / 0-2.0
dyspepsia / Early / 0-2.0
gastroesophageal reflux / Delayed / 0-2.0
flatulence / Early / 0-2.0
abdominal pain / Early / 0-2.0
pruritus / Rapid / 0-2.0
nightmares / Early / 0-1.0
dizziness / Early / 0-1.0
nausea / Early / 0-1.0
diarrhea / Early / 0-1.0
rash / Early / 0-1.0
paresthesias / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
weakness / Early / Incidence not known
myalgia / Early / Incidence not known
cough / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
fever / Early / Incidence not known
malaise / Early / Incidence not known

Hepatitis B and HIV coinfection, hepatitis B exacerbation

Cautious administration is recommended for patients with hepatitis. Patients with hepatitis B virus coinfection may be at increased risk for worsening or development of elevated hepatic enzymes following treatment with abacavir; dolutegravir; lamivudine. Patients who present with HIV infection should be screened for hepatitis B virus (HBV) coinfection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection 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 abacavir; dolutegravir; lamivudine is used to treat HIV, an additional therapy should be considered for appropriate treatment of HBV; otherwise, consider an alternative regimen. If tenofovir cannot be used, entecavir should be given 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 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 patients with coinfection should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. It should also be noted that following discontinuation of lamivudine in patients with HBV and HIV coinfection, some patients experienced clinical or laboratory evidence of hepatitis B exacerbation, which has been fatal in some cases. This reaction may be more severe in patients with decompensated hepatic disease. Thus, patients with HBV and HIV coinfection should have transaminase concentrations monitored every 6 weeks for the first 3 months after stopping abacavir; dolutegravir; lamivudine, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires 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 with hepatitis and HIV coinfection to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [46638]

TRIUMEQ, Triumeq PD

Rx

Combination of nucleoside analogue reverse transcriptase inhibitors (abacavir and lamivudine) and an integrase strand transfer inhibitor (dolutegravir)
For the treatment of human immunodeficiency virus (HIV-1) infection
Black Box warnings for fatal hypersensitivity reactions and exacerbations of hepatitis B

For the treatment of human immunodeficiency virus (HIV) infection. Oral dosage (Triumeq only)

NOTE: Do not interchange tablets (Triumeq) and tablets for oral suspension (Triumeq PD) on a milligram-per-milligram basis due to differing pharmacokinetic profiles.

Adults

One tablet (600 mg abacavir; 50 mg dolutegravir; 300 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 50 mg twice daily; therefore, an ADDITIONAL 50 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Children and Adolescents weighing 25 kg or more

One tablet (600 mg abacavir; 50 mg dolutegravir; 300 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 50 mg twice daily; therefore, an ADDITIONAL 50 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Oral dosage (Triumeq PD only)

NOTE: Do not interchange tablets (Triumeq) and tablets for oral suspension (Triumeq PD) on a milligram-per-milligram basis due to differing pharmacokinetic profiles.

Children weighing 20 to 24 kg

Six tablets (360 mg abacavir; 30 mg dolutegravir; 180 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 30 mg twice daily; therefore, an ADDITIONAL 30 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Children weighing 14 to 19 kg

Five tablets (300 mg abacavir; 25 mg dolutegravir; 150 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 25 mg twice daily; therefore, an ADDITIONAL 25 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Children weighing 10 to 13 kg

Four tablets (240 mg abacavir; 20 mg dolutegravir; 120 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 20 mg twice daily; therefore, an ADDITIONAL 20 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Children weighing 6 to 9 kg

Three tablets (180 mg abacavir; 15 mg dolutegravir; 90 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 15 mg twice daily; therefore, an ADDITIONAL 15 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Infants 3 to 11 months weighing 10 to 13 kg

Four tablets (240 mg abacavir; 20 mg dolutegravir; 120 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 20 mg twice daily; therefore, an ADDITIONAL 20 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Infants 3 to 11 months weighing 6 to 9 kg

Three tablets (180 mg abacavir; 15 mg dolutegravir; 90 mg lamivudine) PO once daily. During coadministration with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin, the dolutegravir dose needs to be increased to 15 mg twice daily; therefore, an ADDITIONAL 15 mg/day of dolutegravir (separated by 12 hours from abacavir; dolutegravir; lamivudine) should be given. Avoid use in patients with history of resistance to abacavir, dolutegravir, or lamivudine. In addition, avoid use in patients with clinically suspected integrase strand transfer inhibitor (INSTI) resistance or an INSTI-associated resistance substitution.

Hepatic Impairment

Because abacavir may require a dose adjustment in the presence of hepatic impairment, the fixed-dose combination of abacavir; dolutegravir; lamivudine is not recommended for patients with impaired hepatic function.

