Zalcitabine (Dideoxycytidine; ddC)

A to Z Drug Facts

 Action Inhibits replication of DNA in HIV.

 Indications Combination therapy: For the treatment of selected patients with advanced HIV infection.

 Contraindications Standard considerations.

 Route/Dosage

Combination therapy

ADULTS & ADOLESCENTS > 13 YR: PO 0.75 mg (coadministered with other antiviral agents) q 8 hr (total daily dose 2.25 mg zalcitabine).

 Interactions

Amphotericin, foscarnet, aminoglycosides: May increase risk of peripheral neuropathy and other zalcitabine toxicities caused by decreased clearance of zalcitabine. Chloramphenicol, cisplatin, dapsone, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine: May increase risk of peripheral neuropathy. Drugs associated with pancreatitis (eg, pentamidine): Fatal pancreatitis has occurred, possibly related to zalcitabine and IV pentamidine given concurrently.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Chest pain; cardiomyopathy; CHF. CNS: Headache; dizziness; confusion; impaired concentration; peripheral neuropathy. DERM: Rash; pruritus; dermatitis. EENT: Pharyngitis. GI: Pancreatitis; oral ulcers; nausea; dysphagia; anorexia; abdominal pain; vomiting; diarrhea; dry mouth; esophageal ulcers; dyspepsia; glossitis. META: Weight decrease; weight gain; increased amylase; hyperglycemia; hyponatremia; hypoglycemia; loss of appetite. RESP: Nasal discharge; cough; respiratory distress. OTHER: Myalgia; arthralgia; foot pain; fatigue; anaphylactoid reaction; abnormal GGT.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. It is recommended that HIV-positive women do not breastfeed. Lactic acidosis: Fatal cases of lactic acidosis have been reported. Children: Safety and efficacy in children < 13 yr not established. Anaphylactoid reaction: Has occurred. Urticaria has occurred without other signs of anaphylaxis. Cardiomyopathy/CHF: May develop. Use drug with caution in patients with history of cardiomyopathy or CHF. Esophageal ulcers: Have occurred. Hepatic impairment: In patients with history of liver disease or alcoholism, zalcitabine may exacerbate hepatic dysfunction. Dosage reduction or interruption of therapy may be needed. Hepatitis B: Hepatic failure and death, possibly related to underlying hepatitis B and zalcitabine, have been reported. Hepatomegaly: Fatal cases of severe hepatomegaly with steatosis have been reported. HIV infection complications: Patients receiving zalcitabine or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection. Pancreatitis: Fatal pancreatitis has occurred. Peripheral neuropathy: Most common major toxicity. May be clinically disabling and require reduction of dose or discontinuation of drug. Renal impairment: Patients with renal impairment (creatinine clearance < 55 mL/min) may be at greater risk of toxicity because of decreased drug clearance. Dosage reduction may be needed.

 Administration/Storage

• Administer on empty stomach 1 hr before or 2 hr after meals for maximum absorption.
• Administer q 8 hr around clock.
• If Ccr is decreased, reduced dose (0.75 mg) may be given q 12 hr (Ccr 10 to 40 mL/min) or q 24 hr (Ccr < 10 mL/min).
• Store at room temperature in tight containers.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note cardiac, hepatic and renal dysfunction; peripheral neuropathy; and pancreatitis.
• Perform clinical chemistry tests before and periodically during therapy. Monitor CBC, renal function studies (BUN, serum uric acid, urine creatinine clearance), liver function tests (bilirubin, AST, ALT, alkaline phosphatase), and baseline serum amylase and triglyceride levels in patients with prior history of pancreatitis, increased amylase or ethanol abuse, and those on parenteral nutrition.
• Prior to therapy and throughout treatment, assess for signs of peripheral neuropathy: Tingling, burning, or pain in distal extremities. In patients with moderate symptoms of peripheral neuropathy, discontinue drug then reintroduce at 50% of initial dose only if neuropathy symptoms have improved to mild. Use of drug may be discontinued permanently if severe discomfort due to neuropathy or moderate discomfort progresses ³ 1 wk.
• Assess for pancreatitis: Abdominal pain, nausea, vomiting, elevated liver enzymes. Withhold zalcitabine and zidovudine and notify health care provider of these symptoms immediately.
• Observe for signs of infection; monitor temperature q 4 hr. Antibiotics may be ordered prophylactically.
• Frequently monitor hematologic indices to detect serious anemia or granulocytopenia. Development of anemia (hemoglobin < 7.5/dL or reduction > 25% of baseline) or granulocytopenia (granulocyte count < 750/min³ or reduction > 50% of baseline) may require interruption of treatment with both zalcitabine and zidovudine until marrow recovers. Transfusion may be needed.
• In patients developing hematologic toxicity, decreases in hemoglobin may occur as early as 2 to 4 wk after therapy begins and granulocytopenia may occur after 6 to 8 wk of therapy.
• Reduction of dose is not required for patients weighing ³ 30 kg.

 Patient/Family Education

• Advise patient to take around the clock as prescribed and not to increase the dose.
• Advise patient not to share the drug with others.
• Inform patient and family that patient may continue to develop opportunistic infections and other complications of HIV infection and should remain under close medical supervision.
• Explain that zalcitabine is not a cure but may offer symptomatic improvement.
• Reinforce fact that zalcitabine does not decrease risk of transmission of HIV through sexual contact or blood contamination.
• Instruct patient to notify health care provider immediately of signs of peripheral neuropathy (numbness and burning feeling in arms and legs) or pancreatitis (abdominal pain, nausea, vomiting).
• Encourage patient to report all changes in conditions to health care provider.
• Inform patient that long-term effects of this drug alone and in combination with zidovudine are unknown.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts