Non-Nucleoside Reverse Transcriptase Inhibitors
Examples
- Efavirenz
- Etravirine
- Nevirapine
Indications
HIV 1 (not active against HIV 2)
Contraindications
Contraindications
- Acute porphyria
- Hepatitis B and C
- Hepatic Impairment
- Pregnancy
- Women (nevirapine hepatotoxicity more common)
Mechanism
Non-Nucleoside Reverse Transcriptase Inhibitors primarily block HIV replication by preventing reverse transcriptase from completing reverse transcription of the viral single-stranded RNA genome into DNA. However, some NNRTIs, such as efavirenz, have been shown to inhibit the late stages of HIV replication by interfering with HIV polyprotein processing.
Administration
Oral for all.
Adverse Reactions
- Nausea and vomiting, abdominal pain and diarrhoea common
- Hypersensitivity reaction
- Rash (can be severe)
- CNS / psychiatric disturbance
- Hepatotoxicity
- Lipodystrophy
- Osteonecrosis
Interactions
Interactions are complex. The BNF should be consulted.
- Metabolised by cytochrome P450, so can have toxicity increased by enzyme inhibitors such as grapefruit juice and macrolides
- Enzyme-inducing drugs e.g. carbamazepine will reduce the efficacy of these drugs
- Interactions with other HIV drugs are common
- NNRTIs affect the metabolism of other drugs such as the oral contraceptive, warfarin, statins, calcium channel blockers and ciclosporin
- There is an increased risk of hypokalaemia when efavirenz is administered with steroids and diuretics.
- There in an increased risk of QT prolongation when efavirenz is administered with SSRIs, fluconazole, methadone or any other medicines associated with QT prolongation.
Education
Patients should be told how to recognise hypersensitivity reactions.
Treatment regimes for HIV are no longer as complex as they once were, however patient education about compliance is still important.
Additional contraceptive methods are advised with the oral contraceptive pill.
Treatment regimes for HIV are no longer as complex as they once were, however patient education about compliance is still important.
Additional contraceptive methods are advised with the oral contraceptive pill.
Pharmacokinetics
NNRTIs are given orally and absorbed in the gastrointestinal tract. They are metabolised by the liver and excreted in the urine.
