Second-generation HIV protease inhibitor
Brand names: Prezista, Prezcobix
Updated · Methodology
Second line
Darunavir is a second-line HIV-1 protease inhibitor. GeSIDA 2024 recommends darunavir-based combinations (Symtuza, Rezolsta, Prezcobix) in patients with resistance to earlier protease inhibitors or when an integrase-inhibitor-free regimen is required. Booster (ritonavir 100 mg or cobicistat 150 mg) is mandatory.
Sources
ICD-10: B20 · ICD-11: 1C62
Highly selective HIV-1 protease inhibitor with an improved resistance profile – active against strains resistant to earlier protease inhibitors. Metabolised by CYP3A4; itself inhibits CYP3A4 and CYP2D6. Always given with a pharmacokinetic booster (ritonavir or cobicistat).
Can be used in pregnancy at the discretion of HIV specialist. Pregnancy registry shows no significant increase in defects.
Breastfeeding by HIV-positive women not recommended in Spain.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
5 pairs found. Sorted from critical to minor.
Mechanism
CYP3A4 inhibition – fatal ergotism.
Symptoms
Limb ischaemia, stroke.
Management
Combination contraindicated.
Sources
Mechanism
Strong CYP3A4 induction – darunavir falls 80%. ART failure.
Symptoms
Rising viral load.
Management
Combination contraindicated. Alternative – rifabutin.
Sources
Mechanism
Darunavir inhibits CYP3A4. Simvastatin rises 10+ fold – fatal rhabdomyolysis.
Symptoms
Myalgia, CK above 50× ULN.
Management
Combination contraindicated. Pravastatin or rosuvastatin.
Sources
Mechanism
Carbamazepine is a strong inducer of the CYP3A4 enzyme, and darunavir is cleared through CYP3A and is always given with a booster, ritonavir or cobicistat (darunavir SmPC). In a study of darunavir with ritonavir and carbamazepine 200 mg twice daily, carbamazepine exposure rose: area under the curve (AUC) by 45% and trough concentration by 54%, while the darunavir trough fell by 15% with an unchanged AUC (darunavir SmPC, 4.5). Darunavir boosted with cobicistat is more sensitive to CYP3A induction: strong inducers, carbamazepine among them, can lower cobicistat and darunavir concentrations to the point of lost antiviral effect, so the combination with cobicistat is contraindicated (darunavir SmPC, 4.3).
Symptoms
With ritonavir the main risk is carbamazepine toxicity from its higher concentration: drowsiness, dizziness, double vision, unsteadiness, nausea. With a cobicistat-based regimen the risk is loss of antiviral effect: rising viral load and darunavir resistance (darunavir SmPC, 4.3).
Management
Management depends on the booster. Darunavir boosted with cobicistat, including fixed-dose tablets, is contraindicated with carbamazepine (darunavir SmPC, 4.3). With ritonavir no darunavir dose adjustment is needed; if the combination is necessary, the patient is monitored for carbamazepine adverse reactions, carbamazepine blood levels are checked and the dose is adjusted: by the darunavir SmPC the carbamazepine dose sometimes has to be reduced by 25–50% in this combination (darunavir SmPC, 4.5). The documents do not name a replacement antiepileptic; the treating physician chooses it by indication.
Sources
Mechanism
Hepatic enzymes clear zolpidem, mainly CYP3A4 with a contribution from CYP1A2. Darunavir is always given with a booster, ritonavir or cobicistat, and the boosted combination strongly inhibits CYP3A4, so zolpidem concentration rises. The darunavir label lists zolpidem among sedatives/hypnotics that are 'extensively metabolised by CYP3A' and warns that their concentration may rise substantially. The pair itself was not studied. The zolpidem label confirms the direction: ketoconazole, a potent CYP3A4 inhibitor, raised zolpidem exposure 1.83-fold, prolonged its half-life and increased sedation. Zolpidem is not among the hypnotics contraindicated with darunavir; that list contains only triazolam and oral midazolam.
Symptoms
Expect a stronger and longer zolpidem effect: deeper drowsiness, slowed reactions, impaired attention and coordination, including the next morning and while driving. The risk of falls, confusion, amnesia and complex sleep behaviours rises: sleep-walking, sleep-driving, eating or phone calls with no memory of them. Alcohol, opioids and other central nervous system (CNS) depressants add to the sedation, and with opioids the risk of respiratory depression grows.
Management
The combination is not banned. Among hypnotics, only triazolam and oral midazolam are contraindicated with darunavir, and zolpidem is not on that list (darunavir label, , 4.3). The EMA label recommends clinical monitoring and asks to consider a lower zolpidem dose (darunavir label, EMA, 4.5). The label says the same: titration, a lower dose and monitoring for adverse events (darunavir label FDA, 7). The documents name no specific reduced dose. The zolpidem label has two doses: the usual 10 mg, and 5 mg for elderly or debilitated patients and in hepatic impairment, with a ceiling of 10 mg per night (zolpidem label, 4.2). It does not require a systematic dose reduction with potent CYP3A4 inhibitors but asks to warn the patient about stronger sedation (zolpidem label, 4.5); the FDA label suggests considering a lower zolpidem dose (zolpidem label FDA, 7.2). Zolpidem is taken once, right before bedtime, with no repeat dose the same night, and at least 8 hours should pass before driving or other work that needs alertness (zolpidem label, 4.4). Alcohol and other central nervous system (CNS) depressants are avoided; with opioids the dose and duration are limited (zolpidem label, 4.4 and 4.5). Complex sleep behaviours such as sleep-walking, sleep-driving or eating with no memory of it mean zolpidem is stopped at once (zolpidem label, 4.4). The zolpidem course is kept short: a few days to two weeks, four weeks at most including tapering (zolpidem label, 4.2).
