What is Prezista, and how does it work?
Generic drug: darunavir
Brand name: Prezista
Prezista (darunavir) is a prescription HIV-1 (Human Immunodeficiency Virus-type 1) medicine used with ritonavir and other antiretroviral medicines to treat HIV-1 infection in adults and children 3 years of age and older. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
Prezista should not be used in children under 3 years of age.
What are the side effects of Prezista?
Prezista may cause serious side effects, including:
- Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including Prezista can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking Prezista.
- Changes in body fat can happen in people who take HIV-1 medicines. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
- Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
- Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including Prezista.
- Liver problems. Some people taking Prezista in combination with ritonavir have developed liver problems, which may be life-threatening. Your healthcare provider should do blood tests before and during your Prezista and ritonavir combination treatment. If you have chronic hepatitis B or C infection, yourhealthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. Tell your healthcare provider if you have any of the below signs and symptoms of liver problems.
- dark (tea colored) urine
- yellowing of your skin or whites of your eyes
- pale colored stools (bowel movements)
- nausea
- vomiting
- pain or tenderness on your right side below your ribs
- loss of appetite
- tiredness
- Severe or life-threatening skin reactions or rash. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. Tell your healthcare provider right away if you develop a rash. Stop taking Prezista and ritonavir combination treatment and tell your healthcare provider right away if you have any skin changes with symptoms below:
- fever
- tiredness
- muscle or joint pain
- blisters or skin lesions
- mouth sores or ulcers
- red or inflamed eyes, like “pink eye” (conjunctivitis)
Rash occurred more often in people taking Prezista and raltegravir together than with either drug separately, but was generally mild.
The most common side effects of Prezista include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of Prezista.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is the dosage for Prezista?
Testing Prior To Initiation Of Prezista/Ritonavir
- In treatment-experienced patients, treatment history, genotypic and/or phenotypic testing is recommended to assess drug susceptibility of the HIV-1 virus [see Microbiology]. Refer to Recommended Dosage In Adult Patients, Recommended Dosage During Pregnancy and Recommended Dosage In Pediatric Patients (Age 3 To Less Than 18 Years) below for dosing recommendations.
- Appropriate laboratory testing such as serum liver biochemistries should be conducted prior to initiating therapy with Prezista/ritonavir.
Monitoring During Treatment With Prezista/Ritonavir
- Patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases should be monitored for elevation in serum liver biochemistries, especially during the first several months of Prezista/ritonavir treatment.
Recommended Dosage In Adult Patients
- Prezista must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer Prezista with ritonavir will result in plasma levels of darunavir that will be insufficient to achieve the desired antiviral effect and will alter some drug interactions.
- Patients who have difficulty swallowing Prezista tablets can use the 100 mg per mL Prezista oral suspension.
Treatment-Naive Adult Patients
- The recommended oral dose of Prezista is 800 mg (one 800 mg tablet or 8 mL of the oral suspension) taken with ritonavir 100 mg (one 100 mg tablet or capsule or 1.25 mL of a 80 mg per mL ritonavir oral solution) once daily and with food.
- An 8 mL Prezista dose should be taken as two 4 mL administrations with the included oral dosing syringe.
Treatment-Experienced Adult Patients
- The recommended oral dosage for treatment-experienced adult patients is summarized in Table 1.
- Baseline genotypic testing is recommended for dose selection. However, when genotypic testing is not feasible, Prezista 600 mg taken with ritonavir 100 mg twice daily is recommended.
Table 1: RecommendedPrezista/ritonavirDosage in Treatment-Experienced Adult Patients
| Baseline Resistance | Formulation and Recommended Dosing | |
| Prezista tablets with ritonavir tablets or capsule | Prezista oral suspension(100 mg/mL) with ritonavir oral solution (80 mg/mL) | |
| With no darunavir resistance associated substitutions* | One 800 mg Prezista tablet with one 100 mg ritonavir tablet/capsule,taken once daily with food | 8 mL† Prezista oral suspension with 1.25 mL ritonavir oral solution, taken once daily with food |
| With at least one darunavir resistance associated substitutions* , or with no baseline resistance information | One 600 mg Prezista tablet with one 100 mg ritonavir tablet/capsule,taken twice daily with food | 6 mL Prezista oral suspension with 1.25 mL ritonavir oral solution, taken twice daily with food |
| * V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V † An 8 mL darunavir dose should be taken as two 4 mL administrations with the included oral dosing syringe | ||
Recommended Dosage During Pregnancy
- The recommended dosage in pregnant patients is Prezista 600 mg taken with ritonavir 100 mg twice daily with food.
- Prezista 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable Prezista 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, arevirologically suppressed (HIV-1 RNA less than 50copiespermL), and in whom a change to twice daily Prezista 600 mg with ritonavir 100 mg may compromise tolerability or compliance.
Recommended Dosage In Pediatric Patients (Age 3 To Less Than 18 Years)
- Healthcare professionals should pay special attention to accurate dose selection of Prezista, transcription of the medication order, dispensing information and dosing instruction to minimize risk for medication errors, overdose, and underdose.
- Prescribers should select the appropriate dose of Prezista/ritonavir for each individual child based on body weight (kg) and should not exceed the recommended dose for adults.
- Before prescribing Prezista, children weighing greater than or equal to 15 kg should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, the use of Prezista oral suspension should be considered.
- The recommended dose of Prezista/ritonavir for pediatric patients (3 to less than 18 years of age and weighing at least 10 kg is based on body weight (see Tables 2, 3, 4, and 5) and should not exceed the recommended adult dose. Prezista should be taken with ritonavir and with food.
- The recommendations for the Prezista/ritonavir dosage regimens were based on pediatric clinical trial data and population pharmacokinetic modeling and simulation.
Dosing Recommendations For Treatment-Naive Pediatric Patients Or Antiretroviral Treatment-Experienced Pediatric Patients With No Darunavir Resistance Associated Substitutions
Pediatric Patients Weighing At Least 10 kg but Less than 15 kg
- The weight-based dose in antiretroviral treatment-naive pediatric patients or antiretroviral treatment-experienced pediatric patients with no darunavir resistance associated substitutions is Prezista 35 mg/kg once daily with ritonavir 7 mg/kg once daily using the following table:
Table 2: Recommended Dose for Pediatric Patients Weighing 10 kg to Less Than 15 kg Who are Treatment-Naive or Treatment-Experienced with No Darunavir Resistance Associated Substitutions*
| Body weight (kg) | Formulation: Prezista oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
| Dose: once daily with food | |
| Greater than or equal to 10 kg to less than 11 kg | Prezista 3.6 mL† (350 mg) with ritonavir 0.8 mL (64 mg) |
| Greater than or equal to 11 kg to less than 12 kg | Prezista 4 mL† (385 mg) with ritonavir 0.8 mL (64 mg) |
| Greater than or equal to 12 kg to less than 13 kg | Prezista 4.2 mL (420 mg) with ritonavir 1 mL (80 mg) |
| Greater than or equal to 13 kg to less than 14 kg | Prezista 4.6 mL† (455 mg) with ritonavir 1 mL (80 mg) |
| Greater than or equal to 14 kg to less than 15 kg | Prezista 5 mL† (490 mg) with ritonavir 1.2 mL (96 mg) |
| * darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V † The 350 mg, 385 mg, 455 mg and 490 mg darunavir dose for the specified weight groups were rounded up for suspension dosing convenience to 3.6 mL, 4 mL, 4.6 mL and 5 mL, respectively. | |
Pediatric Patients Weighing At Least 15 kg
- Pediatric patients weighing at least 15 kg can be dosed with Prezista oral tablet(s) or suspension using the following table:
Table 3: RecommendedDose for Pediatric Patients Weighing At Least 15 kg Who are Treatment-Naive or Treatment-Experiencedwith NoDarunavir Resistance Associated Substitutions*
| Body weight (kg) | Formulation: Prezista tablet(s) and ritonavir capsules or tablets(100 mg) | Formulation: Prezista oral suspension (100 mg/mL) andritonavir oral solution (80 mg/mL) |
| Dose: once daily with food | Dose: once daily with food | |
| Greater than or equal to 15 kg to less than 30 kg | Prezista 600 mg with ritonavir 100 mg | Prezista 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) |
| Greater than or equal to 30 kg to less than 40 kg | Prezista 675 mg with ritonavir100 mg | Prezista 6.8 mL†‡ (675 mg) with ritonavir 1.25 mL (100 mg) |
| Greater than or equal to 40 kg | Prezista 800 mg with ritonavir100 mg | Prezista 8 mL‡ (800 mg) with ritonavir 1.25 mL (100 mg) |
| * darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V,I54M, I54L, T74P, L76V, I84V and L89V † The 675mg doseusing darunavirtablets forthis weightgroup is rounded up to 6.8mLforsuspension dosing convenience. ‡ The 6.8mL and 8mL darunavirdose should betaken as two (3.4mL or 4mL respectively)administrationswith the included oral dosing syringe | ||
Dosing Recommendations For Treatment-Experienced Pediatric Patients With At Least One Darunavir Resistance Associated Substitutions
Pediatric Patients Weighing At Least 10 kg but Less than 15 kg
- The weight-based dose in antiretroviral treatment-experienced pediatric patients with at least one darunavir resistance associated substitution is Prezista 20 mg/kg twice daily with ritonavir 3 mg/kg twice daily using the following table:
Table 4: Recommended Dose for Pediatric Patients Weighing 10 kg to Less Than 15 kg Who are Treatment-Experiencedwith AtLeast One Darunavir Resistance Associated Substitution*
| Body weight (kg) | Formulation: Prezista oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
| Dose: twice daily with food | |
| Greater than or equal to 10 kg to less than 11 kg | Prezista 2 mL (200 mg) with ritonavir 0.4 mL (32 mg) |
| Greater than or equal to 11 kg to less than 12 kg | Prezista 2.2 mL (220 mg) with ritonavir 0.4 mL (32 mg) |
| Greater than or equal to 12 kg to less than 13 kg | Prezista 2.4 mL (240 mg) with ritonavir 0.5 mL (40 mg) |
| Greater than or equal to 13 kg to less than 14 kg | Prezista 2.6 mL (260 mg) with ritonavir 0.5 mL (40 mg) |
| Greater than or equal to 14 kg to less than 15 kg | Prezista 2.8 mL (280 mg) with ritonavir 0.6 mL (48 mg) |
| * darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V | |
Pediatric Patients Weighing At Least 15 kg
Pediatric patients weighing at least 15 kg can be dosed with Prezista oral tablet(s) or suspension using the following table:
Table 5: Recommended Dose for Pediatric Patients Weighing At Least 15 kg Who are Treatment-Experienced with AtLeast One Darunavir Resistance Associated Substitution*
| Body weight (kg) | Formulation: Prezista tablet(s) and ritonavir tablets, capsules (100 mg) or oral solution(80 mg/mL) | Formulation: Prezista oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
| Dose: twice daily with food | Dose: twice daily with food | |
| Greater than or equal to 15 kg to less than 30 kg | Prezista 375 mg with ritonavir 0.6 mL (48 mg) | Prezista 3.8 mL (375 mg)† with ritonavir 0.6 mL (48 mg) |
| Greater than or equal to 30 kg to less than 40 kg | Prezista 450 mg with ritonavir 0.75 mL (60 mg) | Prezista 4.6 mL (450 mg)† with ritonavir 0.75 mL (60 mg) |
| Greater than or equal to 40 kg | Prezista 600 mg with ritonavir 100 mg | Prezista 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) |
| * darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V † The 375 mg and 450 mg dose using darunavir tablets for this weight group is rounded up to 3.8 mL and 4.6 mL for suspension dosing convenience. | ||
- The use of Prezista/ritonavir in pediatric patients below 3 years of age is not recommended.
Not Recommended In Patients With Severe Hepatic Impairment
- No dosage adjustment is required in patients with mild or moderate hepatic impairment.
- No data are available regarding the use of Prezista/ritonavir when co-administered to subjects with severe hepatic impairment; therefore, Prezista/ritonavir is not recommended for use in patients with severe hepatic impairment.
SLIDESHOW
A Timeline of the HIV/AIDS Pandemic See SlideshowWhat drugs interact with Prezista?
Potential For Prezista/Ritonavir To Affect Other Drugs
- Prezista co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6, and P-gp. Co-administration of Prezista and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events.
- Prezista co-administered with ritonavir with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of their therapeutic effect (see Table 10).
Potential For Other Drugs To Affect Darunavir
- Darunavir and ritonavir are metabolized by CYP3A. In vitro data indicate that darunavir may be a P-gp substrate.
- 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, or P-gp may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (see Table 10).
Established And Other Potentially Significant Drug Interactions
- Table 10 provides 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.
- The table includes potentially significant interactions but is not all inclusive.
Table 10: Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May be Recommended Based on Drug Interaction Studies or Predicted Interaction
| Concomitant Drug Class Drug Name | Effect on Concentration of Darunavir Or Concomitant Drug | Clinical Comment |
| HIV-1-Antiviral Agents: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||
| didanosine | ↔ darunavir | Didanosine should be administered one hour before or two hours after Prezista/ritonavir (which are administered with food). |
| ↔ didanosine | ||
| HIV-1-Antiviral Agents: HIV-Protease Inhibitors (PIs) | ||
| indinavir | ↑ darunavir | The appropriate dose of indinavir in combination with Prezista/ritonavir has not been established. |
| (The reference regimen for indinavir was indinavir/ritonavir 800/100 mg twice daily.) | ↑ indinavir | |
| lopinavir/ritonavir | ↓ darunavir | Appropriate doses of the combination have not beenestablished. Hence, it is not recommended to co-administer lopinavir/ritonavir and Prezista,with or without ritonavir. |
| ↔ lopinavir | ||
| saquinavir | ↓ darunavir | Appropriate doses of the combination have not beenestablished. Hence, it is not recommended to co-administer saquinavir and Prezista, with or without ritonavir. |
| ↔ saquinavir | ||
| Other HIV protease inhibitors, except atazanavir [see Drugs Without Clinically Significant Interactions With Prezista] | As co-administration with Prezista/ritonavir has not been studied, co-administration is not recommended. | |
| HIV-1-Antiviral Agents: CCR5 co-receptor antagonists | ||
| maraviroc | ↑ maraviroc | When used in combination with Prezista/ritonavir, the dose of maraviroc shouldbe 150 mg twice daily. |
| Other Agents Alpha 1-adrenoreceptor antagonist: | ||
| alfuzosin | ↑ alfuzosin | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such ashypotension. |
| Antibacterial: | ||
| clarithromycin | ↔ darunavir | No dose adjustment of the combination is required for patients with normal renal function. Forco-administration of clarithromycin and Prezista/ritonavir in patients with renalimpairment, the following dose adjustments shouldbe considered:
|
| ↑ clarithromycin | ||
| Anticoagulants: | ||
| Direct Oral Anticoagulants (DOACs) | ||
| apixaban | ↑ apixaban | Due to potentially increased bleeding risk, dosing recommendations for co-administration of apixabanwith Prezista depends on the apixaban dose.Refer to apixaban dosing instructions for co-administration with strong CYP3A and P-gpinhibitors in apixaban prescribing information. |
| rivaroxaban | ↑ rivaroxaban | Co-administration of Prezista/ritonavir andrivaroxaban is not recommended because it maylead to an increased bleeding risk. |
| betrixaban | ↔ betrixaban | No dose adjustment is needed when betrixaban,dabigatran, or edoxaban is co-administered with Prezista. |
| dabigatran | ↔ dabigatran | |
| edoxaban | ↔ edoxaban | |
| Other Anticoagulants | ||
| warfarin | ↓ warfarin | Warfarin concentrations are decreased when co-administered with Prezista/ritonavir. It is recommended that the international normalized ratio (INR) be monitored when warfarin is combined with Prezista/ritonavir. |
| ↔ darunavir | ||
| Anticonvulsants: | ||
| carbamazepine | ↔ darunavir | The dose of either Prezista/ritonavir or carbamazepine does not need to be adjusted when initiating co-administration with Prezista/ritonavir and carbamazepine. Clinical monitoring of carbamazepine concentrations and its dose titration is recommended to achieve the desired clinical response. |
| ↑ carbamazepine | ||
| clonazepam | ↑ clonazepam | Clinical monitoring of anticonvulsants that are metabolized by CYP3A is recommended. |
| phenobarbital, phenytoin | ↔ darunavir | Phenytoin and phenobarbital levels should be monitored when co-administering with Prezista/ritonavir. |
| ↓ phenytoin | ||
| ↓ phenobarbital | ||
| Antidepressants: | ||
| Selective Serotonin Reuptake Inhibitors (SSRIs): | ||
| paroxetine, sertraline | ↓ paroxetine | If either sertraline or paroxetine is initiated in patients receiving Prezista/ritonavir, dose titrating the SSRI based on a clinical assessment of antidepressant response is recommended. Monitor for antidepressant response in patients on a stable dose of sertraline or paroxetine who start treatment with Prezista/ritonavir. |
| ↓ sertraline | ||
| Tricyclic Antidepressants (TCAs): | ||
| amitriptyline, desipramine, imipramine, nortriptyline | ↑ amitriptyline | Use a lower dose of the tricyclic antidepressants and trazodone due to potential increased adverse events such as nausea, dizziness, hypotension and syncope. |
| ↑ desipramine | ||
| ↑ imipramine | ||
| ↑ nortriptyline | ||
| Other: trazodone | ↑ trazodone | |
| Antifungals: | ||
| itraconazole, isavuconazole, ketoconazole, posaconazole | ↑ darunavir | Monitor for increased Prezista/ritonavir and/or antifungal adverse events with concomitant use of these antifungals. When co-administration is required, the daily dose of ketoconazole or itraconazole should not exceed 200 mg with monitoring for increased antifungal adverse events. |
| ↑ itraconazole | ||
| ↑ isavuconazole | ||
| ↑ ketoconazole | ||
| ↔ posaconazole | ||
| voriconazole | ↓ voriconazole | Voriconazole is not recommended for patients receiving Prezista/ritonavir unless an assessment comparing predicted benefit to risk ratio justifies the use of voriconazole. |
| Anti-gout: | ||
| colchicine | ↑ colchicine | Co-administration is contraindicated in patients with renal and/or hepatic impairment due to potential for serious and/or life-threatening reactions. |
For patients without renal or hepatic impairment:
| ||
| Antimalarial: | ||
| artemether/lumefantrine | ↓ artemether | The combination of Prezista/ritonavir and artemether/lumefantrine can be used without dose adjustments. However, the combination should be used with caution as increased lumefantrine exposure may increase the risk of QT prolongation. |
| ↓ dihydroartemisinin | ||
| ↑ lumefantrine | ||
| ↔ darunavir | ||
| Antimycobacterials: | ||
| rifampin | ↓ darunavir | Co-administration is contraindicated due to potential for loss of therapeutic effect and development of resistance. |
| rifabutin | ↑ darunavir | Dose reduction of rifabutin by at least 75% of the usual dose (300 mg once daily) is recommended (i.e., a maximum dose of 150 mg every other day). Increased monitoring for adverse events is warranted in patients receiving this combination and further dose reduction of rifabutin may be necessary. |
| ↑ rifabutin | ||
| (The reference regimen for rifabutin was 300 mg once daily.) | ↑ 25-O-desacetylrifabutin | |
| rifapentine | ↓ darunavir | Co-administration of Prezista/ritonavir with rifapentine is not recommended. |
| Antineoplastics: | ||
| dasatinib, nilotinib | ↑ antineoplastics | A decrease in the dosage or an adjustment of the dosing interval of dasatinib and nilotinib may be necessary for patients. Please refer to the dasatinib and nilotinib prescribing information for dosing instructions. |
| vinblastine, vincristine | For vincristine and vinblastine, consideration should be given to temporarily withholding the ritonavircontaining antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects when Prezista/ritonavir is a dministered concurrently with vincristine or vinblastine. If the antiretroviral regimen must be withheld for a prolonged period, consideration should be given to initiating a revised regimen that does not include a CYP3A or P-gp inhibitor. | |
| Antipsychotics: | ||
| lurasidone | ↑ lurasidone | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions. |
