ri-TOE-na-veer

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

• HIV infection (in combination with other antiretrovirals).

• Inhibits the action of HIV protease and prevents the cleavage of viral polyproteins.

• Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.

Absorption: Appears to be well absorbed after oral administration.

Distribution: Poor CNS penetration.

Protein Binding: 98–99%.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 and CYP2D6 isoenzymes; one metabolite has antiretroviral activity; 3.5% excreted unchanged in urine.

Half-life: 3–5 hr.

(plasma concentrations)

*Nonfasting.

Contraindicated in:

• Hypersensitivity
• Concurrent use of alfuzosin, amiodarone, apalutamide, colchicine, dihydroergotamine, dronedarone, ergotamine, flecainide, fluticasone, lomitapide, lovastatin, lurasidone, meperidine, methylergonovine, midazolam (PO), pimozide, propafenone, quinidine, ranolazine, simvastatin, sildenafil (Revatio), St. John's wort, triazolam, or voriconazole
• Lactation: Breastfeeding not recommended in patients with HIV.

Use Cautiously in:

• Hepatic impairment or a history of hepatitis
• Diabetes mellitus
• Hemophilia (↑ risk of bleeding)
• Structural heart disease, conduction abnormalities, ischemic heart disease, or HF (↑ risk of heart block)
• Pedi: Children <1 mo (safety and effectiveness not established).

CV: heart block, orthostatic hypotension, PR interval prolongation, syncope.

Derm: rash, skin eruptions, STEVENS-JOHNSON SYNDROME (SJS), sweating, TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria.

EENT: pharyngitis, throat irritation.

Endo: hyperglycemia.

F and E: dehydration.

GI: abdominal pain, altered taste, anorexia, diarrhea, nausea, vomiting, constipation, dyspepsia, flatulence.

GU: renal impairment.

Metab: fat redistribution, hyperlipidemia.

MS: ↑creatine kinase, myalgia.

Neuro: abnormal thinking, weakness, dizziness, headache, malaise, paresthesia, SEIZURES, somnolence.

Resp: bronchospasm.
Misc: fever, (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS , immune reconstitution syndrome.

Drug-Drug:

