Retrovir

Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)s

Hazardous Drugs Classification
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.
INJECTABLE Drugs: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
ORAL TABLETS/CAPSULES/LIQUID: 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.

May be administered without regard to meals.

Use a calibrated spoon, oral syringe, or container to measure the oral solution for accurate dosing. To ensure accurate dosing in neonates, use an appropriate-sized oral syringe with 0.1 mL graduation.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Use of the injectable formulation is only recommended until oral therapy can be administered.

Dilution:
Withdraw the appropriate dose from the vial containing 10 mg/mL injection solution and dilute in D5W to a concentration not to exceed 4 mg/mL.
Storage: After dilution, the solution is stable for 24 hours at room temperature of 25 degrees C (77 degrees F) and 48 hours if refrigerated at 2 to 8 degrees C (36 to 46 degrees F); however, the manufacturer recommends administering the diluted solution within 8 hours if stored at room temperature or within 24 hours if refrigerated to minimize the risk of administering a microbially contaminated solution.[28305]
 
Intravenous infusion:
Administer as a continuous IV infusion over 60 minutes.
Neonates receiving zidovudine to prevent maternal-fetal HIV transmission are administered the infusion over 30 minutes.
Rapid infusion or bolus injection should be avoided.[28305]

heart failure / Delayed / 0-6.0
pancytopenia / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
red cell aplasia / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
cardiomyopathy / Delayed / 0-1.0
seizures / Delayed / 0-1.0
lactic acidosis / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
macular edema / Delayed / 0-1.0
vasculitis / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
hearing loss / Delayed / 0-1.0
esophageal ulceration / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known

anemia / Delayed / 1.0-22.0
neutropenia / Delayed / 0-21.0
hepatomegaly / Delayed / 0-11.0
lymphadenopathy / Delayed / 0-9.0
wheezing / Rapid / 7.0-7.0
erythema / Early / 7.0-7.0
constipation / Delayed / 6.0-6.0
stomatitis / Delayed / 6.0-6.0
edema / Delayed / 0-6.0
hematuria / Delayed / 0-6.0
splenomegaly / Delayed / 5.0-5.0
elevated hepatic enzymes / Delayed / 1.0-3.0
hyperamylasemia / Delayed / 3.0-3.0
leukopenia / Delayed / 0-1.0
thrombocytopenia / Delayed / 1.0-1.0
myopathy / Delayed / 0-1.0
confusion / Early / 0-1.0
depression / Delayed / 0-1.0
mania / Early / 0-1.0
oral ulceration / Delayed / 0-1.0
dysphagia / Delayed / 0-1.0
chest pain (unspecified) / Early / 0-1.0
hepatitis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
steatosis / Delayed / 0-1.0
photophobia / Early / 0-1.0
amblyopia / Delayed / 0-1.0
dyspnea / Early / 0-1.0
hyperbilirubinemia / Delayed / 0-0.8
peripheral neuropathy / Delayed / 5.0
bone marrow suppression / Delayed / Incidence not known
lipodystrophy / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known

headache / Early / 63.0-63.0
malaise / Early / 53.0-53.0
nausea / Early / 8.0-51.0
fever / Early / 25.0-25.0
anorexia / Delayed / 20.0-20.0
vomiting / Early / 8.0-17.0
cough / Delayed / 15.0-15.0
rash / Early / 12.0-12.0
asthenia / Delayed / 9.0-9.0
diarrhea / Early / 8.0-8.0
rhinorrhea / Early / 8.0-8.0
nasal congestion / Early / 8.0-8.0
otalgia / Early / 7.0-7.0
irritability / Delayed / 0-6.0
weight loss / Delayed / 0-6.0
back pain / Delayed / 0-1.0
tremor / Early / 0-1.0
drowsiness / Early / 0-1.0
paresthesias / Delayed / 0-1.0
anxiety / Delayed / 0-1.0
dizziness / Early / 0-1.0
vertigo / Early / 0-1.0
flatulence / Early / 0-1.0
dysgeusia / Early / 0-1.0
influenza / Delayed / 0-1.0
syncope / Early / 0-1.0
increased urinary frequency / Early / 0-1.0
urticaria / Rapid / 0-1.0
hyperhidrosis / Delayed / 0-1.0
nail discoloration / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
rhinitis / Early / 0-1.0
sinusitis / Delayed / 0-1.0
musculoskeletal pain / Early / 5.0
arthralgia / Delayed / 5.0
myalgia / Early / 5.0
insomnia / Early / 5.0
dyspepsia / Early / 5.0
abdominal pain / Early / 5.0
chills / Rapid / 5.0
fatigue / Early / 5.0
macrocytosis / Delayed / 10.0