| pimozide | ↑ pimozide | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| quetiapine | ↑ quetiapine | Initiation of Prezista with ritonavir in patients taking quetiapine: |
| Consider alternative antiretroviral therapy to avoid increases in quetiapine exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. | ||
| Initiation of quetiapine in patients taking Prezista with ritonavir: | ||
| Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine. | ||
| e.g. perphenazine, risperidone, thioridazine | ↑ antipsychotics | A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed when co-administered with Prezista/ritonavir. |
| β-Blockers: | ||
| e.g. carvedilol, metoprolol, timolol | ↑ beta-blockers | Clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with Prezista/ritonavir and a lower dose of the beta blocker should beconsidered. |
| Calcium Channel Blockers: | ||
| amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil | ↑ calcium channel blockers | Clinical monitoring of patients is recommended. |
| Cardiac Disorders: | ||
| ranolazine, ivabradine | ↑ ranolazine | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions. |
| ↑ ivabradine | ||
| dronedarone | ↑ dronedarone | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Other antiarrhythmics | ↑ antiarrhythmics | Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when co-administered with Prezista/ritonavir. |
| e.g. amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine 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. |
| Systemic/Inhaled/ Nasal/Ophthalmic Corticosteroids: e.g. | ||
| betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone | ↓ darunavir | Co-administration of Prezista/ritonavir with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to darunavir. Consider alternative corticosteroids. |
| ↑ corticosteroids | ||
| Co-administration with corticosteroids of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone (for which PK and/or PD are less affected by strong CYP3A inhibitors relative to other steroids) should be considered, particularly for long term use. | ||
| Endothelin receptor antagonist: | ||
| bosentan | ↑ bosentan | Co-administration of bosentan in patients on 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. | ||
| Ergot derivatives: | ||
| e.g. dihydroergotamine, ergotamine, methylergonovine | ↑ ergot derivatives | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
| GI motility agent: | ||
| cisapride | ↑ cisapride | Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Hepatitis C virus (HCV): | ||
| Direct-Acting Antivirals: | ||
| elbasvir/grazoprevir | ↑elbasvir/grazoprevir | Co-administration is contraindicated due to potential for the increased risk of alanine transaminase (ALT) elevations. |
| glecaprevir/pibrentasvir | ↑ glecaprevir | Co-administration of Prezista/ritonavir with glecaprevir/pibrentasvir is not recommended. |
| ↑ pibrentasvir | ||
| Herbal product: | ||
| St. John’s wort (Hypericum perforatum) | ↓ darunavir | Co-administration is contraindicated due to potentialfor reduced plasma concentrations of darunavir,which may result in loss of therapeutic effect and development of resistance. |
| Hormonal contraceptives: | Effective alternative (non-hormonal) contraceptivemethod or a barrier method of contraception is recommended [see Use In Specific Populations]. | |
| ethinyl estradiol, norethindrone,drospirenone | ↓ ethinyl estradiol | For co-administration with drospirenone, clinical monitoring is recommended due to the potential forhyperkalemia. |
| ↓ norethindrone drospirenone: effects unknown | No data are available to make recommendations on co-administration with other hormonal contraceptives. | |
| Immunosuppressants: | ||
| e.g. cyclosporine, tacrolimus,sirolimus | ↑ immunosuppressants | Therapeutic concentration monitoring of theimmunosuppressive agent is recommended whenco-administered with Prezista/ritonavir. |
| Immunosuppressant/neoplastic: | ||
| everolimus | Co-administration of everolimus and Prezista/ritonavir is not recommended. | |
| irinotecan | Discontinue Prezista/ritonavir at least 1 week prior to starting irinotecan therapy. Do notadminister Prezista/ritonavir with irinotecanunless there are no therapeutic alternatives. | |
