Zalcitabine

Zalcitabine may be found in some form under the following brand names:

• Hivid

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Zalcitabine falls into category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

OR

There are no well-controlled studies that have been done in pregnant women. Zalcitabine should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

OR

No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Zalcitabine should be given to a pregnant woman only if clearly needed.

Take zalcitabine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Zalcitabine dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Zalcitabine is available in the following doses:

• Zalcitabine 0.375 Mg Oral Tablet
• Zalcitabine 0.75 Mg Oral Tablet

Zalcitabine is available in the following forms:

• Oral Tablet

Administration

Oral Administration

Administer orally without regard to meals.1 141 169

Dosage

Must be used in conjunction with other antiretrovirals.1

Modification of zalcitabine dosage may be necessary in patients who develop peripheral neuropathy.1

Pediatric Patients

Children <13 years of age†: 0.01 mg/kg every 8 hours under investigation.141 Dosage recommendations not available for neonates and infants.141

Children ≥13 years of age: 0.75 mg every 8 hours.1 141

Adults

0.75 mg every 8 hours.1 169

If reintroduced following a temporary interruption due to peripheral neuropathy, 0.375 mg every 8 hours.1

Special Populations

Renal Impairment

Clcr 10–40 mL/minute: 0.75 mg every 12 hours.1 169

Clcr <10 mL/minute: 0.75 mg every 24 hours.1 169

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Drugs Associated with Peripheral Neuropathy

Concomitant use with other drugs associated with peripheral neuropathy (e.g., chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold compounds, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, stavudine, vincristine) increases risk of peripheral neuropathy and should be avoided if possible.1 2 86

Specific Drugs

Absorption

Bioavailability

Rapidly absorbed; peak plasma concentrations achieved in 0.5–2 hours.1 37 38 82 84 89 Bioavailability is 70–88% (range: 23–127%).1 2 37 38 62 77 82 84 89

Food

Food may decrease the rate and extent of absorption.1 62 89

Special Populations

Plasma concentrations increased in patients with renal impairment.1 89

Oral bioavailability lower in children than adults; bioavailability is 54% (range: 29–100%) in children.1 35

Distribution

Extent

Not well characterized.1

Distributed into CSF in low concentrations.1 2 37 82 89

Not known whether zalcitabine crosses the placenta or is distributed into milk.1

Plasma Protein Binding

<4%.1

Elimination

Metabolism

Not metabolized substantially in the liver.1

Intracellularly, zalcitabine is phosphorylated and converted by cellular enzymes to the active metabolite, dideoxycytidine 5′-triphosphate.1 23 29 38

Elimination Route

Principally eliminated in urine as unchanged drug.1 2 35 37 38 82 89

Not known whether removed by hemodialysis or peritoneal dialysis.1

Half-life

1.2–2 hours (range: 0.5–3 hours).1 2 37 82 84

Children 6 months to 13 years of age: 0.2–1.9 hours.35

Special Populations

Half-life prolonged in patients with renal impairment; half-life of 8.5 hours reported in patients with Clcr <55 mL/minute.1 89

• Critical nature of compliance with HIV therapy.1 Importance of using zalcitabine in conjunction with other antiretroviralsnot for monotherapy.1

• Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.1 HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.1

• Patients should be advised that peripheral neuropathy is the major toxicity associated with zalcitabine therapy.1 They should be advised to report early symptoms of peripheral neuropathy (numbness, tingling, burning) to their clinician.1 Dosage modification may be necessary; importance of following clinician’s instructions regarding dosage adjustment.1

• Patients should be advised of the early symptoms of pancreatitis (nausea, vomiting, abdominal pain) and hepatic toxicity and that the development of manifestations of these conditions should be reported promptly to their clinician.1

• Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of advising patients of other important precautionary information.1 (See Cautions.)

Applies to zalcitabine: oral tablets

Side effects include:

Peripheral neuropathy, abnormal hepatic function, fatigue.