Zidovudine Information
Zidovudine (Lamivudine; zidovudine; nevirapine)
Zidovudine (Lamivudine; zidovudine; nevirapine) Indications And Usage
Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets USP are indicated for the prevention of maternal-fetal HIV-1 transmission [see
]. The indication is based on a dosing regimen that included 3 components:
Points to consider prior to initiating Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets USP in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:
Zidovudine (Lamivudine; zidovudine; nevirapine) Dosage Forms And Strengths
Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets USP, 300 mg are supplied as round, white, biconvex, film-coated tablets which are plain on one side and embossed with “54 777” on the other side.
Zidovudine (Lamivudine; zidovudine; nevirapine) Contraindications
Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets USP are contraindicated in patients who have had potentially life-threatening allergic reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulation.
Zidovudine (Lamivudine; zidovudine; nevirapine) Warnings And Precautions
Zidovudine (Lamivudine; zidovudine; nevirapine) should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count <1,000 cells/mm or hemoglobin <9.5 g/dL. Hematologic toxicities appear to be related to pretreatment bone marrow reserve and to dose and duration of therapy. In patients with advanced symptomatic HIV-1 disease, anemia and neutropenia were the most significant adverse events observed. In patients who experience hematologic toxicity, a reduction in hemoglobin may occur as early as 2 to 4 weeks, and neutropenia usually occurs after 6 to 8 weeks. There have been reports of pancytopenia associated with the use of Zidovudine (Lamivudine; zidovudine; nevirapine) , which was reversible in most instances after discontinuance of the drug. However, significant anemia, in many cases requiring dose adjustment, discontinuation of Zidovudine (Lamivudine; zidovudine; nevirapine) , and/or blood transfusions, has occurred during treatment with Zidovudine (Lamivudine; zidovudine; nevirapine) alone or in combination with other antiretrovirals.
Frequent blood counts are strongly recommended to detect severe anemia or neutropenia in patients with poor bone marrow reserve, particularly in patients with advanced HIV-1 disease who are treated with Zidovudine (Lamivudine; zidovudine; nevirapine) . For HIV-1-infected individuals and patients with asymptomatic or early HIV-1 disease, periodic blood counts are recommended. If anemia or neutropenia develops, dosage interruption may be needed [see
].
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as Zidovudine (Lamivudine; zidovudine; nevirapine) . Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with Zidovudine (Lamivudine; zidovudine; nevirapine) in HIV-1/HCV co-infected patients [see
], exacerbation of anemia due to ribavirin has been reported when Zidovudine (Lamivudine; zidovudine; nevirapine) is part of the HIV regimen. Coadministration of ribavirin and Zidovudine (Lamivudine; zidovudine; nevirapine) is not advised. Consideration should be given to replacing Zidovudine (Lamivudine; zidovudine; nevirapine) in established combination HIV-1/HCV therapy, especially in patients with a known history of Zidovudine (Lamivudine; zidovudine; nevirapine) -induced anemia.
Hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and Zidovudine (Lamivudine; zidovudine; nevirapine) should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia.
Discontinuation of Zidovudine (Lamivudine; zidovudine; nevirapine) 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).
Zidovudine (Lamivudine; zidovudine; nevirapine) Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of Zidovudine (Lamivudine; zidovudine; nevirapine) . Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Zidovudine (Lamivudine; zidovudine; nevirapine) .
Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain, redistribution/accumulation of body fat [see ].
Cardiovascular: Cardiomyopathy, syncope.
Endocrine: Gynecomastia.
Eye: Macular edema.
Gastrointestinal: Dysphagia, flatulence, oral mucosa pigmentation, mouth ulcer.
General: Sensitization reactions including anaphylaxis and angioedema, vasculitis.
Hemic and Lymphatic: Aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia.
Hepatobiliary Tract and Pancreas: Hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis, pancreatitis.
Musculoskeletal: Increased CPK, increased LDH, muscle spasm, myopathy and myositis with pathological changes (similar to that produced by HIV-1 disease), rhabdomyolysis, tremor.
Nervous: Anxiety, confusion, depression, dizziness, loss of mental acuity, mania, paresthesia, seizures, somnolence, vertigo.
Respiratory: Dyspnea, rhinitis, sinusitis.
Skin: Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria.
Special Senses: Amblyopia, hearing loss, photophobia, taste perversion.
Urogenital: Urinary frequency, urinary hesitancy.
Zidovudine (Lamivudine; zidovudine; nevirapine) Use In Specific Populations
Zidovudine (Lamivudine; zidovudine; nevirapine) is excreted in human milk [see
].
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Zidovudine (Lamivudine; zidovudine; nevirapine) .
Zidovudine (Lamivudine; zidovudine; nevirapine) Overdosage
Acute overdoses of Zidovudine (Lamivudine; zidovudine; nevirapine) have been reported in pediatric patients and adults. These involved exposures up to 50 grams. No specific symptoms or signs have been identified following acute overdosage with Zidovudine (Lamivudine; zidovudine; nevirapine) apart from those listed as adverse events such as fatigue, headache, vomiting, and occasional reports of hematological disturbances. All patients recovered without permanent sequelae. Hemodialysis and peritoneal dialysis appear to have a negligible effect on the removal of Zidovudine (Lamivudine; zidovudine; nevirapine) while elimination of its primary metabolite, 3´-azido-3´-deoxy-5´-0-b-D-glucopyranuronosylthymidine (GZDV), is enhanced.
