*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
| Drug | Effect of Interaction | Recommendations/Comments |
|
Abacavir (ABC)
| May increase serum levels of alprazolam. | Applies to all PIs and DLV: Consider alternative benzodiazepine (i.e lorazepam, temazepam, or oxazepam). |
|
Delavirdine (DLV)
| May increase LPV levels. | No data. Use standard dose; consider TDM. |
|
Efavirenz (EFV)
| LPV/r AUC decreased by 19% and Cmin decreased by 39%; EFV levels unaffected. | Dose: Consider LPV/r 600/150 mg (3 tabs) bid + EFV 600 mg qhs, especially in pts with PI resistance. Standard doses may be acceptable in PI-naive pts. LPV/r 600/150mg bid + EFV 600 mg qhs resulted in 32% higher LPV Cmin compared to LPV/r 400/100 mg bid (historical control). |
|
Indinavir (IDV)
| IDV AUC increased by 20% and Cmin increased by 46%; IDV Cmin increased by 247%. | Dose: IDV 600 mg or 666 mg bid + LPV/r 400/100 mg bid. |
|
Metronidazole
| Disulfiram-like reaction. | Applies to LPV liquid formulation. Warn pts of LPV alcohol content (liquid). Use LPV/r caps. |
|
NFV
| LPV AUC decreased by 27% and Cmin decreased by 33% NFV Cmin increased by 113%. | Do not co-administer or consider LPV/r 600/150 mg (3 tabs) + NFV 1250 mg bid with TDM |
|
Nevirapine (NVP)
| LPV AUC decreased by 22%. NVP levels unaffected. | Dose: Consider LPV/r 600/150 mg (3 tabs) bid + NVP standard dose, especially in pts. with PI resistance. Standard doses may be acceptable for PI-naive pts. |
|
Rifampin
| LPV/r AUC decreased by 75% and Cmin decreased by 99%. | Generally not recommended. With co-administration consider LPV/r 400/100 mg (3 caps) + RTV 300 mg bid (note: monitor LFTs, GI intolerance, and lipids). A more recent study of LPV/r 3 to 4 tabs BID + rifampin found high incidence of nausea, vomiting, and grade 4 LFTs elevation. Rifabutin preferred w/ LPV/r co-administration. |
|
Saquinavir (SQV)
| SQV AUC increased by 836% and Cmin increased by 1700%. | Dose: SQV 1000 mg bid + LPV/r 400/100 mg bid. |
|
Fluconazole
| Interaction unlikely. | Use standard doses for both drugs. |
|
Atazanavir (ATV)
| ATV geometric mean Cmin increased by 45% with LPV/r 400/100 mg BID co-administration (compared to ATV-r 300/100 mg QD). LPV PK comparable to historical data. | Dose: ATV 300 mg QD + LPV/r 400/100 mg BID |
|
Fosamprenavir (FPV)
| Decreased APV and LPV levels | Not recommended by some. Consider FPV 1400 mg bid + LPV/r 600/150 mg (3 tabs) bid (and consider TDM). |
|
TPV (tipranavir)
| LPV AUC decreased by 49% (studied dose TPV 500 mg bid + LPV/r 400/100 mg bid.) | Not generally recommended. LPV/r 400/100 mg BID with TPV/r 500/200 mg BID (additional RTV 200 mg BID) resulted in "adequate" LPV Cmin, but significant interpatient variability and small sample size suggest confirmation of these findings before this dosing regimen can be recommended. |
|
Darunavir
| DRV AUC and Cmin decreased 53% and 65%, respectively. LPV AUC and Cmin increased 37% and 72%, respectively. | Avoid co-administration. |
| Alfuzosin | May significantly increase alfuzosin levels. | Contraindicated. Consider doxazosin and terazosin for BPH (with close monitoring). |
| Amiodarone | May significantly increase amiodarone serum level. | Applies to all PIs and DLV: Data limited to case report of increased amiodarone levels with IDV co-administration. RTV, APV, and ATV manufacturers recommend against use of amiodarone, but all PIs and DLV have the same potential of significantly increasing amiodarone serum levels. If co-administration can not be avoided, monitor for amiodarone ADR (PFTs and TSH). Consider monitoring serum levels of amiodarone, but its long half-life may make titration difficult. |
| Amlodipine | May increase serum levels of amlodipine. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
|
Amprenavir (APV)
| APV Cmin higher than unboosted APV (1200 mg bid; 0.8 mcg/mL vs. 0.32 mcg/mL) but lower than boosted APV (APV 600 mg + RTV100 mg bid); LPV AUC decreased by 30-50%. | Co-administration generally not recommended. Dose: LPV/r 600/150 mg (3 tabs) OR + APV 750 mg bid (consider TDM). See also fosamprenavir. |
| Artemether (artemisinin) | May increase serum levels of artemether. | Data available only for EFV. Co-administration of EFV with artesunate + amodiaquine resulted in significant LFT elevations. Close monitoring for artemether toxicity (bone marrow suppression, bradycardia and seizure). |
| Astemizole | May significantly increase astemizole serum levels. | Contraindicated due to the potential for cardiac arrhythmias. Recommended alternative antihistamine: loratadine, fexofenadine, desloratadine, or cetirizine. |
|
Atorvastatin
| Atorvastatin AUC increased by 488%. | Use with caution at lower end of dosing range (10-40 mg/d). Monitor for Sx of atorvastatin toxicity (rhabdomyolysis and myopathy). Consider alternative agents: pravastatin, fluvastatin, or rosuvastatin. |
| Azathioprine | Interaction unlikely. | Applies to all PIs and NNRTIs: Use standard dose. |
| Bepridil | May significantly increase bepridil serum levels. | Applies to all PIs and DLV: No data. The manufacturer of ATV, RTV, and APV does not recommend bepridil co-administration, this contraindication should extend to all PIs and DLV since a significant increase in bepridil serum level can result in pro-arrhythmic events such as VT, PVC, and VFib. |
| Carbamazepine | LPV serum levels may be significantly decreased. | Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). With coadministration, monitor anticonvulsants level and consider TDM of LPV. |
| Chlordiazepoxide | May increase serum levels of chlordiazepoxide. | Applies to all PIs and DLV: Consider an alternative benzodiazepine (lorazepam, temazepam, or oxazepam). |
| Cisapride | May significantly increase cisapride serum levels. | Contraindicated due to potential for cardiac arrhythmias. Recommended alternative: metoclopramide. |
|
Clorazepate
| May increase serum levels of clorazepate. | Applies to all PIs and DLV: Consider an alternative benzodiazepine (lorazepam, temazepam, or oxazepam). |
| Cyclophosphamide | May increase serum level of cyclophosphamide. | Applies to all PIs and DLV: Data limited to an interaction study conducted with IDV resulting in a 50% increase in cyclophosphamide serum levels. Since all PIs and DLV have the potential of increasing cyclophosphamide levels, close monitoring of cyclophosphamide-induced toxicity is recommended. |
| Cyclosporine | May significantly increase serum levels of cyclosporine. | Applies to all PIs: Monitor serum levels of cyclosporine closely with co-administration. Cyclosporine dose may need to be decreased. |
| Desipramine | Desipramine AUC may be increased. LPV not affected. | Clinical significance unknown. Monitor for desipramine adverse drug reaction and serum level (if available). Consider alternative antidepressant: escitalopram, citalopram, sertraline, or fluoxetine. |
| Digoxin | Digoxin AUC increased 81% with LPV/r co-administration. | Monitor digoxin plasma concentration closely with co-administration |
| Diltiazem | May increase serum levels of diltiazem. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with diltiazem co-administration. Diltiazem should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
| Disopyramide | May increase disopyramide serum levels. | Applies to all PIs and DLV: No data. Monitor disopyramide serum levels (target: 2 to 7.5 mcg/mL). |
| Docetaxel | May increase serum levels of docetaxel. | Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended. |
| Dofetilide | May significantly increase serum levels of dofetilide. | Applies to all PIs and DLV: No data. Use with caution. Monitor QTc closely and adjust dofetilide dosing based on QTc prolongation and renal function. Consider an alternative class III antiarrhythmic such as bretylium or ibutilide. |
| Echinacea | May decrease LPV/r serum levels. Echinacea (400 mg 4xd) decreased CYP3A4 substrate (midazolam) by 23%. | Clinical significance unknown but should avoided until the safety of this combination is further evaluated. |
| Ergot Alkaloid | May significantly increase serum levels of ergotamine resulting in acute ergot toxicity. | Contraindicated. Consider alternative agent for migraine such as sumatriptan (but not eletriptan since it is a CYP3A4 substrate and significant drug-drug interaction occurred with CYP3A4 inhibitor). |
| Estazolam | May increase serum levels of estazolam. | Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, temazepam, or oxazepam). |
| Ethinyl estradiol | Ethinyl estradiol AUC decreased by 42%. | Recommend an alternative or additional form of contraception. |
| Ethosuximide | May increase serum levels of ethosuximide. | Applies to all PIs and DLV: Consider switching to valproic acid for the treatment of absence seizure. |
| Etoposide | May increase serum levels of etoposide. | Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended. |
| Etravirine | LPV AUC decreased 20%. Etravirine area under the curve increased 17%. | Clinical significance unclear, but the manufacturer recommends co-administration with caution. Usual dose recommended. |
