Concomitant Drug Class/Name
|
NNRTIa
|
Effect on NNRTI or Concomitant Drug Concentrations
|
Dosing Recommendations and Clinical Comments
|
Acid Reducers |
Antacids |
RPV |
↓ RPV expected when given simultaneously |
Give antacids at least 2 hours before or at least 4 hours after RPV. |
H2-Receptor Antagonists |
RPV |
↓ RPV |
Give H2-receptor antagonists at least 12 hours before or at least 4 hours after RPV. |
Proton Pump Inhibitors (PPI) |
RPV |
↓ RPV |
Contraindicated. Do not co-administer. |
Anticoagulants/Antiplatelets |
Warfarin |
EFV, NVP |
↑ or ↓ warfarin possible |
Monitor INR and adjust warfarin dose accordingly. |
ETR |
↑ warfarin possible |
Monitor INR and adjust warfarin dose accordingly. |
Clopidogrel |
ETR |
↓ activation of clopidogrel possible |
ETR may prevent metabolism of clopidogrel (inactive) to its active metabolite. Avoid co-administration, if possible. |
Anticonvulsants |
Carbamazepine
Phenobarbital
Phenytoin |
EFV |
carbamazepine + EFV: carbamazepine AUC ↓ 27% and EFV AUC ↓ 36%
phenytoin + EFV: ↓ EFV and
↓ phenytoin possible |
Monitor anticonvulsant and EFV levels or, if possible, use alternative anticonvulsant to those listed. |
ETR |
↓ anticonvulsant and ETR possible |
Do not co-administer. Consider alternative anticonvulsant |
NVP |
↓ anticonvulsant and NVP possible |
Monitor anticonvulsant and NVP levels and virologic responses or consider alternative anticonvulsant. |
RPV |
↓ RPV possible |
Contraindicated. Do not co-administer. Consider alternative anticonvulsant. |
Antidepressants |
Bupropion |
EFV |
bupropion AUC ↓ 55% |
Titrate bupropion dose based on clinical response. |
Paroxetine |
EFV, ETR |
No significant effect |
No dosage adjustment necessary. |
Sertraline |
EFV |
sertraline AUC ↓ 39% |
Titrate sertraline dose based on clinical response. |
Antifungals |
Fluconazole |
EFV |
No significant effect |
No dosage adjustment necessary. |
ETR |
ETR AUC ↑ 86% |
No dosage adjustment necessary. Use with caution. |
NVP |
NVP AUC ↑ 110% |
Increased risk of hepatotoxicity possible with this combination. Monitor NVP toxicity or use alternative ARV agent. |
RPV |
↑ RPV possible |
No dosage adjustment necessary. Clinically monitor for breakthrough fungal infection (RPV 150 mg/day reduces ketoconazole exposure; no data on interaction with fluconazole). |
Itraconazole |
EFV |
itraconazole and OH-itraconazole AUC, Cmax, and Cmin ↓ 35%–44% |
Failure to achieve therapeutic itraconazole concentrations has been reported. Avoid this combination if possible. If co-administered, closely monitor itraconazole concentration and adjust dose accordingly. |
ETR |
↓ itraconazole possible
↑ ETR possible |
Dose adjustments for itraconazole may be necessary. Monitor itraconazole level and antifungal response. |
NVP |
↓ itraconazole possible
↑ NVP possible |
Avoid combination if possible. If co-administered, monitor itraconazole concentration and adjust dose accordingly. |
RPV |
↑ RPV possible |
No dosage adjustment necessary. Clinically monitor for breakthrough fungal infection. (RPV 150 mg/day reduces ketoconazole exposure; no data on interaction with itraconazole.) |
Posaconazole |
EFV |
posaconazole AUC ↓ 50%
↔ EFV |
Avoid concomitant use unless the benefit outweighs the risk. If co-administered, monitor posaconazole concentration and adjust dose accordingly. |
ETR |
↑ ETR possible |
No dosage adjustment necessary. |
RPV |
↑ RPV possible |
No dosage adjustment necessary. Clinically monitor for breakthrough fungal infection. (RPV 150 mg/day reduces ketoconazole exposure; no data on interaction with posaconazole.) |
Voriconazole |
EFV |
voriconazole AUC ↓ 77%
EFV AUC ↑ 44% |
Contraindicated at standard doses.
