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Zalcitabine Side Effects

Applies to zalcitabine: oral tablet


The adverse effects of zalcitabine are sometimes difficult to distinguish from the symptomatology observed during the clinical course of AIDS, as well as from the possible adverse effects of other drugs used in the treatment of HIV infection. Many of the side effects associated with nucleoside reverse transcriptase inhibitor therapy (myopathy, pancreatitis, liver failure, lactic acidosis, etc.) are attributable to their direct toxic effect on mitochondria which causes decreased mitochondrial energy-generating capacity. Patients with reduced renal function may have an increased risk of toxicity due to decreased clearance.[Ref]

Nervous system

Nervous system toxicity is the major dose-limiting adverse effect of zalcitabine. Peripheral neuropathy occurred in 28.3% of patients enrolled in a monotherapy study of zidovudine intolerant/failure patients who were administered zalcitabine or didanosine. Peripheral neuropathy presents as numbness,tingling, and burning dysesthesia in the distal extremities. Zalcitabine should be used with extreme caution in patients with preexisting neuropathy or if being treated with other neurotoxic drugs. Headache (2.1%), convulsions (1.3%), and dizziness have also been reported. Ototoxicity has been observed on rare occasions.[Ref]

Peripheral neuropathy has been reported in up to 50% of patients who receive greater than 0.03 mg/kg every 8 hours. Sensorimotor neuropathy generally presents at 8 to 12 weeks with numbness and burning dysesthesia in the soles of the feet. With continued treatment patients develop diminished light touch, temperature, and vibration sensation. The loss of ankle deep tendon reflexes may occur. Symptoms may worsen for up to 5 weeks after discontinuation and begin to remit over several weeks or months. The incidence is less with dosages of 0.01 mg/kg every 8 hours. Sensory neuropathy is common in patients with AIDS and it may be difficult to distinguish HIV sensory neuropathy from zalcitabine induced neuropathy.

Bilateral sensorineural hearing loss and tinnitus have been reported.[Ref]


Patients with a history of pancreatitis, taking other pancreatoxic drugs, or with known risk factors for the development of pancreatitis should be monitored closely while on zalcitabine. Exacerbation of pancreatitis occurs rarely with zalcitabine therapy, however, patients with a history of pancreatitis are at a greater risk. Of 528 zalcitabine treated patients enrolled in an expanded-access study who had a history of prior pancreatitis or increased amylase, 5.3% developed pancreatitis and an additional 4.4% developed asymptomatic elevated serum amylase.

Treatment with zalcitabine should be stopped immediately if clinical signs/symptoms or abnormal laboratory values develop which are suggestive of pancreatitis. It should not be restarted until the patient's condition has improved. If clinical pancreatitis develops during zalcitabine administration the manufacture recommends permanently discontinuing the drug.[Ref]

Gastrointestinal adverse effects such as abdominal pain (3%), oral lesions/stomatitis (3%), vomiting/nausea (3.4%), and diarrhea/constipation (2.5%) have been reported from a zalcitabine monotherapy trial of zidovudine intolerant/failure HIV patients. Esophageal ulceration (1.6%) and pancreatitis (1.1%) have also been reported.[Ref]


Dermatologic side effects such as rash, pruritus, and urticaria have been observed in approximately 3% of patients enrolled in clinical trials. An acute dermatologic reaction has been associated with zalcitabine in one study. This reaction most frequently appears as a maculopapular rash during the first 10 to 12 days of therapy.[Ref]

In a limited study of 20 patients treated with zalcitabine, an acute reaction generally characterized by a maculopapular rash occurred in 14 patients. Dosages given were 0.03 mg/kg every 8 hours or greater. Nine of these 14 patients also had mucocutaneous lesions, and seven had a systemic reaction which included fever, malaise, myalgias, and pruritus. Onset occurred after 9 to 12 days of treatment. Systemic symptoms generally resolve in 2 to 3 days and lesions in 4 to 10 days despite continued treatment with zalcitabine. However, other larger studies have not reported similarly high incidences of skin reactions.[Ref]


Hematologic adverse effects have occurred, although, substantially less often than with zidovudine. Thrombocytopenia (1.3%), leukopenia (13.1%), eosinophilia (2.5%), and neutropenia (16.9%) were reported in a monotherapy study of zidovudine intolerant/failure patients comparing zalcitabine or didanosine therapy. Anemia and granulocytopenia have also been reported.[Ref]


Rare cases of hepatic failure and death have occurred and may be related to the use of zalcitabine in patients with underlying Hepatitis B infection. The drug should be used with caution in patients with hepatomegaly, hepatitis, or other known risk factors for liver disease.[Ref]

Hepatic side effects have generally included elevation in liver function tests and exacerbation of preexisting hepatic dysfunction.[Ref]


Metabolic side effects have included hypertriglyceridemia and hyperlipidemia.[Ref]


Cardiovascular adverse effects are uncommon, however, cardiomyopathy and congestive heart failure in patients with AIDS have been associated with the use of nucleoside reverse transcriptase inhibitors. Caution should be exercised in patients with baseline cardiomyopathy or a history of congestive heart failure if zalcitabine is to be administered.[Ref]


Hypersensitivity reactions have included one case of an anaphylactoid reaction in a patient receiving zalcitabine and zidovudine. Other cases of hypersensitivity reactions have been reported including anaphylactic reactions and urticaria without other signs of anaphylaxis. Erythema multiforme has also been reported.[Ref]


Other side effects have included fever and fatigue.[Ref]


Psychiatric adverse effects have occurred in less than 1% of patients enrolled in clinical trials. Depression, however, was experienced in 0.4% to 1.8% of patients administered zalcitabine monotherapy or combination therapy.[Ref]


Musculoskeletal adverse effects are uncommon. However, painful and swollen joints were observed in approximately 0.4% to 1.0% of patients enrolled in clinical trials. Myalgia, arthralgia, and muscle weakness have also been reported.[Ref]


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Further information

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Some side effects may not be reported. You may report them to the FDA.