| Ezetimibe | No significant interaction | Observational PK substudy involving 6 patients did not find reduction in LPV AUC. |
| Ezetimibe | No significant change in lopinavir/ritonavir trough measurements after the addition of ezetimibe. | Separate administration time if possible. Observation pharmacokinetic substudy that needs confirmation |
| Felodipine | May increase serum levels of felodipine. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum level (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
| Fentanyl | May significantly increase fentanyl serum levels. | Use with caution. Consider morphine. |
| Flecainide | May significantly increase serum levels of flecainide. | Contraindicated. |
|
Flurazepam
| May increase serum levels of flurazepam. | Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, temazepam, or oxazepam). |
| Fluticasone | With RTV co-administration fluticasone AUC and Cmax increased by 350-fold and 25-fold, respectively. | Data limited to RTV co-administration. With chronic RTV co-administration plasma cortisol AUC decreased by 86%. Cushing's syndrome and adrenal suppression have been reported. Co-administration not recommended by manufacturer. Avoid long-term co-administration. |
| Food | Increases LPV AUC. | LPV/r tabs can be taken with or without food. |
| Garlic supplement | 49% and 51% reduction of SQV Cmin and AUC, respectively when co-administered with garlic supplement (3.5 mg bid).
| Studies only done with SQV but garlic may affect the serum levels of other PIs or NNRTIs. Co-administration of garlic supplements should be avoided with PIs and NNRTIs. |
| Granisetron | May increase serum levels of granisetron. | Applies to all PIs and DLV: Due to the large therapeutic index of granisetron, potential interaction is unlikely to be clinically significant. |
| Heroin (Diamorphine) | Drug interactions unlikely. | Applies to PIs and NNRTIs: Interaction unlikely but illicit drug use should be avoided for obvious reasons. |
| Ifosphamide | May increase serum levels of ifosphamide. | Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended. |
| Irinotecan | May increase irinotecan serum levels. | Applies to all PIs and DLV: Co-administration of ATV is contraindicated by manufacturer. All PIs and DLV also have the potential for significant interaction with Irinotecan, therefore co-administration should be done with extreme caution. |
|
Itraconazole
| CYP3A4 inhibitor and substrate - bidirectional inhibition with increase levels of PIs and itraconazole.
| Use standard dose with itraconazole and LPV/r co-administration. Consider monitoring itraconazole levels. |
|
Ketoconazole
| LPV increased 13%. Ketoconazole increased by 3-fold. | Do not exceed ketoconazole 200 mg qd with LPV/r co-administration. |
| Lamotrigine | Lamotrigine Cmin decreased by 56% | Increase lamotrigine dose to 200 mg bid when coadministering with LPV/r. |
| Lidocaine | May increase antiarrhythmic serum levels. | Applies to all PIs and DLV: No data. Use with caution, monitor lidocaine serum levels (target: 1.5 to 6 mcg/mL) with co-administration. |
|
Lovastatin
| May significantly increase lovastatin levels. | Contraindicated. Recommended alternatives include pravastatin, rosuvastatin, and fluvastatin (and possibly atorvastatin - start at 10 mg qd). Monitor for adverse effect due to limited clinical data. |
| Maraviroc | Maraviroc AUC increased 283% | Dose: MVC 150 mg bid + LPV/r 400/100 mg bid. |
|
Mefloquine
| May increase serum levels of mefloquine. | Applies to all PIs and DLV: Monitor mefloquine serum levels. Monitor for mefloquine toxicity (i.e dizziness, LFTs, and periodic ophthalmic examination). |
|
Methadone
| Methadone AUC decreased by 26-36%. | No withdrawal Sx observed in 2 of 3 studies. Standard methadone dose recommended, but may need to increase methadone dose in a small subset of pts. |
| Mexiletine | May increase antiarrhythmic serum levels. | Applies to all PIs and DLV: No data. Use with caution. Monitor EKG and serum levels. Serum levels exceeding 1.5 to 2 mcg/mL have been associated with an increased risk of toxicity. |
| Midazolam | May significantly increase midazolam levels. | Concurrent administration of midazolam is contraindicated. Consider alternative benzodiazepines (temazepam, oxazepam, or lorazepam). |
| Milk thistle | Data limited to an interaction study with milk thistle and IDV. IDV AUC: unchanged and IDV Cmin decreased by 47%.
