Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of human immunodeficiency virus type 1 (HIV-1) when used in combination with a boosted protease inhibitor and other antiretroviral drugs in antiretroviral treatment experienced patients aged 2 years and older.

Contraindications

Children under 2 years
Children weighing less than 10kg
Acute porphyria
Breastfeeding
Galactosaemia
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Moderate hepatic impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Some formulations contain lactose
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Monitor blood glucose
Monitor serum lipids
Advise patient to seek immediate medical advice if rash occurs
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently

Examples of fatal severe hypersensitivity syndromes, including DRESS (Drug rash with eosinophilia and systemic symptoms) and TEN (toxic epidermal necrosis) have been reported with etravirine use. The DRESS syndrome is characterised by rash, fever, eosinophilia and systemic involvement (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, eosinophilia). The time to onset is usually 3-6 weeks after treatment starts and the outcome in most cases is favourable upon discontinuation and after initiation of corticosteroid therapy. Patients who delay in stopping treatment with etravirine after the onset of severe rash may result in a life threatening reaction. Once a patient has stopped treatment due to hypersensitivity reactions re-start of treatment with etravirine is not recommended.

Pregnancy and Lactation

Pregnancy

Use etravirine with caution in pregnancy.

Briggs suggests the etravirine should not be withheld because of pregnancy. The manufacturer suggests, based on limited data no dose adjustment is required, however caution is advised with concurrent medication or other conditions which may further increase etravirine exposure.

When considering the treatment of HIV infected women during pregnancy, the present and future health of the mother, the prevention of maternal to foetal transmission and the limitations from the drug toxicity to the HIV-exposed foetus should be considered. The optimal antiretroviral therapy regimen for each patient depends on their HIV RNA levels, previous disease history, and obstetric history.

At the time of writing, there is no adequate published experience concerning exposed pregnancies and their outcomes. Placental transfer has been observed in rats, however, it is not known whether placental transfer occurs in humans. Studies in animals have not indicated any direct of indirect harmful effects with respect to pregnancy, embryo or foetal development, parturition or postnatal development.

Briggs suggests administering zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.

Lactation

Etravirine is contraindicated during breastfeeding.

It is not known whether etravirine is excreted into breast milk. HIV can be transmitted from mother to child through breast milk. Therefore it is recommended that HIV-infected women do not breastfeed their infants under any circumstances in order to avoid transmission of HIV.

Side Effects

Abdominal distension
Abdominal pain
Amnesia
Anaemia
Angina pectoris
Angioneurotic oedema
Anorexia
Anxiety
Atrial fibrillation
Attention disturbances
Autoimmune hepatitis
Blistering
Blurred vision
Bronchospasm
Confusion
Conjunctivitis
Constipation
Convulsions
Cytolytic hepatitis
Diabetes mellitus
Diarrhoea
Disorientation
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dry skin
Dyslipidaemia
Dyspnoea
Elevated amylase levels
Elevated serum LDL cholesterol
Elevated serum lipase
Elevated triglyceride levels
Eosinophilia
Erythema multiforme
Facial swelling
Fatigue
Fever
Flatulence
Gastritis
Gastroesophageal reflux disease
Graves' disease
Gynaecomastia
Haematemesis
Headache
Hepatic steatosis
Hepatitis
Hepatomegaly
Hypercholesterolaemia
Hyperglycaemia
Hyperhidrosis
Hyperlipidaemia
Hypersensitivity reactions
Hypersomnia
Hypertension
Hypertriglyceridaemia
Hypoaesthesia
Immune Reactivation/Reconstitution Syndrome
Increase in plasma cholesterol
Increase in serum ALT/AST
Increase in serum glucose
Insomnia
Joint ache
Lassitude
Lipodystrophy
Lipohypertrophy
Malaise
Muscle ache
Myocardial infarction
Nausea
Nervousness
Night sweats
Nightmares
Oral lesions
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Prurigo
Rash
Reduced neutrophil count
Renal failure
Retching
Serum creatinine increased
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Stroke
Syncope
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Vertigo
Vomiting
White blood cell count decreased

Presentation

Tablets containing etravirine

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of human immunodeficiency virus type 1 (HIV-1) when used in combination with a boosted protease inhibitor and other antiretroviral drugs in antiretroviral treatment experienced patients aged 2 years and older.

Dosage

Adults

Elderly

Children

Contraindications

Children under 2 years
Children weighing less than 10kg
Acute porphyria
Breastfeeding
Galactosaemia
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Moderate hepatic impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Some formulations contain lactose
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Monitor blood glucose
Monitor serum lipids
Advise patient to seek immediate medical advice if rash occurs
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently

Examples of fatal severe hypersensitivity syndromes, including DRESS (Drug rash with eosinophilia and systemic symptoms) and TEN (toxic epidermal necrosis) have been reported with etravirine use. The DRESS syndrome is characterised by rash, fever, eosinophilia and systemic involvement (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, eosinophilia). The time to onset is usually 3-6 weeks after treatment starts and the outcome in most cases is favourable upon discontinuation and after initiation of corticosteroid therapy. Patients who delay in stopping treatment with etravirine after the onset of severe rash may result in a life threatening reaction. Once a patient has stopped treatment due to hypersensitivity reactions re-start of treatment with etravirine is not recommended.