| Inhaled beta agonist: | ||
| salmeterol | ↑ salmeterol | Co-administration of salmeterol and Prezista/ritonavir is not recommended. The combination may result in increased risk ofcardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. |
| Lipid Modifying Agents: | ||
| HMG-CoA reductase inhibitors: | ||
| lovastatin, simvastatin | ↑ lovastatin | Co-administration is contraindicated due to potentialfor serious reactions such as myopathy including rhabdomyolysis. |
| ↑ simvastatin | ||
| atorvastatin, pravastatin, rosuvastatin | ↑ HMG-CoA reductase inhibitors | Co-administration of Prezista/ritonavir with HMG-Co A reductase inhibitors may lead toadverse events such as myopathy. Titrateatorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose whilemonitoring for adverse events. Do not exceed atorvastatin 20 mg/day. |
| Other lipid modifying agents: | ||
| lomitapide | ↑ lomitapide | Co-administration is contraindicated due to potential for markedly increased transaminases. |
| Narcotic analgesicsmetabolized by CYP3A: | ||
| e.g. fentanyl, oxycodone | ↑ fentanyl | Careful monitoring of therapeutic effects andadverse reactions associated with CYP3Ametabolized narcotic analgesics (includingpotentially fatal respiratory depression) isrecommended with co-administration. |
| ↑ oxycodone | ||
| tramadol | ↑ tramadol | A dose decrease may be needed for tramadol withconcomitant use. |
| Narcotic analgesics/treatmentof opioid dependence: | ||
| buprenorphine,buprenorphine/naloxone | ↔ buprenorphine,naloxone | No dose adjustment for buprenorphine orbuprenorphine/naloxone is required with concurrent administration of Prezista/ritonavir. Clinical monitoring is recommended if Prezista/ritonavirand buprenorphine or buprenorphine/naloxone are co-administered. |
| ↑ norbuprenorphine (metabolite) | ||
| methadone | ↓ methadone | No adjustment of methadone dosage is required when initiating co-administration ofPrezista/ritonavir. However, clinical monitoringis recommended as the dose of methadone during maintenance therapy may need to be adjusted insome patients. |
| Opioid Antagonist | ||
| naloxegol | ↑ naloxegol | Co-administration of Prezista/ritonavir andnaloxegol is contraindicated due to potential forprecipitating opioid withdrawal symptoms. |
| PDE-5 inhibitors: | ||
| e.g. avanafil, sildenafil, tadalafil,vardenafil | ↑ PDE-5 inhibitors (only the use of sildenafil at doses used for treatment of erectile dysfunction has been studied with Prezista/ritonavir) | Co-administration with Prezista/ritonavir mayresult in an increase in PDE-5 inhibitor-associated adverse events, including hypotension, syncope,visual disturbances and priapism. |
| Use of PDE-5 inhibitors for pulmonary arterialhypertension (PAH): Co-administration with sildenafil used for PAH is contraindicated due to potential for sildenafil associated adverse reactions (which include visual disturbances, hypotension, prolonged erection, andsyncope). The following dose adjustments are recommended for use of tadalafil with Prezista/ritonavir:
| ||
| 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 exceeding2.5 mg dose in 72 hours, or tadalafil at a single dose not exceeding 10 mg dose in 72 hours can be usedwith increased monitoring for PDE-5 inhibitor-associated adverse events. | ||
| Co-administration of Prezista/ritonavir andavanafil is not recommended. | ||
| Platelet aggregation inhibitor: | ||
| ticagrelor | ↑ ticagrelor | Co-administration of Prezista/ritonavir andticagrelor is not recommended. |
| clopidogrel | ↓ clopidogrel active metabolite | Co-administration of Prezista/ritonavir andclopidogrel is not recommended due to potential reduction of the antiplatelet activity of clopidogrel. |
| prasugrel | ↔ prasugrel active metabolite | No dose adjustment is needed when prasugrel is co-administered with Prezista/ritonavir. |
| Proton pump inhibitor: | ||
| omeprazole | ↓ omeprazole | When omeprazole is co-administered with Prezista/ritonavir, monitor patients for decreasedefficacy of omeprazole. Consider increasing theomeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mgper day of omeprazole. |
| ↔ darunavir | ||
| Sedatives/hypnotics: | ||