Zidovudine (Lamivudine; zidovudine; nevirapine) Description
Zidovudine (Lamivudine; zidovudine; nevirapine) (formerly called azidothymidine [AZT]), a pyrimidine nucleoside analogue active against HIV-1. The chemical name of Zidovudine (Lamivudine; zidovudine; nevirapine) is 3'-azido-3'-deoxythymidine; it has the following structural formula:
Zidovudine (Lamivudine; zidovudine; nevirapine) is a white to beige, odorless, crystalline solid with a molecular weight of 267.24 and a solubility of 20.1 mg/mL in water at 25°C. The molecular formula is CHN0.
Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets are for oral administration. Each film-coated tablet contains 300 mg of Zidovudine (Lamivudine; zidovudine; nevirapine) and the inactive ingredients are colloidal silicon dioxide, hypromellose, lactose (anhydrous), magnesium stearate, microcrystalline cellulose, polyethylene glycol, polydextrose, sodium starch glycolate, titanium dioxide, and triacetin.
Zidovudine (Lamivudine; zidovudine; nevirapine) Nonclinical Toxicology
Zidovudine (Lamivudine; zidovudine; nevirapine) was administered orally at 3 dosage levels to separate groups of mice and rats (60 females and 60 males in each group). Initial single daily doses were 30, 60, and 120 mg/kg/day in mice and 80, 220, and 600 mg/kg/day in rats. The doses in mice were reduced to 20, 30, and 40 mg/kg/day after day 90 because of treatment-related anemia, whereas in rats only the high dose was reduced to 450 mg/kg/day on day 91 and then to 300 mg/kg/day on day 279.
In mice, 7 late-appearing (after 19 months) vaginal neoplasms (5 nonmetastasizing squamous cell carcinomas, 1 squamous cell papilloma, and 1 squamous polyp) occurred in animals given the highest dose. One late-appearing squamous cell papilloma occurred in the vagina of a middle-dose animal. No vaginal tumors were found at the lowest dose.
In rats, 2 late-appearing (after 20 months), nonmetastasizing vaginal squamous cell carcinomas occurred in animals given the highest dose. No vaginal tumors occurred at the low or middle dose in rats. No other drug-related tumors were observed in either sex of either species.
At doses that produced tumors in mice and rats, the estimated drug exposure (as measured by AUC) was approximately 3 times (mouse) and 24 times (rat) the estimated human exposure at the recommended therapeutic dose of 100 mg every 4 hours.
It is not known how predictive the results of rodent carcinogenicity studies may be for humans.
Zidovudine (Lamivudine; zidovudine; nevirapine) was mutagenic in a 5178Y/TK mouse lymphoma assay, positive in an in vitro cell transformation assay, clastogenic in a cytogenetic assay using cultured human lymphocytes, and positive in mouse and rat micronucleus tests after repeated doses. It was negative in a cytogenetic study in rats given a single dose.
Zidovudine (Lamivudine; zidovudine; nevirapine) , administered to male and female rats at doses up to 7 times the usual adult dose based on body surface area, had no effect on fertility judged by conception rates.
Two transplacental carcinogenicity studies were conducted in mice. One study administered Zidovudine (Lamivudine; zidovudine; nevirapine) at doses of 20 mg/kg/day or 40 mg/kg/day from gestation day 10 through parturition and lactation with dosing continuing in offspring for 24 months postnatally. The doses of Zidovudine (Lamivudine; zidovudine; nevirapine) administered in this study produced Zidovudine (Lamivudine; zidovudine; nevirapine) exposures approximately 3 times the estimated human exposure at recommended doses. After 24 months, an increase in incidence of vaginal tumors was noted with no increase in tumors in the liver or lung or any other organ in either gender. These findings are consistent with results of the standard oral carcinogenicity study in mice, as described earlier. A second study administered Zidovudine (Lamivudine; zidovudine; nevirapine) at maximum tolerated doses of 12.5 mg/day or 25 mg/day (~1,000 mg/kg nonpregnant body weight or ~450 mg/kg of term body weight) to pregnant mice from days 12 through 18 of gestation. There was an increase in the number of tumors in the lung, liver, and female reproductive tracts in the offspring of mice receiving the higher dose level of Zidovudine (Lamivudine; zidovudine; nevirapine) .
Zidovudine (Lamivudine; zidovudine; nevirapine) Clinical Studies
Therapy with Zidovudine (Lamivudine; zidovudine; nevirapine) has been shown to prolong survival and decrease the incidence of opportunistic infections in patients with advanced HIV-1 disease and to delay disease progression in asymptomatic HIV-1-infected patients.
Zidovudine (Lamivudine; zidovudine; nevirapine) How Supplied/storage And Handling
Zidovudine (Lamivudine; zidovudine; nevirapine) Tablets USP, 300 mg (Round, white, film-coated tablet) (Identified 54 777)
0054-0052-21 Bottles of 60 tablets
Storage
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
Zidovudine (Lamivudine; zidovudine; nevirapine) Package Label - Zidovudine Tablets Usp, Mg
0054-0052-21 Bottles of 60 Tablets
Rx Only
Roxane Laboratories, Inc.
