Drug | Possible interaction | Management | Action at enrollment | Action after enrollment |
---|---|---|---|---|
Amiodarone | Increased risk of amiodarone toxicity (hypotension, bradycardia, sinus arrest). Increased QT-interval prolongation | Concurrent use is contraindicated | At the time of enrollment, amiodarone therapy with no alternative is an exclusion criterion | Consider alternatives to amiodarone. If no alternative to amiodarone is available, consider using a reduced dose. Monitor for increased amiodarone serum concentrations, altered liver function test results and evidence of QT-interval prolongation |
Fentanyl | Concurrent use of fentanyl and CYP3A4 inhibitors may result in an increased risk of fentanyl toxicity, resulting in fatal respiratory depression | In non-mechanically ventilated patients, concurrent use is contraindicated. In mechanically ventilated patients, avoid fentanyl or use reduced doses | Consider alternatives to fentanyl. Use lower doses and adjust the dose to target analgesia and sedative effects | Consider alternatives to fentanyl. Use lower doses and adjust the dose to target analgesia and sedative effects |
Fluconazole | Increased ritonavir exposure and risk of QT-interval prolongation | Avoid concomitant use if possible If fluconazole is required, closely monitor electrocardiogram for QT-interval prolongation | Use alternatives to fluconazole | Use alternatives to fluconazole. Fluconazole-mediated CYP3A4 inhibition may continue for 4–5 days after discontinuation because of its long half-life |
Midazolam | Increased midazolam plasma concentrations, which can lead to midazolam toxicity | In non-mechanically ventilated patients, concurrent use is contraindicated. In mechanically ventilated patients, avoid use of midazolam if possible. If needed, use reduced midazolam doses and monitor effects | Consider alternatives to midazolam. Use lower doses and adjust the dose to target sedative effects | Consider alternatives to midazolam. Use lower doses and adjust the dose to target sedative effects. If the concomitant use of midazolam and lopinavir/ritonavir is required, closely monitor patients for midazolam adverse effects (excessive sedation, confusion and respiratory depression) and consider using a reduced midazolam dose |
Quetiapine | Increased risk of QT-interval prolongation, torsades de pointes or other notable ventricular tachyarrhythmias | Concomitant administration is contraindicated | Use alternatives to quetiapine | Use alternatives to quetiapine. If concomitant use is required, reduce the quetiapine dose to one sixth of the standard dose, and when the lopinavir/ritonavir is discontinued, the dose of quetiapine should subsequently be increased to the standard dose |
Rifampin | Decreased lopinavir/ritonavir plasma concentrations. Rifampin may enhance the toxic effect of lopinavir, specifically increasing the risk of hepatocellular toxicity | Concurrent use is contraindicated | If concomitant use is required, rifabutin 150 mg every other day or 150 mg three times a week is recommended for concomitant use with lopinavir/ritonavir | If concomitant use is required, rifabutin 150 mg every other day or 150 mg three times a week is recommended for concomitant use with lopinavir/ritonavir |
Sildenafil | Increased sildenafil plasma levels, thereby increasing the risk for sildenafil adverse effects (hypotension, visual changes and priapism) | Concurrent use of lopinavir/ritonavir and sildenafil is contraindicated | Stop sildenafil if possible. If not possible, sildenafil use is an exclusion criterion for this study | Do not use sildenafil |
Simvastatin | Increased risk of myopathy or rhabdomyolysis | Concomitant use of lopinavir/ritonavir with simvastatin is contraindicated | Stop simvastatin if possible. If needed, consider fluvastatin, pitavastatin or pravastatin as alternatives, because these drugs have the least potential for interaction | Do not use simvastatin. If needed, consider fluvastatin, pitavastatin or pravastatin as alternatives, because these drugs have the least potential for interaction |
Atorvastatin | Atorvastatin AUC increased by 488%. Increased risk of myopathy or rhabdomyolysis | Monitor for signs of atorvastatin toxicity (rhabdomyolysis and myopathy) | Consider discontinuation of atorvastatin. If discontinuation is not possible, use with caution at the lower end of the dosing range (10–40 mg per day) | Consider alternative agents (pravastatin, fluvastatin or rosuvastatin), because these drugs have the least potential for interaction |
Voriconazole | Decreased plasma concentrations of voriconazole and decreased voriconazole efficacy | Concomitant administration is contraindicated | Use alternatives to voriconazole. If no alternative exists, voriconazole use is an exclusion criterion for this study | Use alternatives to voriconazole or use with therapeutic drug monitoring. Voriconazole dose may need to be increased. If no alternative is available, discontinue lopinavir/ritonavir and continue the use of IFN-β1b. Consider another antifungal for aspergillosis |
Phenytoin | Both phenytoin and ritonavir plasma concentrations may be decreased | Use with caution | Use with caution | Monitor phenytoin levels during co-administration. Adjustment of the phenytoin or fosphenytoin dose may be warranted |