Hyperglycemia, new onset of diabetes mellitus, or diabetic ketoacidosis have been reported with protease inhibitors (PI); it is not clear if pregnancy increases this risk. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Mechanism of Action Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. Because of its mechanism of action, ritonavir is currently under investigation . Consider alternative antimicrobial for a non-MAC infection. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times a day (for adults). Management: Monitor closely for signs and symptoms of vinblastine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Monitor therapy, Calcium Channel Blockers (Nondihydropyridine): Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Temporary or permanent discontinuation may be clinically indicated. Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Management: Monitor for decreased bupropion effects. Solution: Consider mixing oral solution with chocolate milk or a liquid nutritional supplement and taking within 60 minutes to improve taste. Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat. Avoid combination, Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Monitor therapy, Estrogen Derivatives (Contraceptive): Protease Inhibitors may decrease the serum concentration of Estrogen Derivatives (Contraceptive). 1. Plasma levels are lower during pregnancy compared to postpartum; however, dosage adjustment is not needed when used as a low-dose booster in pregnant females. Avoid exposure to excessive heat. Lopinavir is a novel protease inhibitor (PI) developed from ritonavir. Avoid combination, Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Avoid combination, Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Monitor therapy, Propafenone: Ritonavir may increase the serum concentration of Propafenone. Temporarily stop bosentan (for at least 36 hrs) before starting ritonavir; wait until at least 10 days on ritonavir before restarting. Exceptions discussed in separate monograph. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. Avoid combination, Fosphenytoin: May decrease the serum concentration of Ritonavir. Avoid combination, Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Consider therapy modification, Mebendazole: Ritonavir may decrease the serum concentration of Mebendazole. Avoid combination, Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Consider therapy modification, Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Consider therapy modification, Enfortumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enfortumab Vedotin. Avoid concurrent use in patients with impaired hepatic or renal function. Avoid combination, Tricyclic Antidepressants: Protease Inhibitors may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy, Elagolix: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Consider therapy modification, Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Saquinavir is an HIV-1 protease inhibitor used in combination with ritonavir and other antiretrovirals for the treatment of human immunodeficiency virus-1 (HIV-1) infection. Exceptions are discussed in separate monograph. Consider therapy modification, Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Monitor therapy, Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Monitor serum lipase and amylase, and for symptoms of nausea, vomiting, and/or abdominal pain. Reduced venetoclax doses are required during ramp-up for patients with AML, and reduced doses are required for all patients during maintenance therapy. Avoid combination, Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination, Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. Management: See full monograph for recommended dose limits. Monitor tacrolimus concentrations closely to determine dose; doses of tacrolimus 0.5 mg to 1 mg every week may be adequate. Management: Concurrent voriconazole and high-dose ritonavir (adult doses of 400 mg every 12 hrs or greater) is contraindicated. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Consider therapy modification, Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Management: Combined use is considered contraindicated per US labeling. Management: If such combinations cannot be avoided, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Protect from light. Avoid combination, Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. "Vitamn C njdete v ovoc, ako s pomarane a jahody, a vitamn E v . Avoid combination, Simvastatin: Protease Inhibitors may increase the serum concentration of Simvastatin. The tour begins on Aug. 3 in Sterling Heights, Mi. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. Consider therapy modification, Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Generic Name Lopinavir DrugBank Accession Number DB01601 Background. Tablet: Store at 30C (86F); exposure to temperatures 50C (122F) permitted for 7 days. Exceptions are discussed in separate monographs. Preterm neonates: Oral solution contains ethanol and propylene glycol; ethanol competitively inhibits propylene glycol metabolism; preterm infants may be at increased risk of toxicity due to decreased ability to metabolize propylene glycol. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. Avoid combination, Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Consider therapy modification, Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. 