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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(zal SITE a been)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Pregnancy Risk Factor
C
Pregnancy Considerations
It is not known if zalcitabine crosses the human placenta. Animal studies have shown zalcitabine to be teratogenic, developmental toxicities were also observed. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogue drugs. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
Lactation
Excretion in breast milk unknown/contraindicated
Breast-Feeding Considerations
HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV.
Contraindications
Hypersensitivity to zalcitabine or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Lactic acidosis/hepatomegaly: See “Concerns related to adverse effects” below.
• Pancreatitis: See “Concerns related to adverse effects” below.
• Peripheral neuropathy: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Esophageal/oral ulcers: There have been reports of esophageal (rare) and/or oral ulcers with use.
• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; some cases may possibly be related to underlying hepatitis B. Use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Pancreatitis: [U.S. Boxed Warning]: Discontinue use immediately if pancreatitis is suspected; 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.
• Peripheral neuropathy: [U.S. Boxed Warning]: Zalcitabine can cause severe peripheral neuropathy; avoid use, if possible, in patients with pre-existing neuropathy or at risk of developing neuropathy. Risk factors include CD4 counts <50 cells/mm3, diabetes mellitus, weight loss, other drugs known to cause peripheral neuropathy.
Disease-related concerns:
• Heart failure (HF): Use with caution in patients with HF; cardiomyopathy and HF have occurred.
• Hyperphosphatemia: Use with caution in patients with hyperphosphatemia.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Digitalis: Use with caution in patients on digitalis.
Adverse Reactions
>10%:
Central nervous system: Fever (5% to 17%), malaise (2% to 13%)
Neuromuscular & skeletal: Peripheral neuropathy (28%)
1% to 10%:
Central nervous system: Headache (2%), fatigue (4%), seizure (1.3%), dizziness (1%)
Dermatologic: Rash (2% to 11%), pruritus (3% to 5%)
Endocrine & metabolic: Hypoglycemia (2% to 6%), hyperglycemia (1% to 6%), hyponatremia (4%)
Gastrointestinal: Diarrhea (<1% to 10%), abdominal pain (3% to 8%), amylase increased (3% to 8%), oral ulcers (3% to 7%), anorexia (4%), dysphagia (1% to 4%), vomiting (1% to 3%), nausea (3%), weight loss
Hematologic: Anemia (occurs as early as 2-4 weeks), granulocytopenia (usually after 6-8 weeks)
Hepatic: Abnormal hepatic function (9%), hyperbilirubinemia (2% to 5%)
Neuromuscular & skeletal: Myalgia (1% to 6%), foot pain
Respiratory: Nasal discharge (4%), cough (6%), pharyngitis (2%)
<1% (Limited to important or life-threatening): Atrial fibrillation, chest pain, constipation, edema, epistaxis, heart racing, hepatic failure, hepatitis, hepatomegaly, hypersensitivity (including anaphylaxis), hypertension, hypocalcemia, jaundice, lactic acidosis, myositis, night sweats, pain, palpitation, pancreatitis, redistribution/accumulation of body fat, syncope, tachycardia, weakness
Drug Interactions
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy
LamiVUDine: May diminish the therapeutic effect of Zalcitabine. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Food decreases peak plasma concentrations by 39%. Extent and rate of absorption may be decreased with food.
Storage
Tablets should be stored in tightly closed bottles at room temperature (59°F to 86°F).
Mechanism of Action
Purine nucleoside (cytosine) analog, 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.
Pharmacodynamics/Kinetics
Absorption: Well, but variable; decreased 39% with food
Distribution: Minimal data available; variable CSF penetration
Protein binding: <4%
Metabolism: Intracellularly to active triphosphorylated agent
Bioavailability: >80%
Half-life elimination: 2.9 hours; Renal impairment: ?8.5 hours
Excretion: Urine (>70% as unchanged drug)
Dosage
Oral:
Neonates: Dose unknown
Infants and Children <13 years: Safety and efficacy have not been established; investigational dose: 0.01 mg/kg every 8 hours
Adolescents and Adults: 0.75 mg 3 times/day
Dosing adjustment in renal impairment: Adults:
Clcr 10-40 mL/minute: 0.75 mg every 12 hours
Clcr <10 mL/minute: 0.75 mg every 24 hours
Moderately dialyzable (20% to 50%)
Administration: Oral
Food decreases absorption; take on an empty stomach. Administer around-the-clock. Do not take at the same time with dapsone.
