Drugs List

Therapeutic Indications

Uses

HIV infection combined with other antiretrovirals.

Administration

Oral suspension
The bottle should be shaken gently prior to use. It is important that the entire measured dose of nevirapine oral suspension is administered. This is assisted by using a dispensing syringe (provided). If an alternative measuring device is used, the device should be rinsed to ensure all residual oral suspension is removed.

Tablets
Take with water. Not to be crushed or chewed.

Contraindications

Previous discontinuation due to severe rash Previous discontinuation due to rash with constitutional symptoms Previous discontinuation secondary to hepatitis Severe hepatic impairment - Child-Pugh score greater than or equal to 10 Elevated serum transaminases - greater than 5 times upper limit of normal Recurrent drug induced serum transaminases over 5 times normal upper limit Breastfeeding Acute porphyria Post-exposure prophylaxis

Additional contraindications for oral suspension
Hereditary fructose intolerance

Precautions and Warnings

Hepatitis B. Hepatitis C. Elevated serum transaminases - greater than 2.5 times upper limit of normal. Hepatic impairment - Child-Pugh score greater than 7. Glucose-galactose malabsorption syndrome. Males with CD4 cell counts greater than 400 cells/cubic mm. Females with CD4 cell counts greater than 250 cells/cubic mm. Renal dialysis.
Must be used in combination with other antiretrovirals.
Treatment should be initiated by doctor experienced in HIV management. The first 18 weeks of therapy are a critical period and close monitoring of the patient is required in order to detect the appearance of severe and life-threatening reactions.
Treatment does not prevent risk of transmission of HIV.

Monitor serum lipids.
Monitor blood glucose.

Blood lipid and glucose levels may increase requiring treatment.

Monitor for skin reactions for first 18 weeks of therapy.

Monitor body weight in children and review dose if necessary.

Nevirapine should not be initiated in females with CD4 cell counts greater than 250 cells/cubic millimetre or in males with CD4 cell counts greater than 400 cells/cubic millimetre who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk. There is a greater risk of hepatic adverse events in these patients.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted.

Perform liver function tests before commencing therapy and during therapy. Monitor liver function every 2 weeks for 8 weeks then monthly and as required.

Hepatic tests should be performed more frequently in patients with AST/ALT levels equal to or greater than 2.5 ULN before or during therapy. Nevirapine therapy should be discontinued immediately if AST/ALT levels increase to greater than 5 ULN during treatment. Treatment may be restarted (at the lead-in dose) if AST/ALT levels return to baseline values and the patient had no symptoms of hepatitis, rash, constitutional symptoms, or other symptoms suggestive of organ impairment. In these patients more frequent liver monitoring is recommended.

Nevirapine therapy may cause abnormal liver function tests, some in the first few weeks of treatment. Asymptomatic elevations of hepatic enzymes do not necessarily require the discontinuation of nevirapine. Asymptomatic GGT elevations are not a contraindication to continue therapy.
Risk of developing opportunistic infections.
Advise patient to seek immediate medical advice if rash occurs. Do not increase dose if rash is present. Perform liver function tests if rash develops.

Discontinue if severe skin reaction (including Stevens-Johnson syndrome and toxic epidermal necrolysis) or rash accompanied by constitutional symptoms occur. Constitutional symptoms include fever, blistering, oral lesions, conjunctivitis, facial oedema, muscle or joint aches or general malaise.
Discontinue if rash with systemic, allergic or mucosal symptoms occurs.
Advise patients that hypersensitivity reactions may be life threatening. Warn patient to report symptoms of allergic type hypersensitivity. Discontinue if hypersensitivity reactions occur. Never re-challenge treatment after a hypersensitivity reaction. These reactions are characterised by rash with constitutional symptoms plus visceral involvement (such as hepatitis, eosinophilia, granulocytopenia and renal impairment).
Advise patients to seek medical advice if signs of hepatotoxicity occur. Severe and life-threatening hepatotoxicity, including fatal fulminant hepatitis, have occurred during nevirapine therapy. The greatest risk of these reactions is during the first 6 weeks of therapy. However the risk continues past this period and monitoring should continue at frequent intervals throughout treatment.
Interrupt therapy if hepatic transaminases greater than 5 times upper limit of normal.

Discontinue if abnormal liver function tests persist or worsen.
Discontinue if hepatitis develops. This is characterised by anorexia, nausea, vomiting, icterus and moderate to severe liver function test abnormalities.
Discontinue if hepatic function deteriorates in patients with hepatic impairment. Patients with pre-existing hepatic impairment are at an increased risk of developing hepatic function abnormalities and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Discontinue permanently if abnormal liver function tests accompanied by hypersensitivity reactions (rash, fever, arthralgia, myalgia, lymphadenopathy, hepatitis, renal impairment, eosinophilia, granulocytopenia) occur. Treatment should be suspended if abnormal liver function tests without hypersensitivity occurs.