Renal Impairment

CrCl 50 mL/minute or more: No dosage adjustment is needed.
CrCl 30 to 49 mL/minute: No dosage adjustment is needed, but monitor for lamivudine-related hematologic toxicities. If new or worsening neutropenia or anemia develops, discontinue use of the fixed-dose combination product and administer the individual components to allow for a lamivudine dose adjustment.
CrCl less than 30 mL/minute and pediatric patients with a similar degree of renal impairment based on age-appropriate renal function assessment: Use not recommended.

Abrocitinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with abrocitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Moderate) Coadministration of acalabrutinib and dolutegravir may increase dolutegravir exposure and increase the risk of dolutegravir toxicity. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Dolutegravir is a BCRP transporter substrate in vitro.
Adagrasib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with adagrasib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor.
Adefovir: (Major) Patients who are concurrently taking adefovir with antiretrovirals (i.e., anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs)) 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).
Alogliptin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Aluminum Hydroxide: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain magnesium and calcium which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing gastrointestinal medications such as magnesium hydroxide. The chemical structure of these GI drugs that contain polyvalent cations, such as magnesium hydroxide, can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing gastrointestinal medications such as magnesium hydroxide. The chemical structure of these GI drugs that contain polyvalent cations, such as magnesium hydroxide, can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain magnesium which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Amiloride: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Apalutamide: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with apalutamide; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Apalutamide is a strong CYP3A inducer and dolutegravir is partially metabolized by this isoenzyme.
Aprepitant, Fosaprepitant: (Moderate) Use caution if dolutegravir and aprepitant, fosaprepitant are used concurrently and monitor for an increase in dolutegravir-related adverse effects for several days after administration of a multi-day aprepitant regimen. Dolutegravir is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and may increase plasma concentrations of dolutegravir. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Armodafinil: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with armodafinil; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Armodafinil is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and uridine glucuronyltransferase (UGT). Atazanavir is an inhibitor of CYP3A4 and UGT1A1. (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Berotralstat: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with berotralstat. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A4 and P-gp substrate and berotralstat is a P-gp and moderate CYP3A4 inhibitor.
Bexarotene: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bexarotene; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bexarotene is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like lamivudine; the risk of peripheral neuropathy may be additive.
Bosentan: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bosentan; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bosentan is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Brigatinib: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with brigatinib is necessary. Dolutegravir 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.
Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with cabozantinib is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Calcium Acetate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Carbonate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Carbonate; Simethicone: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Chloride: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium Gluconate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Calcium; Vitamin D: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Canagliflozin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Cannabidiol: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with cannabidiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with capmatinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor.
Carbamazepine: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and carbamazepine is an inducer of CYP3A4.
Carvedilol: (Moderate) Increased concentrations of dolutegravir may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and dolutegravir is a P-gp substrate in vitro.
Cenobamate: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with cenobamate. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer.
Ceritinib: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with ceritinib is necessary. Dolutegravir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chromium: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Clobazam: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with clobazam; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Clobazam is a weak inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Conivaptan: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with conivaptan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A and P-gp substrate and conivaptan is a moderate CYP3A and P-gp inhibitor.
Daclatasvir: (Moderate) Systemic exposure of dolutegravir, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of dolutegravir; monitor patients for potential adverse effects.
Dalfampridine: (Moderate) Concurrent treatment with OCT2 inhibitors, such as dolutegravir, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dolutegravir concurrently with dalfampridine should be considered against the risk of seizures.
Dapagliflozin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Darolutamide: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with darolutamide is necessary. Dolutegravir is a BCRP substrate and darolutamide is a BCRP inhibitor.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine. (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Dofetilide: (Contraindicated) Concurrent use of dolutegravir with dofetilide is contraindicated due of the potential for serious and life-threatening adverse events, such as QT prolongation and torsade de pointes (TdP). Dolutegravir inhibits the renal organic cation transporter OCT2, dofetilide is eliminated via this transporter. If coadministered, the plasma concentration of dofetilide may increase. (Moderate) Drugs that are actively secreted via cationic secretion, such as lamivudine, should be co-administered with dofetilide with caution since they could increase dofetilide plasma concentrations via potential competition for renal tubular secretion.
Donepezil; Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Duvelisib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with duvelisib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
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: (Major) When possible, avoid concurrent use of dolutegravir with efavirenz or efavirenz-containing products (e.g., efavirenz; emtricitabine; tenofovir) in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with efavirenz. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and efavirenz is an inducer of CYP3A4.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine. (Major) When possible, avoid concurrent use of dolutegravir with efavirenz or efavirenz-containing products (e.g., efavirenz; emtricitabine; tenofovir) in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with efavirenz. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and efavirenz is an inducer of CYP3A4.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) When possible, avoid concurrent use of dolutegravir with efavirenz or efavirenz-containing products (e.g., efavirenz; emtricitabine; tenofovir) in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with efavirenz. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and efavirenz is an inducer of CYP3A4.
Elacestrant: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with elacestrant. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of BCRP and P-gp and elacestrant is a BCRP and P-gp inhibitor.
Elagolix: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine. (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine. (Moderate) Caution is warranted when cobicistat is administered with dolutegravir as there is a potential for elevated dolutegravir concentrations. Dolutegravir is a substrate of CYP3A4 and P-glycoprotein (P-gp). Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of P-gp.
Empagliflozin; Linagliptin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Empagliflozin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Emtricitabine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Enasidenib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with enasidenib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and enasidenib is a P-gp and BCRP inhibitor.
Encorafenib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with encorafenib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and encorafenib is a BCRP inhibitor.
Enzalutamide: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with enzalutamide; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Enzalutamide is a strong CYP3A inducer and dolutegravir is partially metabolized by this isoenzyme.
Ertugliflozin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking abacavir. Abacavir is metabolized via alcohol dehydrogenase. Alcohol decreases the elimination of abacavir causing an increase in overall exposure to abacavir. In a study involving HIV-infected men, coadministration of alcohol and abacavir resulted in a 41% increase in abacavir AUC and a 26% increase in abacavir half-life. In males, abacavir had no effect on the pharmacokinetic properties of alcohol; this interaction has not been studied in females. Abacavir has no effect on the pharmacokinetic properties of alcohol. (Major) Because abacavir is metabolized via alcohol dehydrogenase, alcohol decreases the elimination of abacavir causing an increase in overall exposure to abacavir. In a study involving HIV-infected men, coadministration of alcohol and abacavir resulted in a 41% increase in abacavir AUC and a 26% increase in abacavir half-life. In males, abacavir had no effect on the pharmacokinetic properties of alcohol; this interaction has not been studied in females. Abacavir has no effect on the pharmacokinetic properties of alcohol.
Etravirine: (Major) Coadministration of dolutegravir with etravirine should be avoided, unless also administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. When administered with etravirine (a CYP3A4 inducer), the plasma concentration of dolutegravir (a CYP3A4 substrate) is significantly reduced; however, this effect is diminished by the presence of one of the above mentioned protease inhibitors.
Fedratinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with fedratinib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; fedratinib is a moderate CYP3A inhibitor.
Felbamate: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with felbamate; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Felbamate is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Ferric Maltol: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Folic Acid, Vitamin B9: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Fosamprenavir: (Major) Avoid concurrent use of dolutegravir and fosamprenavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For INSTI-naive adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with fosamprenavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations.
Fosphenytoin: (Major) Avoid concurrent use of dolutegravir with phenytoin or fosphenytoin, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Phenytoin is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Fostamatinib: (Moderate) Monitor for dolutegravir toxicities that may require dolutegravir dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a CYP3A4, BCRP, or P-gp substrate may increase the concentration of the CYP3A4, BCRP, or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a CYP3A4 and BCRP inhibitor; dolutegravir is a substrate for CYP3A4, BCRP, and P-gp. Coadministration of fostamatinib with a sensitive CYP3A4 substrate increased the substrate AUC by 64% and Cmax by 113%. 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%.
Fostemsavir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with fostemsavir. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and fostemsavir is a BCRP inhibitor.
Futibatinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with futibatinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate and futibatinib is a P-gp and BCRP inhibitor.
Gilteritinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with gilteritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of P-gp and BCRP and gilteritinib is a P-gp and BCRP inhibitor.
Glipizide; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Glyburide; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolutegravir, a CYP3A substrate, as dolutegravir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Interferon Alfa-2b: (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.
Interferon Alfa-n3: (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.
Interferon Beta-1a: (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.
Interferon Beta-1b: (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.
Interferon Gamma-1b: (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.
Interferons: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. 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 score greater than 6). (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.
Iron Salts: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Iron: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with dolutegravir may result in increased serum concentrations of dolutegravir. Dolutegravir is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
Isoniazid, INH; Rifampin: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
Itraconazole: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministered with itraconazole. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is an in vitro substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); itraconazole inhibits both P-gp and BCRP.
Lasmiditan: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lasmiditan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Lenacapavir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lenacapavir. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A, P-gp, and BCRP substrate and lenacapavir is a moderate CYP3A, P-gp, and BCRP inhibitor.
Leniolisib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with leniolisib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and leniolisib is a BCRP inhibitor.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of dolutegravir may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Dolutegravir is partially metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Linagliptin; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Lonafarnib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lonafarnib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A4 and P-gp substrate and lonafarnib is a P-gp and strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown.
Lorlatinib: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with lorlatinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate as well as a substrate of P-glycoprotein (P-gp). Lorlatinib is a moderate CYP3A4 inducer and a P-gp inducer.
Lumacaftor; Ivacaftor: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with lumacaftor; ivacaftor; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Dolutegravir is partially metabolized by CYP3A and, in vitro, is a substrate for the P-glycoprotein (P-gp) drug transporter. Lumacaftor is a strong CYP3A inducer; in vitro data suggest lumacaftor; ivacaftor may also induce and/or inhibit P-gp.
Magnesium Citrate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing laxatives such as magnesium citrate. The chemical structure contains polyvalent cations which can bind dolutegravir in the GI tract. Taking magnesium citrate simultaneously may result in reduced bioavailability of dolutegravir.
Magnesium Hydroxide: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing gastrointestinal medications such as magnesium hydroxide. The chemical structure of these GI drugs that contain polyvalent cations, such as magnesium hydroxide, can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Magnesium Salts: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain magnesium which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Maribavir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with maribavir. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and maribavir is a P-gp and BCRP inhibitor.
Mavacamten: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with mavacamten. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Repaglinide: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Rosiglitazone: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Saxagliptin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems

involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Sitagliptin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Methadone: (Moderate) In a study of 11 adult HIV-infected subjects receiving methadone maintenance therapy (40 to 90 mg/day) and abacavir 600 mg twice daily (twice the current recommended dose), methadone clearance increased by 22% (6% to 42%). While this interaction will not require dosage adjustment in the majority of patients, a small number of patients may require increased doses of methadone. In addition, a significant decrease in abacavir Cmax (34%) and increase in Tmax (67%) were noted, but no changes in overall abacavir clearance or half-life were reported. The clinical significance regarding abacavir therapy is not known.
Midostaurin: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with midostaurin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitapivat: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with mitapivat. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and mitapivat is a P-gp inhibitor.
Mitotane: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with mitotane; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Mitotane is a strong CYP3A inducer and dolutegravir is partially metabolized by this isoenzyme.
Modafinil: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with modafinil; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Modafinil is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Neratinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with neratinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nevirapine: (Major) Avoid concurrent use of nevirapine and dolutegravir. Concomitant use may decrease plasma concentrations of dolutegravir and there are insufficient data to make dosing recommendations. Dolutegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nirmatrelvir; Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Oritavancin: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with oritavancin; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Dolutegravir is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer.
Orlistat: (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 dolutegravir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is a BCRP and P-glycoprotein (P-gp) substrate and osimertinib is a BCRP and P-gp inhibitor.
Oteseconazole: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with oteseconazole. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Oxcarbazepine: (Major) Avoid concurrent use of dolutegravir with oxcarbazepine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Oxcarbazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Pacritinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pacritinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP and P-gp substrate; pacritinib is a BCRP and P-gp inhibitor.
Peginterferon Alfa-2a: (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.
Peginterferon Alfa-2b: (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.
Peginterferon beta-1a: (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.
Pexidartinib: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with pexidartinib. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Phenobarbital: (Major) Avoid concurrent use of dolutegravir with phenobarbital, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Phenobarbital is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concurrent use of dolutegravir with phenobarbital, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Phenobarbital is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Phentermine; Topiramate: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme.
Phenytoin: (Major) Avoid concurrent use of dolutegravir with phenytoin, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Phenytoin is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Pioglitazone; Metformin: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Pirtobrutinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pirtobrutinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and pirtobrutinib is a P-gp and BCRP inhibitor.
Polysaccharide-Iron Complex: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Pretomanid: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with pretomanid. Concurrent use may increase the exposure of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and pretomanid is a P-gp and BCRP inhibitor.
Primidone: (Major) Avoid concurrent use of dolutegravir with primidone, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Primidone is metabolized to phenobarbital, which is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Procainamide: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
Pyridoxine, Vitamin B6: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Regorafenib: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with regorafenib is necessary. Dolutegravir is a BCRP substrate and regorafenib is a BCRP inhibitor.
Ribavirin: (Moderate) Use abacavir 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. (Moderate) Use lamivudine 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. In addition, ribavirin has been shown in cell culture to inhibit phosphorylation of lamivudine, which could lead to decreased antiretroviral activity; however, while ribavirin inhibits the phosphorylation reactions required to activate lamivudine, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed.
Ribociclib: (Moderate) Use caution if coadministration of ribociclib with dolutegravir is necessary, as the systemic exposure of dolutegravir may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor. Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
Ribociclib; Letrozole: (Moderate) Use caution if coadministration of ribociclib with dolutegravir is necessary, as the systemic exposure of dolutegravir may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor. Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
Rifampin: (Major) When possible, avoid concurrent use of dolutegravir with rifampin in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with rifampin. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and rifampin is an inducer of CYP3A4.
