Interactions : אינטראקציות

7 DRUG INTERACTIONS
See also Contraindications (4) and Clinical Pharmacology (11.3).

7.1 Potential for PREZISTA/ritonavir to Affect Other Drugs
PREZISTA co-administered with ritonavir is an inhibitor of CYP3A and CYP2D6. Co-administration of PREZISTA and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events (see Table 3).

7.2 Potential for Other Drugs to Affect Darunavir
Darunavir and ritonavir are metabolized by CYP3A. Drugs that induce CYP3A activity would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma concentrations of darunavir and ritonavir. Co-administration of darunavir and ritonavir and other drugs that inhibit CYP3A may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (see Table 3).

7.3 Established and Other Potentially Significant Drug Interactions

Darunavir and ritonavir are both inhibitors of the CYP3A isoform. Co-administration of darunavir and ritonavir and medicinal products primarily metabolised by CYP3A may result in increased systemic exposure to such medicinal products, which could increase or prolong their therapeutic effect and adverse reactions.
PREZISTA co-administered with low dose ritonavir must not be combined with medicinal products that are highly dependent on CYP3A for clearance and for which increased systemic exposure is associated with serious and/or life-threatening events (narrow therapeutic index). These medicinal products include amiodarone, bepridil, quinidine, systemic lidocaine, astemizole, alfuzosin, terfenadine, sildenafil (when used for the treatment of pulmonary arterial hypertension), avanafil ,quetiapine, midazolam administered orally, triazolam, cisapride, pimozide, sertindole, simvastatin, lovastatin and the ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine and methylergonovine), Rifampin, St. John’s Wort (Hypericum perforatum), Co-administration with the combination product lopinavir/ritonavir.

Table 3provides dosing recommendations as a result of drug interactions with PREZISTA/ritonavir. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy.


Table 3: Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended
Based on Drug Interaction Studies or Predicted Interaction
[See Clinical Pharmacology (11.3) for Magnitude of Interaction, Tables 8 and 9] 

Concomitant Drug                       Effect on                      Clinical Comment Class:                                 Concentration of
Drug Name                              Darunavir or
Concomitant Drug
Integrase strand tranfer inhibitors
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.
PREZISTA co-administered with low dose ritonavir and raltegravir can be used without dose adjustments.
Elvitegravir                          elvitegravir AUC ↔               When PREZISTA co-administered with low elvitegravir Cmin ↔              dose ritonavir (600/100 mg twice daily) is used in combination with elvitegravir, the dose of elvitegravir Cmax ↔              elvitegravir should be 150 mg once daily.
darunavir AUC ↔ darunavir Cmin 17%              The pharmacokinetics and dosing darunavir Cmax ↔                recommendations for other doses of darunavir or with elvitegravir/cobicistat have not been established. Therefore,
co-administration of PREZISTA with low dose ritonavir in doses other than 600/100 mg twice daily and elvitegravir is not recommended. Co-administration of
PREZISTA with low dose ritonavir and elvitegravir in the presence of cobicistat is not recommended
HIV-1-Antiviral Agents: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) didanosine                            ↔ darunavir                     Didanosine should be administered one hour ↔ didanosine                    before or two hours after
PREZISTA/ritonavir (which are administered with food).
HIV-1-Antiviral Agents: HIV-Protease Inhibitors (PIs) indinavir                             ↑ darunavir                     The appropriate dose of indinavir in ↑ indinavir                     combination with PREZISTA/ritonavir has (The reference regimen for indinavir                                  not been established.
was indinavir/ritonavir 800/100 mg twice daily.) lopinavir/ritonavir                   ↓ darunavir                     Appropriate doses of the combination have ↔ lopinavir                     not been established. Hence, it is not recommended to co-administer lopinavir/ritonavir and PREZISTA, with or without ritonavir.
saquinavir                            ↓ darunavir                     Appropriate doses of the combination have ↔ saquinavir                    not been established. Hence, it is not recommended to co-administer saquinavir and PREZISTA, with or without ritonavir.
HIV-1-Antiviral Agents: CCR5 co-receptor antagonists maraviroc                             ↑ maraviroc                     Maraviroc concentrations are increased when co-administered with
PREZISTA/ritonavir. When used in combination with PREZISTA/ritonavir, the

                                                            dose of maraviroc should be 150 mg twice daily.



ANAESTHETIC
Alfentanil                Not studied. The metabolism      The concomitant use with boosted of alfentanil                    PREZISTA may require to lower is mediated via CYP3A, and       the dose of alfentanil and requires may as such                      monitoring for risks of prolonged or be inhibited by boosted          delayed respiratory depression.
PREZISTA.

