Zalcitabine
(Dideoxycytidine, ddC)
Zalcitabine (Hivid)
Dideoxycytidine (Hivid)
ddC (Hivid)
Zalcitabine
(zal- SIGH-tah-been)
Pregnancy Category: C Hivid (Rx)

Classification: Antiviral

See Also: See also Antiviral Drugs and Anti-Infective Drugs .

Action/Kinetics: Converted in cells to the active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by cellular enzymes. ddCTP serves as an alternative substrate to deoxycytidine triphosphate for HIV-reverse transcriptase, thereby inhibiting the in vitro replication of HIV-1 and inhibiting viral DNA synthesis. The incorporation of ddCTP into the growing DNA chain leads to premature chain termination. ddCTP serves as a competitive inhibitor of the natural substrate for deoxycytidine triphosphate for the active site of the viral reverse transcriptase, which further inhibits viral DNA synthesis. Food reduces the rate of absorption. Does not appear to undergo significant metabolism by the liver. Elimination t 1/2: 1-3 hr. Approximately 70% of a PO dose is excreted through the kidneys and 10% in the feces. Prolonged elimination (t 1/2 up to 8.5 hr) is observed in clients with impaired renal function.

Uses: In combination with AZT in advanced HIV infections (CD ₄ cell count of 300/mm ³ or less and who have shown significant clinical or immunologic deterioration). Alone for HIV-infected adults with advanced disease who are intolerant to AZT or where the disease has progressed while taking AZT.

Contraindications: Hypersensitivity. Use in moderate or severe peripheral neuropathy or with drugs that have the potential to cause peripheral neuropathy (see Drug Interactions). Concomitant use with didanosine. Lactation.

Special Concerns: Use with extreme caution in clients with low CD ₄ cell counts ( < 50/mm ³). Use with caution in clients with a history of pancreatitis or known risk factors for the development of pancreatitis. Clients with a C _CR less than 55 mL/min may be at a greater risk for toxicity due to decreased clearance. Clients may continue to develop opportunistic infections and other complications of HIV infection. Safety and efficacy have not been determined in HIV-infected children less than 13 years of age.

