Durart

Durart Drug Interactions

darunavir

Manufacturer:

Viatris

Distributor:

Atlanta Medicare

Marketer:

Atlanta Medicare
Full Prescribing Info
Drug Interactions
Darunavir should be used in combination with low dose ritonavir as a pharmacokinetic enhancer.
Darunavir should not be used in combination with other antiretrovirals that also require pharmacokinetic boosting with ritonavir.
Darunavir when used in combination with ritonavir is an inhibitor of CYP3A, CYP2D6 and P-gp. Co-administration of darunavir/rtv and medicinal products primarily metabolized by CYP3A, CYP2D6, or transported by P-gp may result in increased plasma concentrations of such medicinal products, which could increase or prolong their therapeutic effects and adverse events.
The following list of drug-drug interactions is not all-inclusive.
Antiretroviral medicinal products: Integrase strand transfer inhibitors: Dolutegravir: Darunavir/rtv (600/100 mg b.i.d.) did not have a clinically relevant effect on dolutegravir exposure. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir has no clinically significant effect on the pharmacokinetics of darunavir.
Darunavir/rtv co-administered with dolutegravir can be used without dose adjustment.
Elvitegravir: When darunavir/rtv (600/100 mg b.i.d.) is used in combination with elvitegravir, the dose of elvitegravir should be 150 mg once daily.
The pharmacokinetics and dosing recommendations for other doses of darunavir or with elvitegravir/cobicistat have not been established. Therefore, co-administration of darunavir/rtv in dose other than 600/100 mg b.i.d. and elvitegravir is not recommended.
Co-administration of darunavir/rtv and elvitegravir in the presence of cobicistat is not recommended.
Raltegravir: Some clinical studies suggest raltegravir may cause a modest decrease in darunavir plasma concentrations. At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant.
Darunavir co-administered with low dose ritonavir and raltegravir can be used without dose adjustments.
Nucleoside/nucleotide reverse transcriptase inhibitor [N(t) RTIs]: Didanosine: Darunavir/rtv (600/100 mg b.i.d.) did not significantly affect didanosine exposure.
The combination of darunavir co-administered with low dose ritonavir and didanosine can be used without dose adjustments. It is recommended that didanosine be administered on an empty stomach. Didanosine should be administered 1 hour before or 2 hours after darunavir/rtv (which are administered with food).
Tenofovir disoproxil fumarate: The results of an interaction trial with tenofovir (tenofovir disoproxil fumarate 300 mg once daily [q.d.] demonstrated that the systemic exposure of tenofovir was increased by 22% when co-administered with darunavir/rtv (300/100mg b.i.d.). This finding is of considered to be clinically relevant. There was no change in the urinary excretion of tenofovir or darunavir during co-administration. Tenofovir does not have a significant influence on darunavir exposure.
No dose adjustments of darunavir, ritonavir, or tenofovir disoproxil fumarate are required when these drugs are co-administered.
Emcitrabine/tenofovir alafenamide: Other NRTIs: Based on the different elimination pathways of the other NRTIs (zidovudine, zalcitabine, emtricitabine, stavudine, lamivudine, and abacavir) that are primarily renally excreted, no drug interactions are expected for these medicinal compounds and darunavir/rtv.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Delavirdine: Co-administration of darunavir/rtv and delavirdine may increase darunavir and delavirdine concentration (inhibitor of CYP3A). The appropriate dose of darunavir/rtv and delavirdine have not been established. The combination of darunavir/rtv and delavirdine is not recommended.
Etravirine: In an interaction trial between darunavir/rtv (600/100 mg b.i.d.) and etravirine, there was a 37% decrease in etravirine exposure in the presence of darunavir/rtv and no relevant change in exposure to darunavir. Therefore, darunavir/rtv can be co-administered with etravirine 200 mg b.i.d. without dose adjustments.
Efavirenz: An interaction trial between darunavir/rtv (300/100 mg b.i.d.) and efavirenz (600 mg q.d.) has been performed. In the presence of efavirenz, a decrease of 13% for darunavir exposure was observed. Exposure to efavirenz was decreased by 21% when administered in combination with darunavir/rtv. Since the difference is considered not to be clinically relevant, the combination of darunavir/rtv and efavirenz can be used without dose adjustments.