Use zidovudine with caution in patients who have pre-existing bone marrow suppression evidenced by neutropenia (absolute neutrophil count less than 1000/mm3) or anemia (hemoglobin less than 9.5 mg/dL).[28305] Zidovudine is known to cause hematologic toxicity, particularly in neonates and those with advanced HIV disease. Hematologic toxicity appears to be related to pretreatment bone marrow reserve and to dose and duration of therapy. Cytotoxic chemotherapy or radiation therapy may also increase the risk of myelosuppression. Monitor blood counts frequently in patients with poor bone marrow reserve, particularly those with advanced HIV. The HIV guidelines recommend monitoring complete blood counts (CBC) with differential at entry to care and before initiating or modifying treatment. For patients started on an antiretroviral regimen containing zidovudine, a follow-up CBC with differential should be obtained after 2 to 8 weeks of treatment, followed by periodic monitoring every 3 to 6 months or as clinically indicated.[42452] [46638] A complete blood count and differential should be performed in a neonate prior to administration of zidovudine; those with anemia at birth, those exposed in utero to antiretrovirals, or those who are born premature warrant more intensive monitoring due to increased risk of anemia. Consider repeating CBC at 4 weeks in high-risk neonates. Repeat measurement of hemoglobin is required minimally with any signs of anemia, after the completion of the 6-week regimen, and at 12 weeks of age. Severe anemia and/or granulocytopenia may necessitate interruption of therapy, dosage adjustment, discontinuation of zidovudine, and/or blood transfusions until bone marrow recovery is observed. Use of erythropoietin or colony stimulating factors (e.g., GM-CSF, G-CSF) may be necessary in some patients.[23512] [42452]
 

Zidovudine is primarily eliminated by hepatic metabolism and concentrations appear to be increased in patients with hepatic disease, which may increase the risk for toxicity. Zidovudine should be used with caution in patients with hepatic disease or in those with known risk factors for liver disease (e.g., alcoholism); however, cases of hepatotoxicity or lactic acidosis, including fatal cases, have been reported in patients with no risk factors. A majority of these cases occurred in females; it is unknown if pregnant women are at increased risk. In addition, obesity may be risk factors for nucleoside analog-induced lactic acidosis and hepatotoxicity. Clinicians need to be alert for early diagnosis of this syndrome. Pregnant women receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester and any new symptoms should be evaluated thoroughly. Treatment should be discontinued 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 increases in transaminases.

Monitor patients for signs of myopathy and myositis, as they have been reported, along with pathological changes similar to that produced by HIV, with prolonged use of zidovudine.

Retrovir

Rx

Nucleoside reverse transcriptase inhibitor (NRTI)
Used to treat HIV-1 infections and for perinatal HIV prophylaxis
Associated with hematologic toxicity and bone marrow suppression

300 mg PO twice daily.

300 mg PO twice daily, or alternatively, 180 to 240 mg/m2/dose (Max: 300 mg/dose) PO twice daily. The FDA-approved dose is 300 mg PO twice daily or 200 mg PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily (Max: 600 mg/day).

9 mg/kg/dose PO twice daily, or alternatively, 180 to 240 mg/m2/dose PO twice daily. The FDA-approved dose is 9 mg/kg/dose PO twice daily or 6 mg/kg/dose PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily.

12 mg/kg/dose PO twice daily, or alternatively, 180 to 240 mg/m2/dose PO twice daily. The FDA-approved dose is 12 mg/kg/dose PO twice daily or 8 mg/kg/dose PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily.

12 mg/kg/dose PO twice daily.

4 mg/kg/dose PO twice daily.

12 mg/kg/dose PO twice daily.

