Nucleoside reverse transcriptase inhibitors (NRTIs), Nucleoside analogues or "Nukes".
BRAND NAME:
Zerit
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HOW STAVUDINE WORKS: Stavudine (or d4T) belongs to the group of drugs referred to as nucleoside reverse transcriptase inhibitors (NRTIs) or nucleoside analogues. This class of drugs combat viral replication by disrupting the essential transcription process of HIV genetic material (RNA) into DNA. D4T is usually taken in combination with at least two other anti-retroviral drugs.
HISTORY: In 1996 d4T was approved in Europe for use in HIV-positive patients who were either unable to tolerate AZT or for whom AZT treatment had failed. One year later it received approval for initial treatment with adults and children in combination with other anti-retrovirals.
COMBINATION THERAPY: d4T is established as an alternative to AZT in combination anti-retroviral therapy. Its effectiveness as a nucleoside analogue component of combination therapy has been proven and in some studies has been shown to be more effective than AZT. There appears to be no conclusive evidence that indicates any therapeutic benefit in initiating therapy with either AZT or d4T first.
d4T DOSING: d4T is produced in 15mg, 20mg, 30mg and 40mg capsules. Dosing of d4T is dependent on weight. For patients over 60kg, 40mg twice daily is usually prescribed; for patients under 60kg, 30mg twice daily is usually prescribed. Paediatric dosing is also weight-based. For children over 30kg, 30mg twice daily is usually prescribed, for children under 30kg, 1mg per kg is usually prescribed.
Dosing restrictions are usually indicated for patients with reduced kidney function or peripheral neuropathy.
DOSING RESTRICTIONS: There are no food restrictions or recommendations with d4T and the dose may be taken with or without food, although in paediatric use it should be taken on an empty stomach.
d4T should not be combined with AZT as they counteract each other's efficacy.
SIDE EFFECTS OF d4T: Most side effects of d4T are likely to occur during the initial weeks of treatment. They include:
Nausea and vomiting
Diarrhoea or constipation
Abdominal pain
Fatigue
Headache
Fever
The most commonly reported side effect of d4T is peripheral neuropathy, occurring in approximately 15-20% of patients. This is more likely for those on higher doses or with advance HIV. The risk is also increased in those patients also taking ddI or hydroxyurea.
Peripheral neuropathy is characterised by heightened sensitivity or numbness of hands and/or feet. Severe or untreated peripheral neuropathy can become extremely painful.
Lipodystrophy has also been associated with the use of d4T.
Very often side effects can be combated with simple measures and/or over the counter treatments.
Taking d4T prior to eating and making small adjustments to diet often reduces nausea and vomiting. Eating little and often, avoiding fried, spicy and sweet foods, eating more cool foods and drinks and increasing fluid intake generally can all produce positive results.
While the above side effects should cause little concern and are relatively easy to remedy it should be noted that some side effects should be taken more seriously.
PRE-EXISTING CONDITIONS: d4T is not recommended for those patients with existing neuropathy.
RARE SIDE EFFECTS: In rare cases d4T treatment has been associated with pancreatitis, a potentially fatal condition. Pancreatitis is characterised by abdominal or back pain together with vomiting. Diagnosis is confirmed by blood test. Discontinuation or changing anti-retrovirals can prevent or stop pancreatitis developing.
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. d4T is the NRTI that is most commonly associated with this condition.
PAEDIATRIC USE OF d4T: An oral suspension is available for use in young children over the age of 3 months, which should be taken on an empty stomach or one hour prior to a meal.
d4T TREATMENT DURING PREGNANCY: d4T is not contraindicated in pregnancy but careful monitoring for certain adverse events (e.g. lactic acidosis) is recommended.
d4T RESISTANT HIV: Cross resistance is common among nucleoside analogues. There is evidence to suggest that d4T is effective against HIV that has acquired resistance to AZT.
