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How Nelfinavir works
Nelfinavir is a member of the group of drugs referred to as protease inhibitors (Pis). This class of drug combats viral replication of HIV by blocking HIV's protease protein. This protein or enzyme is used by HIV to break up large viral proteins into smaller particles from which new HIV particles can be formed.
Protease inhibitors ensure that these new particles are immature and incapable of infecting new cells, thus inhibiting the HIV replication process.
History: Nelfinavir was formerly known as AG1343. It was first licensed in Europe in January 1998. The licence was originally granted for the use of nelfinavir in combination with antiretroviral nucleoside analogues for the treatment of HIV-1 in adults, adolescents and children three years of age and older. Nelfinavir is now licensed for antiretroviral combination therapy.
Combination therapy
Nelfinavir is established as an effective component of combination antiretroviral therapy against an optimal antiretroviral background. It should not be used as monotherapy as resistant viruses rapidly emerge. Careful consideration needs to be applied when incorporating nelfinavir into HIV combination therapy, as several interactions with other antiretrovirals have been observed.
If used in combination with the NNRTI delavardine, nelfinavir levels are reduced and delavardine levels are increased, this combination is not recommended; no significant interactions have been observed with other NNRTIs - efavirenz or nevirapine. If nelfinavir is used alongside other protease inhibitors, interactions should be carefully considered. If used with ritonavir then nelfinavir concentrations are increased. If used with indinavir both nelfinavir and indinavir concentrations are increased, if used with saquinavir then both concentrations are increased. If used with amprenavir then amprenavir concentrations are increased. These interactions may indicate the necessity for dose modifications.
Dosing
Nelfinavir is produced in a 250mg film-coated blue tablet and also as an oral powder for paediatric use. The recommended adult daily dose of nelfinavir is five 250mg tablets taken twice daily or three 250mg tablets taken three times daily with food.
The recommended dose for three to 13-year-olds is 50-55mg per kilo body weight twice daily or 25-30mg per kilo body weight three times daily.
Dosing restrictions
You should take nelfinavir tablets with food. Nelfinavir is metabolised by the CYP3A4 enzyme. Any drug that inhibits or accelerates this process is likely to impact on the levels of nelfinavir in the blood. Sub-optimal levels of nelfinavir in the blood increase the risk of resistance developing. Similarly, any drug that shares this metabolic pathway is likely to be affected by the co-administration of nelfinavir, for this reason there are a number of dosing restrictions or recommended dose modifications.
Drug interactions with nelfinavir include:
St. John's Wort should not be taken alongside nelfinavir: it reduces plasma levels of nelfinavir and can potentially reduce its efficacy
Nelfinavir should not be taken alongside delavirdine
If nelfinavir is co-administered with didanosine then nelfinavir should be taken with food one hour after or more than two hours before ddl
Levels of sildenafil (Viagra) in the body are increased in the presence of nelfinavir, a reduced dose of 25mg sildenafil is recommended
Co-administration of nelfinavir and rifabutin (TB medication) results in increased blood levels of rifabutin and decreased levels of nelfinavir and as a consequence rifabutin dosing should be reduced from 300mg to 150mg per day
Nelfinavir should not be administered alongside triazolam, cisapride, astemizole, terfenadine, midazolam or rifampicin
HMG-CoA reductase inhibitors (cholesterol lowering drugs), which are highly dependent on CYP3A4 metabolism, are expected to have increased plasma concentrations when co-administered with nelfinavir: this may cause myopathy (muscle disorder), so combining these drugs (e.g. lovastatin or simvastatin) with nelfinavir is not recommended. Atorvastatin is less dependent on CYP3A4 for metabolism, but caution must be exercised. If treatment with a HMG-CoA reductase inhibitor is needed, pravastatin or fluvastatin is recommended
If nelfinavir is administered alongside phenytoin (epilepsy medication) then levels of phenytoin will be reduced and should be monitored to ensure therapeutic levels are maintained
When nelfinavir is administered alongside methadone, reductions in methadone levels have been observed and may therefore require dose adjustment
The efficacy of the oral contraceptive is reduced if nelfinavir is administered, other contraceptive methods are recommended
Side effects
The most common side effects of nelfinavir are those related to gastro-intestinal disturbance. These are likely to occur in the first few weeks after commencing treatment. The most common side effects include
Diarrhoea
Flatulence
Nausea
Vomiting
Abdominal pain/distension
Rash
Other side effects associated with nelfinavir and common to all the protease inhibitors include
Lipodystrophy (although incidence and degree varies between all Pis)
Myopathy (muscle disease)
Increased bleeding in those with bleeding disorders
Increase in blood fats
Diabetes
Pancreatitis
Pre-existing conditions
Nelfinavir tablets and powder should be used with caution in patients with renal or hepatic impairment. All protease inhibitors, including nelfinavir, have been associated with increased bleeding in patients with bleeding disorders: these patients may require additional clotting agents if protease inhibitors are included in their antiretroviral combination therapy.
Patients with TB should not be co-administered nelfinavir and rifampicin. Those taking rifabutin and nelfinavir should reduce their rifabutin dose to 150mg per day.
Women should not breastfeed if taking nelfinavir.
Paediatric use
Nelfinavir is licensed for use in children three years of age or older. An oral powder is available for those children unable to swallow tablets. The powder can be mixed with water, milk, jam or desserts. It is not advised to mix with fruit juice.
Use during pregnancy
There are no adeguate and well-controlled studies of nelfinavir in pregnant women. Therefore nelfinavir should only be used during pregnancy if the benefits justify any potential risks. In addition, as nelfinavir is excreted into breast milk, mothers should be advised not to breastfeed their infants if receiving nelfinavir.
Nelfinavir resistant HIV
It is widely accepted that all protease inhibitors experience an element of cross-resistance within the group.
