See DDC.
[zal- (perhaps alteration of (de)s-, variant of DE– + AL(COHOL), from the missing hydroxyl groups of cytidine) + citabine (alteration of CYTIDINE).]
zalcitabine
Dictionary:
zal·ci·ta·bine (zăl'sĭ-tə-bīn')  |
| 5min Related Video: zalcitabine |
| Dental Dictionary: zalcitabine |
n
trade name: Hivid; drug class: synthetic pyrimidine antiviral; action: converted by cellular enzymes to active drug; functions as antimetabolite to inhibit replication of HIV in vitro; uses: used in combination with zidovudine in advanced HIV infection, secondline monotherapy if AZT tolerant.
| Drug Info: Zalcitabine, ddC |
Brand names: Hivid®
Chemical formula:
- Drug Forms:
- Zalcitabine, ddC tablets (below)
- Zalcitabine Oral tablet
Zalcitabine, ddC tablets
What are zalcitabine tablets?
ZALCITABINE, ddC is an antiretroviral drug. It is used with other medicines to treat HIV. This medicine is not a cure for HIV. It will not stop the spread of HIV to others.
NOTE: This drug is discontinued in the United States.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
• if you frequently drink alcohol-containing beverages
• high cholesterol
• kidney disease
• liver disease
• pancreatitis
• tingling or numbness in the hands or feet
• an unusual or allergic reaction to zalcitabine, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding
How should I take this medicine?
Take zalcitabine tablets by mouth. Follow the directions on the prescription label. Swallow tablets with a drink of water. Take zalcitabine on an empty stomach, 1 hours before or 2 hours after food. Take your doses at regular intervals. Do not take your medicine more often than directed.
To help to make sure that your anti-HIV therapy works as well as possible, be very careful to take all of your medicine exactly as prescribed. Do not stop taking except on your prescriber's advice.
Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.
What drug(s) may interact with zalcitabine?
• alcohol
• amphotericin
• certain antibiotics (usually given in the hospital)
• didanosine, ddI
• foscarnet
• lamivudine, 3TC
• stavudine, d4T
• ribavirin
Tell your prescriber or health care professional about all other medicines you are taking, including nonprescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.
What should I watch for while taking zalcitabine?
Visit your prescriber or health care professional for regular checks on your progress. Discuss any new symptoms with your prescriber or health care professional.
Alcohol can increase the risk of developing severe side effects when taken with zalcitabine. Avoid alcoholic drinks while you are taking zalcitabine. Do not treat yourself for nausea, vomiting, or stomach pain. Call your prescriber or health care professional for advice.
Tell your prescriber or health care professional if you get tingling, pain or numbness in your hands or feet.
Zalcitabine will not cure HIV and you can still get other illnesses or complications associated with your disease. Taking zalcitabine does not reduce the risk of passing HIV infection to others through sexual or blood contact. It is best to avoid sexual contact so that you do not spread the disease to others. For any sexual contact, use a condom. Be careful about cuts, abrasions and other possible sources of blood contact. Never share a needle or syringe with anyone.
What side effects may I notice from taking zalcitabine?
• back pain
• changes in body appearance (such as weight gain or loss around the waist and/or face)
• fever or chills, sore throat
• nausea, vomiting
• stomach pain
• tingling, pain or numbness in the hands or feet
• unusual bleeding or bruising
• unusual tiredness or weakness
Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• muscle and joint pain
• skin rash, itching
• sore or ulcerated mouth
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15—30 degrees C (59—86 degrees F). Keep container tightly closed. Throw away any unused medicine after the expiration date.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
| Wikipedia: Zalcitabine |
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Zalcitabine
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| Systematic (IUPAC) name | |
| 4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one | |
| Identifiers | |
| CAS number | |
| ATC code | J05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C9H13N3O3 |
| Mol. mass | 211.218 g/mol |
| Pharmacokinetic data | |
| Bioavailability | >80% |
| Protein binding | <4% |
| Metabolism | Hepatic |
| Half life | 2 hours |
| Excretion | Renal (circa 80%) |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | Oral |
Zalcitabine (2'-3'-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse transcriptase inhibitor (NARTI) sold under the trade name Hivid.
