Zalcitabine

(BAN, USAN, rINN)
Zalcitabine Chemical formula
Synonyms: ddC; ddCyd; Dideoxycytidine; NSC-606170; Ro-24-2027; Ro24-2027/000; Tsalsitabiini; Zalcitabin; Zalcitabina; Zalcitabinum; Zalsitabin. 2′,3′-Dideoxycytidine.
Cyrillic synonym: Зальцитабин.

💊 Chemical information

Chemical formula: C9H13N3O3 = 211.2.
CAS — 7481-89-2.
ATC — J05AF03.
ATC Vet — QJ05AF03.

Pharmacopoeias.

In US.

USP 31

(Zalcitabine). A white to off-white, crystalline powder. Soluble in water and in methyl alcohol; sparingly soluble in alcohol, in acetonitrile, in chloroform, and in dichloromethane; slightly soluble in cyclohexane. Store in airtight containers. Protect from light.

💊 Adverse Effects

The most serious adverse effects of zalcitabine are peripheral neuropathy, which can affect up to one-third of patients, and pancreatitis which is rare, affecting up to about 1% of patients, but which can be fatal. Other severe adverse effects include oral and oesophageal ulceration, hypersensitivity reactions including anaphylaxis, cardiomyopathy and heart failure, lactic acidosis and severe hepatomegaly with steatosis (both potentially life-threatening), and hepatic failure.

💊 Precautions

Zalcitabine should be interrupted or stopped if peripheral neuropathy develops. Neuropathy is usually slowly reversible if treatment is stopped promptly but may be irreversible if treatment is continued after symptoms develop. Zalcitabine should be avoided in patients who already have peripheral neuropathy and used with caution in patients at risk of developing it (especially those with a low CD4+ cell count) or taking other drugs that may cause it (see Interactions, below). Treatment should be interrupted in patients who develop abdominal pain, nausea, or vomiting or with abnormal biochemical test results until pancreatitis has been excluded. Zalcitabine should be permanently withdrawn if pancreatitis develops. Patients with a history of pancreatitis or of raised serum amylase should be monitored closely. Zalcitabine should not be used with other drugs known to cause pancreatitis (see Interactions, below). Zalcitabine should be used with caution in patients with hepatic impairment and treatment interrupted or stopped if hepatic function deteriorates or there are signs of hepatic damage or lactic acidosis. It should be used with caution in patients with renal impairment, and dosage reductions may be necessary. It should also be used with caution in patients with cardiomyopathy or heart failure. Complete blood count and biochemical tests should be carried out before treatment starts and at regular intervals throughout therapy.

Handling.

Exposure of the skin to zalcitabine and inhalation of zalcitabine powder should be avoided.

💊 Interactions

Zalcitabine should not be used with other drugs known to cause pancreatitis (for example intravenous pentamidine). Caution is necessary when zalcitabine is given with other drugs that may cause peripheral neuropathy, such as other nucleoside reverse transcriptase inhibitors, chloramphenicol, dapsone, ethionamide, isoniazid, metronidazole, nitrofurantoin, ribavirin, and vincristine. Use of zalcitabine with didanosine is not recommended. The absorption of zalcitabine is reduced by about 25% when given with aluminium- or magnesium-containing antacids. Cimetidine, probenecid, or trimethoprim can reduce the renal excretion of zalcitabine, resulting in elevated plasma concentrations. Renal excretion of zalcitabine may also be reduced by amphotericin B, aminoglycosides, or foscarnet, potentially increasing its toxicity. The antiviral action of zalcitabine may be antagonised by lamivudine and the two drugs should not be used together.

💊 Antiviral Action

Zalcitabine is converted intracellularly in stages to the triphosphate. This triphosphate halts the DNA synthesis of retroviruses, including HIV, through competitive inhibition of reverse transcriptase and incorporation into viral DNA. The emergence of zalcitabine-resistant strains of HIV has been reported.
1. Jeffries DJ. The antiviral activity of dideoxycytidine. J Antimicrob Chemother 1989; 23 (suppl A): 29–34.

💊 Pharmacokinetics

Zalcitabine is absorbed from the gastrointestinal tract with a bioavailability of greater than 80%. The rate of absorption is reduced if given with food. Peak plasma concentrations in the fasting state are achieved within about 1 hour. Zalcitabine crosses the blood-brain barrier producing CSF concentrations ranging from 9 to 37% of those in plasma. Binding to plasma proteins is negligible. The plasma elimination half-life is about 2 hours. Zalcitabine is metabolised intracellularly to the active antiviral triphosphate. It does not appear to undergo any substantial hepatic metabolism and is excreted mainly in the urine, in part by active tubular secretion.

💊 Uses and Administration

Zalcitabine is a nucleoside reverse transcriptase inhibitor derived from cytidine with antiviral activity against HIV. It is used in the treatment of HIV infection and AIDS. Viral resistance emerges rapidly when zalcitabine is used alone in the treatment of HIV infection, and it is therefore used with other antiretrovirals. Zalcitabine is given orally in a dose of 750 micrograms every 8 hours. Doses should be reduced in patients with renal impairment (see below).

Administration in renal impairment.

Doses of zalcitabine should be reduced for patients with renal impairment according to creatinine clearance (CC):
CC 10 to 40 mL/minute: 750 micrograms every 12 hours
CC less than 10 mL/minute: 750 micrograms every 24 hours

💊 Preparations

USP 31: Zalcitabine Tablets.

Proprietary Preparations

Arg.: Hivid†; Inxibir†; Austral.: Hivid; Austria: Hivid; Belg.: Hivid; Braz.: Hivid†; Canad.: Hivid; Chile: Hivid†; Cz.: Hivid†; Denm.: Hivid†; Fin.: Hivid; Fr.: Hivid†; Ger.: Hivid; Gr.: Hivid; Hong Kong: Hivid†; Irl.: Hivid†; Israel: Hivid; Ital.: Hivid; Jpn: Hivid; Mex.: Arlevid; Hivid; Neth.: Hivid; Port.: Hivid†; S.Afr.: Hivid†; Singapore: Hivid†; Spain: Hivid; Swed.: Hivid†; Switz.: Hivid†; Thai.: Hivid; Turk.: Hivid; UK: Hivid†; USA: Hivid†; Venez.: Hivid.
Published December 31, 2018.