| Antiepileptic Medications: Carbamazepine, phenytoin, and phenobarbital may ↓ PI and NNRTI levels substantially. |
Carbamazepine
CYP450 inducer
| PIs: may ↓ PI levels
- ATV: ↑ carbamazepine levels
- DRV: ↑ carbamazepine levels; ↓ DRV levels
- RTV: ↑ carbamazepine levels
- TPV: ↑ carbamazepine levels; ↓ TPV levels
Other PIs: may also ↑ carbamazepine levels
| - Avoid concomitant use if possible; use alternative antiepileptics.
- Two-way interactions also affect PI and NNRTI levels.
|
NNRTIs: may ↓ levels of all NNRTIs
- EFV: ↓ carbamazepine AUC 27%; ↓ EFV levels
- ETR, RPV: expect ↓ NNRTIs levels
| - Avoid use with EFV, if possible; use alternative antiepileptics.
- ETR and RPV should not be coadministered.
|
| MVC:↓ MVC levels | If used concurrently, give MVC 600 mg BID. |
Phenobarbital
CYP450 inducer
| PIs: may ↓ PI levels
- DRV: ↓ phenobarbital levels
- RTV: ↓ phenobarbital levels
- TPV: ↓ phenobarbital levels and ↓ TPV levels
| - Avoid concomitant use if possible; use alternative antiepileptics.
- Two-way interactions also affect PI and NNRTI levels.
|
NNRTIs: may ↓ NNRTI levels
- EFV and NVP: ↓ phenobarbital levels
- ETR: ↓ ETR levels
- RPV: expect ↓ RPV levels
| - Avoid with EFV and NVP, if possible; use alternative antiepileptics.
- ETR and RPV should not be coadministered.
|
| MVC:↓ MVC levels | If used concurrently, give MVC 600 mg BID. |
Phenytoin
CYP450 inducer
| PIs: may ↓ PI levels
- DRV: ↓ phenytoin levels
- FPV: ↓ phenytoin levels
- LPV/r: ↓ LPV Cmin 46%, ↓ RTV Cmin 47%; ↓ phenytoin Cmin 34%
- NFV: ↓ M8 levels 20-30%, ↓ phenytoin Cmin 39%
- RTV: anticipate ↓ phenytoin levels
- TPV: ↓ TPV levels
| - Avoid if possible; use alternative antiepileptics.
- Two-way interactions also affect PI and NNRTI levels.
|
NNRTIs: may ↓ NNRTI levels
- EFV: ↓ phenytoin levels, ↓ EFV levels
- ETR: ↓ ETR levels
| - Avoid use with EFV if possible.
- ETR and RPV should not be coadministered.
|
| MVC:↓ MVC levels | If used concurrently, give MVC 600 mg BID. |
| Valproate | PIs- LPV/r: ↑ LPV Cmax 33%, ↑ AUC 75%, may ↓ valproate levels
- RTV and TPV: ↓ valproate levels
| Titrate to effect. |
| NNRTIs: no significant changes in NNRTI or valproate levels |
| Lamotrigine | - LPV/r: ↓ lamotrigine levels 50%
- RTV: ↓ lamotrigine levels
| Titrate to effect. |
| Antifungal Medications |
Fluconazole
Inhibitor of CYP 2C9
| PIs- ATV/r: no significant change
- TPV: ↑ TPV levels
| TPV: Avoid fluconazole >200 mg daily. |
| NNRTIs- NVP: 100% ↑ in NVP levels
- EFV: no significant change
- ETR, RPV: potential ↑ in NNRTI levels
| - Avoid use with NVP.
- EFV, ETR: dosage adjustment not required.
- RPV: no data
|
Itraconazole
Inhibitor and substrate of CYP 3A4
| PIs:↑ PI levels and ↑ itraconazole levels
- LPV/r: ↑ itraconazole levels
| Avoid itraconazole dosages >200 mg daily with patients who take PIs. |
NNRTIs- EFV: ↓ itraconazole levels
- ETR: ↓ itraconazole levels and ↑ ETR
- NVP: ↓ itraconazole levels and ↑ NVP
- RPV: not studied
| - If used concomitantly, consider monitoring itraconazole levels and adjust itraconazole dosage as necessary.
- Avoid with ETR.
|
| MVC:↑ MVC levels | MVC 150 mg BID |
Ketoconazole:
Inhibitor and substrate of CYP 3A4
| PIs: may ↑ PI levels and ↑ itraconazole levels
- ATV/r, FPV/r: ↑ ketoconazole levels
- DRV/r: ↑ ketoconazole levels, ↑ DRV levels
- LPV/r: ↑ ketoconazole levels; may ↑ or ↓ LPV/r levels
| Avoid ketoconazole dosages >200 mg daily with patients who take RTV-boosted PIs. |
NNRTIs- EFV: no data
- NVP, ETR, RPV: ↓ ketoconazole levels; ↑ NNRTI levels
| - Not recommended for use with NVP.