The recommended dosage is 0.750 mg (one tablet) every 8 hours, as part of a combination regimen.
Zalcitabine appears less potent than some other nucleoside RTIs, has an inconvenient three-times daily frequency and is associated with serious adverse events. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV), and even removed from pharmacies entirely in some countries.[citation needed]
Contents |
History
Zalcitabine was first synthetized in the sixties by Jerome Horwitz[1][2] and subsequently developed as an anti-HIV agent by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan at the National Cancer Institute (NCI). Like didanosine, it was then licensed because the NCI may not market or sell drugs. The National Institutes of Health (NIH) thus licensed it to Hoffman LaRoche.
Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV infection and AIDS. It was approved on Jun 19, 1992 as a monotherapy and again in 1996 for use in combination with Zidovudine (AZT). Using combinations of NRTIs was in practice prior to the second FDA approval and the triple drug combinations with dual NRTIs and a protease inhibitor (PI) were not far off by this time.
The sale and distribution of zalcitabine has been discontinued since December 31, 2006.[3]
Mechanism of action
Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3' with a hydrogen.
It is phosphorylated in T cells and other HIV target cells into its active triphosphate form, ddCTP. This active metabolite works as a substrate for HIV reverse transcriptase, and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing hydroxyl group. Since zalcitabine is a reverse transcriptase inhibitor it possess activity only against retroviruses.
Pharmacokinetics
Zalcitabine has a very high oral absorption rate of over 80%. It is predominantly eliminated by the renal route, with a half-life of 2 hours.[4]
Drug interactions
Lamivudine (3TC) significantly inhibits the intracellular phosphorylation of zalcitabine to the active form, and accordingly the drugs should not be administered together.[4]
Additionally, zalcitabine should not be used with other drugs that can cause peripheral neuropathy, such as didanosine and stavudine.[4]
Adverse events
The most common adverse events at the beginning of treatment are nausea and headache. More serious adverse events are peripheral neuropathy, which can occur in up to 33% of patients with advanced disease, oral ulcers, oesophageal ulcers and, rarely, pancreatitis.[4]
Resistance
Resistance to zalcitabine develops infrequently compared with other nRTIs, and generally only occurs at a low level.[5] The most common mutation observed in vivo is T69D, which does not appear to give rise to cross-resistance to other nRTIs; mutations at positions 65, 74, 75, 184 and 215 in the pol gene are observed more rarely.[4][5]
Sources
- ^ J.P. Horwitz et al.. J. Org. Chem. 32. 817 (1967)
- ^ Oral account of the history of AZT, d4T and ddC by Jerome Horwitz and Hiroaki Mitsuya in the documentary film I am alive today - History of an AIDS drug.
- ^ HIVID (zalcitabine) tablets. Dear Health Care Professional Letter. (June 2006)
- ^ a b c d e HIVID (zalcitabine) tablets. Product information. (September 2002)
- ^ a b Moyle GJ. Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences. Drugs 1996;52:168-185
Further reading
- Yarchoan R, Mitsuya H, Broder S. AIDS therapies. Scientific American 1988;259(4):110-9.
- Harvey Stewart C. in Remington's Pharmaceutical Sciences 18th edition: (ed. Gennard, Alfonso R.) Mack Publishing Company, 1990
- Rang H.P., Dale M.M., Ritter J.M.: Pharmacology, 3rd edition. Pearson Professional Ltd, 1995.
- Mitsuya H, Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy virus-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc Natl Acad Sci USA 1986;83:1911-5.
- 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 1988;1:76-81.
- Mitsuya H, Yarchoan R, Broder S. Molecular targets for AIDS therapy. Science 1990;249:1533-44.
- NIH Bio and Oral History of Samuel Broder describing the development of anti-HIV drugs: http://aidshistory.nih.gov/transcripts/bios/Samuel_Broder.html
- NIH Bio and Oral History of Robert Yarchoan describing the development of anti-HIV drugs: http://aidshistory.nih.gov/transcripts/bios/Robert_Yarchoan.html
- Moyle G. A re-evaluation of zalcitabine. Expert Opin Investig Drugs 1998;7:451-62
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- dideoxycytidine
- DDC (nucleoside analogue antiviral drug)
- saquinavir mesylate
- Zalcitabine, ddC tablets
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