Efavirenz

Registered South African indications:

• HIV-1 infection

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids
• Co-administration with St. John's wort
• History of previous hepatic impairment with efavirenz-containing regimens 

Cautions

• Hepatic impairment
• Elderly
• Porphyria
• Previous life-threatening cutaneous reaction while taking another non-nucleoside reverse transcriptase inhibitor
• Psychiatric disorders
• History of seizure
• Immune reactivation syndrome
• Long-term antiretroviral treatment
• Metabolic disturbances
• Osteonecrosis
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

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

First line treatment of HIV infection 
HIV positive pregnant women 

Weight less than 40kg

• Oral (cap, tab): 400mg, dly, at night

Weight greater than 40kg

• Oral (cap, tab): 600mg, dly, at night

Not to be used as monotherapy

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

First line treatment of HIV infection in children older than 3 years and greater than 10kg

Less than 40kg or younger than 15 years

• Oral (cap, tab): 10-13.9kg: 200mg, dly, at night 
• Oral (cap, tab): 14-24.9kg: 300mg, dly, at night 
• Oral (cap, tab): 25-39.9kg: 400mg, dly, at night 

Greater than 40kg or older than 15 years

• Oral (cap, tab): 600mg, dly, at night

Not to be used as monotherapy

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

Pregnancy

• Safe
• There have been seven retrospective reports of findings consistent with neural tube defects, including meningomyelocele, all in mothers exposed to efavirenz-containing regimens (excluding any efavirenz-containing fixed-dose combination tablets) in the first trimester. Two additional cases (1 prospective and 1 retrospective) including events consistent with neural tube defects have been reported with the fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir disoproxil fumarate. A causal relationship of these events to the use of efavirenz has not been established, and the denominator is unknown. As neural tube defects occur within the first 4 weeks of foetal development (at which time neural tubes are sealed), this potential risk would concern women exposed to efavirenz during the first trimester of pregnancy
• As of July 2013, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 904 pregnancies with first trimester exposure to efavirenz-containing regimens, resulting in 766 live births. One child was reported to have a neural tube defect, and the frequency and pattern of other birth defects were similar to those seen in children exposed to non-efavirenz-containing regimens, as well as those in HIV negative controls. The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live births. Malformations have been observed in foetuses from efavirenz-treated monkeys
• SA HIV guidelines recommend the use of standard first-line, second-line and third-line regimens be used during pregnancy. The WHO endorses the use of efavirenz in pregnancy and in women who intend to fall pregnant based on a meta-analysis which found that the incidence of neural tube defects and all congenital abnormalities among women exposed to efavirenz in the first trimester was similar to that of the general population

Breastfeeding

• Compatible
• Efavirenz has been shown to be excreted in human milk. There is insufficient information on the effects of efavirenz in newborns/infants. Breastfeeding mothers may breastfeed their infants
• South African HIV guidelines recommend exclusive breastfeeding for the first 6 months, after which the nutritional needs of the child will require the introduction of complementary foods, while breastfeeding continues. Mothers failing 2nd or 3rd line regimens should not breastfeed, provided the mother fulfils the AFASS (affordable, feasible, acceptable, sustainable and safe) criteria

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate (Child-Pugh class A and B): Caution; no dose adjustment recommended
  Monitor LFTs and document any observed changes in transaminases (mainly ALT)
  Any decision related to ARV dose adjustment and/or discontinuation must be supported by HIV clinician and expert
• Severe (Child-Pugh class C): Caution; no dose adjustment recommended
  Consider discontinuing treatment in patients with persistent serum transaminase elevations >5 x ULN or if serum transaminase elevations are accompanied by signs/symptoms of hepatitis or hepatic decompensation
  Document patients' CD-4 count and VL;  Discuss possible ARV switch with expert HIV clinician
  Any decision related to ARV dose adjustment and/or discontinuation must be supported by HIV clinician and expert

