HividŽ (ddC/zalcitabine), a nucleoside analogue, was one of the first ever anti-HIV treatments and is commonly used today, as Tracy Barnes explains.
DRUG NAME:
Zalcitabine (ddC)
DRUG CLASS:
Nucleoside reverse transcriptase inhibitors (NRTIs), Nucleoside analogues or "Nukes".
BRAND NAME:
HividŽ
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HOW ddC WORKS: Zalcitabine or (ddC) belongs to the group of drugs referred to as nucleoside reverse transcriptase inhibitors (NRTIs) or nucleoside analogues. This class of drugs combat viral replication of HIV by disrupting the essential transcription process of HIV genetic material (RNA) into DNA. Zalcitabine is usually taken in combination with at least two other anti-retroviral drugs.
HISTORY: Zalcitabine was first licensed in the US in June 1992. The UK licence was granted on 01st September 1994 and in Ireland on 14th April 1994. The initial indication was for second-line monotherapy following AZT intolerance or failure. Since then there have been many changes to the recommended indications and zalcitabine is now used widely in antiretroviral therapy combinations.
COMBINATION THERAPY: ddC is an established component of combination anti-retroviral therapy. Its effectiveness as a nucleoside analogue component of combination therapy has been proven. Studies comparing its efficacy with ddI have shown both drugs to be comparable in patients who had previously taken AZT.
DOSING: Zalcitabine is produced in both 0.75mg and 0.375 mg oval-shaped greyish capsules. The recommended regime is 0.75 mg tablet, taken orally, every 8 hours; this equates to a total daily dose of 2.25mg.
DOSING RESTRICTIONS: There are no dietary restrictions with ddC.
Dosing modification is recommended in the presence of any kidney function impairment.
In order to reduce the risk of peripheral neuropathy developing, ddC is not usually used in combination with other anti-retrovirals associated with this condition, e.g. its use with ddI or d4T is contraindicated.
There is evidence to suggest that the efficacy of ddC is affected by 3TC, so these two drugs are not usually combined.
SIDE EFFECTS: Patients with decreased CD4 counts appear to have an increased incidence of side effects.
As with most anti-retrovirals common side effects are more likely to occur during the first few weeks after commencing treatment. The most frequently reported side effects of ddC are:
Diarrhoea or constipation;
Nausea or vomiting;
Abdominal pain;
Fatigue;
Headache;
Fever;
Rash;
Mouth ulcers;
Peripheral neuropathy.
Apart from peripheral neuropathy, most of the above side effects are remedied with dietary change and/or over the counter medications to alleviate symptoms. It is always wise to check with your doctor before taking any other medication in case it interferes with the efficacy of your treatment.
RARE SIDE EFFECTS: Lactic acidosis is a potentially life-threatening condition, characterised by unexplained and often severe tiredness, sickness and nausea, abdominal and/or liver pain, unexplained weight loss, breathlessness, poor circulation and sudden onset of peripheral neuropathy. Combinations that include ddC have been associated with this condition.
Severe peripheral neuropathy has also been associated with zalcitabine.
Pancreatitis is a potentially fatal (though rare) side effect of ddC. It is characterised by abdominal or back pain together with vomiting.
Diagnosis is confirmed by a blood test. Discontinuation of, or changing your anti-HIV treatment regime can help to either prevent or stop pancreatitis from developing.
The risk of developing pancreatitis is increased with alcohol - it is recommended to cease or decrease alcohol consumption while taking ddC.
Patients who develop symptoms of pancreatitis should consult their docotr immediately. If pancreatitis is suspected, then treatment will usually be suspended until a pancreatitis diagnosis has been confirmed or excluded.
PRE-EXISTING CONDITIONS: ddC can cause peripheral neuropathy and should be used with caution in those with pre-existing neuropathy.
In addition, rare cases of kidney failure, possibly fatal, have been related to those infected with hepatitis B and then treated with anti-HIV drugs that include ddC.
PAEDIATRIC USE: ddC is not licensed for use in children.
USE DURING PREGNANCY: There are no adequate and well-controlled studies of the use and effects of zalcitabine in pregnant women.
Because of this lack of data, zalcitabine is not recommended for use in fertile women unless effective contraception is used.
ddC RESISTANT HIV: Within the whole nucleoside analogue class of drugs there is considerable cross-resistance. However, strains of HIV that are resistant to ddC are usually quite slow to develop.