Nevirapine: The results of an interaction trial with darunavir/rtv (400/100 mg b.i.d.) and nevirapine (200 mg b.i.d.) demonstrated that darunavir exposure was not affected when administered concomitantly with nevirapine. Exposure to nevirapine increased by 27% (compared to historical controls) when administered in combination with darunavir/rtv.
Since the difference is not considered to be clinically relevant, the combination of darunavir/rtv and nevirapine can be used without dose adjustments.
Rilpivirine: In an interaction trial between darunavir/rtv (800/100 mg q.d.) and rilpivirine (150 mg q.d.), no clinically relevant effect on darunavir exposure was observed. Exposure to ralpivirine increased by 130% (2-3 folds) when administered in combination with darunavir/rtv.
Since the difference is not considered to be clinically relevant, the combination of darunavir/rtv and rilpivirine can be used without dose adjustments.
HIV Protease inhibitors (PIs): Ritonavir: The overall pharmacokinetic enhancement effect by ritonavir was an approximate 14-fold increase in the systemic exposure of darunavir when a single dose of 600 mg darunavir was given orally in combination with ritonavir at 100 mg b.i.d. Therefore, darunavir should only be used in combination with a pharmacokinetic enhancer such as cobicistat or low dose ritonavir (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Lopinavir/Ritonavir: Results of interaction trials with darunavir with or without ritonavir and lopinavir/ritonavir (1200 mg darunavir b.i.d. with or without 100 mg ritonavir b.i.d. and lopinavir/ritonavir (400/100 mg darunavir b.i.d or 533/133.3 mg b.i.d) demonstrated a decrease in the exposure (AUC) of darunavir by 40%.
The appropriate doses of the combination have not been established. Hence, it is not recommended to co-administer darunavir/rtv with lopinavir/ritonavir.
Saquinavir: In an interaction trial between darunavir (400 mg b.i.d.), saquinavir (1000 mg b.i.d.) and ritonavir (100 mg b.i.d.), darunavir exposure was decreased by 26% in the presence of 365 saquinavir/rtv; saquinavir exposure was not affected by the presence of darunavir/rtv.
It is not recommended to combine saquinavir and darunavir, with or without low dose ritonavir.
Atazanavir: An interaction trial between darunavir/rtv (400/100 mg b.i.d.) and atazanavir (300 mg q.d.) demonstrated that systemic exposure to darunavir and atazanavir was not significantly affected when co-administered.
Atazanavir can be co-administered with darunavir/rtv.
Indinavir: In an interaction trial between darunavir/rtv (400/100 mg b.i.d.) and indinavir (800 mg b.i.d.), darunavir exposure was increased by 24% in the presence of indinavir/rtv; indinavir exposure was increased by 23% in the presence of darunavir/rtv.
When used in combination with darunavir/rtv, dose adjustment of indinavir 800 mg b.i.d. to 600 mg b.i.d, may be warranted in case of intolerance.
Other HIV PIs: The co-administration of darunavir/rtv and PIs other than lopinavir/ritonavir, saquinavir, atazanavir, and indinavir have not been studied.
Therefore, such co-administration is not recommended.
CCR5 antagonist: When used in combination with darunavir/rtv, the dose of maraviroc should be 150 mg twice daily. An interaction trial between darunavir/rtv (600/100 mg b.i.d.) and maraviroc (150 mg b.i.d.) demonstrated that in the presence of darunavir/rtv the exposure of maraviroc was increased by 305%. There was no apparent effect of maraviroc on darunavir/ritonavir exposure.
Other medicinal products: Acid reducing agents: Antacids e.g. Aluminium/magnesium hydroxide, calcium carbonate: No interaction is expected between antacids and darunavir/rtv. Darunavir/rtv and antacids can be used concomitantly without dose adjustments.
H2-receptor antagonists e.g. Cimetidine, famotidine, nizatidine, ranitidine: Co-administration of ranitidine (150 mg b.i.d.) and darunavir/rtv (400/100 mg b.i.d.) did not affect the exposure to darunavir.
Darunavir/rtv can be co-administered with H2-receptor antagonists without dose adjustments.
Proton pump inhibitors e.g. Esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole: Co-administration of omeprazole (20 mg q.d.) and darunavir/rtv (400/100 mg b.i.d.) did not affect the exposure to darunavir.
Darunavir/rtv and proton pump inhibitors can be co-administered without dose adjustment.
Alpha 1-adrenoreceptor antagonist: Alfuzosin: Exposure to alfuzosin may be increased when co-administered with darunavir/rtv.