| orally administered midazolam,triazolam | ↑ midazolam | Co-administration is contraindicated due to potentialfor serious and/or life-threatening reactions such asprolonged or increased sedation or respiratory depression. Triazolam and orally administeredmidazolam are extensively metabolized by CYP3A.Co-administration of triazolam or orally administered midazolam with Prezista maycause large increases in the concentrations of these benzodiazepines. |
| ↑ triazolam | ||
| metabolized by CYP3A e.g. buspirone, diazepam,estazolam, zolpidem | ↑ sedatives/hypnotics | Titration is recommended when co-administeringPrezista/ritonavir with sedatives/hypnoticsmetabolized by CYP3A and a lower dose of the sedatives/hypnotics should be considered withmonitoring for adverse events. |
| parenterally administeredmidazolam | Co-administration of parenteral midazolam shouldbe done in a setting which ensures close clinicalmonitoring and appropriate medical management in case of respiratory depression and/or prolongedsedation. Dosagereduction for midazolam should be considered, especially if more than a single dose ofmidazolam is administered. | |
| Urinary antispasmodics | ||
| fesoterodine | ↑ fesoterodine | When fesoterodine is co-administered with Prezista/ritonavir, do not exceed a fesoterodine dose of 4 mg once daily. |
| solifenacin | ↑ solifenacin | When solifenacin is co-administered with Prezista/ritonavir, do not exceed a solifenacin dose of 5 mg once daily. |
Drugs Without Clinically Significant Interactions With Prezista
- No dosage adjustments are recommended when Prezista/ritonavir is co-administered with the following medications:
- atazanavir,
- dolutegravir,
- efavirenz,
- etravirine,
- nevirapine,
- nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine),
- pitavastatin,
- raltegravir,
- ranitidine, or
- rilpivirine.
Is Prezista safe to use while pregnant or breastfeeding?
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Prezista during pregnancy.
- Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263.
- The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
Summary
Prezista (darunavir) is a prescription HIV-1 (Human Immunodeficiency Virus-type 1) medicine used with ritonavir and other antiretroviral medicines to treat HIV-1 infection in adults and children 3 years of age and older. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). Serious side effects of Prezista include diabetes and high blood sugar (hyperglycemia), changes in body fat, changes in your immune system (Immune Reconstitution Syndrome), increased bleeding for hemophiliacs, and liver problems, and severe or life-threatening skin reactions or rash.
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- Retrovirus & Opportunistic Infections Part II
- HIV Transmission and Progression to AIDS Continues
- Physical and Biochemical Changes in HIV Disease
- Babies On The Breast Of HIV Moms
- HIV Urine Test Approved
- HIV Treatment - To Interrupt or Not
- Unprotected Sex Between HIV-Infected Partners: What's the Harm?
- Can HIV Cause Kaposi's Sarcoma?
- Do You Need Antiretroviral Therapy for HIV with No Symptoms?
- Does HIV Cause Colorectal Cancer?
- Does Anti-Retroviral Therapy for HIV Cause Diabetes?
- How Long Should You Wait to Get an HIV Test?
- What Liver Problems Does HIV Cause?
- Does Circumcision Prevent HIV and AIDS?
- HIV Infection Facts, History, Causes, and Risk Factors
- HIV Tests, Symptoms, Signs, and Stages of Infection
- Baby "Cured" of HIV Infection
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- How Effective Is ART for HIV Infection?
- How Do Protease Inhibitors Work in Antiretroviral Therapy for HIV Infection?
- What Are NNRTIs In Antiretroviral Therapy for HIV Infection?
- Symtuza (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide)
- What ART Drugs Prevent HIV Entry into the Human Immune Cell?
- What Are the Single-Tablet ART Regimens for HIV Infection?
- How Do Integrase Strand-Transfer Inhibitors Work in Antiretroviral Therapy for HIV Infection?
- What Are NRTIs in Antiretroviral Therapy For HIV Infection?
- darunavir, TMC-114; Prezista
- Prezcobix (darunavir and cobicistat)
Prevention & Wellness
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References
All sections courtesy of the U.S. Food and Drug Administration