Evaluate for physical signs of fat redistribution.
Inflammatory symptoms should be evaluated and treated appropriately.
Advise patient to seek medical advice if joint aches or pain occur.

Advise patient to seek medical advice if movement becomes difficult.

Repeat dose titration if treatment is stopped for more than 7 days.
Female: Barrier or non-hormonal contraception advised during treatment.

Advise patient not to take St John's wort concurrently.

Ability to drive or operate machinery may be affected by side effects.

Additional precautions for tablet formulation
Galactosaemia. Lactose intolerance. Some formulations contain lactose.
Children under 3 years. Not all formulations are suitable for use in children under 3 years.

Additional precautions for oral suspension
Presentations with sorbitol unsuitable in hereditary fructose intolerance.

Oral solution contains sucrose and hydroxybenzoates.

Pregnancy and Lactation

Pregnancy

Use nevirapine with caution during pregnancy.

The manufacturer advises caution if nevirapine is used during pregnancy. At the time of writing there is limited published information regarding the use of nevirapine during pregnancy. Potential risks are unknown.

Lactation

Nevirapine is contraindicated during breastfeeding.

Use of nevirapine when breastfeeding is contraindicated by the manufacturer. Nevirapine is present in human breast milk. Effects on exposed infants are unknown.

Side Effects

Stevens-Johnson syndrome Toxic epidermal necrolysis Abnormal liver function tests Increase in serum ALT/AST Gamma glutamyl transferase (GGT) increased Serum bilirubin increased Increase in alkaline phosphatase Rash Nausea Fatigue Fever Headache Hypersensitivity reactions Anaphylactic reaction Angioedema Urticaria Pruritus Malaise Neuropsychiatric disturbances Hepatitis Hepatic failure Eosinophilia Granulocytopenia Anaemia Vomiting Diarrhoea Abdominal pain Jaundice Hepatotoxicity Fulminant hepatitis Arthralgia Myalgia Blistering Oral lesions Conjunctivitis Facial oedema Renal impairment Lymphadenopathy Lipodystrophy Metabolic disorders Hypertriglyceridaemia Hypercholesterolaemia Insulin resistance Hyperglycaemia Hyperlactataemia Immune Reactivation/Reconstitution Syndrome Osteonecrosis Pancreatitis Drug rash with eosinophilia and systemic symptoms (DRESS) Pyrexia Peripheral neuropathy Thrombocytopenia Inflammatory reactions Transaminases abnormal Increases in hepatic enzymes Hypophosphataemia Increased blood pressure

Presentation

Oral formulations containing nevirapine.

Drugs List

Therapeutic Indications

Uses

HIV infection combined with other antiretrovirals.

Dosage

Most of the experience with nevirapine is in combination with nucleoside reverse transcriptase inhibitors (NRTIs). The choice of a subsequent therapy after nevirapine should be based on clinical experience and resistance testing.

To avoid rapid emergence of resistant virus always administer nevirapine in combination with at least 2 additional antiretroviral agents.

A lower dose is recommended for the first 2 weeks of therapy as this 'lead-in' period lessens the frequency of rash. Prolonged release tablets are not suitable for the 14-day lead-in phase for patients starting nevirapine, immediate release formulations should be used. If rash does occur during this period, the nevirapine dose should not be increased until the rash has resolved. The isolated rash should be closely monitored. The 200mg once daily regimen should not be continued beyond 28 days at which point in time an alternative treatment should be sought due to the possible risk of underexposure and resistance.

The total daily dose at any time during treatment should not exceed 400mg for any patient. Total daily dosages above the recommended may increase the risk of serious adverse events.

Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing regimen using the two week lead-in period of immediate-release nevirapine.

Patients currently on a regimen containing immediate-release nevirapine twice daily in combination with other antiretroviral agents, can be switched to nevirapine 400mg prolonged-release tablets once daily in combination with other antiretroviral agents, without a lead-in period of nevirapine immediate-release.

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

Oral suspension
The bottle should be shaken gently prior to use. It is important that the entire measured dose of nevirapine oral suspension is administered. This is assisted by using a dispensing syringe (provided). If an alternative measuring device is used, the device should be rinsed to ensure all residual oral suspension is removed.

Tablets
Take with water. Not to be crushed or chewed.