Other Agents
Antiarrhythmics:          ↑ antiarrhythmics                Concentrations of these drugs may be flecainide,                                                increased when co-administered with propafenone                                                PREZISTA/ritonavir. Caution is warranted Disopyramide                                               and therapeutic concentration monitoring, if Mexiletine                                                 available, is recommended for antiarrhythmics when co-administered with
PREZISTA/ritonavir.
 digoxin                    ↑ digoxin                        The lowest dose of digoxin should initially be prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical effect.
Anticoagulant:            Not studied. Co-administration   The use of PREZISTA of                               co-administered with low dose
Apixaban                  PREZISTA with these              ritonavir and these anticoagulants is Dabigatran etexilate      anticoagulants may               not recommended.
Rivaroxaban               increase concentrations of the anticoagulant.
(CYP3A and/or P-gp inhibition).
Anticoagulant:             ↓ warfarin                      Warfarin concentrations are decreased when warfarin                   ↔ darunavir                     co-administered with PREZISTA/ritonavir.
It is recommended that the international normalized ratio (INR) be monitored when warfarin is combined with
PREZISTA/ritonavir.
Anticonvulsant:           ↔ darunavir                      The dose of either darunavir/ritonavir or carbamazepine             ↑ carbamazepine                  carbamazepine does not need to be adjusted when initiating co-administration with darunavir/ritonavir and carbamazepine.
Clinical monitoring of carbamazepine concentrations and its dose titration is recommended to achieve the desired clinical response.
Anticonvulsant:          Not studied. Phenobarbital and    PREZISTA co-administered with phenobarbital,           phenytoin are expected to         low dose ritonavir should not be phenytoin                decrease plasma                   used in combination with these medicines.
concentrations of darunavir.
(induction of CYP450 enzymes)
Antidepressant:            ↑ trazodone                     Concomitant use of trazodone or 
trazodone,                ↑ desipramine                    desipramine and PREZISTA/ritonavir may desipramine                                                increase plasma concentrations of trazodone or desipramine which may lead to adverse events such as nausea, dizziness,
hypotension and syncope. If trazodone or desipramine is used with
PREZISTA/ritonavir, the combination should be used with caution, and a lower dose of trazodone or desipramine should be considered.


Antidepressant:           Concomitant use of               Clinical monitoring is Amitriptyline             PREZISTA                         recommended when Desipramine               co-administered wirth low        co-administering PREZISTA with Imipramine                dose ritonavir                   low dose ritonavir with these Nortriptyline             and these antidepressants may    antidepressants and a dose Trazodone                 increase concentrations of the   adjustment of the antidepressant may be antidepressant.                  needed.
(CYP2D6 and/or CYP3A inhibition).
Anti-infective:            ↔darunavir                      No dose adjustment of the combination is clarithromycin             ↑clarithromycin                 required for patients with normal renal function. For patients with renal impairment,
the following dose adjustments should be considered:

-    For subjects with CLcr of 30-60 mL/min, the dose of clarithromycin should be reduced by 50%.

-    For subjects with CLcr of < 30 mL/min, the dose of clarithromycin should be reduced by 75%.
Antifungals:              ↑ketoconazole                    Ketoconazole and itraconazole are potent ketoconazole,             ↑darunavir                       inhibitors as well as substrates of CYP3A.
itraconazole,             ↑itraconazole                    Concomitant systemic use of ketoconazole, voriconazole              (not studied)                    itraconazole, and darunavir/ritonavir may ↓voriconazole                    increase plasma concentration of darunavir.
(not studied)
Plasma concentrations of ketoconazole or itraconazole may be increased in the presence of darunavir/ritonavir. When co- administration is required, the daily dose of ketoconazole or itraconazole should not exceed 200 mg.

Plasma concentrations of voriconazole may be decreased in the presence of darunavir/ritonavir. Voriconazole should not be administered to patients receiving darunavir/ritonavir unless an assessment of the benefit/risk ratio justifies the use of voriconazole.
Antifungals:              Not studied. Concomitant         Caution is warranted and clinical Clotrimazole              systemic use of                  monitoring is recommended, when clotrimazole andboosted          co-administration of clotrimazole is PREZISTAmay                         required.
increase plasma concentrations of darunavir and/or clotrimazole. darunavir
AUC24h ↑ 33% (based on population pharmacokinetic model)
Antifungals:              Not studied. PREZISTA may           Caution is warranted and clinical Fluconazole               increase                            monitoring is recommended.
Posaconazole              antifungal plasma concentrations (P-gp inhibition) and posaconazole may increase darunavir concentrations.
(CYP3A inhibition)
Anti-gout:                 ↑colchicine                        Treatment of gout-flares – co-administration colchicine                                                    of colchicine in patients on PREZISTA/ritonavir:
0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Treatment course to be repeated no earlier than 3 days.

Prophylaxis of gout-flares – co- administration of colchicine in patients on
PREZISTA/ritonavir:
If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day.
If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.

Treatment of familial Mediterranean fever
– co-administration of colchicine in patients on PREZISTA/ritonavir: maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Co-administration of PREZISTA/rtv with colchicine in patients with renal or hepatic impairment is contraindicated.

ANTIMYCOBACTERIAL:        Not studied. Rifapentine is         The combination of rifapentine and Rifapentine               strong CYP3A inducers and           boosted PREZISTA is not recommended.
have been shown to cause profound decreases in concentrations of other protease inhibitors,which can result in virological failure and resistance development
(CYP450 enzyme induction).
During attempts to overcome the decreased exposure by increasing the dose of other protease inhibitors with low dose ritonavir, a high frequency of liver reactions
                                       was seen with rifampicin.
Antimycobacterial:                     ↑darunavir                        Dose reduction of rifabutin by at least 75% rifabutin                              ↑rifabutin                        of the usual dose (300 mg once daily) is ↑25-O-desacetylrifabutin          recommended (i.e., a maximum dose of The reference regimen for rifabutin                                      150 mg every other day). Increased was 300 mg once daily                                                    monitoring for adverse events is warranted in patients receiving this combination and further dose reduction of rifabutin may be necessary.
ANTINEOPLASTICS:                       Not studied. PREZISTA is         Concentrations of these medicinal expected to                      products may be increased when
Dasatinib                              increase these antineoplastic    co-administered with PREZISTA Nilotinib                              plasma concentrations.           with low dose ritonavir resulting in Vinblastine                            (CYP3A inhibition)               the potential for increased adverse Vincristine                                                             events usually associated with these agents.
Caution should be exercised when combining one of these antineoplastic agents with
PREZISTA with low dose ritonavir.

Everolimus                                                              Concominant use of everolimus and PREZISTA co-administered with low dose ritonavir is not recommended.

β-Blockers:                            ↑beta-blockers                   Caution is warranted and clinical monitoring metoprolol,                                                             of patients is recommended. A dose decrease timolol                                                                 may be needed for these drugs when co- Carvedilol                                                               administered with PREZISTA/ritonavir.
Buspirone                              Not studied.                     Clinical monitoring is Clorazepate                            Sedative/hypnotics are           recommended when Diazepam                               extensively metabolised by       co-administering boosted Estazolam                              CYP3A.Co-administration          PREZISTA with these Flurazepam                             with boosted PREZISTA may        sedatives/hypnotics and a lower Midazolam (parenteral)                 cause a large increase in the    dose of the sedatives/hypnotics should be Zoldipem                               concentration of these           considered.
medicines.

If parenteral midazolam is co-   If parenteral midazolam is administered with boosted        co-administered with boosted
PREZISTA it may cause a          PREZISTA, it should be done in an large increase in the            intensive care unit (ICU) or similar concentration of this            setting, which ensures close clinical benzodiazepine. Data from        monitoring and appropriate medical concomitant use of parenteral    management in case of respiratory midazolam with other             depression and/or prolonged sedation. Dose protease inhibitors suggest a    adjustment for midazolam should be possible 3-4 fold increase in    considered, especially if more than a single midazolam plasma levels.         dose of midazolam is administered.

Calcium Channel                        ↑calcium channel blockers        Plasma concentrations of calcium channel Blockers:                                                               blockers may increase when felodipine,                                                             PREZISTA/ritonavir are co-administered.
nifedipine,                                                             Caution is warranted and clinical monitoring nicardipine                                                             of patients is recommended.
Amlodipine
Diltiazem
Verapamil

CORTICOSTEROIDS                     In a clinical study where          Concomitant administration of Fluticasone                         ritonavir 100 mg                   PREZISTA co-administered with Budesonide                          capsules twice daily were co-      low dose ritonavir and these administered                       glucocorticoids is not recommended with 50 µg intranasal              unless the potential benefit of fluticasone                        treatment outweighs the risk of propionate (4 times daily) for 7   systemic corticosteroid effects. A days in                            dose reduction of the glucocorticoid healthy subjects, fluticasone      should be considered with close propionate                         monitoring of local and systemic plasma concentrations              effects or a switch to a increased                          glucocorticoid which is not a significantly, whereas the         substrate for CYP3A (e.g.,
intrinsic cortisol                 beclomethasone). Moreover, in case levels decreased by                of withdrawal of glucocorticoids,
approximately 86%                  progressive dose reduction may
(90% CI 82-89%). Greater           have to be performed over a longer effects may be expected when       period.
fluticasone is inhaled.
Systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone; this could also occur with other corticosteroids metabolised via the P4503A pathway, e.g.,
budesonide. The effects of high fluticasone systemic exposure on ritonavir plasma levels are unknown
Prednisone                          Not studied. Darunavir may         Concomitant use of PREZISTA increase                           with low dose ritonavir and plasma concentrations of           prednisone may increase the risk for prednisone.                        development of systemic corticosteroid effects, (CYP3A inhibition)                 including Cushing’s syndrome and adrenal suppression. Clinical monitoring is recommended when co-administering
PREZISTA with low dose ritonavir with corticosteroids.
Corticosteroid:                     ↓darunavir                          Systemic dexamethasone induces CYP3A Systemic:                                                               and can thereby decrease darunavir plasma dexamethasone                                                           concentrations. This may result in loss of therapeutic effect to PREZISTA.
Endothelin receptor antagonists:    ↑bosentan                           Co-administration of bosentan in patients on bosentan                                                                PREZISTA/ritonavir: 

                                                                      In patients who have been receiving
PREZISTA/ritonavir for at least 10 days,
start bosentan at 62.5 mg once daily or every other day based upon individual tolerability.

Co-administration of PREZISTA/ritonavir in patients on bosentan:
Discontinue use of bosentan at least 36 hours prior to initiation of
PREZISTA/ritonavir. After at least 10 days following the initiation of
PREZISTA/ritonavir, resume bosentan at
62.5 mg once daily or every other day based upon individual tolerability.
Hepatitis C Virus (HCV) Direct-    ↓darunavir                        Concomitant administration of Acting Agents:                     ↓boceprevir                       PREZISTA/ritonavir and boceprevir or NS3-4A protease inhibitors:        ↓telaprevir                       telaprevir resulted in reduced steady-state boceprevir                                                           exposures to darunavir and boceprevir or telaprevir                                                           telaprevir. It is not recommended to co- administer boceprevir or telaprevir and
PREZISTA/ritonavir.
Simeprevir                         simeprevir AUC ↑ 159%            It is not recommended to simeprevir Cmin ↑ 358%           co-administer boosted PREZISTA simeprevir Cmax ↑ 79%            and simeprevir.
darunavir AUC ↑ 18% darunavir Cmin ↑ 31% darunavir Cmax ↔

The dose of simeprevir in this interaction study was 50 mg when co- administered in combination with darunavir/ritonavir,
compared to 150 mg in the simeprevir alone treatment group.
HMG-CoA                             ↑pravastatin                     Titrate atorvastatin, pravastatin or Reductase Inhibitors:               ↑atorvastatin                    rosuvastatin dose carefully and use the pravastatin,                        ↑rosuvastatin                    lowest necessary dose while monitoring for atorvastatin,                                                        safety. Do not exceed atorvastatin 20 rosuvastatin                                                         mg/day.
Lovastatin                         Not studied. Lovastatin and      Increased plasma concentrations of Simvastatin                        simvastatin are                  lovastatin or simvastatin may cause expected to have markedly        myopathy, including increased                        rhabdomyolysis. Concomitant use plasma concentrations when       of boosted PREZISTA with co-administered with boosted     lovastatin and simvastatin is
PREZISTA.                        therefore contraindicated
(CYP3A inhibition)
Immunosuppressants:                 ↑immunosuppressants             Plasma concentrations of cyclosporine, cyclosporine,                                                       tacrolimus or sirolimus may be increased tacrolimus,                                                         when co-administered with sirolimus                                                           PREZISTA/ritonavir. Therapeutic concentration monitoring of the immunosuppressive agent is recommended
                                                                  when co-administered with
PREZISTA/ritonavir.