3 mg/kg/dose PO twice daily.

2 mg/kg/dose PO twice daily.

12 mg/kg/dose PO twice daily.

3 mg/kg/dose PO twice daily.

2 mg/kg/dose PO twice daily.

1 mg/kg/dose IV every 4 hours, which is approximately equivalent to 100 mg PO every 4 hours.

120 mg/m2/dose IV every 6 hours. Current guidelines do not contain IV dosing for pediatric patients. The FDA-approved adult dose is 1 mg/kg/dose IV every 4 hours, which is approximately equivalent to 100 mg PO every 4 hours.

120 mg/m2/dose IV every 6 hours. Current guidelines do not contain IV dosing for infants and children 4 weeks of age and older.

9 mg/kg/dose IV twice daily.

3 mg/kg/dose IV twice daily.

9 mg/kg/dose IV twice daily.

2.25 mg/kg/dose IV twice daily.

1.5 mg/kg/dose IV twice daily.

9 mg/kg/dose IV twice daily.

2.25 mg/kg/dose IV twice daily.

1.5 mg/kg/dose IV twice daily.

4 mg/kg/dose PO twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.

4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 2 weeks. Prophylaxis may be extended to 4 to 6 weeks for infants who are breastfeeding. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.

4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 4 to 6 weeks.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 4 to 6 weeks.

NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.

3 mg/kg/dose IV twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.

3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 2 weeks. Prophylaxis may be extended to 4 to 6 weeks for infants who are breastfeeding. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.

3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 4 to 6 weeks.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 4 to 6 weeks.

4 mg/kg/dose PO twice daily to complete 6 weeks of therapy with lamivudine and either nevirapine or raltegravir at treatment doses for 2 to 6 weeks. If the infant is receiving a 2-drug ARV prophylaxis regimen and received 3 nevirapine doses in the first week of life, continue therapy with zidovudine monotherapy to complete 6 weeks of treatment. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.

4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Treat for 6 weeks in combination with lamivudine and either nevirapine or raltegravir (37 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 6 weeks in combination with lamivudine and nevirapine (32 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 6 weeks.

NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.

3 mg/kg/dose IV twice daily to complete 6 weeks of therapy with lamivudine and either nevirapine or raltegravir at treatment doses for 2 to 6 weeks. If the infant is receiving a 2-drug ARV prophylaxis regimen and received 3 nevirapine doses in the first week of life, continue therapy with zidovudine monotherapy to complete 6 weeks of treatment. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.

3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Treat for 6 weeks in combination with lamivudine and either nevirapine or raltegravir (37 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 6 weeks in combination with lamivudine and nevirapine (32 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 6 weeks.

2 mg/kg/dose IV over 1 hour, followed by 1 mg/kg/hour IV continuous infusion for 2 hours (minimum of 3 hours total). The FDA-approved labeling recommends continuation until clamping of the umbilical cord. Initiate the infusion upon presenting in labor or at least 3 hours before a cesarean delivery. For cases of unscheduled cesarean delivery for both maternal and fetal indications, consideration can be given to administering only the 1-hour loading dose, and not waiting to complete additional administration before proceeding with delivery.

2 mg/kg/dose IV over 1 hour, followed by 1 mg/kg/hour IV continuous infusion for 2 hours (minimum of 3 hours total). The FDA-approved labeling recommends continuation until clamping of the umbilical cord. Initiate the infusion upon presenting in labor or at least 3 hours before a cesarean delivery. For cases of unscheduled cesarean delivery for both maternal and fetal indications, consideration can be given to administering only the 1-hour loading dose, and not waiting to complete additional administration before proceeding with delivery.

4 mg/kg/dose PO twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.

4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 4 to 6 weeks.

2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 4 to 6 weeks.

NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.

3 mg/kg/dose IV twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.

3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 4 to 6 weeks.

1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 4 to 6 weeks.