Concomitant use of darunavir/rtv with alfuzosin is contraindicated.
Anti-anginal: Ranolazine: Exposure to ranolazine may be increased (CYP3A inhibition) when co-administered with darunavir/rtv.
Concomitant use of darunavir/rtv with ranolazine is contraindicated.
Antiarrhythmics: Amiodarone, bepridil, disopyramide, dronedarone, flecainide, mexiletine, propafenone, systemic lidocaine, and quinidine: Exposure to these antiarrhythmics may be increased when co-administered with darunavir/rtv.
Caution is warranted and therapeutic drug monitoring of antiarrhytmics is recommended when available.
Concomitant use of darunavir/rtv with dronedarone is contraindicated.
Digoxin: An interaction trial with darunavir/rtv (600/100 mg b.i.d.) and a single dose of digoxin (0.4 mg) showed an increase of digoxin AUClast of 77% (ratio of Least Square Means (LSM) was 1.77 with a 90% Cl of 0.90 to 3.50).
It is recommended that the lowest dose of digoxin should initially be prescribed and digoxin dose should be titrated to obtain the desired clinical effect when co-administered with darunavir/rtv.
Serum digoxin concentrations should be monitored to assist in the titration.
Antibacterial: Clarithromycin: An interaction trial between darunavir/rtv (400/100 mg b.i.d.) and clarithromycin (500 mg b.i.d.) showed an increase in exposure to clarithromycin by 57%, while exposure to darunavir was not affected.
Darunavir/rtv and clarithromycin can be used without dose adjustment in patients with normal renal function. For patients with renal impairment, a dose reduction of clarithromycin should be considered. Consult the prescribing information for clarithromycin for the recommended dosage.
Anticoagulants: Apixaban, dabigatran etexilate, rivaroxaban: Co-administration of Darunavir/rtv with these anticoagulants may increase concentrations of the anticoagulant (inhibition of CYP3A and/or P-glycoprotein).
Co-administration of Darunavir/rtv and rivaroxaban is not recommended.
The combination of Darunavir/rtv and dabigatran etexilate should be used with caution and is not recommended in subjects with severe renal impairment.
The recommended dose of apixaban when co-administered with darunavir/rtv is 2.5 mg twice daily.
Warfarin: Warfarin concentrations may be affected when co-administered with darunavir/rtv.
It is recommended that the international normalized ratio (INR) is monitored when warfarin is combined with darunavir/rtv.
Anticonvulsants: Phenobarbital and phenytoin: Phenobarbital and phenytoin are inducers of CYP450 enzymes. Darunavir/rtv should not be used in combination with these medicines, as co-administration may cause significant decreases in darunavir plasma concentrations. This may result in loss of therapeutic effect to Darunavir.
Carbamazepine: An interaction trial between darunavir/rtv (600/100 mg b.i.d.) and carbamazepine (200 mg b.i.d.) showed that the exposure to darunavir, co-administered with ritonavir, was unaffected by carbamazepine. Ritonavir exposure (AUC12h) was decreased by 49%. For carbamazepine, AUC12h was increased by 45%.
No dose adjustment for darunavir/rtv is recommended. If there is a need to combine darunavir/rtv and carbamazepine, patients should be monitored for potential carbamazepine-related adverse events. Carbamazepine concentrations should be monitored and its dose should be titrated for adequate response. Based upon the findings, the carbamazepine dose may need to be reduced by 25% to 50% in the presence of darunavir/rtv.
Clonazepam: Co-administration of darunavir/rtv with clonazepam may increase concentrations of clonazepam, clinical monitoring is recommended when co-administering darunavir/rtv with clonazepam.
Antidepressants: Paroxetine and sertraline: In an interaction trial between paroxetine (20 mg q.d.) or sertraline (50 mg q.d.) and darunavir/rtv (400/100 mg b.i.d.), the exposure to darunavir was not affected by the presence of sertraline or paroxetine. Exposure to sertraline and paroxetine, was decreased by 49% and 39% respectively, in the presence of darunavir/rtv.
If SSRIs are co-administered with darunavir/rtv, the recommended approach is a careful dose titration of the SSRI based on a clinical assessment of antidepressant response. In addition, patients on a stable dose of sertraline or paroxetine who start treatment with darunavir/rtv should be monitored for an antidepressant response.
