Zalcitabine
Zalcitabine Uses, Dosage, Side Effects, Food Interaction and all others data.
A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of 5' to 3' phosphodiester linkages, which are needed for the elongation of DNA chains, thus resulting in the termination of viral DNA growth. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.
Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
| Trade Name | Zalcitabine |
| Availability | Discontinued |
| Generic | Zalcitabine |
| Zalcitabine Other Names | 2',3'-Dideoxycytidine, DDCYD, Dideoxycytidine, Zalcitabine |
| Related Drugs | Biktarvy, Truvada, tenofovir, ritonavir, Complera, Atripla, Stribild |
| Type | |
| Formula | C9H13N3O3 |
| Weight | Average: 211.2178 Monoisotopic: 211.095691297 |
| Protein binding | Less than 4% |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zalcitabine is a dideoxynucleoside used to treat HIV.
For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals.
How Zalcitabine works
Zalcitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Within cells, zalcitabine is converted to its active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. ddCTP interferes with viral RNA-directed DNA polymerase (reverse transcriptase) by competing for utilization of the natural substrate deoxycytidine 5'-triphosphate (dCTP), as well as incorpating into viral DNA. Due to it's lack of a 3'-OH group, the formation of a 5' to 3' phosphodiester linkage that is necessary for DNA chain elongation is inhibited, thus leading to the termination of viral DNA growth.
Toxicity
Acute overdose: Inadvertent pediatric overdoses have occurred with doses up to 1.5 mg/kg zalcitabine. Chronic overdose: in an initial dose-finding study in which zalcitabine was administered at doses 25 times (0.25 mg/kg every 8 hours) the currently recommended dose, one patient discontinued zalcitabine after 1½ weeks of treatment subsequent to the development of a rash and fever.
Food Interaction
- Avoid multivalent ions. Magnesium and aluminum containing products can reduce the absorption of this medication.
- Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.
[Minor] Zalcitabine bioavailability may be decreased by 14% if taken with meals.
The mechanism and clinical significance are unknown.
Zalcitabine Cholesterol interaction
[Major] The reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC), stavudine (d4T) and lamivudine (3TC), may cause pancreatitis.
The incidence is generally low but is approximately 7% with ddI, and up to 15% in pediatric patients given 3TC.
Patients with a history of or known risk factors for pancreatitis, such as alcohol abuse or hypertriglyceridemia, should be monitored closely during therapy with these agents.
Therapy should be discontinued at the first signs or symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.
Zalcitabine Drug Interaction
Unknown: bretylium, epoetin alfa, heparin, tamoxifen, olanzapine, cetirizine
Zalcitabine Disease Interaction
Major: cardiomyopathy, bone marrow suppression, hepatotoxicity, pancreatitis, peripheral neuropathy, renal dysfunction
Volume of Distribution
- 0.304 to 0.734 L/kg
Elimination Route
Bioavailability is over 80% following oral administration.
Half Life
2 hours
Clearance
- 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour]
Elimination Route
Renal excretion of unchanged drug appears to be the primary route of elimination, accounting for approximately 80% of an intravenous dose and 60% of an orally administered dose within 24 hours after dosing (n=19). Renal clearance exceeds glomerular filtration rate suggesting renal tubular secretion contributes to the elimination of zalcitabine by the kidneys.
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