| Unknown effect on LPV serum levels. Avoid co-administration with PIs and NNRTIs until it can be further evaluated. |
| Mirtazapine | May increase serum levels of mirtazapine. | Applies to all PIs and DLV: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine.) |
| Mycophenolate | Interaction unlikely. No significant interaction observed with NVP. | Applies to all PIs and NNRTI: No significant interaction observed with NVP. Use standard dose. |
| Nefazodone | May increase serum levels of nefazodone. | Applies to all PIs and DLV: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine). |
| Nifedipine | May increase serum levels of nifedipine. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
| Nisoldipine | May increase serum levels of nisoldipine. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
| Omeprazole | No change in lopinavir/ritonavir pharmacokinetics. | Use standard dose LPV/r tablet with omeprazole co-administration. |
| Paclitaxel | May increase serum levels of paclitaxel. Reports of toxicity associated with LPV/r and paclitaxel co-administration. | Monitor closely for paclitaxel-induced toxicity. |
| PCP | May significantly increase serum levels of PCP. | Applies to all PIs and DLV: Avoid all illicit drug use for obvious reasons. |
| Phenobarbital | LPV levels may be significantly decreased. | Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor anticonvulsants level when applicable and consider TDM of LPV. |
| Phenytoin | LPV AUC decreased by 33%. Phenytoin AUC decreased by 31%. | Avoid co-administration. Monitor anticonvulsants levels. Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Consider empirically increasing LPV/r to 600/150 mg (3 tabs) bid (with TDM). |
| Pimozide | May significantly increase pimozide serum levels resulting in QTc prolongation. | Contraindicated. Consider alternative: Olanzapine. |
| Prednisone | May increase prednisone serum concentration. | May require dose adjustment with long-term co-administration. |
| Propafenone | May significantly increase serum levels of propafenone. | Contraindicated. |
|
Quinidine
| May increase antiarrhythmic serum levels. | Applies to all PIs and DLV: No data. Contraindicated with RTV. With all PIs and NNRTI co-administration, monitor EKG (QTc) and serum levels: Target: 2 to 5 mcg/mL. |
| Raltegravir | Interaction unlikely. | No data with LPV/r. RTV (100 mg BID) did not affect RAL PK parameters. Consider usual dose with close monitoring of virologic efficacy. |
| Ranitidine | No interaction | Use standard dose LPV/r tablet with ranitidine co-administration. |
|
Rifabutin
| Rifabutin AUC increased by 203%. LPV serum level increased 20% (NS). | Dose: LPV/r 3 caps bid + rifabutin 150 mg qod. |
|
Rifapentine
| LPV serum levels may be significantly decreased. | Avoid co-administration. Consider using rifabutin. |
| Rosiglitazone | LPV AUC increased by 20% and Cmin increased by 21%. | Use standard dose. Limited sample size (NS) (n=4). |
|
Rosuvastatin
| Rosuvastatin AUC and Cmax increased 2.1 to 4.7-fold, respectively. LPV and RTV PK parameters not significantly affected. | Use with close monitoring due to limited clinical data. Use low dose rosuvastatin and titrate slowly. |
| Sildenafil | May increase sildenafil serum levels. | Applies to all PIs and DLV: Use with close monitoring. Do not exceed 25 mg in 48-hrs. |
| Simvastatin | May significantly increase simvastatin levels. | Contraindicated. Alternative HMG-CoA reductase inhibitor that may be used include pravastatin, cerivastatin, fluvastatin. Monitor for adverse effects due to limited clinical data. |
| Sirolimus | May significantly increase serum levels of sirolimus. | Applies to all PIs: Dose sirolimus based on serum levels. A significantly reduction of sirolimus dose with all PIs co-administration is highly likely. |