Amitriptyline, desipramine, imipramine, nortriptyline, and trazodone: Concomitant use of darunavir/rtv and these antidepressants may increase concentrations of the antidepressant (inhibition of CYP2D6 and/or CYP3A).
Clinical monitoring is recommended when co-administering darunavir/rtv with these antidepressants and a dose adjustment of the antidepressant may be needed.
Antifungals: Itraconazole, ketoconazole, posaconazole, and voriconazole: Itraconazole, ketoconazole, posaconazole, and voriconazole are potent inhibitors of CYP3A and some are substrates of CYP3A.
Concomitant systemic use of these antifungals with darunavir/rtv may increase plasma concentrations of darunavir. Simultaneously, plasma concentrations of some of these antifungals may be increased by darunavir/rtv. This was confirmed in an interaction trial where the concomitant administration of ketoconazole (200 mg b.i.d.) with darunavir/rtv (400/100 mg b.i.d.) increased exposure of ketoconazole and darunavir by 212% and 42%, respectively.
Plasma concentrations of voriconazole may be decreased in the presence of darunavir/rtv. Voriconazole should not be administered to patients receiving darunavir/rtv unless an assessment of the benefit/risk ratio justifies the use of voriconazole.
Clinical monitoring is recommended when co-administering datunavir/rtv with posaconazole. When co-administration is required the daily dose of ketoconazole or itraconazole should not exceed 200 mg.
Clotrimazole and fluconazole: Co-administration of darunavir/rtv with these antifungals may increase concentrations of darunavir, ritonavir and/or the antifungal.
Clinical monitoring is recommended when co-administering darunavir/rtv with these antifungals.
Anti-gout: Colchicine: Concomitant use of colchicine and darunavir/rtv may increase the exposure to colchicine.
The following dose adjustments are recommended for colchicine. For the treatment of gout-flares in patients on darunavir/rtv, the recommended dose of colchicine is 0.6 mg, followed by 0.3 mg 1 hour later. Treatment course to be repeated no earlier than 3 days. For the prophylaxis of gout-flares in patients on darunavir/rtv, the recommended dose of colchicine is 0.3 mg q.d. or q.o.d. For the treatment of familial Mediterranean fever in patients on darunavir/rtv, the maximum dose of colchicine is 0.6 mg q.d. (may be given as 0.3 mg b.i.d.).
Co-administration of darunavir/rtv with colchicine in patients with renal or hepatic impairment is contraindicated.
Antihistamines: Astemizole, terfenadine: Exposure to these antihistamines may be increased when co-administered with darunavir/rtv.
Concomitant use of darunavir/rtv with astemizole and terfenadine is contraindicated.
Antimalarial: Artemether/lumefantrine: An interaction trial between darunavir/rtv (600/100 mg b.i.d.) and artemether/lumefantrine (80/480 mg, 6 doses at 0, 8, 24, 36, 48, and 60 hours) showed an increase in exposure to lumefantrine by 2.75-fold, while exposure to darunavir was not affected. The exposure to artemether and its active metabolite, dihydroartemisinin, decreased by 16% and 18%, respectively.
The combination of darunavir/rtv and artemether/lumefantrine can be used without dose adjustments; however, due to the increase in lumefantrine exposure, the combination should be used with caution.
Antimycobacterials: Rifampin and rifapentin: Co-administration of darunvir/rtv with rifampin and rifapentine may decrease darunavir concentrations (induction of CYP3A), which may result in loss of therapeutic effect of darunavir.
Co-administration of darunavir/rtv with rifampin is contraindicated.
Co-administration of darunavir/rtv with rifapentine is not recommended.
Rifabutin: Rifabutin is a substrate of CYP450 enzymes. In an interaction trial, an increase of systemic exposure to darunavir by 57% was observed, when darunavir/rtv (600/100 mg b.i.d.) was administered with rifabutin (150 mg once every other day [q.o.d.]). Based on the safety profile of darunavir/rtv, the increase in darunavir exposure in the presence of rifabutin does not warrant a dose adjustment for darunavir/rtv. The interaction trial showed a comparable systemic exposure for rifabutin between treatment at 300 mg q.d. alone and at 150 mg q.o.d. in combination with darunavir/rtv (600/100 mg b.i.d.) with an increase in exposure to the active metabolite 25-0-desacetylrifabutin.
