Efavirenz

CLINICAL USE

Non-nucleoside reverse transcriptase inhibitor:HIV infection in combination with other antiretroviral drugs

DOSE IN NORMAL RENAL FUNCTION

600 mg once daily (tablets and capsules should be taken on an empty stomach to minimise side effects)Oral solution: 720 mg once daily

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :315.7

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :99.5–99.75

%Excreted unchanged in urine &nbsp &nbsp : <1

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :2–4

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :40–55 (multiple dosing); 52–76 (single dosing)/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Not dialysed. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antidepressants: concentration reduced by St John’s wort – avoid concomitant use; concentration of sertraline reduced

Antifungals: itraconazole and voriconazole concentration reduced; voriconazole increases efavirenz concentration – reduce dose of efavirenz by 50% and increase dose of voriconazole to 400 mg twice daily; possibly reduces caspofungin concentration – may possibly need to increase caspofungin dose

Antipsychotics: possibly increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly reduces aripiprazole concentration – increase aripiprazole doseAnxiolytics and hypnotics: risk of prolonged sedation with midazolam – avoid concomitant use

Antivirals: saquinavir concentration significantly reduced; concentration of amprenavir, darunavir, indinavir, lopinavir and atazanavir reduced – increase atazanavir dose; concentration reduced by nevirapine; monitor LFTs when used in combination with ritonavir

Ciclosporin: concentration of ciclosporin possibly reduced

Ergot alkaloids: risk of ergotism – avoid concomitant use

Grapefruit juice: concentration possibly increased

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

Induces its own metabolism Metabolised by CYP450 3A4 and 2B6 systemsMonitor cholesterol levels as increases of

10 to 20

% in total cholesterol have been reportedHalf-life of 10 hours in haemodialysis patients has been reported

Bioavailability of oral solution is less than that for capsules or tablets – therefore not interchangeable

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