Side Effects: The incidence of certain side effects is dependent on the duration of use and the dose of the drug. Neurologic: Peripheral neuropathy (may be severe) characterized by numbness and burning dysesthesia involving the distal extremities; this may be followed by sharp shooting pains or severe continuous burning pain if the drug is not withdrawn. The neuropathy may progress to severe pain requiring narcotic analgesics and may be irreversible. GI: Fatal pancreatitis when given alone or with AZT. Esophageal ulcers, oral ulcers, nausea, dysphagia, anorexia, abdominal pain, vomiting, constipation, ulcerative stomatitis, aphthous stomatitis, diarrhea, dry mouth, dyspepsia, glossitis, rectal hemorrhage hemorrhoids, enlarged abdomen, gum disorders, flatulence, anorexia, tongue ulceration, dysphagia, eructation, gastritis, GI hemorrhage left quadrant pain, salivary gland enlargement, esophageal pain, esophagitis, rectal ulcers, melena, painful swallowing, mouth lesion, acute pharyngitis, abdominal bloating or cramps, anal/rectal pain, colitis, dental abscess, epigastric pain, gagging with pills, gingivitis, heartburn, hemorrhagic pancreatitis increased salivation, odynophagia, painful sore gums, rectal mass, sore tongue, sore throat, tongue disorder, toothache, unformed/loose stools. Dermatologic: Rash (including erythematous, maculopapular, follicular), pruritus, night sweats, dermatitis, skin lesions, acne, alopecia, bullous eruptions, increased sweating, urticaria, hot flashes, lip blister or lesions, carbuncle/furuncle, cellulitis, dry skin, dry rash desquamation, exfoliative dermatitis, finger inflammation, impetigo, infection, itchy rash, moniliasis, mucocutaneous/skin disorder, nail disorder, photosensitivity, skin fissure, skin ulcer. CNS: Headache, dizziness, seizures, ataxia, abnormal coordination, Bell's palsy, dysphonia, hyperkinesia, hypokinesia, migraine, neuralgia, neuritis, stupor, aphasia, decreased neurologic function, disequilibrium, facial nerve palsy, focal motor seizures, memory loss, paralysis, speech disorder, status epilepticus tremor, vertigo, hypertonia, hand tremor, twitching, confusion, impaired concentration, insomnia, agitation, depersonalization, hallucinations, emotional lability, nervousness, anxiety, depression, euphoria, manic reaction, dementia, amnesia, somnolence, abnormal thinking, crying, loss of memory, decreased concentration, acute psychotic disorder, acute stress reaction, decreased motivation, decreased sexual desire, mood swings, paranoid states, suicide attempt. Respiratory: Coughing, dyspnea, respiratory distress, rales/rhonchi, nasal discharge, flu-like symptoms, cyanosis, acute nasopharyngitis, chest congestion, dry nasal mucosa, hemoptysis, sinus congestion, sinus pain, sinusitis, wheezing. Musculoskeletal: Myalgia, arthralgia, arthritis, arthropathy, cold extremities, leg cramps, myositis, joint pain or inflammation, weakness in leg muscle, generalized muscle weakness, back pain, backache, bone aches and pains, bursitis, pain in extremities, joint swelling, muscle disorder, muscle stiffness, muscle cramps, arthrosis, myopathy, neck pain, rib pain, stiff neck. Hepatic: Exacerbation of hepatic dysfunction, especially in those with preexisting liver disease or with a history of alcohol abuse. Abnormal hepatic function, hepatitis, jaundice, hepatocellular damage, hepatomegaly with steatosis, cholecystitis. CV: Cardiomyopathy CHF, abnormal cardiac movement arrhythmia, atrial fibrillation, cardiac failure cardiac dysrhythmias, heart racing, hypertension, palpitations, subarachnoid hemorrhage syncope, tachycardia, ventricular ectopy, epistaxis. Hematologic: Anemia, leukopenia, thrombocytopenia, alteration of absolute neutrophil count, granulocytosis, eosinophilia, neutropenia, hemoglobinemia, neutrophilia, platelet alteration, purpura, thrombus, unspecified hematologic toxicity, alteration of WBCs. Hypersensitivity: Urticaria, anaphylaxis (rare). Endocrine: Diabetes mellitus, gout, hot flushes, hypoglycemia, hyperglycemia, hypocalcemia, hypophosphatemia, hypernatremia, hyponatremia, hypomagnesemia, hyperkalemia, hypokalemia, hyperlipidemia, polydipsia. GU: Dysuria, toxic nephropathy, polyuria, renal calculi, acute renal failure hyperuricemia, increased frequency of micturition, abnormal renal function, renal cyst, albuminuria, bladder pain, genital lesion/ulcer, nocturia, painful/sore penis, penile edema, testicular swelling, urinary retention, vaginal itch/ulcer/pain, vaginal/cervix disorder. Ophthalmologic: Abnormal vision, burning or itching eyes, xerophthalmia, eye pain or abnormality, blurred or decreased vision, eye inflammation/irritation, eye redness/hemorrhage, increased tears, mucopurulent conjunctivitis, photophobia, dry eyes, unequal sized pupils, yellow sclera. Otic: Ear pain/blockage, fluid in ears, hearing loss, tinnitus. Body as a whole: Fatigue, fever, rigors, chest pain or tightness, weight decrease, pain, malaise, asthenia, generalized edema, general debilitation, chills, difficulty moving, facial pain or swelling, flank pain, flushing, pelvic/groin pain. Miscellaneous: Lymphadenopathy, taste perversion, decreased taste, parosmia, lactic acidosis.

Laboratory Test Alterations: ALT, AST, alkaline phosphatase, CPK, amylase, nonprotein nitrogen. Abnormal gamma-glutamyl transferase, GGT, LDH, lactate dehydrogenase, triglycerides, lipase. Bilirubinemia. Hematocrit.

Drug Interactions: The following drugs have the potential to cause peripheral neuropathy and should probably not be used concomitantly with zalcitabine: chloramphenicol, cisplatin, dapsone, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine. Drugs such as amphotericin, foscarnet, and aminoglycosides may increase the risk of peripheral neuropathy by interfering with the renal clearance of zalcitabine, thus increasing plasma levels. Antacids (Mg/Al-containing) / Zalcitabine absorption Cimetidine / Zalcitabine elimination by renal tubular secretion Pentamidine / Risk of fulminant pancreatitis Probenecid / Zalcitabine elimination by renal tubular secretion

How Supplied: Tablet: 0.375 mg, 0.75 mg

Dosage
?Tablets In combination with AZT in advanced HIV infection.
Adults: 0.75 mg given at the same time with 200 mg AZT q 8 hr for a total daily dose of 2.25 mg zalcitabine and 600 mg AZT.
Alone in advanced HIV infection.
0.75 mg q 8 hr (2.25 mg/day).