A dosage reduction of rifabutin by 75% of the usual dose of 300 mg/day (i.e. rifabutin 150 mg q.o.d.) and increased monitoring for rifabutin-related adverse events is warranted in patients receiving the combination.
Antineoplastics: Dasatinib, everolimus, nilotinib, vinblastine, vincristine: The plasma concentrations of these antineoplastics are expected to increase with co-administration of darunavir/rtv (inhibition of CYP3A), resulting in the potential for adverse events usually associated with these agents.
Caution should be exercised when combining one of these antineoplastic agents with darunavir/rtv.
Concomitant use of everolimus and darunavir/rtv is not recommended.
Antipsychotics/neuroleptics: Lurasidone: Concomitant use of lurasidone and darunavir/rtv may increase the exposure to lurasidone (inhibition of CYP3A4).
Concomitant use of darunavir/rtv with lurasidone is contraindicated.
Pimozide: Concomitant use of pimozide and darunavir/rtv may increase the exposure to pimozide (inhibition of CYP3A and CYP2D6).
Concomitant use of darunavir/rtv with pimozide is contraindicated.
Perphenazine: Co-administration of darunavir/rtv and perphenazine may increase concentrations of the neuroleptic (inhibition of CYP3A or CYP2D6).
Clinical monitoring is recommended when co-administering darunavir/rtv with perphenazine and a lower dose of the neuroleptic should be considered.
Risperidone, thioridazine: Concomitant use of risperidone or thioridazine and darunavir/rtv may increase the exposure to these antipsychotics (inhibition CYP2D6 and/or P-gp).
Decrease of risperidone or thioridazine dose may be needed when co-administered with darunavir/rtv.
Quetiapine: Concomitant use of quetiapine and darunavir/rtv may increase the exposure to quetiapine (inhibition of CYP3A).
The quetiapine dose should be substantially reduced when co-administered with darunavir.
For details, refer to the quetiapine prescribing information.
β-Blockers: Carvedilol, metoprolol, timolol: Co-administration of darunavir/rtv and beta-blockers may increase concentrations of the beta-blocker (inhibition of CYP2D6).
Clinical monitoring is recommended when co-administering darunavir/rtv with beta-blockers and a lower dose of the beta-blocker should be considered.
Calcium channel blockers: Amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil: The exposure to calcium channel blockers may increase when darunavir/rtv are used concomitantly (inhibition of CYP2D6 and/or CYP3A).
Caution is warranted and careful clinical monitoring is recommended.
Contraceptives: Ethinylestradiol and norethindrone: The results of an interaction trial between darunavir/rtv (600/100 mg b.i.d.) and ethinylestradiol and norethindrone demonstrated that at steady-state systemic exposures to ethinylestradiol and norethindrone are decreased by 44% and 14%, respectively.
Ethinylestradiol and drospirenone: The effect of darunavir/rtv on drospirenone exposure is not known.
When darunavir/rtv is co-administered with a drospirenone-containing product, clinical monitoring is recommended due to the potential of hyperkalemia.
No data are available to make recommendations on the use of darunavir/rtv with other hormonal contraceptives.
Therefore, additional or alternative (non-hormonal) methods of contraception are recommended.
Corticosteroids: systemic/inhaled/nasal: Corticosteroids primarily metabolized by CYP3A (betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone).
Concomitant use of corticosteroids and darunavir/rtv may increase plasma concentrations of these corticosteroids. Concomitant use may increase the risk for development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.
Clinical monitoring is recommended when co-administering darunavir/rtv with corticosteroids. Alternatives should be considered, particularly for long term use.
Systemic dexamethasone: Systemic dexamethasone induces CYP3A and thereby may decrease darunavir exposure. This may result in loss of therapeutic effect.
Therefore this combination should be used with caution.
Endothelin receptor antagonist: Bosentan: Concomitant use of bosentan and darunavir/rtv may increase plasma concentrations of bosentan. In patients who have been receiving darunavir/rtv for at least 10 days, start bosentan at 62.5 mg q.d. or q.o.d. based upon individual tolerability. For patients on bosentan and initiating darunavir/rtv, discontinue the use of bosentan at least 36 hours prior to initiation of darunavir/rtv. After at least 10 days following the initiation of darunavir/rtv, resume bosentan at 62.5 mg q.d. or q.o.d. based upon individual tolerability.
Ergot alkaloids: e.g., Ergotamine, ergonovine, dihydroergotamine, and methylergonovine: Exposure to the ergot alkaloids may be increased when co-administered with darunavir/rtv. Concomitant use of darunavir/rtv with ergot alkaloids is contraindicated.
