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Common Medications: ARV Interactions

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Common Medications: ARV Interactions

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MedicationARV InteractionsComments
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 levelsIf 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 levelsIf 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 levelsIf used concurrently, give MVC 600 mg BID.
ValproatePIs
  • 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 levelsMVC 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 levelsMVC 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 changesNo dosage adjustments necessary.
NNRTIs: no significant changesNo 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 levelsMVC 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.

From Common Medications
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009