Rifapentine: (Major) Do not administer rifapentine and dolutegravir together in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance who are receiving twice daily doses of dolutegravir. Additionally, avoid use of once daily rifapentine in any patient receiving dolutegravir. However, once weekly doses of rifapentine may be administered with caution to treatment-naive or treatment-experienced, but INSTI-naive patients receiving once daily dolutegravir. Monitor for virologic efficacy if these drugs are administered concurrently. In a drug interaction study, administration of rifapentine (900 mg once weekly) decreased the AUC and trough concentration of dolutegravir by 26% and 47%, respectively. Dolutegravir is a CYP3A and UGT1A substrate and rifapentine is a strong CYP3A and UGT1A inducer.
Riociguat: (Moderate) Monitor for an increase in riociguat-related adverse effects like hypotension if concomitant use with abacavir is necessary. Consider a riociguat dose reduction in patients who may not tolerate the hypotensive effect of riociguat. Concomitant use of riociguat and abacavir may increase riociguat exposure although the magnitude of increase is unknown. Riociguat is a CYP1A1 substrate; abacavir may inhibit CYP1A1.
Ritlecitinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with ritlecitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) Caution is advised when administering abacavir and ritonavir concurrently. Ritonavir appears to induce glucuronosyl transferase, and therefore, has the potential to reduce plasma concentrations of drugs that undergo glucuronidation, such as abacavir. The clinical significance of the potential for this interaction is unknown.
Ropeginterferon alfa-2b: (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.
Selpercatinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with selpercatinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with taurursodiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and taurursodiol is a P-gp and BCRP inhibitor.
Sorafenib: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with sorafenib is necessary. Dolutegravir is a P-glycoprotein (P-gp) and UGT1A1 substrate. Sorafenib inhibits both P-gp and UGT1A1 in vitro, and may increase the concentrations of concomitantly administered drugs that are P-gp or UGT1A1 substrates.
Sorbitol: (Major) Avoid coadministration of lamivudine oral solution and sorbitol if possible due to sorbitol dose-dependent reduction in lamivudine exposure. An all-tablet regimen should be used when possible to avoid a potential interaction with sorbitol. Consider more frequent monitoring of viral load when treating with lamivudine oral solution. In a drug interaction study in 16 healthy adult patients, coadministration of a single 300 mg dose of lamivudine oral solution with sorbitol 3.2 g, 10.2 g, or 13.4 g resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC24 and 28%, 52%, and 55% in the Cmax of lamivudine.
Sotorasib: (Moderate) Monitor for decreased efficacy or increased toxicity of dolutegravir if coadministered with sotorasib. Concurrent use may alter the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A4, BCRP, and P-gp substrate; sotorasib is a moderate CYP3A4 inducer and a BCRP and P-gp inhibitor.
Sparsentan: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with sparsentan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp and BCRP substrate and sparsentan is a P-gp and BCRP inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Avoid concurrent use of dolutegravir with St. John's Wort, Hypericum perforatum as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. St. John's Wort is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Sucralfate: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking sucralfate. The chemical structure of sucralfate contains aluminum, which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and dolutegravir as coadministration may increase the plasma concentrations of dolutegravir increasing the risk of adverse effects. Dolutegravir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tedizolid: (Moderate) If possible, stop use of dolutegravir temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for dolutegravir-associated adverse events. Dolutegravir plasma concentrations may be increased when dolutegravir is administered concurrently with oral tedizolid. Dolutegravir is a in vitro substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
Temsirolimus: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with temsirolimus is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of dolutegravir.
Tepotinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with tepotinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tipranavir: (Major) When possible, avoid concurrent use of dolutegravir and tipranavir boosted with ritonavir in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with tipranavir/ritonavir. Use of these drugs together results in decreased dolutegravir plasma concentrations. Dolutegravir is a substrate of uridine glucuronyltransferase (UGT), P-glycoprotein (P-gp), and CYP3A4 (minor). Tipranavir is an inducer of P-gp and inhibitor of CYP3A4; while ritonavir is an inducer of UGT, an inhibitor of P-gp, and a mixed inducer/inhibitor of CYP3A4. (Moderate) Concurrent administration of tipranavir and ritonavir with abacavir results in decreased abacavir concentrations. The clinical significance of this interaction has not been established, and no recommendations for abacavir dosage adjustments are available.
Topiramate: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme.
Trospium: (Moderate) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion including lamivudine. In theory, coadministration of trospium with lamivudine may increase the serum concentrations of trospium or lamivudine due to competition for the drug elimination pathway.
Tucatinib: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with tucatinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A4 and P-glycoprotein (P-gp) substrate and tucatinib is a strong CYP3A4 inhibitor and P-gp inhibitor.
Voclosporin: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voclosporin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and voclosporin is a P-gp inhibitor.
Voriconazole: (Moderate) Use caution if coadministration of voriconazole with dolutegravir is necessary, as the systemic exposure of dolutegravir may be increased resulting in an increase in treatment-related adverse reactions. Voriconazole is a strong CYP3A4 inhibitor. Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
Voxelotor: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voxelotor. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.