Gastrointestinal motility agent: Cisapride: Exposure to cisapride may be increased when co-administered with darunavir /rtv.
Concomitant use of darunavir/rtv with cisapride is contraindicated.
Hepatitis C virus (HCV) direct-acting antivirals: Elbasvir/Grazoprevir: Concomitant use of elbasvir/grazoprevir and darunavir/rtv may increase the exposure to grazoprevir (inhibition of CYP3A).
Concomitant use of darunavir/rtv with elbasvir/grazoprevir is contraindicated.
Boceprevir: In an interaction trial between darunavir/rtv (600/100 mg b.i.d.) and boceprevir (800 mg three times daily), darunavir exposure was reduced by 44% and boceprevir exposure was reduced by 32%.
It is not recommended to co-administer darunavir/rtv with boceprevir.
Telaprevir: In an interaction trial between darunavir/rtv (600/100 mg b.i.d.) and telaprevir (750 mg every 8 hours), darunavir exposure was reduced by 40% and telaprevir exposure was reduced by 35%.
It is not recommended to co-administer darunavir/rtv with telaprevir.
Simeprevir: Co-administration of darunavir/rtv (800/100 mg q.d.) and simeprevir increased darunavir and simeprevir concentrations (inhibition of CYP3A). In an interaction trial between darunavir/rtv (800/100 mg q.d.) and simeprevir (50 mg q.d.), simeprevir exposure increased 2.59-fold and darunavir exposure increased by 1.18-fold.
The combination of darunavir/rty and simeprevir is not recommended.
Herbal product: St. John's wort: Co-administration of darunavir/rtv with products containing St. John's wort (Hypericum perforatum) may cause significant decreases in darunavir concentrations (induction of CYP3A), which may result in loss of therapeutic effect to darunavir.
Co-administration of darunavir/rtv with products containing St. John's wort (Hypericum perforatum) is contraindicated.
HMG-CoA reductase inhibitors: Atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: HMG-CoA reductase inhibitors, such as lovastatin and simvastatin, which are highly dependent on CYP3A metabolism, are therefore expected to have markedly increased plasma concentrations when co-administered with darunavir/rtv. Increased concentrations of HMG-CoA reductase inhibitors may cause myopathy, including rhabdomyolysis.
Concomitant use of darunavir/rtv with lovastatin and simvastatin is contraindicated.
The results of an interaction trial with atorvastatin show that atorvastatin (10 mg q.d.) in combination with darunavir/rtv (300/100 mg b.i.d.) provides an exposure to atorvastatin, which is only 15% lower than that obtained with atorvastatin (40 mg q.d.) alone. When administration of atorvastatin and darunavir/rtv is desired, it is recommended to start with an atorvastatin dose of 10 mg q.d. A gradual dose increase of atorvastatin may be tailored to the clinical response.
Darunavir/rtv (600/100 mg b.i.d.) increased exposure to a single dose of pravastatin (40 mg) by approximately 80%, but only in a subset of subjects.
When administration of pravastatin and darunavir/rtv is required, it is recommended to start with the lowest possible dose of pravastatin and titrate up to the desired clinical effects while monitoring safety.
An interaction study evaluating darunavir/rtv (600/100 mg b.i.d.) in combination with rosuvastatin (10 mg q.d.) resulted in an increase in rosuvastatin exposure.
When administration of rosuvastatin and darunavir/rtv is desired, it is recommended to start with the lowest possible dose of rosuvastatin and titrate up to the desired clinical effect while monitoring for safety.
An interaction study evaluating darunavir/rtv (800/100 mg q.d.) in combination with pitavastatin (4 mg q.d.) resulted in a decrease in pitavastatin exposure, which is not considered clinically relevant. Darunavir/rtv and pitavastatin can be co-administered without dose adjustment.
Other Lipid modifying agents: Lomitapide: Darunavir/rtv is expected to increase the exposure of lomitapide when co-administered.
Co-administration is contraindicated.
Immunosuppressants: Cyclosporin, everolimus, sirolimus, tacrolimus: Exposure to these immunosuppressants may be increased when co-administered with darunavir/rtv. Therapeutic drug monitoring of the immunosuppressive agent is recommended when co-administered with darunavir/rtv.
Concomitant use of everolimus and darunavir/rtv is not recommended.