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Depression
• Insomnia
• Affect lability
• Aggression
• Confusional state
• Euphoric mood
• Hallucination
• Mania
• Paranoia
• Psychosis
• Suicide attempt
• Suicide ideation
• Delusion 
• Neurosis
• Balance disturbances
• Disturbance in attention
• Dizziness 
• Headache 
• Somnolence 
• Agitation
• Amnesia
• Ataxia
• Convulsions
• Abnormal thinking 
• Tremor
• Fatigue

Cardiovascular Disorders

• Flushing 

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Nausea and vomiting
• Pancreatitis

Hepatobiliary Disorders

• Aspartate aminotransferase (AST) increase
• Alanine aminotransferase (ALT) increased
• Gamma-glutamyltransferase (GGT) increased
• Acute hepatitis 
• Hepatic failure

Endocrine and Metabolic Disorders

• Gynaecomastia
• Hypertriglyceridaemia
• Hypercholesterolaemia

Skin and Subcutaneous Tissue Disorders

• Rash 
• Pruritus
• Erythema multiforme
• Stevens-Johnson syndrome
• Photoallergic dermatitis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

Sensory Disorders

• Blurred vision 
• Tinnitus
• Vertigo

• Erfenadine
• Astemizole
• Cisapride
• Midazolam
• Triazolam
• Pimozide
• Bepridil
• Ergot alkaloids 
• CYP3A4 substrates
• CYP2B6 substrates
• UGT1A1substrates
• CYP450 substrates
• St. John's wort
• Atazanavir/ritonavir
• Ritonavir
• Simeprevir 
• Itraconazole
• Posaconazole
• Artemether/lumefantrine
• Atovaquone/proguanil
• Warfarin
• Acenocoumarol
• Phenytoin
• Phenobarbital

• Hepatic function
• Coagulation studies

Specific cases may require

• Renal function

Efavirenz is a non-nucleoside reverse transcriptase inhibitor. It is a non-competitive inhibitor of HIV-1 reverse transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases.

Tablet 50mg

• Efamat (Mylan)
• Stocrin (MSD) originator

Tablet 200mg

• Efamat (Mylan)
• Stocrin (MSD) originator

Tablet 600mg

• Adco Efavirenz (Adcock)
• Aspen Efavirenz (Pharmacare)
• Arrow-Efavirenz (Arrow)
• Cipla Efavirenz (Cipla Medpro)
• Efavirenz Winthrop (Zentiva)
• Efrin (Mylan)
• Erige (Novagen)
• Hevaz (Hetero)
• Macleods Efavirenz (Macleods)
• Sonke Efavirenz (Sonke)
• Stocrin (MSD) originator
• Viref (Emcure)
• Zenfar (Macleods Pharma)

Capsule 50mg

• Adco Efavirenz (Adcock)
• Erige (Novagen)
• Stocrin (MSD) originator
• Zenvir (Aurobindo)

Capsule 200mg

• Adco Efavirenz (Adcock)
• Erige (Novagen)
• Sonke Efavirenz (Sonke)
• Stocrin (MSD) originator
• Zenvir (Aurobindo)

COMBINATION PREPARATIONS

Efavirenz/ Zidovudine/ Lamivudine

Tablet 600mg/300mg/150mg

• Cipla Duovir and Efavirenz Co-Pack (Cipla Medpro)

Efavirenz/ Emtricitabine/ Tenofovir

Tablet 600mg/200mg/300mg

• Atenef (Sonke)
• Atreslawin (Sanofi)
• Atripla (MSD) originator
• Atroiza (Mylan)
• Citenvir (Novagen)
• Odimune (Cipla)
• Rizene (Adcock)
• Trenvir (Cipla Life Sciences)
• Tribuss (Pharmacare)
• Triolar (Macleods)
• Trivenz (Adcock)
• Truno 600/200/300 (Aurobindo)

Efavirenz/ Tenofovir disoproxil/ Lamivudine

Tablet 600mg/300mg/300mg

• Arion (Novagen)
• Eflaten (Mylan)
• Tenarenz (Pharmacare)
• Virlaten (Sandoz)