Dose: voriconazole 400 mg BID, EFV 300 mg daily. |
ETR |
voriconazole AUC ↑ 14%
ETR AUC ↑ 36% |
No dosage adjustment necessary; use with caution. Consider monitoring voriconazole level. |
NVP |
↓ voriconazole possible
↑ NVP possible |
Monitor for toxicity and antifungal response and/or voriconazole level. |
RPV |
↑ RPV possible |
No dosage adjustment necessary. Clinically monitor for breakthrough fungal infection (RPV 150 mg/day reduces ketoconazole exposure; no data on interaction with voriconazole). |
Antimycobacterials |
Clarithromycin |
EFV |
clarithromycin AUC ↓ 39% |
Monitor for effectiveness or consider alternative agent, such as azithromycin, for MAC prophylaxis and treatment. |
ETR |
clarithromycin AUC ↓ 39%
ETR AUC ↑ 42% |
Consider alternative agent, such as azithromycin, for MAC prophylaxis and treatment. |
NVP |
clarithromycin AUC ↓ 31% |
Monitor for effectiveness or use alternative agent, such as azithromycin, for MAC prophylaxis and treatment. |
RPV |
↔ clarithromycin expected
↑ RPV possible |
Consider alternative macrolide, such as azithromycin, for MAC prophylaxis and treatment |
Rifabutin |
EFV |
rifabutin ↓ 38% |
Dose: rifabutin 450–600 mg once daily or 600 mg three times a week if EFV is not co-administered with a PI. |
ETR |
rifabutin and metabolite AUC ↓ 17%
ETR AUC ↓ 37% |
If ETR is used with an RTV-boosted PI, rifabutin should not be co-administered.
Dose: rifabutin 300 mg once daily if ETR is not co-administered with an RTV-boosted PI
|
NVP |
rifabutin AUC ↑ 17% and metabolite AUC ↑ 24%
NVP Cmin ↓ 16% |
No dosage adjustment necessary. Use with caution. |
RPV |
RPV AUC ↓ 46% |
Contraindicated. Do not co-administer. |
Rifampin |
EFV |
EFV AUC ↓ 26% |
Maintain EFV dose at 600 mg once daily and monitor for virologic response. Consider therapeutic drug monitoring.
Some clinicians suggest EFV 800 mg dose in patients who weigh more than 60 kg. |
ETR |
Significant ↓ ETR possible |
Do not co-administer. |
NVP |
NVP ↓ 20%–58% |
Do not co-administer. |
RPV |
RPV AUC ↓ 80% |
Contraindicated. Do not co-administer. |
Rifapentine |
EFV, ETR, NVP, RPV |
↓ NNRTI expected |
Do not co-administer. |
Benzodiazepines |
Alprazolam |
EFV, ETR, NVP, RPV |
No data |
Monitor for therapeutic effectiveness of alprazolam. |
Diazepam |
ETR |
↑ diazepam possible |
Decreased dose of diazepam may be necessary. |
Lorazepam |
EFV |
lorazepam Cmax ↑ 16%,
AUC ↔ |
No dosage adjustment necessary. |
Midazolam |
EFV |
Significant ↑ midazolam expected |
Do not co-administer with oral midazolam.
Parenteral midazolam can be used with caution as a single dose and can be given in a monitored situation for procedural sedation. |
Triazolam |
EFV |
Significant ↑ triazolam expected |
Do not co-administer. |
Cardiac Medications |
Dihydropyridine calcium channel blockers (CCBs) |
EFV, NVP |
↓ CCBs possible |
Titrate CCB dose based on clinical response. |
Diltiazem
Verapamil |
EFV |
diltiazem AUC ↓ 69%
↓ verapamil possible |
Titrate diltiazem or verapamil dose based on clinical response. |
NVP |
↓ diltiazem or verapamil possible |
Corticosteroids |
Dexamethasone |
EFV, ETR, NVP |
↓ EFV, ETR, NVP possible |
Consider alternative corticosteroid for long-term use. If dexamethasone is used with NNRTI, monitor virologic response. |
RPV |
Significant ↓ RPV possible |
Contraindicated with more than a single dose of dexamethasone. |
Hepatitis C NS3/4A - Protease Inhibitors |
Boceprevir |
EFV |
EFV AUC ↑ 20%
boceprevir AUC ↓ 19%,
Cmin ↓ 44% |
Co-administration is not recommended. |
ETR |
ETR AUC ↓ 23%
boceprevir AUC, Cmax ↑ 10% |
No dosage adjustment necessary. |
Telaprevir |
EFV |
EFV AUC ↔
telaprevir AUC ↓ 26%,
Cmin ↓ 47%
With TDF:
EFV AUC ↓ 15%–18%, telaprevir AUC ↓ 18%–20% |
Increase telaprevir dose to 1125 mg q8h. |