Monitoring Parameters
Renal function, viral load, liver function tests, CD4 counts, CBC, serum amylase, triglycerides, calcium
Patient Education
Do not take any new prescriptions, over-the-counter medications, or herbal products without consulting prescriber. This drug will not cure HIV, nor has it been found to reduce transmission of HIV; use appropriate precautions to prevent spread to other persons. This drug is prescribed as one part of a multidrug combination; take exactly as directed; preferably on an empty stomach, 1 hour before or 2 hours after meals. Do not take antacids or other medication within 1 hour of taking this medication. Maintain adequate hydration (2-3 L/day of fluids) unless advised by prescriber to restrict fluids. You may be susceptible to infection (avoid crowds and exposure to known infections and do not have any vaccinations without consulting prescriber). Frequent blood tests may be required with prolonged therapy. May cause dizziness, fatigue, or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, lack of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report muscle weakness or pain; tingling, numbness, or pain in toes or fingers; weakness of extremities; 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); skin rash, irritation; or any other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.
Additional Information
Potential compliance problems, frequency of administration, and adverse effects should be discussed with patients before initiating therapy to help prevent the emergence of resistance.
Anesthesia and Critical Care Concerns/Other Considerations
Potential compliance problems, frequency of administration, and adverse effects should be discussed with patients before initiating therapy to help prevent the emergence of resistance.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral ulcerations and dysphagia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common; may cause dizziness
Mental Health: Effects on Psychiatric Treatment
May cause granulocytopenia; use caution with clozapine; concurrent use with disulfiram can enhance peripheral neuropathy; avoid combination
Nursing: Physical Assessment/Monitoring
Assess closely for any previous allergy history prior to beginning treatment. Assess other pharmacological or herbal products patient may be taking (especially those that increase risk of peripheral neuropathy). Assess results of laboratory tests (CD4 count, renal function), therapeutic response, and adverse reactions (lactic acidosis [elevated transaminases]; gastrointestinal disturbance [nausea, vomiting, diarrhea]; myalgia; peripheral neuropathy) on a regular basis throughout therapy. Teach patient proper use (eg, timing of multiple medications and drugs that should not be used concurrently), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet:
Hivid®: 0.375 mg, 0.75 mg [DSC]
Pricing: U.S. (www.drugstore.com)
Tablets (Hivid)
0.375 mg (90): $176.00
0.75 mg (90): $221.00
References
Adkins JC, Peters DH, and Faulds D, “Zalcitabine. An Update of Its Pharmacodynamic and Pharmacokinetic Properties and Clinical Efficacy in the Management of HIV Infection,” Drugs, 1997, 53(6):1054-80.
Bakshi SS, Britto P, Capparelli E, et al, “Evaluation of Pharmacokinetics, Safety, Tolerance, and Activity of Combination of Zalcitabine and Zidovudine in Stable, Zidovudine-Treated Pediatric Patients With Human Immunodeficiency Virus Infection. AIDS Clinical Trials Group Protocol 190 Team,” J Infect Dis, 1997, 175(5):1039-50.
Bazunga M, Tran HT, Kertland H, et al, “The Effects of Renal Impairment on the Pharmacokinetics of Zalcitabine,” J Clin Pharmacol, 1998, 38(1):28-33.
Chadwick EG, Nazareno LA, Nieuwenhuis TJ, et al, “Phase I Evaluation of Zalcitabine Administered to Human Immunodeficiency Virus-Infected Children,” J Infect Dis, 1995, 172(6):1475-9.
“Drugs for AIDS and Associated Infections,” Med Lett Drugs Ther, 1993, 35(904):79-86.
“Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Panel on Clinical Practices for Treatment of HIV Infection,” February 5, 2001. Available at: http://www.aidsinfo.nih.gov. Accessed February 14, 2001.
Hilts AE and Fish DN, “Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction,” Am J Health Syst Pharm, 1998, 55:2528-33.
Hirsch MS and D'Aquila RT, “Therapy for Human Immunodeficiency Virus Infection,” N Engl J Med, 1993, 328(23):1686-95.
Pizzo PA, Butler K, Balis F, et al, “Dideoxycytidine Alone and in an Alternating Schedule With Zidovudine in Children With Symptomatic Human Immunodeficiency Virus Infection,” J Pediatr, 1990, 117(5):799-808.
“Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States,” October 12, 2006. Available at: http://www.aidsinfo.nih.gov.
Shelton MJ, O'Donnell AM, and Morse GD, “Zalcitabine,” Ann Pharmacother, 1993, 27(4):480-9.
Skowron G, Bozzette SA, Lim L, et al, “Alternating and Intermittent Regimens of Zidovudine and Dideoxycytidine in Patients With AIDS or AIDS-Related Complex,” Ann Intern Med, 1993, 118(5):321-30.
Spector SA, Blanchard S, Wara DW, et al, “Comparative Trial of Two Dosages of Zalcitabine in Zidovudine-Experienced Children With Advanced Human Immunodeficiency Virus Disease. Pediatric AIDS Clinical Trials Group,” Pediatr Infect Dis J, 1997, 16(6):623-6.
Spector SA, “HIV Therapy Advances. Pediatric Antiretroviral Choices,” AIDS, 1994, 8(Suppl 3):15-8.
Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, “Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection,” October 26, 2006. Available at: http://www.aidsinfo.nih.gov.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2009
Content last modified January 2009
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