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EFFECTIVE IN HIV & HEPATITIS B?

Lamivudine is known as Epivir® in the treatment of HIV, but goes under the name of Zeffix® when used in patients with hepatitis B, as Tracy Barnes explains. 
 

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HOW LAMIVUDINE WORKS:
Lamivudine 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. Lamivudine is usually taken in combination with at least two other anti-retroviral drugs. Lamivudine is also approved in the UK for the treatment of hepatitis B, for this purpose its brand name is Zeffix®.

HISTORY:
In 1996 Lamivudine was approved in Europe for use in combination anti-retroviral therapy for HIV-positive adults. Lamivudine (3TC) is also combined with the nucleoside analogue zidovudine, in a drug called Combivir(r). It appears in one other drug formulation consisting of lamivudine, zidovudine and abacavir, and branded Trizivir®.

COMBINATION THERAPY:
Lamivudine is established as an effective component of combination anti-retroviral therapy when used with at least two other anti-retrovirals. Several studies have indicated that the use of Combivir(r) with its lamivudine and zidovudine component is as effective as the two drugs taken separately.

DOSING:
Lamivudine is produced in a white diamond shaped 150 mg tablet that is taken twice daily, 12 hours apart, with or without food. Combivir(r) and Trizivir® are also taken twice daily, with or without food. Lamivudine is also available as a clear to pale yellow, strawberry-banana flavoured oral suspension for paediatric use. 1ml of solution contains 10mg of lamivudine. Paediatric dosing consists of 4mg per kg body weight twice daily up to a maximum dose of 300mg per day.

DOSING RESTRICTIONS:
3TC should not be taken with intravenous foscarnet or ganciclovir, both are anti-CMV drugs.

Lamivudine is not recommended to be used in combination with zalcitabine (ddC). Dosing reductions may be necessary in people with impaired kidney function.

SIDE EFFECTS:
As with most anti-retrovirals, common side effects are most likely to occur during the first few weeks after commencing treatment. The most frequently reported side effects of lamivudine are nausea, vomiting, diarrhoea, headache, tiredness, abdominal pain, peripheral neuropathy and insomnia. There has been some evidence to indicate that side effects may be more severe among those with low CD4 counts. Less frequently reported side-effects have been low white blood cell counts, rash, hair loss and severe anaemia. Side effects may be more severe among people with low CD4 counts. There have been reports of lactic acidosis (a serious increase in levels of lactic acid in the blood).

RARE SIDE EFFECTS:
Severe anaemia has been associated with lamivudine. Lactic acidosis, a potentially life-threatening condition, has been reported in a small number of cases. The condition is 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. This rare, but potential fatal side effect is associated with all NRTIs, including lamivudine; women and those who are overweight appear to be at greater risk of lactic acidosis. In children extra vigilance for the signs and symptoms of Pancreatitis is advised. Pancreatitis is the inflammation of the pancreas, an important organ involved in the production of enzymes essential for digestion. Signs and symptoms of pancreatitis include nausea, vomiting and abdominal pain; pancreatitis can be confirmed by blood tests, x-rays, ultrasound and CT scan.

PRE-EXISTING CONDITIONS:
Lamivudine is licensed as a treatment for hepatitis B and is prescribed to people with chronic HBV infection with liver damage or liver inflammation or fibrosis. The inclusion of lamivudine in anti-retroviral therapy regimens for co-infected individuals has been questioned on the grounds that it would mean lamivudine monotherapy with the inherent risk of developing lamivudine resistant hepatitis B. A flare-up in hepatitis B may occur in co-infected people if they stop taking 3TC, or their hepatitis B virus may develop resistance to 3TC. Unlike many other anti-retrovirals it is not necessary to reduce dosage in those with impaired liver function although people with reduced kidney function may require dose reductions.

PAEDIATRIC USE:
Lamivudine is approved for use in HIV-positive children from the age of 3 months to 16 years when administered in combination with other anti-retroviral agents. It is not approved for monotherapy.

USE DURING PREGNANCY:
Unfortunately little data exists to provide adequate information relating to the use of Lamivudine in pregnancy. However, small studies have revealed its efficacy in reducing mother to baby transmission when used in combination with AZT. Unfortunately, when this drug combination is used, resistance to lamivudine is likely to occur over a period of time, especially in those with high viral loads and low CD4 counts.

LAMIVUDINE RESISTANT HIV:
It is essential to ensure that viral load is suppressed below detectable levels in order to safeguard against development of lamivudine resistance. Resistance to lamivudine is unlikely to cause resistance to some of the other nucleoside analogues and vice versa, indicating that exposure to AZT or d4T does not necessarily mean lamivudine will be ineffective in suppressing viral load. Prior treatment with abacavir, ddI or ddC may result in cross-resistance to 3TC. The mutation associated with lamivudine is very common, although continued benefits from combinations that include lamivudine are regularly witnessed. Explanations for this occurrence include the likelihood that lamivudine-resistance reduces the risk of AZT resistance or that lamivudine resistant HIV is less likely to further mutate and develop resistance to other HIV drugs.