Zidovudine Information
Zidovudine (Oral solution)
Zidovudine (Oral solution) Indications And Usage
Zidovudine (Oral solution) 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 (Oral solution) Tablets USP in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:
Zidovudine (Oral solution) Dosage Forms And Strengths
Zidovudine (Oral solution) 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 (Oral solution) Contraindications
Zidovudine (Oral solution) 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 (Oral solution) Warnings And Precautions
Zidovudine (Oral solution) should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count
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 (Oral solution) . 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 (Oral solution) . 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 (Oral solution) in HIV-1/HCV co-infected patients [see ], exacerbation of anemia due to ribavirin has been reported when Zidovudine (Oral solution) is part of the HIV regimen. Coadministration of ribavirin and Zidovudine (Oral solution) is not advised. Consideration should be given to replacing Zidovudine (Oral solution) in established combination HIV-1/HCV therapy, especially in patients with a known history of Zidovudine (Oral solution) -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 (Oral solution) should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia.
Discontinuation of Zidovudine (Oral solution) 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 (Oral solution) 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 (Oral solution) . 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 (Oral solution) .
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 (Oral solution) Use In Specific Populations
Zidovudine (Oral solution) 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 (Oral solution) .
Zidovudine (Oral solution) Overdosage
Acute overdoses of Zidovudine (Oral solution) 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 (Oral solution) 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 (Oral solution) while elimination of its primary metabolite, 3´-azido-3´-deoxy-5´-0-b-D-glucopyranuronosylthymidine (GZDV), is enhanced.
Zidovudine (Oral solution) Description
Zidovudine (Oral solution) (formerly called azidothymidine [AZT]), a pyrimidine nucleoside analogue active against HIV-1. The chemical name of Zidovudine (Oral solution) is 3'-azido-3'-deoxythymidine; it has the following structural formula:
Zidovudine (Oral solution) 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 (Oral solution) Tablets are for oral administration. Each film-coated tablet contains 300 mg of Zidovudine (Oral solution) 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 (Oral solution) Nonclinical Toxicology
Zidovudine (Oral solution) 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 (Oral solution) 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 (Oral solution) , 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 (Oral solution) 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 (Oral solution) administered in this study produced Zidovudine (Oral solution) 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 (Oral solution) 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 (Oral solution) .
Zidovudine (Oral solution) Clinical Studies
Therapy with Zidovudine (Oral solution) 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 (Oral solution) How Supplied/storage And Handling
Zidovudine (Oral solution) 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 (Oral solution) Package Label - Zidovudine Tablets Usp, Mg
0054-0052-21 Bottles of 60 Tablets
Rx Only
Roxane Laboratories, Inc.
