No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

In combination with at least two other antiretrovirals in the treatment of patients with HIV infection; it is not recommended that zalcitabine be given in combination with didanosine, stavudine, or lamivudine due to overlapping toxicities, virologic interactions, or lack of clinical data

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 zalcitabine or any component

Careful monitoring of pancreatic enzymes and liver function tests in patients with a history of pancreatitis, increased amylase, those on parenteral nutrition or with a history of ethanol abuse; discontinue use immediately if pancreatitis is suspected; lactic acidosis and severe hepatomegaly and failure have rarely occurred with zalcitabine resulting in fatality; some cases may possibly be related to underlying hepatitis B; use with caution in patients on digitalis, congestive heart failure, renal failure, hyperphosphatemia; zalcitabine can cause severe peripheral neuropathy; avoid use, if possible, in patients with pre-existing neuropathy

>10%:

Central nervous system: Fever (5% to 17%), malaise (2% to 13%)

Neuromuscular & skeletal: Peripheral neuropathy (28.3%)

1% to 10%:

Central nervous system: Headache (2.1%), dizziness (1.1%), fatigue (3.8%), seizures (1.3%)

Endocrine & metabolic: Hypoglycemia (1.8% to 6.3%), hyponatremia (3.5%), hyperglycemia (1% to 6%)

Hematologic: Anemia (occurs as early as 2-4 weeks), granulocytopenia (usually after 6-8 weeks)

Dermatologic: Rash (2% to 11%), pruritus (3% to 5%)

Gastrointestinal: Nausea (3%), dysphagia (1% to 4%), anorexia (3.9%), abdominal pain (3% to 8%), vomiting (1% to 3%), diarrhea (0.4% to 9.5%), weight loss, oral ulcers (3% to 7%), increased amylase (3% to 8%)

Hepatic: Abnormal hepatic function (8.9%), hyperbilirubinemia (2% to 5%)

Neuromuscular & skeletal: Myalgia (1% to 6%), foot pain

Respiratory: Pharyngitis (1.8%), cough (6.3%), nasal discharge (3.5%)

<1%: Edema, hypertension, palpitations, syncope, atrial fibrillation, tachycardia, heart racing, chest pain, night sweats, pain, hypocalcemia, constipation, pancreatitis, jaundice, hepatitis, hepatomegaly, hepatic failure, myositis, weakness, epistaxis

Symptoms of overdose include delayed peripheral neurotoxicity; following oral decontamination

Treatment is supportive

Decreased effect: Magnesium/aluminum-containing antacids and metoclopramide may reduce zalcitabine absorption

Increased toxicity:

Amphotericin, foscarnet, cimetidine, probenecid, and aminoglycosides may potentiate the risk of developing peripheral neuropathy or other toxicities associated with zalcitabine by interfering with the renal elimination of zalcitabine

Other drugs associated with peripheral neuropathy which should be avoided, if possible, include chloramphenicol, cisplatin, dapsone, disulfiram, ethionamide, glutethimide, didanosine, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, and vincristine

It is not recommended that zalcitabine be given in combination with didanosine, stavudine, or lamivudine due to overlapping toxicities, virologic interactions, or lack of clinical data

Tablets should be stored in tightly closed bottles at 59°F to 86°F

Purine nucleoside analogue, zalcitabine or 2',3'-dideoxycytidine (ddC) is converted to active metabolite ddCTP; lack the presence of the 3'-hydroxyl group necessary for phosphodiester linkages during DNA replication. As a result viral replication is prematurely terminated. ddCTP acts as a competitor for binding sites on the HIV-RNA dependent DNA polymerase (reverse transcriptase) to further contribute to inhibition of viral replication.

Absorption: Well but variably absorbed from GI tract; food decreases absorption by 39%

Distribution: Minimal data available; CSF penetration is variable

Protein binding: Minimal, <4%

Metabolism: Intracellularly to active triphosphorylated agent

Bioavailability: >80%

Half-life: 2.9 hours, may be prolonged to 8.5 hours in patients with renal impairment

Elimination: Mainly renal, >70% unchanged

Oral:

Adults: Daily dose: 0.75 mg every 8 hours

Dosing adjustment in renal impairment: Adults:

Cl_cr 10-40 mL/minute: 0.75 mg every 12 hours

Cl_cr <10 mL/minute: 0.75 mg every 24 hours

Moderately dialyzable (20% to 50%)

Food: Extent and rate of absorption may be decreased with food

Renal function, viral load, liver function tests, CD4 counts, CBC, serum amylase, triglycerides, calcium

Drowsiness is common; may cause dizziness

May cause granulocytopenia; use caution with clozapine; concurrent use with disulfiram can enhance peripheral neuropathy; avoid combination

No information available to require special precautions

Oral ulceration in >10% of patients

Zalcitabine is not a cure for AIDS, nor has it been found to reduce transmission of AIDS. Take as directed, preferably on an empty stomach (1 hour before or 2 hours after meals). Take around-the-clock; do not take with other medications. You may experience headache or insomnia; if these persist notify prescriber. Report chest pain, palpitations, or rapid heartbeat; swelling of extremities; weight gain or loss >5 lb/week; signs of infection (eg, fever, chills, sore throat, burning urination, fatigue); unusual bleeding (eg, tarry stools, easy bruising, or blood in stool, urine, or mouth); pain, tingling, or numbness of toes or fingers; skin rash or irritation; or muscles weakness or tremors. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Tablet: 0.375 mg, 0.75 mg

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