Abacavir, Dolutegravir, Lamivudine Oral Tab for Susp: 60-5-30mg
TRIUMEQ Oral Tab: 600-50-300mg

Adults

1 Triumeq tablet per day PO (abacavir 600 mg/day PO; dolutegravir 50 mg/day PO; lamivudine 300 mg/day PO).

Geriatric

1 Triumeq tablet per day PO (abacavir 600 mg/day PO; dolutegravir 50 mg/day PO; lamivudine 300 mg/day PO).

Adolescents

1 Triumeq tablet per day PO (abacavir 600 mg/day PO; dolutegravir 50 mg/day PO; lamivudine 300 mg/day PO).

Children

weighing 25 kg or more: 1 Triumeq tablet per day PO (abacavir 600 mg/day PO; dolutegravir 50 mg/day PO; lamivudine 300 mg/day PO).
weighing 20 to 24 kg: 6 Triumeq PD tablets per day PO (abacavir 360 mg/day PO; dolutegravir 30 mg/day PO; lamivudine 180 mg/day PO).
weighing 14 to 19 kg: 5 Triumeq PD tablets per day PO (abacavir 300 mg/day PO; dolutegravir 25 mg/day PO; lamivudine 150 mg/day PO).
weighing 10 to 13 kg: 4 Triumeq PD tablets per day PO (abacavir 240 mg/day PO; dolutegravir 20 mg/day PO; lamivudine 120 mg/day PO).
weighing 6 to 9 kg: 3 Triumeq PD tablets per day PO (abacavir 180 mg/day PO; dolutegravir 15 mg/day PO; lamivudine 90 mg/day PO).

Infants

3 to 11 months weighing 10 to 13 kg: 4 Triumeq PD tablets per day PO (abacavir 240 mg/day PO; dolutegravir 20 mg/day PO; lamivudine 120 mg/day PO).
3 to 11 months weighing 6 to 9 kg: 3 Triumeq PD tablets per day PO (abacavir 180 mg/day PO; dolutegravir 15 mg/day PO; lamivudine 90 mg/day PO).
1 to 2 months or weighing less than 6 kg: Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Abacavir; dolutegravir; lamivudine is active against infections caused by human immunodeficiency virus type 1 (HIV-1). Both abacavir and lamivudine are nucleoside analogs that work by inhibiting HIV reverse transcriptase, while dolutegravir works by inhibiting the catalytic activity of HIV integrase.
 
•Abacavir: Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate. Carbovir triphosphate is an analog of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-hydroxyl group in the incorporated nucleoside analog prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is inhibited.
 
Abacavir hypersensitivity may be related to an induced autoimmunity process related to HLA-B*5701. Human Leukocyte Antigens (HLAs) help the body to distinguish “self” versus “foreign” proteins (peptides). A study determined that abacavir alters the quantity and quality of self-peptide loading into HLA-B*5701. These self-peptides are then presented for the first time and because the body has not previously recognized them, it mistakenly treats them as foreign, resulting in a polyclonal T-cell autoimmune response and multi-organ systemic toxicity. Once the drug is discontinued, reactive T-cells would be reduced and then differentiate into T memory cells. Re-exposure would again generate these peptides leading to a rapid expansion of T memory cells which could cause severe and potentially life-threatening reactions.
 
•Lamivudine: In vitro activity has been assessed in a number of cell lines where lamivudine showed anti-HIV activity in all virus-cell infections tested. Intracellular phosphorylation produces the 5'-triphosphate metabolite, lamivudine triphosphate (3TC-TP). This active metabolite inhibits reverse transcriptase and viral DNA synthesis. 3TC-TP also inhibits cellular DNA polymerase.
 
•Dolutegravir: Antiviral activity results from inhibition of HIV integrase, one of the three HIV-1 enzymes required for viral replication. Integration of HIV into cellular DNA is a multi-step process. First, the assembly of integrase in a stable complex with the viral DNA occurs. Second, the terminal dinucleotides from each end of the viral DNA are removed by endonucleolytic processing. Lastly, the viral DNA 3' ends are covalently linked to the cellular (target) DNA by strand transfer. The last 2 processes, which are catalytic, require integrase to be appropriately assembled on a specific viral DNA substrate. Inhibition of integrase by dolutegravir prevents the covalent insertion, or integration, of unintegrated linear HIV DNA into the host cell genome preventing the formation of the HIV provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection.
 
Antiviral drug resistance is a problem in the treatment of HIV infection. The combination of abacavir and lamivudine has demonstrated decreased susceptibility to viruses with certain viral mutations, including M184V/I, K65R, L74V, and Y115F. Decreases in dolutegravir susceptibility have been observed in HIV-1 with the following amino acid substitutions: E92Q, G118R, S153F, S153Y, G193E, and R263K. Combination therapy targets different points in the life cycle of HIV, reducing the ability of HIV to mutate to drug-resistant strains.
 
Cross-resistance between abacavir/lamivudine and other nucleoside reverse transcriptase inhibitors has been observed in strains of HIV-1 containing multiple reverse transcriptase mutations. Cross-resistance between abacavir/lamivudine and non-nucleoside reverse transcriptase inhibitors or HIV protease inhibitors is unlikely because of different binding sites on reverse transcriptase and different targets enzymes. Cross-resistance to dolutegravir has not been observed in reverse transcriptase inhibitor-resistant nor protease inhibitor-resistant strains; however, decrease dolutegravir susceptibility has occurred in integrase stand transfer inhibitor-resistant HIV-1 and HIV-2 strains.

Abacavir; dolutegravir; lamivudine is administered orally.
Abacavir: Once in the systemic circulation, abacavir distributes into extravascular space. Protein binding is approximately 50% and is independent of concentration. Based on radiolabeled studies, the drug readily distributes into erythrocytes. In humans, abacavir is not significantly metabolized by cytochrome P450 enzymes. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronyl transferase (to form the 5'glucuronide). The metabolites have no antiviral activity. In vitro experiments reveal that abacavir does not inhibit human CYP3A4, CYP2D6, or CYP2C9 activity at clinically relevant concentrations. Elimination of abacavir was quantified in a mass balance study after administration of a 600-mg dose of (14)C-abacavir: 83% of the radioactivity was recovered in urine, 1.2% as unchanged drug, 30% as the 5'-carboxylic acid metabolite, 36% as the 5'-glucuronide metabolite, and 15% as unidentified minor metabolites. Fecal elimination accounted for 16% of the dose. In single-dose studies, the observed elimination half-life was 1.54 +/- 0.63 hours.[29710] [57813]
Lamivudine: It distributes into extravascular spaces. The volume of distribution ranges from 0.9 to 1.7 L/kg, is independent of dose, and does not correlate with body weight. Plasma protein binding is less than 36%. Hepatic metabolism is a minor route of elimination; most of an oral dose (71%) is excreted unchanged in the urine by active organic cationic secretion. The only known metabolite in humans is the trans-sulfoxide metabolite, which accounts for approximately 5% of a dose appearing in the urine. The mean elimination half-life after a single dose ranges from 5 to 7 hours.[29240] [46708] [57813]
Dolutegravir: The drug is highly bound (98.9% or more) to human plasma protein, with an estimated volume of distribution of 17.4 L. Although the clinical relevance has not been established, dolutegravir distributes into the cerebrospinal fluid (CSF) at a median concentration of 18 ng/mL. Metabolism occurs via UDP-glucuronosyltransferase (UGT)1A1 (major) and by the hepatic isoenzyme CYP3A (minor). The terminal half-life is approximately 14 hours, with more than half of the total dose (53%) excreted unchanged in the feces. Excretion in the urine accounts for 31% of the total dose; however, less than 1% of the renally eliminated drug is unchanged.[55594] [57813]
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A1, CYP3A4, UGT1A1, UGT1A3, UGT1A9, P-gp, BCRP, OCT2, MATE1
Data from in vitro studies show abacavir has the potential to inhibit CYP1A1 and the limited potential to inhibit CYP3A4. Other CYP isoenzymes (e.g., CYP2C9 and CYP2D6) are not inhibited or induced by abacavir. Similarly, abacavir at therapeutic drug exposures is not expected to affect the pharmacokinetics of substrates of the following drug transporters: organic anion transporter polypeptide (OATP)1B1/3, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic cation transporter (OCT)1, OCT2, or multidrug and toxic extrusion protein (MATE)1 and MATE2-K.
Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A4. When administered with atazanavir, an inhibitor of UGT1A1, the dolutegravir Cmax increased by 50%, and the AUC increased by 91%; however, no dolutegravir dosage adjustment was recommended. Dolutegravir is a substrate, in vitro, for the enzymes UGT1A3 and UGT1A9. It is also a substrate, in vitro, for the transporters P-gp and BCRP. It is an inhibitor of renal OCT2 and potentially MATE1. Dolutegravir is an inhibitor of the renal organic anion transporters OAT1 and OAT3 in vitro; however, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir, which is a substrate of OAT1 and OAT3. The drug does not inhibit the following: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, UGT1A1, UGT2B7, P-gp, BCRP, bile salt export pump (BSEP), OATP1B1, OATP1B3, OCT1, multidrug resistant protein (MRP)2, or MRP4. Additionally, the drug does not induce CYP1A2, CYP2B6, or CYP3A4.[57813]