300 mg PO twice daily with either lamivudine or emtricitabine is recommended as an acceptable nucleoside reverse transcriptase inhibitor (NRTI) backbone for HIV post-exposure prophylaxis (PEP) by the US Public Health Service and the New York State Department of Health AIDS Institute (NYSDOH AI). Another alternative regimen suggested by the NYSDOH AI combines zidovudine with tenofovir plus either emtricitabine or lamivudine. According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however, if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

300 mg PO twice daily in combination with lamivudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults with renal dysfunction (CrCl 59 mL/minute or less). Zidovudine and lamivudine doses should be adjusted to degree of renal impairment. Zidovudine in combination with lamivudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

300 mg PO twice daily in combination with lamivudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents with renal dysfunction (CrCl 59 mL/minute or less). Zidovudine and lamivudine doses should be adjusted to degree of renal impairment. Zidovudine in combination with lamivudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

9 mg/kg/dose (Max: 300 mg/dose) PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

9 mg/kg/dose PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. Zidovudine in combination with emtricitabine and raltegravir or lopinavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

12 mg/kg/dose PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. Zidovudine in combination with emtricitabine and raltegravir or lopinavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

4 mg/kg/dose PO twice daily for 4 to 6 weeks total (including initial 2 weeks of zidovudine prophylaxis after birth).

4 mg/kg/dose PO twice daily for 4 to 6 weeks total (including initial 2 weeks of zidovudine prophylaxis after birth).

In a small study, the combination of interferon alfa with zidovudine 200 mg PO every four hours while awake (i.e., 5 doses/day or 1,000 mg/day) produced major responses in 11 of 19 patients (58%), including complete remissions in 5 of 19 (26%). Doses were adjusted for hematologic toxicity. Treatment was continued for at least 4 weeks after the onset of complete remission, or, for up to 1 year in the absence of remission.

600 mg PO every 6 hours in combination with valganciclovir or ganciclovir for 7 to 21 days.

600 mg PO every 6 hours in combination with valganciclovir or ganciclovir for 7 to 21 days.

†Indicates off-label use

There are insufficient data to recommend dosage adjustments in patients with hepatic impairment or liver cirrhosis; however, zidovudine is primarily eliminated by hepatic metabolism and elevated concentrations have been noted in patients with hepatic impairment. Monitor closely for hematologic toxicities.

Adult patients
CrCl 15 mL/minute or more: No dosage adjustment needed.
CrCl less than 15 mL/minute: 100 mg PO every 6 to 8 hours or 1 mg/kg/dose IV every 6 to 8 hours.
 
Pediatric patients†
GFR 10 mL/minute/1.73 m2 or more: No dosage adjustment needed.
GFR less than 10 mL/minute/1.73 m2: Reduce recommended dose by 50%.
 
Intermittent hemodialysis
The recommended dose in adults is 100 mg PO every 6 to 8 hours or 1 mg/kg/dose IV every 6 to 8 hours. For pediatric patients, reduce the recommended dose by 50%.
 
Peritoneal dialysis
The recommended dose in adults is 100 mg PO every 6 to 8 hours or 1 mg/kg/dose IV every 6 to 8 hours. For pediatric patients, reduce the recommended dose by 50%.
 
Continuous renal replacement therapy (CRRT)†
No dosage adjustment necessary.

Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Codeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Diphenhydramine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Hydrocodone: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Ibuprofen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Oxycodone: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Phenylephrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Acetaminophen; Pseudoephedrine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
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).
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Amphotericin B lipid complex (ABLC): (Moderate) The use of ABLC with zidovudine, ZDV has lead to an increase in myelotoxicity and nephrotoxicity in dogs. If these medications are used concomitantly, monitor renal and hematologic function closely.
Aspirin, ASA; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Atovaquone: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Atovaquone; Proguanil: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Azathioprine: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive, such as azathioprine. A significant toxicity of zidovudine, ZDV is myelosuppression and resulting neutropenia and anemia.
Benzhydrocodone; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like zidovudine; the risk of peripheral neuropathy may be additive.
Butalbital; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Butalbital; Acetaminophen; Caffeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Cidofovir: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine.
Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Clofarabine: (Moderate) Concomitant use of clofarabine and zidovudine, ZDV may result in altered clofarabine levels because both agents are substrates of OAT1 and OAT3. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 substrates.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with zidovudine is necessary as there is an increased risk of hematologic toxicity and immunosuppression.
Dapsone: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.
Doxorubicin Liposomal: (Major) Avoid concomitant administration of zidovudine, ZDV, and doxorubicin as an antagonistic relationship has been demonstrated in vitro.
Doxorubicin: (Major) Avoid concomitant administration of zidovudine, ZDV, and doxorubicin as an antagonistic relationship has been demonstrated in vitro.
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.
Fluconazole: (Minor) During concomitant administration with fluconazole, the clearance of zidovudine may be reduced. Although the clinical significance of this interaction has not been established, patients receiving fluconazole with zidovudine should be closely monitored for zidovudine-induced adverse effects, especially hematologic toxicity. Zidovudine dosage reduction may be considered.
Flucytosine: (Moderate) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression, such as flucytosine, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted.
Foscarnet: (Minor) Concurrent use of foscarnet and zidovudine, ZDV may be associated with a higher incidence of anemia; clinicians should follow normal recommendations for blood count monitoring and other parameters.
Fosphenytoin: (Minor) Coadministration with zidovudine may result in either increased or decreased phenytoin concentrations.
Ganciclovir: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
Indinavir: (Moderate) When indinavir and zidovudine, ZDV were administered concurrently, the AUC of indinavir and zidovudine was increased by 13% +/- 48% and 17% +/- 23%, respectively. Dosage adjustments are not recommended when zidovudine is administered with indinavir.
Interferons: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with 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 therapy may also reduce zidovudine clearance.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Isoniazid, INH; Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Leflunomide: (Moderate) Closely monitor for zidovudine-induced side effects such as hematologic toxicity when these drugs are used together. In some patients, a dosage reduction of zidovudine may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with zidovudine, a substrate of OAT3, may increase zidovudine plasma concentrations.
Lopinavir; Ritonavir: (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Methadone: (Moderate) Methadone increases exposure zidovudine, ZDV. Patients should be monitored for zidovudine toxicity during concurrent methadone treatment; however, the manufacturer of zidovudine states that routine dosage adjustment of zidovudine is not required during coadministration of methadone. Patients who receive both methadone and zidovudine may experience symptoms characteristic of opiate withdrawal and attribute the cause to decreased methadone levels due to zidovudine. However, it is more likely patients are actually experiencing zidovudine side effects due to increased levels since zidovudine has no effect on methadone metabolism. In one pharmacokinetic study (n=9), coadministration of methadone increased the AUC of zidovudine by about 43% (range: 16-64%). It appears methadone inhibits zidovudine glucuronidation and, to a lesser extent, decreases zidovudine renal clearance.
Nirmatrelvir; Ritonavir: (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Rifabutin may accelerate the metabolism of zidovudine. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required. The CDC currently considers the nucleoside reverse transcriptase inhibitors, including zidovudine, compatible for concomitant use with rifamycins, including rifampin, rifabutin and rifapentine.
