No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

Treatment of adults with HIV infection in combination with other antiretroviral agents

C

Clinical effects on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Hypersensitivity to stavudine

Use with caution in patients who demonstrate previous hypersensitivity to zidovudine, didanosine, zalcitabine, pre-existing bone marrow suppression, renal insufficiency, or peripheral neuropathy. Peripheral neuropathy may be the dose-limiting side effect. Zidovudine should not be used in combination with stavudine. Potentially fatal lactic acidosis and hepatomegaly have been reported, use with caution in patients at risk of hepatic disease

All adverse reactions reported below were similar to comparative agent, zidovudine, except for peripheral neuropathy, which was greater for stavudine.

Central nervous system: Headache, chills/fever, malaise, insomnia, anxiety, depression, pain

Dermatologic: Rash

Gastrointestinal: Nausea, vomiting, diarrhea, pancreatitis, abdominal pain

Neuromuscular & skeletal: Peripheral neuropathy (15% to 21%)

1% to 10%:

Hematologic: Neutropenia, thrombocytopenia

Hepatic: Increased hepatic transaminases, increased bilirubin

Neuromuscular & skeletal: Myalgia, back pain, weakness

<1%: Lactic acidosis, hepatomegaly, hepatic failure, anemia, pancreatitis

Drugs associated with peripheral neuropathy (chloramphenicol, cisplatin, dapsone, ethionamide, gold, hydralazine, iodoquinol, isoniazid, lithium, metronidazole, nitrofurantoin, pentamidine, phenytoin, ribavirin, vincristine) may increase risk for stavudine peripheral neuropathy

Oral solution should be refrigerated and is stable for 30 days.

Stavudine is a thymidine analog which interferes with HIV viral DNA dependent DNA polymerase resulting in inhibition of viral replication; nucleoside reverse transcriptase inhibitor

Distribution: V_d: 0.5 L/kg

Peak serum level: 1 hour after administration

Bioavailability: 86.4%

Half-life: 1-1.6 hours

Elimination: Renal (40%)

Oral:

Adults:

greater than or equal to 60 kg: 40 mg every 12 hours

<60 kg: 30 mg every 12 hours

Dose may be cut in half if symptoms of peripheral neuropathy occur

Dosing adjustment in renal impairment:

Cl_cr >50 mL/minute:

greater than or equal to 60 kg: 40 mg every 12 hours

<60 kg: 30 mg every 12 hours

Cl_cr 26-50 mL/minute:

greater than or equal to 60 kg: 20 mg every 12 hours

<60 kg: 15 mg every 12 hours

Hemodialysis:

greater than or equal to 60 kg: 20 mg every 24 hours

<60 kg: 15 mg every 24 hours

Monitor liver function tests and signs and symptoms of peripheral neuropathy; monitor viral load and CD4 count

May cause drowsiness, insomnia, anxiety, or depression

May cause neutropenia; use caution with clozapine and carbamazepine; concurrent use with lithium may increase the risk of peripheral neuropathy

No information available to require special precautions

No effects or complications reported

This medication does not cure HIV. Use appropriate precautions to prevent transmission to others. Take as directed, around-the-clock, and take for full length of prescription. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. Frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or vomiting. Buttermilk or yogurt may help reduce diarrhea. Report immediately any tingling, unusual pain, or numbness in extremities. Report fever, chills, unusual fatigue or acute depression, acute abdominal or back pain, persistent muscle pain or weakness, or unusual bruising or bleeding. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not breast-feed.

Monitor liver function tests and signs and symptoms of peripheral neuropathy

Capsule: 15 mg, 20 mg, 30 mg, 40 mg

Powder for oral solution: 1 mg/mL (200 mL)

Browne MJ, Mayer KH, Chafee SB, et al, "2',3'-Didehydro-3'-deoxythymidine (d4T) in Patients With AIDS or AIDS-Related Complex - A Phase I Trial," J Infect Dis, 1993, 167(1):21-9.

Dudley MN, Graham KK, Kaul S, et al, "Pharmacokinetics of Stavudine in Patients With AIDS and AIDS-Related Complex," J Infect Dis, 1992, 166(3):480-5.

Hilts AE and Fish DN, "Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction," Am J Health Syst Pharm, 1998, 55:2528-33.

Kline MW, Dunkle LM, Church JA, et al, "A Phase I/II Evaluation of Stavudine (d4T) in Children With Human Immunodeficiency Virus Infection," Pediatrics, 1995, 96(2 Pt 1):247-52.

Lea AP and Faulds D, "Stavudine: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Clinical Potential in HIV Infection," Drugs, 1996, 51(5):846-64.

Sandstrom E and Oberg B, "Antiviral Therapy in Human Immunodeficiency Virus Infections. Current Status," Drugs, 1993, 45(4):488-508.

Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," April 15, 1999, http://www.hivatis.org.