DOSAGE AND ADMINISTRATION
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2.1 Adults - Treatment of HIV-1 Infection
Oral Dosing
The recommended oral dose of RETROVIR is 300 mg twice daily in combination with other antiretroviral agents.
Intravenous (IV) Dosing
The recommended intravenous dose is 1 mg per kg infused at a constant rate over 1 hour every 4 hours. Patients should receive RETROVIR injection only until oral therapy can be administered.
•RETROVIR injection must be diluted prior to administration. The calculated dose should be removed from the 20 mL vial and added to 5% Dextrose injection solution to achieve a concentration no greater than 4 mg per mL.
•After dilution, the solution is physically and chemically stable for 24 hours at room temperature and 48 hours if refrigerated at 2° to 8°C (36° to 46°F). As an additional precaution, the diluted solution should be administered within 8 hours if stored at 25°C (77°F) or 24 hours if refrigerated at 2° to 8°C to minimize potential administration of a microbially contaminated solution.
•Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit and discarded if either is observed.
•Rapid infusion or bolus injection should be avoided. RETROVIR injection should not be given intramuscularly.
2.2 Pediatric Patients (Aged 4 Weeks to Less than 18 Years)
Healthcare professionals should pay special attention to accurate calculation of the dose of RETROVIR, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.
Prescribers should calculate the appropriate dose of RETROVIR for each child based on body weight (kg) and should not exceed the recommended adult dose.
Before prescribing RETROVIR capsules, children should be assessed for the ability to swallow capsules. If a child is unable to reliably swallow a RETROVIR capsule, the RETROVIR syrup formulation should be prescribed.
The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. RETROVIR syrup should be used to provide accurate dosage when capsules are not appropriate.
Table 1. Recommended Pediatric Oral Dosage of RETROVIR
|
Body Weight
(kg)
|
Total Daily Dose
|
Dosage Regimen and Dose
|
|
Twice Daily
|
Three Times Daily
|
|
4 to <9
|
24 mg/kg/day
|
12 mg/kg
|
8 mg/kg
|
|
≥9 to <30
|
18 mg/kg/day
|
9 mg/kg
|
6 mg/kg
|
|
≥30
|
600 mg/day
|
300 mg
|
200 mg
|
Alternatively, dosing for RETROVIR can be based on body surface area (BSA) for each child. The recommended oral dose of RETROVIR is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.
2.3 Prevention of Maternal-Fetal HIV-1 Transmission
The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is:
Maternal Dosing
100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous RETROVIR should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord.
Neonatal Dosing
Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered RETROVIR intravenously. See Table 2.
2.4 Patients with Severe Anemia and/or Neutropenia
Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoietin level and patient tolerance.
2.5 Patients with Renal Impairment
In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours. The intravenous dosing regimen equivalent to the oral administration of 100 mg every 6 to 8 hours is approximately 1 mg per kg every 6 to 8 hours [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.6 Patients with Hepatic Impairment
There are insufficient data to recommend dose adjustment of RETROVIR in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].
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Monitoring of Patients
Hematologic toxicities appear to be related to pretreatment bone marrow reserve and to dose and duration of therapy. In patients with poor bone marrow reserve, particularly in patients with advanced symptomatic HIV disease, frequent monitoring of hematologic indices is recommended to detect serious anemia or neutropenia (see WARNINGS). In patients who experience hematologic toxicity, reduction in hemoglobin may occur as early as 2 to 4 weeks, and neutropenia usually occurs after 6 to 8 weeks.
Dose Adjustment
Anemia:
Significant anemia (hemoglobin of <7.5 g/dL or reduction of >25% of baseline) and/or significant neutropenia (granulocyte count of<750 cells/mm3 or reduction of >50% from baseline) may require a dose interruption until evidence of marrow recovery is observed (see WARNINGS). In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoetin level and patient tolerance.
For patients experiencing pronounced anemia while receiving chronic coadministration of zidovudine and some of the drugs (e.g., fluconazole, valproic acid) listed in Table 4, zidovudine dose reduction may be considered.
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