Hivid Side Effects

Generic Name: zalcitabine

Note: This page contains information about the side effects of zalcitabine. Some of the dosage forms included on this document may not apply to the brand name Hivid.

Not all side effects for Hivid may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to zalcitabine: oral tablet

In addition to its needed effects, some unwanted effects may be caused by zalcitabine (the active ingredient contained in Hivid). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking zalcitabine:

More common
  • Lab results that show problems with liver
  • tingling, burning, numbness, or pain in the hands, arms, feet, or legs
Less common
  • Fever
  • joint pain
  • muscle pain
  • nausea and vomiting
  • seizures
  • skin rash
  • stomach pain (severe)
  • ulcers in the mouth and throat
Rare
  • Discouragement, feeling sad or empty, irritability, lack of appetite, loss of interest or pleasure, tiredness, trouble concentrating, trouble sleeping
  • fever and sore throat
  • yellow eyes or skin

Some of the side effects that can occur with zalcitabine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common
  • Constipation
  • diarrhea
  • headache
  • hives or welts
  • itching skin
  • swelling or inflammation of the mouth

For Healthcare Professionals

Applies to zalcitabine: oral tablet

General

The adverse effects of zalcitabine (the active ingredient contained in Hivid) 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 (the active ingredient contained in Hivid) 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]

Gastrointestinal

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 (the active ingredient contained in Hivid) 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

In a limited study of 20 patients treated with zalcitabine (the active ingredient contained in Hivid) 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]

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]

Hematologic

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 (the active ingredient contained in Hivid) or didanosine therapy. Anemia and granulocytopenia have also been reported.[Ref]

Hepatic

Rare cases of hepatic failure and death have occurred and may be related to the use of zalcitabine (the active ingredient contained in Hivid) 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

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

Cardiovascular

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 (the active ingredient contained in Hivid) is to be administered.[Ref]

Hypersensitivity

Hypersensitivity reactions have included one case of an anaphylactoid reaction in a patient receiving zalcitabine (the active ingredient contained in Hivid) 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

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

Psychiatric

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 (the active ingredient contained in Hivid) monotherapy or combination therapy.[Ref]

Musculoskeletal

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]

References

1. Kakuda TN "Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity." Clin Ther 22 (2000): 685-708

2. Merigan TC, Skowron G, et al "Safety and tolerance of dideoxycytidine as a single agent." Am J Med 88 (1990): s11-5

3. "Product Information. HIVID (zalcitabine)." Roche Laboratories, Nutley, NJ.

4. Pulda JM, Mitsuta H "Hematologic effects of AIDS therapies." Hematol Oncol Clin North Am 5 (1991): 229-48

5. Adkins JC, Peters DH, Faulds D "Zalcitabine: An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection." Drugs 53 (1997): 1054-80

6. Yarchoan R, Perno CF, Thomas RV, et al. "Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT)." Lancet 1 (1988): 76-81

7. "Drugs for HIV infection." Med Lett Drugs Ther 43 (2001): 103-8

8. Meng TC, Fischl MA, Boota AM, et al "Combination therapy with zidovudine and dideoxycytidine in patients with advanced human immunodeficiency virus infection: a phase I/II study." Ann Intern Med 116 (1992): 13-20

9. Neff GW, Sherman KE, Eghtesad B, Fung J "Review article: current status of liver transplantation in HIV-infected patients." Aliment Pharmacol Ther 20 (2004): 993-1000

10. Walker UA, Bauerle J, Laguno M, et al. "Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine." Hepatology 39 (2004): 311-7

11. Broder S, Yarchoan R "Dideoxycytidine: current clinical experience and future prospects." Am J Med 88 (1990): s31-3

12. Jeffries DJ "The antiviral activity of dideoxycytidine." Antimicrob Agents Chemother 23 (1989): 29-34

13. LeLacheur SF, Simon GL "Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine." J Acquir Immune Defic Syndr 4 (1991): 538-9

14. Dubinsky RM, Yarchoan R, Dalakas M, Broder S "Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2',3'-dideoxycytidine (ddC)." Muscle Nerve 12 (1989): 856-60

15. Whittington R, Brogden RN "Zalcitabine: a review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS)." Drugs 44 (1992): 656-83

16. Dubinsky RM, Dalakas M, Yarchoan R, Broder S "Follow-up of neuropathy from 2'3'-dideoxycytidine." Lancet 1 (1988): 832

17. Moore RD, Fortgang I, Keruly J, Chaisson RE "Adverse events from drug therapy for human immunodeficiency virus disease." Am J Med 101 (1996): 34-40

18. Matthews SJ, Cersosimo RJ, Spivack ML "Zidovudine and other reverse transcriptase inhibitors in the management of human immunodeficiency virus-related disease." Pharmacotherapy 11 (1991): 419-49

19. Bozzette SA, Richman DD "Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine." Am J Med 88 (1990): s24-6

20. Meng TC, Fischl MA, Richman DD "AIDS clinical trials group: phase I/II study of combination 2',3'-dideoxycytidine and zidovudine in patients with acquired immunodeficiency syndrome and advanced AID." Am J Med 88 (1990): s27-30

21. Blum AS, Dal Pan GJ, Feinberg J, Raines C, Mayjo K, Cornblath DR, McArthur JC "Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors." Neurology 46 (1996): 999-1003

22. Martinez OP, French MA "Acoustic neuropathy associated with zalcitabine-induced peripheral neuropathy." AIDS 7 (1993): 901-2

23. Powderly WG, Klebert MK, Clifford DB "Ototoxicity associated with dideoxycytidine." Lancet 335 (1990): 1106

24. Indorf AS, Pegram PS "Esophageal ulceration related to zalcitabine (ddC)." Ann Intern Med 117 (1992): 133-4

25. McNeely MC, Yarchoan R, Broder S, Lawley TJ "Dermatologic complications associated with administration of 2',3'-dideoxycytidine in patients with human immunodeficiency virus infection." J Am Acad Dermatol 21 (1989): 1213-7

26. Tancrede-Bohin E, Grange F, Bournerias I, Roujeau JC, Guillaume JC "Hypersensitivity syndrome associated with zalcitabine therapy" Lancet 347 (1996): 971

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