Contraindications

Previous discontinuation due to severe rash Previous discontinuation due to rash with constitutional symptoms Previous discontinuation secondary to hepatitis Severe hepatic impairment - Child-Pugh score greater than or equal to 10 Elevated serum transaminases - greater than 5 times upper limit of normal Recurrent drug induced serum transaminases over 5 times normal upper limit Breastfeeding Acute porphyria Post-exposure prophylaxis

Additional contraindications for oral suspension
Hereditary fructose intolerance

Precautions and Warnings

Hepatitis B. Hepatitis C. Elevated serum transaminases - greater than 2.5 times upper limit of normal. Hepatic impairment - Child-Pugh score greater than 7. Glucose-galactose malabsorption syndrome. Males with CD4 cell counts greater than 400 cells/cubic mm. Females with CD4 cell counts greater than 250 cells/cubic mm. Renal dialysis.
Must be used in combination with other antiretrovirals.
Treatment should be initiated by doctor experienced in HIV management. The first 18 weeks of therapy are a critical period and close monitoring of the patient is required in order to detect the appearance of severe and life-threatening reactions.
Treatment does not prevent risk of transmission of HIV.

Monitor serum lipids.
Monitor blood glucose.

Blood lipid and glucose levels may increase requiring treatment.

Monitor for skin reactions for first 18 weeks of therapy.

Monitor body weight in children and review dose if necessary.

Nevirapine should not be initiated in females with CD4 cell counts greater than 250 cells/cubic millimetre or in males with CD4 cell counts greater than 400 cells/cubic millimetre who have a detectable plasma HIV-1 RNA unless the benefit outweighs the risk. There is a greater risk of hepatic adverse events in these patients.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted.

Perform liver function tests before commencing therapy and during therapy. Monitor liver function every 2 weeks for 8 weeks then monthly and as required.

Hepatic tests should be performed more frequently in patients with AST/ALT levels equal to or greater than 2.5 ULN before or during therapy. Nevirapine therapy should be discontinued immediately if AST/ALT levels increase to greater than 5 ULN during treatment. Treatment may be restarted (at the lead-in dose) if AST/ALT levels return to baseline values and the patient had no symptoms of hepatitis, rash, constitutional symptoms, or other symptoms suggestive of organ impairment. In these patients more frequent liver monitoring is recommended.

Nevirapine therapy may cause abnormal liver function tests, some in the first few weeks of treatment. Asymptomatic elevations of hepatic enzymes do not necessarily require the discontinuation of nevirapine. Asymptomatic GGT elevations are not a contraindication to continue therapy.
Risk of developing opportunistic infections.
Advise patient to seek immediate medical advice if rash occurs. Do not increase dose if rash is present. Perform liver function tests if rash develops.

Discontinue if severe skin reaction (including Stevens-Johnson syndrome and toxic epidermal necrolysis) or rash accompanied by constitutional symptoms occur. Constitutional symptoms include fever, blistering, oral lesions, conjunctivitis, facial oedema, muscle or joint aches or general malaise.
Discontinue if rash with systemic, allergic or mucosal symptoms occurs.
Advise patients that hypersensitivity reactions may be life threatening. Warn patient to report symptoms of allergic type hypersensitivity. Discontinue if hypersensitivity reactions occur. Never re-challenge treatment after a hypersensitivity reaction. These reactions are characterised by rash with constitutional symptoms plus visceral involvement (such as hepatitis, eosinophilia, granulocytopenia and renal impairment).
Advise patients to seek medical advice if signs of hepatotoxicity occur. Severe and life-threatening hepatotoxicity, including fatal fulminant hepatitis, have occurred during nevirapine therapy. The greatest risk of these reactions is during the first 6 weeks of therapy. However the risk continues past this period and monitoring should continue at frequent intervals throughout treatment.
Interrupt therapy if hepatic transaminases greater than 5 times upper limit of normal.

Discontinue if abnormal liver function tests persist or worsen.
Discontinue if hepatitis develops. This is characterised by anorexia, nausea, vomiting, icterus and moderate to severe liver function test abnormalities.
Discontinue if hepatic function deteriorates in patients with hepatic impairment. Patients with pre-existing hepatic impairment are at an increased risk of developing hepatic function abnormalities and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Discontinue permanently if abnormal liver function tests accompanied by hypersensitivity reactions (rash, fever, arthralgia, myalgia, lymphadenopathy, hepatitis, renal impairment, eosinophilia, granulocytopenia) occur. Treatment should be suspended if abnormal liver function tests without hypersensitivity occurs.

Evaluate for physical signs of fat redistribution.
Inflammatory symptoms should be evaluated and treated appropriately.
Advise patient to seek medical advice if joint aches or pain occur.

Advise patient to seek medical advice if movement becomes difficult.

Repeat dose titration if treatment is stopped for more than 7 days.
Female: Barrier or non-hormonal contraception advised during treatment.

Advise patient not to take St John's wort concurrently.

Ability to drive or operate machinery may be affected by side effects.