7 Following oral administration of a single 600mg dose of radiolabeled ritonavir, approximately 11.3 2.8% of the dose was excreted into the urine, of which 3.5 1.8% was unchanged parent drug. Monitor therapy, CloZAPine: CYP1A2 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy, Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Monitor therapy, Pimozide: Protease Inhibitors may increase the serum concentration of Pimozide. Avoid combination, Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor. Amiodarone use should be avoided with lopinavir/ritonavir, but if the combination must be used, monitor closely for increased amiodarone serum concentrations and effects. Additional factor VIII may be needed. Ritonavir is a HIV protease inhibitor routinely prescribed to HIV patients that also potently inactivates cytochrome P4503A4 (CYP3A4), the major human drug-metabolizing enzyme. Solution: Lopinavir 520 mg/ritonavir 130 mg (6.5 mL) twice daily. Management: See full interaction monograph. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Avoid combination, Flurazepam: Ritonavir may increase the serum concentration of Flurazepam. Adolescents: Note: Ritonavir as sole protease inhibitor is no longer commonly used in clinical practice and is not recommended in any initial antiretroviral regimen (HHS [adults] 2015): 600 mg twice daily; may use a dose titration schedule to reduce adverse events (nausea/vomiting) by initiating therapy at 300 mg twice daily; increase dose at 2- to 3-day intervals by 100 mg twice daily increments up to a maximum dose of 600 mg twice daily. Diabetes: Hyperglycemia, exacerbation of diabetes, diabetic ketoacidosis, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors. Consider therapy modification. Administration with food may lessen bitter aftertaste. Monitor therapy, CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. This effect has been seen with lopinavir/ritonavir. Monitor therapy, BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. HIV-1 nonoccupational postexposure prophylaxis (nPEP): Oral: 100 mg once daily for 28 days (in combination with other antiretroviral agents). Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. This similarity protects cGMP from degradation because sildenafil can bind to the catalytic site to act as a competitive inhibitor of cGMP-specific PDE-5, the enzyme that normally catalyzes the breakdown of vasodilatory cGMP. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. Monitor therapy, Cobicistat: May enhance the therapeutic effect of Ritonavir. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. When combined use is required, reduce the ivosidenib dose to 250 mg once daily. Consider therapy modification, Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Management: Consider alternatives to this combination when possible. Consider therapy modification, Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Monitor therapy, Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Consider therapy modification, Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. Saquinavir is a selective, peptidomimetic HIV protease inhibitor of the hydroxyethylamine class. Consider therapy modification, Mirtazapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. Consider therapy modification, Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Avoid combination, Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Consider therapy modification, SUNItinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Avoid combination, Methadone: Ritonavir may decrease the serum concentration of Methadone. Monitor therapy, Digoxin: Ritonavir may increase the serum concentration of Digoxin. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. Consider therapy modification, Glecaprevir and Pibrentasvir: Ritonavir may increase the serum concentration of Glecaprevir and Pibrentasvir. Consider therapy modification, Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit. Avoid combination, QuiNINE: Ritonavir may decrease the serum concentration of QuiNINE. Avoid combination, Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Exceptions discussed separately. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib, if possible. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Management: Monitor closely for signs and symptoms of vincristine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Management: Use bosentan 62.5 mg daily or every other day in adult patients who have been on ritonavir for at least 10 days. [3] [4] [5] This combination treatment is known as highly active antiretroviral therapy (HAART). Consider therapy modification, Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Avoid combination, Voriconazole: Ritonavir may decrease the serum concentration of Voriconazole. This is only a brief summary of general information about this medicine. Avoid combination, Piperaquine: CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. Monitor therapy, Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Monitor therapy, DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Monitor therapy, Sildenafil: Protease Inhibitors may increase the serum concentration of Sildenafil. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. HIV-1 infection, treatment: Oral (Note: Not recommended as the primary protease inhibitor in any regimen (HHS [adult] 2017): 600 mg twice daily. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Consider therapy modification, Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy, LamoTRIgine: Ritonavir may decrease the serum concentration of LamoTRIgine. In those with normal renal and hepatic function, reduce colchicine dose as directed. Patients receiving such a combination should also be monitored extra closely for signs or symptoms of hypotension. Consider therapy modification, Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Avoid combination, Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Consider therapy modification, Eluxadoline: Ritonavir may increase the serum concentration of Eluxadoline. Human immunodeficiency virus (HIV) is a virus that strikes the immune system, making it difficult for the body to fight infections and diseases. Consider therapy modification, Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Capsule: Store under refrigeration at 2C to 8C (36F to 46F); may be left out at room temperature of <25C (<77F) if used within 30 days. Note: Norvir capsules have been discontinued in the United States for more than 1 year. Consider therapy modification, Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Consult appropriate manufacturer labeling. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification, Albendazole: Ritonavir may decrease the serum concentration of Albendazole. Both drugs must be taken together, for all of the doses, and for the full 5 days. Oral solution: The oral solution contains large amounts of ethanol (43.2%) and propylene glycol (26.57%). Avoid combination, Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. Monitor therapy, Valbenazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Dosage adjustment for combination therapy with carbamazepine, phenobarbital, phenytoin: Once-daily dosing not recommended. Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Avoid combination, Tacrolimus (Systemic): Ritonavir may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy, PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Ritonavir should only be used as a low-dose booster; when used as a pharmacologic booster for other PIs, ritonavir is the preferred pharmacologic booster for use in pregnancy. Management: Reduce afatinib by 10 mg if not tolerated. Consider therapy modification, Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. This may result in QTc prolongation and malignant cardiac arrhythmias. Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes. Monitor therapy, Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Monitoring of pregnant females is more frequent than in nonpregnant adults. Consider therapy modification, LinaGLIPtin: Ritonavir may increase the serum concentration of LinaGLIPtin. Significant bupropion dose adjustments may be necessary to maintain adequate response. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Monitor therapy, CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy, Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Monitor therapy, Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Management: Consider alternatives to, or reduced doses of, nefazodone in patients treated with HIV protease inhibitors. Consider therapy modification, Bictegravir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. Exceptions are discussed separately. Pancreatitis: Use with caution in patients with increased triglycerides; pancreatitis has been observed (including fatalities). Hepatic impairment: Use is not recommended in patients with severe hepatic impairment (Child-Pugh class C). Consider therapy modification, Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Monitor therapy, Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Consider therapy modification, Dofetilide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. Ritonavir may increase the serum concentration of ARIPiprazole. Avoid combination, Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Avoid combination, Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Monitor therapy, Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Per US prescribing information, avoid this combination. Consider therapy modification, Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Fat redistribution: May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. Consider therapy modification, Rifabutin: Ritonavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Avoid combination, Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Consider therapy modification, Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Avoid combination, Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Ritonavir may decrease the serum concentration of Fosphenytoin. Avoid combination, Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. May consider dose titration schedule to reduce the risk of treatment related adverse events; initiate at a dose of 300 mg twice daily, then increase by 100 mg twice daily every 2 to 3 days to recommended dosage of 600 mg twice daily (maximum: 600 mg twice daily). If combined use cannot be avoided, the pexidartinib dose should be reduced. Avoid combination, Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. Consider therapy modification, Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Avoid combination, Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Note: Norvir tablets are not bioequivalent to Norvir capsules. Consider ethanol content of all medications being administered; monitor for toxicity particularly in pediatric patients. The Health and Human Services (HHS) perinatal HIV guidelines do not recommend treatment doses of ritonavir in pregnant women. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with astemizole, bepridil, fusidic acid, neratinib, rivaroxaban, salmeterol, terfenadine, vardenafil, venetoclax (during dose initiation and the ramp-up phase), or voriconazole (regardless of ritonavir dose). Consider therapy modification, MetroNIDAZOLE (Systemic): Ritonavir may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Management: The ritonavir Canadian labeling states this combination should not be used. Management: Avoid concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. Monitor therapy, Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. 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