Herbal Products |
St. John’s wort |
EFV, ETR, NVP, RPV |
↓ NNRTI |
Do not co-administer. |
Hormonal Contraceptives |
Hormonal Contraceptives |
EFV |
ethinyl estradiol ↔
levonorgestrel AUC ↓ 83%
norelgestromin AUC ↓ 64%
↓ etonogestrel (implant) possible |
Use alternative or additional contraceptive methods. Norelgestromin and levonorgestrel are active metabolites of norgestimate. |
ETR |
ethinyl estradiol AUC ↑ 22%
norethindrone: no significant effect |
No dosage adjustment necessary. |
NVP |
ethinyl estradiol AUC ↓ 20%
norethindrone AUC ↓ 19% |
Use alternative or additional contraceptive methods. |
DMPA: no significant change |
No dosage adjustment necessary |
RPV |
ethinyl estradiol AUC ↑ 14%
norethindrone: no significant change |
No dosage adjustment necessary |
Levonorgestrel
(for emergency contraception) |
EFV |
levonorgestrel AUC ↓ 58% |
Effectiveness of emergency post-coital contraception may be diminished. |
HMG-CoA Reductase Inhibitors |
Atorvastatin |
EFV, ETR |
atorvastatin AUC ↓ 32%–43% |
Adjust atorvastatin according to lipid responses, not to exceed the maximum recommended dose. |
RPV |
atorvastatin AUC ↔
atorvastatin metabolites ↑ |
No dosage adjustment necessary. |
Fluvastatin |
ETR |
↑ fluvastatin possible |
Dose adjustments for fluvastatin may be necessary |
Lovastatin
Simvastatin |
EFV |
simvastatin AUC ↓ 68% |
Adjust simvastatin dose according to lipid responses, not to exceed the maximum recommended dose. If EFV used with RTV-boosted PI, simvastatin and lovastatin should be avoided. |
ETR, NVP |
↓ lovastatin possible
↓ simvastatin possible |
Adjust lovastatin or simvastatin dose according to lipid responses, not to exceed the maximum recommended dose. If ETR or NVP used with RTV-boosted PI, simvastatin and lovastatin should be avoided. |
Pitavastatin |
EFV, ETR, NVP, RPV |
No data |
No dosage recommendation. |
Pravastatin
Rosuvastatin |
EFV |
pravastatin AUC ↓ 44%
rosuvatatin: no data |
Adjust statin dose according to lipid responses, not to exceed the maximum recommended dose. |
ETR |
No significant effect expected |
No dosage adjustment necessary. |
Immunosuppressants |
Cyclosporine
Sirolimus
Tacrolimus |
EFV,
ETR,
NVP |
↓ immunosuppressant possible |
Increase in immunosuppressant dose may be necessary. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary. |
Narcotics/Treatment for Opioid Dependence |
Buprenorphine |
EFV |
buprenorphine AUC ↓ 50%
norbuprenorphineb AUC ↓ 71% |
No dosage adjustment recommended; monitor for withdrawal symptoms. |
ETR |
buprenorphine AUC ↓ 25% |
No dosage adjustment necessary. |
NVP |
No significant effect |
No dosage adjustment necessary. |
Methadone |
EFV |
methadone AUC ↓ 52% |
Opioid withdrawal common; increased methadone dose often necessary. |
ETR |
No significant effect |
No dosage adjustment necessary. |
NVP |
methadone AUC ↓ 37%–51%
NVP: no significant effect |
Opioid withdrawal common; increased methadone dose often necessary. |
RPV |
R-methadonec AUC ↓ 16% |
No dosage adjustment necessary, but monitor for withdrawal symptoms. |
Phosphodiesterase Type 5 (PDE5) Inhibitors |
Avanafil |
EFV, ETR, NVP, RPV |
No data |
Co-administration is not recommended. |
Sildenafil |
ETR |
sildenafil AUC ↓ 57% |
May need to increase sildenafil dose based on clinical effect. |
RPV |
sildenafil ↔ |
No dosage adjustment necessary. |
Tadalafil |
ETR |
↓ tadalafil possible |
May need to increase tadalafil dose based on clinical effect. |
Vardenafil |
ETR |
↓ vardenafil possible |
May need to increase vardenafil dose based on clinical effect. |
Miscellaneous Interactions |
Atovaquone/
proguanil |
EFV |
↓ atovaquone AUC 75%
↓ proguanil AUC 43% |
No dosage recommendation. Consider alternative drug for malaria prophylaxis, if possible. |