Retrovir Infusion

COMBIVIR® (lamivudine and zidovudine) Tablets and TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine) Tablets are combination product tablets that contain zidovudine as one of their components. RETROVIR should not be administered concomitantly with COMBIVIR or TRIZIVIR.

The incidence of adverse reactions appears to increase with disease progression; patients should be monitored carefully, especially as disease progression occurs.

Bone Marrow Suppression:

RETROVIR should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count <1,000 cells/mm3 or hemoglobin <9.5 g/dL. In subjects with advanced symptomatic HIV disease, anemia and neutropenia were the most significant adverse events observed. There have been reports of pancytopenia associated with the use of RETROVIR, which was reversible in most instances, after discontinuance of the drug. However, significant anemia, in many cases requiring dose adjustment, discontinuation of RETROVIR, and/or blood transfusions, has occurred during treatment with RETROVIR alone or in combination with other antiretrovirals.

Frequent blood counts are strongly recommended in patients with advanced HIV disease who are treated with RETROVIR. For HIV-infected individuals and patients with asymptomatic or early HIV disease, periodic blood counts are recommended. If anemia or neutropenia develops, dosage adjustments may be necessary (see DOSAGE AND ADMINISTRATION).

Myopathy:

Myopathy and myositis with pathological changes, similar to that produced by HIV disease, have been associated with prolonged use of RETROVIR.

Lactic Acidosis/Severe Hepatomegaly with Steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including zidovudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged exposure to antiretroviral nucleoside analogues may be risk factors. Particular caution should be exercised when administering RETROVIR to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with RETROVIR should be suspended 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).

Use With Interferon- and Ribavirin-Based Regimens:

In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as zidovudine. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV/HCV virologic suppression) was seen when ribavirin was coadministered with zidovudine in HIV/HCV co-infected subjects (see CLINICAL PHARMACOLOGY: Drug Interactions), hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected subjects receiving combination antiretroviral therapy for HIV and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and RETROVIR should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia. Discontinuation of RETROVIR should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Childs Pugh >6) (see the complete prescribing information for interferon and ribavirin).

RETROVIR IV Infusion, 10 mg zidovudine in each mL.

20-mL Single-Use Vial, Tray of 10 (NDC 49702-213-05).

Store vials at 15° to 25°C (59° to 77°F) and protect from light.

RETROVIR, COMBIVIR, and TRIZIVIR are registered trademarks of the ViiV Healthcare group of companies.

Manufactured for:

ViiV Healthcare

Research Triangle Park, NC 27709

by:

GlaxoSmithKline

Research Triangle Park, NC 27709

©2013, ViiV Healthcare group of companies. All rights reserved.

October 2013

RTV: 4PI

CrCl less than 15 mL/min:
Oral: 100 mg orally every 6 to 8 hours
IV: 1 mg/kg IV (infused over 1 hour) every 6 to 8 hours

For the purposes of drug toxicity monitoring and dosage adjustment, a complete blood count as well as renal and hepatic function tests should be performed at baseline and every 3 months thereafter over the entire duration of therapy.

Zidovudine may cause bone marrow toxicity, most commonly neutropenia and anemia, particularly in patients with advanced symptomatic HIV disease. Hematologic toxicities appear to be associated with bone marrow reserve prior to therapy and to dose and duration of treatment. Zidovudine should be used with extreme caution in patients with bone marrow suppression indicated by a granulocyte count below 1000 cells/mm3 or hemoglobin less than 9.5 g/dL. Routine blood counts are recommended, and generally should occur more frequently in patients with advanced disease. If bone marrow toxicity occurs, a dose adjustment, dosage interruption, or discontinuation of zidovudine therapy and/or blood transfusions may be necessary.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretroviral agents. Risk factors may include female gender, obesity, and prolonged nucleoside exposure. Caution is recommended in patients with risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with zidovudine should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Exacerbation of anemia has been observed with concomitant use of zidovudine and ribavirin. Coadministration of zidovudine and ribavirin is not recommended. Coadministration of zidovudine with interferon alfa with or without ribavirin in HIV/HCV coinfected patients may precipitate hepatic decompensation, fatal in some cases. Patients receiving interferon alfa with or without ribavirin and zidovudine should be closely monitored for treatment-associated toxicities including neutropenia, anemia, and hepatic decompensation. Discontinuation of zidovudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alpha, ribavirin, or both should be considered if any of these toxicities occur.

Immune reconstitution syndrome has occurred during combination antiretroviral therapy. Patients responding to therapy may develop an inflammatory response to indolent or residual opportunistic infections and require evaluation and treatment.

Patients with allergies to nuts or soy should be aware that zidovudine oral capsules contain soya lecithin.

Patients with diabetes should be aware that the oral syrup contains sucrose.

Related drugs not for coadministration with zidovudine include abacavir/lamivudine/zidovudine and lamivudine-zidovudine, in which zidovudine is one of the active components.

The potential for HIV cross-resistance among nucleoside reverse transcriptase inhibitors exists but has not been fully explored. The effect of zidovudine therapy on the activity of subsequently administered nucleoside reverse transcriptase inhibitors has not been fully explored. Selection of antiretroviral agents for a patient's medication regimen should be done carefully and with the assistance of expert consultation.

Pediatric dosages are calculated based on body weight or body surface area. Special vigilance is recommended during calculation of dose, transcription of medication order, dispensing information, and dosing instructions to reduce the risk of medication errors.