- Dosage adjustment for interactions with ETR and RPV not established.
|
| MVC:↑ MVC levels | MVC 150 mg BID |
Posaconazole
Inhibitor of CYP 3A4
| PIs- RTV: ↑ RTV levels
- ATV: ↑ ATV levels
| Monitor laboratory values frequently for signs of toxicity. |
NNRTIs- EFV: ↓ posaconazole levels
- ETR: ↑ ETR levels
- RPV: not studied
| - Consider alternative antifungal or monitor posaconazole level.
- Monitor for ETR-related adverse effects.
|
Terbinafine:
Inhibitor of CYP 2D6
| PIs: no significant changes | No dosage adjustments necessary. |
| NNRTIs: no significant changes | No dosage adjustments necessary. |
Voriconazole
CYP 3A4, CYP 2C9, and CYP 2C19 inhibitor; CYP 2C19 substrate
| PIs: limited data
- RTV: voriconazole AUC ↓ 39% with RTV 100 mg BID
| Not recommended for use with RTV 100 mg QD or BID unless benefit outweighs risk. If used, consider monitoring voriconazole levels. |
NNRTIs- EFV: substantial ↓ voriconazole and ↑ EFV; similar effect expected for NVP
- ETR: ↑ voriconazole and ↑ ETR
- RPV: not studied
| - EFV: contraindicated at standard dosages; use voriconazole 400 mg BID and EFV 300 mg QD.
- ETR: dosage adjustments for ETR and voriconazole not established; use alternative antifungal or monitor voriconazole level and ETR adverse effects.
- RPV: not studied
|
| MVC: anticipated ↑ MVC levels | MVC 150 mg BID |
| Calcium Channel Blockers (CCBs) |
| Amlodipine | - FPV, RTV, and SQV: ↑ amlodipine levels
- IDV: ↑ amlodipine Cmax and AUC 89%
| - Incompletely studied.
- PIs may inhibit metabolism of CCBs, increasing risk of adverse effects including hypotension, conduction block, and bradycardia.
- NNRTIs may induce metabolism of CCBs, reducing their effect.
- Avoid use in patients with CHF.
- Avoid immediate-release forms.
|
| Diltiazem | - ATV: ↑ diltiazem Cmax 200%
- IDV: ↑ diltiazem Cmax 25%
- SQV/r: ↑ diltiazem levels
- EFV: ↓ diltiazem AUC 70%
- NVP: ↓ diltiazem levels
|
| Methadone |
| PIs- ATV: ↓ total methadone AUC 6%; ↑ R-methadone AUC 3%, Cmin 11%
- DRV/r: ↓ methadone AUC 16%
- FPV: ↓ methadone AUC 18%
- LPV/r: ↓ methadone AUC 53%
- NFV: ↓ methadone AUC 47%
- SQV/r: ↓ methadone AUC
- TPV/r: ↓ methadone AUC 48%
| - Most PIs ↓ methadone levels, particularly LPV/r, NFV, and TPV.
- Of NNRTIs, EFV and NVP ↓ methadone, whereas ETR is anticipated to have no effect. DLV ↑ methadone levels.
- Monitor for methadone efficacy, and signs and symptoms of opiate withdrawal. Titrate dosage cautiously as needed.
|
| NNRTIs- EFV: ↓ methadone AUC 60%
- ETR: no change in methadone levels anticipated
- NVP: ↓ methadone AUC 46%
- RPV: ↓ methadone AUC 16%, ↓ Cmin 22%
| - Monitor for methadone efficacy and signs and symptoms of opiate withdrawal. Titrate methadone dosage cautiously as needed.
|
| Warfarin |
| PIs- FPV, IDV, SQV, ATV: ↑ warfarin levels
- LPV/r: may ↑ or ↓ warfarin levels
- RTV: may ↓ warfarin levels
- DRV: ↓ warfarin levels
- TPV: no change in warfarin levels
| - Start at low dosage; monitor INR closely. Adjust warfarin dosage as indicated.
- Monitor INR closely, may need increased warfarin dosage.
|
NNRTIs- EFV: warfarin levels may ↑ or ↓
- NVP: ↓ warfarin levels (anticipated)
- ETR: ↑ warfarin levels (anticipated)
- RPV: not studied
| Monitor INR closely, adjust dosage as indicated. |