Everolimus


Concomitant use of everolimus and boosted PREZISTA is not recommended.
Inhaled beta agonist:             ↑salmeterol                    Concurrent administration of salmeterol and salmeterol                                                       PREZISTA/ritonavir is not recommended.
The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation,
palpitations and sinus tachycardia.
Narcotic Analgesic/Treatment of   ↓methadone                     No adjustment of methadone dosage is Opioid Dependence:                ↔buprenorphine, naloxone       required when initiating co-administration of methadone,                        ↑norbuprenorphine              PREZISTA/ritonavir. However, clinical buprenorphine,                    (metabolite)                   monitoring is recommended as the dose of buprenorphine/naloxone                                           methadone during maintenance therapy may need to be adjusted in some patients.
No dose adjustment for buprenorphine or buprenorphine/naloxone is required with concurrent administration of
PREZISTA/ritonavir. Clinical monitoring is recommended if PREZISTA/ritonavir and buprenorphine or buprenorphine/naloxone are coadministered.
Neuroleptics:                     ↑neuroleptics                  A dose decrease may be needed for these risperidone,                                                     drugs when co-administered with thioridazine                                                     PREZISTA/ritonavir.
Perphenazine
Oral Contraceptives/estrogen:     ↓ethinyl estradiol             Plasma concentrations of ethinyl estradiol ethinyl estradiol,                ↓norethindrone                 are decreased due to induction of its norethindrone                                                    metabolism by ritonavir. Alternative methods of nonhormonal contraception are recommended.
PDE-5 inhibitors:                 ↑PDE-5 inhibitors (only the    Co-administration with PREZISTA/ritonavir sildenafil,                       use of sildenafil at doses     may result in an increase in PDE-5 inhibitor- vardenafil,                       used for treatment of          associated adverse events, including tadalafil                         erectile dysfunction has       hypotension, syncope, visual disturbances been studied with              and priapism.
PREZISTA/ritonavir)
Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH):
-Use of sildenafil is contraindicated when used for the treatment of pulmonary arterial hypertension (PAH)
[see Contraindications (4)].

-The following dose adjustments are recommended for use of tadalafil with
PREZISTA/ritonavir:
Co-administration of tadalafil in patients on PREZISTA/ritonavir:

                                                                               In patients receiving
PREZISTA/ritonavir for at least one week, start tadalafil at 20 mg once daily.
Increase to 40 mg once daily based upon individual tolerability.
Co-administration of
PREZISTA/ritonavir in patients on tadalafil:
Avoid use of tadalafil during the initiation of PREZISTA/ritonavir. Stop tadalafil at least 24 hours prior to starting
PREZISTA/ritonavir. After at least one week following the initiation of
PREZISTA/ritonavir, resume tadalafil at
20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Use of PDE-5 inhibitors for erectile dysfunction:
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 can be used with increased monitoring for PDE-5 inhibitor- associated adverse events.
Selective Serotonin Reuptake             ↔darunavir                       If sertraline or paroxetine is co-administered Inhibitors (SSRIs):                      ↓sertraline                      with PREZISTA/ritonavir, the recommended sertraline,                              ↓paroxetine                      approach is a careful dose titration of the paroxetine                                                                SSRI based on a clinical assessment of antidepressant response. In addition, patients on a stable dose of sertraline or paroxetine who start treatment with
PREZISTA/ritonavir should be monitored for antidepressant response.

Antimalarials:

An interaction trial between PREZISTA/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 PREZISTA and artemether/lumefantrine can be used without dose adjustments; however, due to the increase in lumefantrine exposure, the combination should be used with caution.

In addition to the drugs included in Table 3, the interaction between PREZISTA/ritonavir and the following drugs were evaluated in clinical studies and no dose adjustments are needed for either drug [see Clinical Pharmacology (11.3)]: atazanavir, efavirenz, etravirine, nevirapine, , ranitidine, rilpivirine, and tenofovir disoproxil fumarate.
Using cross-trial comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of darunavir. Darunavir/ritonavir had no clinically significant effect on the pharmacokinetics of dolutegravir.


Proton Pump Inhibitors
Omeprazole, pantoprazole, rabeprazole, Esomeprazole, Lansoprazole
Co-administration of omeprazole (20 mg q.d.) and PREZISTA/rtv (400/100 mg b.i.d.) did not affect the exposure to darunavir. PREZISTA and proton pump inhibitors can be co-administered without dose adjustment 
Other nucleoside reverse transcriptase inhibitors (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 drugs and PREZISTA/ritonavir.

Other PIs: The co-administration of PREZISTA/ritonavir and PIs other than lopinavir/ritonavir, saquinavir, atazanavir, and indinavir has not been studied. Therefore, such co-administration is not recommended.


Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Delavirdine
Co-administration of PREZISTA/rtv and delavirdine may increase darunavir and delavirdine concentrations (inhibition of CYP3A). The appropriate doses of PREZISTA/rtv and delavirdine have not been established. The combination of PREZISTA/rtv and delavirdine is not recommended.

Antacids e.g. Aluminium/magnesium hydroxide, calcium carbonate
No interaction is expected between antacids and PREZISTA/rtv. PREZISTA/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 PREZISTA/rtv (400/100 mg b.i.d.) did not affect the exposure to darunavir. PREZISTA/rtv can be co-administered with H2-receptor antagonists without dose adjustments.