Although rarely used in combination with
other antiretrovirals nowadays, efavirenz alters the levels of most protease
inhibitors and usually requires adjusted dosing. Efavirenz is not administered
with the other NNRTI drugs etravirine and nevirapine due to elevated
side-effect risk.1
The following drugs should be avoided when
taking efavirenz because the possibility of decreased metabolism when
taken with efavirenz could possibly lead to life-threatening adverse events
such as cardiac arrhythmias, prolonged sedation, or respiratory distress:
- Astemizole (Hispaniola)
- Bepidril (Visor).
Vascor discontinued by manufacturer
- Cisapride (Repulsed).
Discontinued in the US
- Dihydroergotamine,
ergotamine, ergonovine, & ergot derivatives (Cafatine,
Ergomar, Migranal)
- Midazolam (Hyponovel,
Versed)
- Pimozide (Orap)
- Terfenadine (Triludine,
Teldane, Seldane). Drug discontinued in US
- Triazolam (Halcion)
should be avoided because of its decreased serum levels; use of
lorazepam, oxazepam, or temazepam may be considered.
Other drugs to be avoided when on efavirenz (Sustiva)
include:
- Amodiaquine (Cameoing,
Flavouring), due to
risk of elevated liver enzymes
- Clarithromycin (Claiosip,
Klaricid, Klaricid XL, Bioxin) levels reduced and there
have been reported high incidences of rash. Use of azithromycin
can be considered
- Gingko biloba can
decrease efavirenz levels2
- Hypericin (St John’s
Wort) can reduce
efavirenz levels
- Milk thistle has a
possibility of interaction.
The following drugs need to be administered at
non-standard doses in people taking efavirenz:
- Anticoagulants.
Warfarin (Coumadin) levels may be increased or decreased. Monitor
INR and adjust warfarin as needed.
- Anticonvulsants.
Phenytoin (Epanutin, Dilantin), phenobarbital (Luminol), and
carbamazepine (Tegretol) may need to be given at lower
doses to prevent reduction in efavirenz level. Anticonvulsant
plasma levels should be monitored or possibly use therapeutic drug
monitoring for efavirenz.3
Alternative anticonvulsants to be considered include valproic acid,
lamotrigine, levetiracetam, or topiramate.
- Antidepressants.
Sertraline (Zoloft) levels may be decreased when given with
efavirenz.
- Antifungals.
Itraconazole (Sporanox) and ketoconazole (Nizoral) may
have decreased plasma concentration. Voriconazole (Vfend) is usually
not co-prescribed with efavirenz because of the risk of low
voriconazole/elevated efavirenz levels. If drugs needed to be used
concomitantly, voriconazole dosing should be increased from 200 to 400mg
and given every 12 hours; once-daily dosing of efavirenz should be
decreased from 600 to 300mg.
- Anti-infectives.
Rifabutin (Mycobutin) levels are decreased by 35%, so consider
dosing rifabutin once daily 450-600mg, or 3 times per week at 600mg, if
efavirenz is not being given with a protease inhibitor.4 5 Rifampicin
(Rifadin, Rimactane) should not be used in people on protease
inhibitor-based antiretroviral therapy. As rifampicin decreases efavirenz
levels by an average of 25%, individuals at the normal efavirenz dose
of 600mg once daily should be monitored for response. In those
weighing over 60kg, consider increasing the daily dose to 800mg. Results
from the British CHIC study indicated that black ethnicity was
associated with higher efavirenz levels and increased weight contributed
to lower efavirenz concentrations.6 An
earlier study in Thai patients, who were mainly under 55kg, found that the
600mg dose of efavirenz was effective.7
- Antimalarials.
Artemether and mefloquine serum levels may be decreased, so monitoring is
needed (i.e. mefloquine serum level, parasite count on blood smear,
clinical signs of improvement).
- Chemotherapy agents
paclitaxel tamoxifen, vinblastine, and vincristine may have lessened serum
concentrations; drug levels should be monitored.
- Contraceptives. Ethinyl
estradiol may have an interaction with efavirenz. Use of barrier
contraception is recommended in addition to oral contraceptives to prevent
pregnancy.
- Immunosuppressants.
Cyclosporine (Neoral,
Sandimmune), sirolimus, tacrolimus, drugs mainly used
after transplant surgery, should be dosed according to serum levels,
as each may be decreased when taken with efavirenz.8
- Opioiods. Methadone
hydrochloride (Methadose) may need to be given at a higher dose in
people taking efavirenz.9
The dose should be increased in 10mg steps if withdrawal symptoms appear.
- Statins. Atorvastatin
(Lipitor), pravastatin (Pravachol), and simvastatin (Zocor)
may need to be given at a higher dose to achieve target lipid goals,
but require monitoring to avoid possible toxicity.10
Efavirenz may cause a false-positive result if
the CEDIA DAU Multi-Level THC assay is used. Other types of tests do not
confuse efavirenz and cannabis.