Nevirapine

Registered South African indications:

• HIV-1 infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment  
• Porphyria
• Readministration to patients who have had prior severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine
• AST or ALT >5 times ULN (pretreatment or during prior nevirapine therapy)
• Coadministration with St. John's wort

Cautions

• Should not be used as monotherapy
• Dose must be strictly adhered to, especially the 14-days lead-in period
• Chronic hepatitis B or C 
• Post exposure prophylaxis
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (tab,sus)  
• Fructose intolerance (sus)
• Sucrase-isomaltase insufficiency (sus)

Forms avail. in SA and covered in this monograph: tab, sus

HIV-1 infection
Pregnant and breastfeeding women with contraindication to efavirenz

• Oral (tab, sus): 200mg, dly for 14 days; Followed by 200mg, 12hrly; Max: 400mg/24hrs

Replace efavirenz with nevirapine in pregnant or breastfeeding women with CD4<250 and contraindication to efavirenz)

Unbooked pregnancy and presents in labour and tests HIV positive

• Oral (tab): 200mg as single dose

Requires combination with truvada as single dose, and zidovudine 3hrly

Emergency caesarean section in unbooked woman with no antiretroviral therapy

• Oral (tab): 200mg as a single dose plus truvada as single dose

Do not use as monotherapy

Patients who experience a rash during first 14 day lead in period should not have dose increased until rash resolved

Omit lead in dose if patient on rifampicin or if changing directly from efavirenz to nevirapine

If therapy interrupted for > 7 days, restart with once daily lead in dosing

Discontinue if patients experience severe rash, rash with systemic findings or abnormal liver function tests

Risk of rash-associated hepatitis is higher in patients with higher baseline CD4 counts (>250 in woman, > 400 in men) therefore avoid in these groups

Paed. forms avail. in SA and covered in this monograph: sus, tab

HIV-1 infection

Between 2 months - 8 years

• Oral (sus): 4mg/kg, dly for 14 days; Followed by 7mg/kg, 12hrly; Max: 400mg/24hrs

Older than 8 years

• Oral (sus, tab): 4mg/kg, dly for 14 days; Followed by 4mg/kg, 12hrly; Max: 400mg/24hrs

Infant on Prevention of Mother To Child Transmission (PMTCT)

Newborn >2kg and infants

Premature <2kg

If infant is severely underweight for age (3 SD or 3 z-scores below the mean) give nevirapine according to weight, (i.e. 4 mg/kg/dose daily) until in the normal weight for age range

Do not use as monotherapy

Patients who experience a rash during first 14 day lead in period should not have dose increased until rash resolved

Omit lead in dose if patient on rifampicin or if changing directly from efavirenz to neviropine

If therapy interrupted for > 7 days, restart with once daily lead in dosing

Discontinue if patients experience severe rash, rash with systemic findings or abnormal liver function tests

Risk of rash-associated hepatitis is higher in patients with higher baseline CD4 counts (>250 in woman, > 400 in men) therefore avoid in these groups

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy

• Safe; no evidence of risk in studies
• Currently, available data on pregnant women indicate no malformative or foetal/neonatal toxicity. To date no other relevant epidemiological data are available. No observable teratogenicity was detected in reproductive studies performed in pregnant rats and rabbits. There are no adequate and well-controlled studies in pregnant women. All the randomised studies addressing this issue specifically excluded pregnant women, and pregnant women were under-represented in cohort studies as well as in meta-analyses

Breastfeeding

• Compatible
• Nevirapine is found in breast milk. South African guidelines recommend that mothers should be encouraged to breastfeed as the advantages of breastfeeding exceed the risks of HIV transmission in a mother on effective antiretroviral treatment

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Fatigue

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea

Hepatobiliary Disorders

• Hepatitis 
• Life-threatening hepatotoxicity
• Jaundice
• Hepatitis fulminant (which may be fatal)

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash 
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis 
• Angioedema
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Granulocytopenia
• Anaemia
• Hypersensitivity 
• Anaphylactic reaction
• Drug reaction with eosinophilia and systemic symptoms

Others

• Pyrexia

• CYP450 substrates
• Zidovudine
• Non-nucleoside reverse transcriptase inhibitors
• Indinavir
• Atazanavir/ritonavir
• Fosamprenavir 
• Lopinavir/ritonavir
• Elvitegravir/ cobicistat
• Clarithromycin
• Rifabutin
• Rifampicin
• Fluconazole
• Itraconazole
• Ketoconazole
• Boceprevir
• Telaprevir
• Warfarin
• Oral hormonal contraceptives
• Methadone
• St. John's Wort

• Full blood count
• Hepatic function at 2, 4, 8 weeks; and periodically thereafter

Nevirapine is a non-competitive, non-nucleoside reverse transcriptase inhibitor of HIV-1. It binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities.  

Tablet 200mg

• Acriptaz (Mylan)
• Adco Nevirapine (Adcock)
• Aspen Nevirapine (Pharmacare)
• Cipla Nevirapine (Cipla Medpro)
• Macleods Nevirapine (Macleods)
• Nevir (Emcure)
• Nevivir (Hetero)
• Sonke Nevirapine (Ranbaxy)
• Vari-Nevirapine (LeBasi)
• Viramune (Ingelheim) originator
• Viropon (Novagen Pharma)

Suspension (per 5ml) 50mg

• Aspen Nevirapine (Pharmacare)
• Bindopin (Aurobindo)
• Cipla Nevirapine (Cipla Medpro)
• Viramune (Ingelheim) originator
• Viropon (Novagen Pharma)

COMBINATION PREPARATIONS

Zidovudine/ Nevirapine/ Lamivudine

Tablet 300mg/200mg/150mg

• Mivirdo (Mylan)
• Triplavar (Cipla Medpro)

Stavudine/ Lamivudine/ Nevirapine

Tablet 30mg/150mg/200mg

• Nevasta (Emcure)
• Sonke-Laminevstav 30 (Ranbaxy)
• Tri-Nestlam 150/30/200 (Adcock)
• Triomune 30 (Cipla Medpro)
• Virtrium 30/150/200 (Pharmacare)

Tablet 40mg/150mg/200mg

• Triomune 40 (Cipla Medpro)