Inhaled beta agonist: Salmeterol: Concomitant use of salmeterol and darunavir/rtv is not recommended.
The combination may result in increased risk of cardiovascular adverse events with salmeterol, including QT prolongation, palpitations and sinus tachycardia.
Narcotic analgesics/treatment of opioid dependence: Buprenorphine/naloxone: The results of an interaction trial with darunavir/rtv and buprenorphine/naloxone demonstrated that buprenorphine exposure was not affected when administered with darunavir/rtv. Exposure of the active metabolite, norbuprenorphine, increased by 46%.
No dose adjustment for buprenorphine was required. Careful clinical monitoring is recommended if darunavir/rtv and buprenorphine are co-administered.
Fentanyl, oxycodone, tramadol: Co-administration of darunavir/rtv with fentanyl, oxycodone or tramadol may increase concentrations of the analgesic.
Clinical monitoring is recommended when co-administering darunavir/rtv with these analgesics.
Methadone: An interaction trial investigating the effect of darunavir/rtv (600/100 mg b.i.d.) on a stable methadone maintenance therapy showed an AUC decrease of 16% for R-methadone.
Based on pharmacokinetic and clinical findings, no adjustment of methadone dosage is required when initiating co-administration of darunavir/rtv. However, clinical monitoring is recommended as maintenance therapy may need to be adjusted in some patients.
PDE-5 inhibitors: Treatment of erectile dysfunction: Avanafil, sildenafil, tadalafil, vardenafil: In an interaction trial a comparable systemic exposure to sildenafil was observed for a single intake of 100 mg sildenafil alone and a single intake of 25 mg sildenafil co-administered with darunavir/rtv (400/100 mg b.i.d.).
Concomitant use of PDE-5 inhibitors for the treatment of erectile dysfunction with darunavir/rtv should be done with caution. If concomitant use of darunavir/rtv with sildenafil, vardenafil or tadalafil is indicated, sildenafil at a single dose not exceeding 25 mg in 48 hours, vardenafil at a single dose not exceeding 2.5 mg dose in 72 hours or tadalafil at a single dose not exceeding 10 mg dose in 72 hours is recommended.
Co-administration of darunavir/rtv and avanafil is not recommended.
Treatment of pulmonary arterial hypertension: Sildenafil, tadalafil: A safe and effective dose of sildenafil when combined with darunavir/rtv for the treatment of pulmonary arterial hypertension has not been established. There is an increased potential for sildenafil-associated adverse events (including visual disturbances, hypotension, prolonged erection and syncope).
Therefore, co-administration of darunavir/rtv with sildenafil when used for pulmonary arterial hypertension is contraindicated.
For the treatment of pulmonary arterial hypertension with tadalafil co-administered with darunavir/rtv, a dose adjustment for tadalafil is warranted. In patients who have been receiving darunavir/rtv for at least 1 week, start tadalafil at 20 mg q.d., and increase to 40 mg q.d. based upon individual tolerability. For patients on tadalafil and initiating darunavir/rtv, discontinue the use of tadalafil at least 24 hours prior to initiating darunavir/rtv and avoid the use of tadalafil during the initiation of darunavir/rtv. After at least 1 week following the initiation of darunavir/rtv, resume tadalafil at 20 mg q.d. and increase to 40 mg q.d. based upon individual tolerability.
Pharmacokinetic enhancer: Darunavir should be used in combination with a pharmacokinetic enhancer such as low dose ritonavir.
Darunavir should not be used in combination with other antiretrovirals that also require pharmacokinetic boosting with ritonavir.
Platelet aggregation inhibitors: Ticagrelor: Co-administration of darunavir/rtv with ticagrelor may increase concentrations of ticagrelor.
Co-administration of darunavir/rtv and ticagrelor is not recommended.
Sedatives/hypnotics: Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, zolpidem: Co-administration of darunavir/rtv with these sedatives/hypnotics may increase concentrations of the sedative/hypnotic (inhibition of CYP3A).
Co-administration of darunavir/rtv with oral midazolam or triazolam is contraindicated.
Co-administration of parenteral midazolam should be done in a setting that ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dose reduction for parenteral midazolam should be considered, especially if more than a single dose of midazolam is administered.
Clinical monitoring is recommended when co-administering darunavir/rtv with the other sedatives/ hypnotics and a lower dose of the sedatives/hypnotics should be considered.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in