Sources
Verbatim lines from the interaction sections, in the language of the label
«amiodarona, bepridilo, dronedarona, ivabradina, quinidina, ranolazina»AEMPS, section 4.3 · Open on CIMA
«cisaprida»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«derivados del cornezuelo de centeno (p.ej., dihidroergotamina, ergometrina, ergotamina, metilergonovina)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«ANTIEMÉTICOS: La administración conjunta de domperidona con darunavir potenciado está contraindicada.»AEMPS, section 4.5 · Open on CIMA
«amiodarona, bepridilo, dronedarona, ivabradina, quinidina, ranolazina»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«derivados del cornezuelo de centeno (p.ej., dihidroergotamina, ergometrina, ergotamina, metilergonovina)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«amiodarona, bepridilo, dronedarona, ivabradina, quinidina, ranolazina»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«INHIBIDORES DE LA HMG CO-A REDUCTASA: El aumento de las concentraciones plasmáticas de lovastatina o simvastatina puede provocar miopatía e incluso rabdomiólisis. Por tanto, está contraindicada la…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«lurasidona , pimozida, quetiapina, sertindol (ver sección 4.5)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«lurasidona , pimozida, quetiapina, sertindol (ver sección 4.5)»AEMPS, section 4.3 · Open on CIMA
«amiodarona, bepridilo, dronedarona, ivabradina, quinidina, ranolazina»AEMPS, section 4.3 · Open on CIMA
«amiodarona, bepridilo, dronedarona, ivabradina, quinidina, ranolazina»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«Inductores potentes del CYP3A como rifampicina y medicamentos a base de plantas que contienen la hierba de San Juan ( Hypericum perforatum ). Se prevé que la administración de forma conjunta reduce…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«INHIBIDORES DE LA HMG CO-A REDUCTASA: El aumento de las concentraciones plasmáticas de lovastatina o simvastatina puede provocar miopatía e incluso rabdomiólisis. Por tanto, está contraindicada la…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«ANTICOAGULANTES /AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Cardiac Disorders : ranolazine, ivabradine dronedarone Other antiarrhythmics e.g. amiodarone, bepridil, disopyramide, flecainide…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Antidepressants : Selective Serotonin Reuptake Inhibitors (SSRIs): paroxetine, sertraline Tricyclic Antidepressants (TCAs)…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Cardiac Disorders : ranolazine, ivabradine dronedarone Other antiarrhythmics e.g. amiodarone, bepridil, disopyramide, flecainide…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Anticoagulants : Direct Oral Anticoagulants (DOACs) apixaban rivaroxaban dabigatran etexilate edoxaban Other Anticoagulants warfarin …»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«ANTICOAGULANTES /AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Anticoagulants : Direct Oral Anticoagulants (DOACs) apixaban rivaroxaban dabigatran etexilate edoxaban Other Anticoagulants warfarin …»FDA, section 7 · Open on DailyMed
«Inhibidores nucleosídicos o nucleotídicos de la transcriptasa inversa (ITINss): La combinación de darunavir administrado de forma conjunta con dosis bajas de ritonavir y atazanavir se puede…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Lipid Modifying Agents: HMG-CoA reductase inhibitors: lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Sedatives/FDA, section 7 · Open on DailyMed
«CORTICOSTEROIDES: Corticosteroides metabolizados principalmente por CYP3A (incluyendo betametasona, budesonida, fluticasona, mometasona, prednisona, triamcinolona).»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Corticosteroids: dexamethasone (systemic) Corticosteroids primarily metabolized by CYP3A: eg. betamethasone budesonide ciclesonide…»FDA, section 7 · Open on DailyMed
«Inhibidores de la CYP3A4: Los inhibidores potentes de la CYP3A4 han demostrado que producen concentraciones notablemente elevadas de atorvastatina (ver Tabla 1 y la información específica a…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Intervention: Concomitant use of tipranavir plus ritonavir or glecaprevir plus pibrentasvir with atorvastatin calcium is not recommended. In patients taking lopinavir plus…»FDA, section 7 · Open on DailyMed
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Darunavir is evaluated for the following indications with varying evidence strength: HIV infection (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Darunavir (≥ 1 in 100): Diarrhoea, Nausea, Headache, Rash, Transaminase rise. See the Safety section for uncommon and serious reactions.
Can be used in pregnancy at the discretion of HIV specialist. Pregnancy registry shows no significant increase in defects.
Breastfeeding by HIV-positive women not recommended in Spain.
Darunavir is contraindicated in: Simvastatin, lovastatin; Pimozide, ergotamine, dihydroergotamine, oral midazolam, cisapride; Rifampicin, St John's wort (loss of ARV effect); Severe hepatic impairment. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Efavirenz, Entecavir, Famciclovir, Inosine pranobex, Lactoferrin, Tilorone, Vitaglutam, Kagocel