Additional precautions for tablet formulation
Galactosaemia. Lactose intolerance. Some formulations contain lactose.
Children under 3 years. Not all formulations are suitable for use in children under 3 years.

Additional precautions for oral suspension
Presentations with sorbitol unsuitable in hereditary fructose intolerance.

Oral solution contains sucrose and hydroxybenzoates.

Pregnancy and Lactation

Pregnancy

Use nevirapine with caution during pregnancy.

The manufacturer advises caution if nevirapine is used during pregnancy. At the time of writing there is limited published information regarding the use of nevirapine during pregnancy. Potential risks are unknown.

Lactation

Nevirapine is contraindicated during breastfeeding.

Use of nevirapine when breastfeeding is contraindicated by the manufacturer. Nevirapine is present in human breast milk. Effects on exposed infants are unknown.

Counselling

Advise patients that treatment with antiretroviral therapy does not cure HIV and that opportunistic infections and other complications of HIV infection may still develop.

Advise patients that current antiretroviral therapy has not been shown to prevent the risk of transmission of HIV to others through sexual contact or blood contamination.

Advise patients taking immediate release formulations, if a dose is recognised as missed within 8 hours of when it was due, the patient should take the missed dose as soon as possible. If a dose is recognised as missed and it is more than 8 hours later, the patient should only take the next dose at the usual time.

Advise patients taking prolonged release formulations, if a dose is recognised as missed within 12 hours of when it was due, the patient should take the missed dose as soon as possible. If a dose is recognised as missed and it is more than 12 hours later, the patient should only take the next dose at the usual time.

Advise patients against taking any herbal preparations containing St. John's wort whilst taking nevirapine.

Advise patients that rash is a sign of major toxicity. Advise patients to report to their physician any rash that occurs and to avoid a delay between the initial symptoms and medical consultation.

Advise patients that hepatic reactions are a sign of major toxicity. Patients and physicians should monitor for any symptoms suggestive of hepatitis (such as anorexia, nausea, jaundice, bilirubinuria, alcoholic stools, hepatomegaly or hepatic tenderness). If these symptoms occur, patients should be advised to seek medical advice immediately.

Advise patients how to recognise hypersensitivity reaction (rash, fever, arthralgia, myalgia, lymphadenopathy, hepatitis, renal impairment, eosinophilia, granulocytopenia) and to seek immediate medical attention should any of these occur.

Advise patients to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

Advise female patients that hormonal methods of birth control other than depot-medroxyprogesterone acetate (DMPA) should not be used as the sole method of contraception in women taking nevirapine. For this reason, and to reduce risk of HIV transmission, barrier contraception (e.g. condoms) is recommended.

Advise patients, they may experience adverse reactions such as fatigue during treatment with nevirapine. Caution should be exercised when driving a car or operating machinery.

Side Effects

Stevens-Johnson syndrome Toxic epidermal necrolysis Abnormal liver function tests Increase in serum ALT/AST Gamma glutamyl transferase (GGT) increased Serum bilirubin increased Increase in alkaline phosphatase Rash Nausea Fatigue Fever Headache Hypersensitivity reactions Anaphylactic reaction Angioedema Urticaria Pruritus Malaise Neuropsychiatric disturbances Hepatitis Hepatic failure Eosinophilia Granulocytopenia Anaemia Vomiting Diarrhoea Abdominal pain Jaundice Hepatotoxicity Fulminant hepatitis Arthralgia Myalgia Blistering Oral lesions Conjunctivitis Facial oedema Renal impairment Lymphadenopathy Lipodystrophy Metabolic disorders Hypertriglyceridaemia Hypercholesterolaemia Insulin resistance Hyperglycaemia Hyperlactataemia Immune Reactivation/Reconstitution Syndrome Osteonecrosis Pancreatitis Drug rash with eosinophilia and systemic symptoms (DRESS) Pyrexia Peripheral neuropathy Thrombocytopenia Inflammatory reactions Transaminases abnormal Increases in hepatic enzymes Hypophosphataemia Increased blood pressure

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2019

Reference Sources

Summary of Product Characteristics: Nevirapine 200mg tablets. Wockhardt UK Ltd. Revised April 2019.
Summary of Product Characteristics: Nevirapine 400mg prolonged-release tablets. Accord Healthcare Ltd . Revised February 2019.
Summary of Product Characteristics: Viramune 50mg/5ml oral suspension. Boehringer Ingelheim Ltd. Revised November 2019.
Summary of Product Characteristics: Viramune 200mg tablets. Boehringer Ingelheim Ltd. Revised August 2018.
Summary of Product Characteristics: Viramune 100mg Prolonged-Release Tablets. Boehringer Ingelheim Ltd. Revised November 2019.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 09 December 2019