zalcitabine (dideoxycytidine, ddC)
Hivid

Available forms
Available by prescription only
Tablets (film-coated): 0.375 mg, 0.75 mg

Indications and dosages
 Patients with advanced HIV infection (CD4⁺ count below 300 cells/mm³) who have significant clinical or immunologic deterioration. Adults and children age 13 and older: 0.75 mg P.O. q 8 hours. Can be taken with zidovudine (200 mg P.O. q 8 hours).
≡ Dosage adjustment. Adjustment may be needed in patients with creatinine clearance of 40 ml/minute or below.

Creatinine clearance (ml/min) Adult dosage 10-40 0.75 mg P.O. q 12 hr <10 0.75 mg P.O. q 24 hr

Pharmacodynamics
Antiviral action: Active against HIV. Within cells, drug is converted by cellular enzymes into its active metabolite, dideoxycytidine 5′-triphosphate. Inhibits replication of HIV by blocking viral DNA synthesis. Also inhibits reverse transcriptase by acting as an alternative for the enzyme’s substrate, deoxycytidine triphosphate.

Pharmacokinetics
Absorption: Mean absolute bioavailability above 80%; food decreases rate and extent of absorption.
Distribution: Steady state volume of distribution is 0.534 to 0.127 L/kg. Drug enters CNS.
Metabolism: Doesn’t appear to undergo significant hepatic metabolism; phosphorylation to the active form occurs within cells.
Excretion: Primarily excreted by kidneys; about 70% of dose appears in urine within 24 hours. Mean elimination half-life is 2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use cautiously in patients with peripheral neuropathy, impaired renal function, hepatic failure, or history of pancreatitis, heart failure, or cardiomyopathy.

Interactions
Drug-drug. Antacids containing aluminum or magnesium: Decreases absorption of zalcitabine. Separate administration times.
Cimetidine, probenecid: Decreases zalcitabine elimination. Monitor patient closely; adjust dosage as needed.
Drugs that cause peripheral neuropathy (such as chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold salts, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine): Increases risk of peripheral neuropathy. Monitor patient closely; adjust dosage as needed.
Drugs that may impair renal function (aminoglycosides, amphotericin, foscarnet): Increases risk of zalcitabine-induced adverse effects. Limit use together; monitor patient closely.
Pentamidine: Causes risk of pancreatitis. Avoid use together.

Adverse reactions
CNS: peripheral neuropathy, headache, fatigue, dizziness, confusion, seizures, impaired concentration, amnesia, insomnia, mental depression, tremor, hypertonia, anxiety.
EENT: pharyngitis, ocular pain, abnormal vision, ototoxicity, nasal discharge.
GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, constipation, stomatitis, esophageal ulcer, glossitis, pancreatitis.
Hematologic: anemia, leukopenia, neutropenia, thrombocytopenia, eosinophilia.
Metabolic: lactic acidosis.
Respiratory: cough.
Skin: rash, pruritus, urticaria.

Effects on lab test results
• May increase glucose, alkaline phosphatase, ALT, and AST levels.
• May decrease hemoglobin and neutrophil, WBC, and platelet counts.

Overdose and treatment
There’s little experience with acute overdose.
 It’s not known if drug is dialyzable. Treat overdose symptomatically.

Special considerations
• If drug is stopped because of toxicity, resume recommended dosage for zidovudine alone, which is 100 mg every 4 hours.
• Monitor patient for peripheral neuropathy. If symptoms indicating peripheral neuropathy occur, stop drug if they’re bilateral and persist beyond 72 hours. If these symptoms persist or worsen beyond 1 week, permanently stop drug. However, if all findings relevant to peripheral neuropathy have resolved to minor symptoms, drug may be reintroduced at 0.375 mg P.O. every 8 hours.
• When drug alone is only treatment, peripheral neuropathy has occurred in 17% to 31% of patients. The peripheral neuropathy seen with zalcitabine therapy is a sensorimotor neuropathy, initially characterized by numbness and burning in the limbs. If drug isn’t withdrawn, symptoms can progress to sharp, shooting pain or severe, continuous burning pain requiring narcotic analgesics; pain may or may not be reversible.
• Patients who had long-term exposure to doses about six times higher than the current recommended dose experienced peripheral neuropathy within 10 weeks; patients exposed to twice the recommended dose experienced peripheral neuropathy within 12 weeks.
• Women of childbearing age should use an effective method of contraception while taking drug.
• Watch for toxic effects. They may cause abnormalities in several laboratory tests, including CBC; hemoglobin; leukocyte, reticulocyte, granulocyte, and platelet counts; and AST, ALT, and alkaline phosphatase levels.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of risk of transmitting virus, HIV-positive women shouldn’t breast-feed.
Pediatric patients
• Safety and efficacy in children younger than age 13 haven’t been established.
• An oral solution is available from the manufacturer through a compassionate use program.

Patient education
• Explain that drug doesn’t cure HIV infection and that HIV can still be transmitted. Opportunistic in

Patient education
• Explain that drug doesn’t cure HIV infection and that HIV can still be transmitted. Opportunistic infections may continue to occur despite use of drug.
• Tell patient that drug may cause peripheral neuropathy and life-threatening pancreatitis. Review signs and symptoms of these reactions, and instruct patient to report them immediately.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use