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.
Phenytoin: (Minor) Coadministration with zidovudine has resulted in altered phenytoin concentrations. Reports have varied, with increased and decreased phenytoin concentrations being reported. Use combination with caution.
Probenecid: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Probenecid; Colchicine: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Pyrimethamine: (Major) Pyrimethamine should be used cautiously with zidovudine, ZDV because of the potential for the development of blood dyscrasias including megaloblastic anemia, agranulocytosis, or thrombocytopenia. Monitor CBCs routinely in patients receiving both drugs simultaneously; if signs of folate deficiency develop, pyrimethamine should be discontinued.
Ribavirin: (Moderate) Use zidovudine 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 may antagonize the cell culture antiviral activity of zidovudine against HIV; however, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed.
Rifabutin: (Minor) Rifabutin may accelerate the metabolism of zidovudine. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required. The CDC currently considers the nucleoside reverse transcriptase inhibitors, including zidovudine, compatible for concomitant use with rifamycins, including rifampin, rifabutin and rifapentine.
Rifampin: (Minor) Rifampin can accelerate the metabolism of zidovudine, causing a decrease in AUC of approximately 50%. However the effectiveness of zidovudine against HIV does not appear to be altered and no dosage adjustments are required.
Rifapentine: (Minor) Rifapentine appears to increase the glucuronidation of zidovudine, ZDV similar to other rifamycins. This may cause a decrease in zidovudine AUC. However, the effectiveness of zidovudine against HIV does not appear to be altered. The activity of zidovudine is dependent on the intracellular concentration of the triphosphate metabolite which is not correlated with plasma concentrations of the parent compound. The CDC currently considers the nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, compatible for concomitant use with rifamycins (including rifampin, rifabutin and rifapentine). No dosing adjustments are necessary.
Ritonavir: (Minor) Since ritonavir induces glucuronidation, there is the potential for reduction in zidovudine, ZDV plasma concentrations during concurrent therapy with ritonavir. When coadministered with ritonavir, the AUC and Cmax of zidovudine, ZDV are decreased by 12% and 27%. The clinical significance of this interaction is unknown.
Stavudine, d4T: (Contraindicated) Zidovudine, ZDV, may competitively inhibit the intracellular phosphorylation of stavudine, d4T. Therefore, use of these drugs together is not recommended. At a molar ratio of 20:1 (stavudine:zidovudine), an antagonistic antiviral effect was detected, while at molar ratios of 100:1 and 500:1, antiviral effects were additive. Administration of zidovudine is recommended during labor and delivery in HIV-infected women; for women who are receiving a stavudine-containing regimen, discontinue stavudine during labor while intravenous zidovudine is being administered. Following delivery, the previous anti-retroviral regimen can be resumed.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Sulfonamides: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Teriflunomide: (Major) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression including teriflunomide because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage or discontinuation of zidovudine may be warranted. Teriflunomide, an organic anion transporter OAT3 renal updake inhibitor, may cause elevated concentrations of zidovudine, an OAT3 substrate.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with zidovudine results in decreased zidovudine concentrations. The clinical significance of this interaction has not been established, and no recommendations for zidovudine dosage adjustments are available.
Tramadol; Acetaminophen: (Minor) Both acetaminophen and zidovudine, ZDV undergo glucuronidation. Competition for the metabolic pathway is thought to have caused a case of acetaminophen-related hepatotoxicity. This interaction may be more clinically significant in patients with depleted glutathione stores, such as patients with acquired immunodeficiency syndrome, poor nutrition, or alcoholism.
Trimethoprim: (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Valganciclovir: (Major) Zidovudine should be used cautiously with other drugs that can cause bone marrow suppression, such as valganciclovir, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted. Occasionally, discontinuation of therapy or the addition of a hematopoietic colony stimulating factor may be necessary.
Valproic Acid, Divalproex Sodium: (Minor) Concomitant administration of valproic acid and oral zidovudine may result in increase in the area under the concentration-time curve of zidovudine and a decrease in the AUC of its glucuronide metabolite. This interaction does not appear to be clinically significant unless the patient is experiencing hematologic toxicities. The dose of zidovudine may be reduced in patients who are experiencing pronounced anemia while receiving chronic coadministration of zidovudine and valproic acid.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Administer clarithromycin and zidovudine at least 2 hours apart. Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine may result in decreased steady-state zidovudine concentrations. The impact of coadministration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Voriconazole: (Minor) Concomitant administration of voriconazole and zidovudine may result in a reduction in the clearance of zidovudine.