Pregnancy and Lactation

Pregnancy

Use etravirine with caution in pregnancy.

Briggs suggests the etravirine should not be withheld because of pregnancy. The manufacturer suggests, based on limited data no dose adjustment is required, however caution is advised with concurrent medication or other conditions which may further increase etravirine exposure.

When considering the treatment of HIV infected women during pregnancy, the present and future health of the mother, the prevention of maternal to foetal transmission and the limitations from the drug toxicity to the HIV-exposed foetus should be considered. The optimal antiretroviral therapy regimen for each patient depends on their HIV RNA levels, previous disease history, and obstetric history.

At the time of writing, there is no adequate published experience concerning exposed pregnancies and their outcomes. Placental transfer has been observed in rats, however, it is not known whether placental transfer occurs in humans. Studies in animals have not indicated any direct of indirect harmful effects with respect to pregnancy, embryo or foetal development, parturition or postnatal development.

Briggs suggests administering zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.

Lactation

Etravirine is contraindicated during breastfeeding.

It is not known whether etravirine is excreted into breast milk. HIV can be transmitted from mother to child through breast milk. Therefore it is recommended that HIV-infected women do not breastfeed their infants under any circumstances in order to avoid transmission of HIV.

Counselling

Advise patients with swallowing difficulties etravirine tablets may be dispersed in a glass of water. Once dispersed, the dispersion should be well stirred and drunk immediately. The glass should be rinsed with water several times and each rinse should be swallowed to ensure that the entire dose is consumed.

Advise patients that treatment does not prevent the transmission of HIV via blood contamination or sexual contact and appropriate precautions should still be used.

Advise patients that treatment is not a cure for HIV infection and they may still develop opportunistic infections and other complications of HIV infection.

Advise patients if a dose if missed within 6 hours of usual dosage time, the dose should be taken as soon as possible following a meal with the following dose at its normal time. If a dose is missed more than 6 hours after usual dosage time, no catch up dose should be taken and the next dose should be at the usual time.

Advise patients if vomiting occurs within 4 hours of taking etravirine, another dose should be taken as soon as possible following a meal. If the patient vomits more than 4 hours after taking etravirine, the patient does not need to take another dose until the next scheduled time.

Advise patients that they should not take St John's Wort during treatment with etravirine.

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

Advise patients to seek immediate medical advice if severe rash or hypersensitivity reactions occur.

Advise patients that the ability to drive or operate machinery may be affected by side effects.

Side Effects

Abdominal distension
Abdominal pain
Amnesia
Anaemia
Angina pectoris
Angioneurotic oedema
Anorexia
Anxiety
Atrial fibrillation
Attention disturbances
Autoimmune hepatitis
Blistering
Blurred vision
Bronchospasm
Confusion
Conjunctivitis
Constipation
Convulsions
Cytolytic hepatitis
Diabetes mellitus
Diarrhoea
Disorientation
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dry skin
Dyslipidaemia
Dyspnoea
Elevated amylase levels
Elevated serum LDL cholesterol
Elevated serum lipase
Elevated triglyceride levels
Eosinophilia
Erythema multiforme
Facial swelling
Fatigue
Fever
Flatulence
Gastritis
Gastroesophageal reflux disease
Graves' disease
Gynaecomastia
Haematemesis
Headache
Hepatic steatosis
Hepatitis
Hepatomegaly
Hypercholesterolaemia
Hyperglycaemia
Hyperhidrosis
Hyperlipidaemia
Hypersensitivity reactions
Hypersomnia
Hypertension
Hypertriglyceridaemia
Hypoaesthesia
Immune Reactivation/Reconstitution Syndrome
Increase in plasma cholesterol
Increase in serum ALT/AST
Increase in serum glucose
Insomnia
Joint ache
Lassitude
Lipodystrophy
Lipohypertrophy
Malaise
Muscle ache
Myocardial infarction
Nausea
Nervousness
Night sweats
Nightmares
Oral lesions
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Prurigo
Rash
Reduced neutrophil count
Renal failure
Retching
Serum creatinine increased
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Stroke
Syncope
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Vertigo
Vomiting
White blood cell count decreased

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: May 2013

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Intelence 25, 100, 200mg tablets. Janssen-Cilag Ltd. Revised April 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 October 2022

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Etravirine. Last revised: August 2, 2011
Last accessed: May 23, 2013