Oral Route

Triumeq and Triumeq PD are bioequivalent for the abacavir and lamivudine components, but not for the dolutegravir component. The relative dolutegravir bioavailability of Triumeq PD is approximately 1.7-fold higher than Triumeq; therefore, the 2 dosage forms are NOT interchangeable on a mg-per-mg basis. Triumeq PD is NOT indicated for use in adults or patients weighing 25 kg or more.
Abacavir: The drug is rapidly and extensively absorbed. Bioavailability is about 83% for the tablets. Administration of Triumeq to healthy adults with a high-fat meal (53% fat, 869 calories) decreased the Cmax by 23%. Administration of Triumeq PD to healthy adults with a high-fat meal (50% fat, 917 calories) resulted in a 55% decrease in the Cmax; the AUC was unaffected.
Lamivudine: Absorption is rapid, with a mean absolute bioavailability of approximately 85%. Food has no significant effect on systemic exposure of Triumeq. Administration of Triumeq PD to healthy adults with a high-fat meal (50% fat, 917 calories) resulted in a 36% decrease in the Cmax; the AUC was unaffected.
Dolutegravir: The absolute bioavailability is unknown. Peak plasma concentrations are obtained 2 to 3 hours after an oral dose, with steady-state concentrations achieved within 5 days. Administration of Triumeq to healthy adults with a high-fat meal (53% fat, 869 calories) increased the Cmax and AUC by 37% and 48%, respectively. Administration of Triumeq PD to healthy adults with a high-fat meal (50% fat, 917 calories) resulted in a 29% decrease in the Cmax; the AUC was unaffected.

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. Guidelines recommend the use of abacavir; dolutegravir; lamivudine as a preferred treatment option for HLA-B*5701 negative pregnant patients, irrespective of the trimester, and for non-pregnant patients who are trying to conceive. Exposure to dolutegravir around the time of conception may be associated with a small increased risk of infant neural tube defects (NTD). Data from an observational surveillance study identified NTD in 9 infants born to 5,860 mothers (0.15%) who were exposed to a dolutegravir-containing regimen around the time of conception (periconception exposure). The incidence of NTD in infants of mothers receiving other antiretroviral regimens at the time of conception was 0.1% (95% CI: -0.03% to 0.2%) and in infants of mothers without HIV was 0.07% (95% CI: 0.01% to 0.23%). Of the 9 dolutegravir-associated cases, 4 infants had myelomeningocele, 3 infants had encephalocele, 1 infant had anencephaly, and 1 infant had iniencephaly. In the same study, NTD was found in 3 infants out of 5,535 (0.05%) deliveries to mothers who started dolutegravir during pregnancy. Data from the Antiretroviral Pregnancy Registry (APR) regarding dolutegravir exposure and central nervious system birth defects are available. Among the reported exposures to dolutegravir, 5 central nervious system birth defects were identified (2 of 571 periconception, 1 of 125 late first trimester, 2 of 434 second/third trimester). One of these defects was an NTD in an infant with periconception exposure; no encephalocele defects were reported. Additional data from the APR, which includes more than 1,410 first trimester exposures to abacavir, more than 695 first trimester exposures to dolutegravir, and more than 5,500 first trimester exposures to lamivudine, 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. The prevalence of defects for abacavir, dolutegravir, and lamivudine when exposure occurred in the first trimester is 3.1% (95% CI: 2.3 to 4.2), 3.2% (95% CI: 2 to 4.8), and 3.1% (95% CI: 2.6 to 3.6), respectively. 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 liver function tests and serum electrolytes assessed more frequently during the last trimester of pregnancy and any new symptoms should be evaluated thoroughly. [46638] [63237] 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 abacavir; dolutegravir; lamivudine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263. [27468]

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).[42452] Although there is no information regarding the effects of abacavir, dolutegravir, or lamivudine on breast-fed infants or milk production, all 3 drug components are present in human milk. Available data show dolutegravir is found in breast milk at concentrations about 3% of those observed in maternal plasma. In 1 study conducted in Botswana, the mean breast milk-to-plasma ratio of abacavir was 0.85 in the 15 women tested. Further, an analysis of 9 breast-feeding infants found detectable plasma drug concentrations in 1 infant. Lamivudine was found to be secreted in human breast milk during a study involving 20 breast-feeding women with HIV who were administered either 300 mg of lamivudine twice daily as a single agent (n = 10) or lamivudine 150 mg twice daily in combination with zidovudine (n = 10). The mean breast milk concentrations of lamivudine in the respective groups were similar at 1.22 mg/L (range less than 0.5 to 6.09 mg/L) and 0.9 mg/L (range less than 0.5 to 8.2 mg/L). Other antiretroviral mediations whose passage into human breast milk have been evaluated include nevirapine, zidovudine, and nelfinavir. [46679] [46680] [46682] [57813]