Retrovir Intravenous Inj Sol: 1mL, 10mg
Retrovir/Zidovudine Oral Cap: 100mg
Retrovir/Zidovudine Oral Sol: 5mL, 50mg
Retrovir/Zidovudine Oral Tab: 300mg

600 mg/day PO or 6 mg/kg/day IV is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label.

600 mg/day PO or 6 mg/kg/day IV is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label.

weight 30 kg or more: 600 mg/day or 480 mg/m2/day PO is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight less than 30 kg: 18 mg/kg/day or 480 mg/m2/day PO is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.

weight 30 kg or more: 600 mg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 9 to 29 kg: 18 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 4 to 8 kg: 24 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.

weight 9 to 29 kg: 18 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 4 to 8 kg: 24 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.

35 weeks gestation and older: 8 mg/kg/day PO; 6 mg/kg/day IV.
30 to 34 weeks gestation: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO or 3 mg/kg/day IV for the first 2 weeks, then 6 mg/kg/day PO or 4.5 mg/kg/day IV have been used off-label.
younger than 30 weeks gestation: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO or 3 mg/kg/day IV for the first 4 weeks, then 6 mg/kg/day PO or 4.5 mg/kg/day IV have been used off-label.

Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits the replication of human and animal retroviruses after first being activated via several phosphorylation steps. Activity is dependent upon intracellular conversion to zidovudine 5'-triphosphate (ZDV-TP). The rate of phosphorylation varies depending on cell type. ZDV-TP inhibits the activity of the HIV reverse transcriptase by both competing for utilization with the natural substrate, deoxythymidine 5'-triphosphate (dTTP), and by incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleoside analog prevents the formation of 5' to 3' phosphodiester linkage essential for DNA chain elongation, and, therefore, viral DNA growth is terminated and production of new virions is inhibited.[28305]
 
Resistance to zidovudine has been reported, and is more likely in those who receive zidovudine for longer than 6 months. Researchers have noted that HIV-1 acquires resistance to zidovudine by a gradual, stepwise accumulation of 5 specific mutations in the gene that encodes its reverse transcriptase enzyme.[24545] Thymidine analog mutation substitutions in HIV-1 reverse transcriptase that confer resistance to zidovudine include M41L, D67N, K70R, L210W, T215Y/F. In general, higher levels of resistance are associated with a greater number of mutations. Combination therapy with zidovudine and lamivudine delays the emergence of mutations conferring resistance to zidovudine; and in some patients harboring zidovudine-resistant virus at baseline, phenotypic sensitivity to zidovudine can be restored by 12 weeks of treatment with zidovudine plus lamivudine. Cross-resistance has been noted among NRTIs. Thymidine analog mutation substitutions are selected by zidovudine and confer cross-resistance to abacavir, didanosine, stavudine, and tenofovir. The potential for cross-resistance between NRTIs and protease inhibitors is low because of the different enzyme targets involved.[28305]

Zidovudine is administered orally or intravenously. Once in systemic circulation, zidovudine has a volume of distribution of 1.6 +/- 0.6 L/kg. The drug crosses the placenta, is excreted in human breast milk, and has a cerebrospinal fluid (CSF): plasma ratio of 0.6:1. Protein binding is low at less than 38%. Rapid metabolism occurs in the liver. The major metabolite (GZDV) is formed by glucuronidation, and the AUC for GZDV is roughly 3-fold greater than the zidovudine AUC. A second metabolite, 3'-amino-3'-deoxythymidine (AMT) has been discovered following single dose intravenous administration of zidovudine. The AUC of AMT is about one-fifth of the zidovudine AUC. Intracellular conversion of zidovudine to the triphosphate is essential for antiviral activity. Both active drug and inactive metabolites are excreted by glomerular filtration and tubular secretion. The elimination half-life of zidovudine is 0.5 to 3 hours in adults.[28305]
 
Affected cytochrome P450 isoenzymes: none

Following oral administration, zidovudine is rapidly absorbed from the GI tract. The first-pass metabolism reduces systemic bioavailability to about 65%. Considerable individual variation occurs regarding the extent and rate of zidovudine absorption. Peak serum concentrations occur within 0.5 to 1.5 hours.

Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend the use of zidovudine plus lamivudine as an alternative 2-NRTI backbone in patients who are pregnant or trying to conceive. Available data from the Antiretroviral Pregnancy Registry, which includes more than 4,230 first trimester exposures to zidovudine, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When exposure occurred in the first trimester, the prevalence of defects was 3.2% (95% CI: 2.7 to 3.8) for zidovudine. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in newborns and in-utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed newborns appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second-trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for 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 zidovudine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.

The manufacturer recommends mothers be instructed to discontinue breast-feeding if they are receiving zidovudine. 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] Zidovudine, administered as 300 mg PO twice daily, was found to be secreted in human breast milk during a study involving 18 breast-feeding mothers with HIV. Data from this study revealed higher median zidovudine concentrations in the breast milk (207 ng/mL) than in the serum of the mothers (58 ng/mL). Other antiretroviral mediations whose passage into human breast milk have been evaluated include nevirapine, lamivudine, and nelfinavir.