| St. John's wort | May significantly decrease LPV serum levels. | Contraindicated. Studies only done with IDV but St. John's wort likely to increase metabolism of other PIs and NNRTIs. Use an alternative (more effective) antidepressant. |
| Tacrolimus | Tacrolimus increased 10-fold with co-administration. Several case reports of toxic serum levels of tacrolimus upon initiation of LPV/r. | Dose tacrolimus based on serum levels. A much lower dose (0.5-1 mg/week or 1/20-1/10 of standard dose) may be sufficient with LPV/r co-administration. |
| Tadalafil | May increase serum level of tadalafil. | Applies to all PIs and DLV: Start with 5 mg. Do not exceed 10 mg in 72 hrs. Consider sildenafil due to more clinical data and shorter half-life allowing for easier titration. |
| Tamoxifen | May increase serum level of tamoxifen. | Applies to all PIs and DLV: No data. Close monitoring of tamoxifen- induced toxicity recommended. |
| Teniposide | May increase serum level of teniposide. | Applies to all PIs and DLV: No data. Close monitoring of teniposide induced toxicity recommended. |
| Terfenadine | May significantly increase terfenadine serum levels. | Contraindicated due to the potential for cardiac arrhythmias. Recommended alternative antihistamine: loratadine, fexofenadine, desloratidine, or cetirizine. |
| THC | Based on data with NFV and IDV interactions are unlikely. | Applies to PIs and NNRTIs: Interactions are unlikely but illicit drug use should be avoided for obvious reasons. |
| Trazadone | May increase serum levels of trazadone. | Applies to all PIs and DLV: Use with caution. Consider an alternative antidepressant (SSRI:escitalopram, citalopram, sertraline, or fluoxetine). |
| Trazodone | Trazodone AUC increased by 2.4 fold with RTV co-administration. | Data limited to RTV co-administration. Use with caution. Nausea, dizziness, hypotension and syncope have been reported with co-administration. Consider decreasing trazodone dose by 50% with co-administration.
|
|
Triazolam
| May significantly increase triazolam serum levels. | Contraindicated. Consider alternative benzodiazepines(temazepam, oxazepam, or lorazepam). |
| Vardenafil | May significantly increase serum levels of vardenafil. | Applies to all PIs and DLV: Do not exceed vardenafil 2.5 mg in 72 hrs (with RTV) or 2.5 mg in 24 hrs (with other PIs and DLV). Consider sildenafil due to more clinical data and less pronounced interaction. Avoid co-administration with IDV. |
| Verapamil | May increase serum levels of verapamil. | Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse. |
| Vinblastine | May increase serum levels of vinblastine. | Applies to all PIs and DLV: No data. Close monitoring of vinblastine- induced toxicity recommended. |
| Vincristine | May increase serum levels of vincristine. | Applies to all PIs and DLV: No data. Close monitoring of vincristine- induced toxicity recommended. |
| Vitamin C | Data limited to interaction study with IDV and vitamin C (1 g/d): IDV AUC decreased by 14% and Cmin by 32%.
| Clinical significance unknown. Other PI and NNRTI serum levels may be affected when co-administered with similar dose of vitamin C. |
| Voriconazole | May significantly decrease voriconazole AUC. Voriconazole may increase LPV. | Significant interaction with EFV and RTV (400mg bid); contraindicated. Voriconazole AUC decreased 39% with RTV 200 mg/d co-administration; avoid co-administration with boosted PI. Consider another antifungal for aspergillosis (i.e ambisome or caspofungin) or use with TDM. Voriconazole dose may need to be increased. |
| Warfarin | A case report of increased warfarin requirement after RTV initiation.
| Other PIs and NNRTIs may also affect warfarin requirements. Monitor INR closely with co-administration. |
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