• ↑levels and risk of toxicity from some antiarrhythmics (amiodarone, dronedarone, flecainide, pimozide, propafenone, quinidine), ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), fluticasone (inhalation), lomitapide, lurasidone, meperidine, ranolazine, sildenafil (Revatio), alfuzosin, lovastatin, simvastatin, voriconazole, midazolam (oral), and triazolam; concurrent use contraindicated.
• May ↑ colchicine levels; concurrent use in patients with renal or hepatic impairment contraindicated; ↓ dose of colchicine in patients without renal or hepatic impairment.
• Apalutamide may ↓ levels and promote resistance; concurrent use contraindicated.
• ↑levels of maraviroc; ↓ maraviroc dose to 150 mg twice daily.
• ↑levels of clarithromycin; ↓ clarithromycin dose if CCr <60 mL/min.
• ↑levels of rifabutin; ↓ rifabutin dose to 150 mg every other day or 3 times weekly.
• May also ↑ levels and effects of some opioid analgesics (fentanyl, hydrocodone, oxycodone, tramadol); some NSAIDs (diclofenac, ibuprofen, indomethacin); some antiarrhythmics (disopyramide, lidocaine, mexiletine); many antidepressants (amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, nefazodone, sertraline, trazodone, fluoxetine, paroxetine, venlafaxine); some antiemetics (dronabinol, ondansetron); some beta blockers (metoprolol, pindolol, propranolol, timolol); many calcium channel blockers (amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil); some immunosuppressants (cyclosporine, tacrolimus); some antipsychotics (chlorpromazine, haloperidol, perphenazine, risperidone, thioridazine); and also atazanavir, darunavir, fosamprenavir, quinidine, tipranavir, bedaquiline, methamphetamine, and warfarin; dosage ↓ may be necessary.
• May ↑ vincristine and vinblastine levels; consider holding or switching to another antiretroviral regimen that does not contain a CYP3A or P-glycoprotein inhibitor.
• May ↑ dasatinib and nilotinib levels; may need to ↓ doses of dasatinib and nilotinib.
• May ↑ venetoclax and ibrutinib levels and ↑ risk of tumor lysis syndrome; avoid concurrent use.
• May ↑ abemaciclib and neratinib levels and risk of toxicity; avoid concurrent use.
• May ↑ levels and risk of toxicity of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir, ombitasvir, and paritaprevir; avoid concurrent use.
• May ↑ levels of systemic, inhaled, nasal, or ophthalmic corticosteroids (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, or triamcinolone; consider alternative corticosteroid such as beclomethasone or prednisolone.
• ↓levels and effects of hormonal contraceptives, zidovudine, bupropion, and theophylline; dose alteration or alternative therapy may be necessary.
• Levels may be ↑ by clarithromycin or fluoxetine.
• ↑risk of heart block with beta blockers, verapamil, diltiazem, digoxin, or atazanavir.
• May ↑ concentrations of phosphodiesterase type 5 inhibitors, causing hypotension, visual changes, priapism; ↓ starting doses not to exceed 25 mg within 48 hr for sildenafil (Viagra), 2.5 mg every 72 hr for vardenafil and 10 mg every 72 hr for tadalafil.
• May ↑ risk of adverse effects with salmeterol; concurrent use not recommended.
• ↑risk of myopathy with atorvastatin or rosuvastatin; use lowest possible dose of statin.
• May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of ritonavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day.
• May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of ritonavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.
• May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.
• May ↑ quetiapine levels; ↓ quetiapine dose to 1/6 of current dose.
• Dexamethasone may ↓ levels/effects; consider use of alternative corticosteroid, such as beclomethasone or prednisolone.
• Encorafenib and ivosidenib may ↑ risk of QT interval prolongation; avoid concurrent use, if possible. If concurrent use necessary, ↓ dose of encorafenib and ivosidenib.
• Concurrent use with elagolix may ↑ elagolix levels and ↓ ritonavir levels; do use with elagolix 200 mg twice daily for longer than 1 mo; do not use with elagolix 150 mg once daily for longer than 6 mo.
• May ↑ levels of active metabolite of fostamatinib, which can ↑ risk of hepatotoxicity and neutropenia; may need to ↓ dose of fostamatinib.

Drug-Natural Products:

• St. John's wort may ↓ levels and promote resistance; concurrent use contraindicated.

Drug-Food:

• Food↑ absorption.

• PO (Adults): 300 mg twice daily for 2–3 days, then 400 mg twice daily for 2–3 days, then 500 mg twice daily for 2–3 days, then 600 mg twice daily as maintenance.
• PO (Children >1 mo): 250 mg/m² twice daily initially; ↑ by 50 mg/m² twice daily every 2–3 days up to 400 mg/m² twice daily (if unable to get up to 400 mg/m² twice daily, consider alternative antiretroviral therapy).

(Generic available)

• Tablets: 100 mg;
• Oral powder: 100 mg/pkt;

• Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
• Assess patient for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, SJS, TEN), therapy must be discontinued immediately.

• Monitor viral load and CD4 counts regularly during therapy.
  • Monitor for hyperglycemia, new onset diabetes mellitus, or an exacerbation of diabetes mellitus. May cause hyperglycemia.
  • Monitor serum triglycerides and total cholesterol prior to and periodically during therapy. May cause ↑ serum AST, ALT, GGT, total bilirubin, CK, triglycerides, and uric acid concentrations.

• Do not confuse ritonavir with Retrovir.
• PO: Administer with a meal or light snack. DNC: Swallow tablets whole; do not crush, break, or chew. Store tablets at room temperature.
  • Oral powder may be mixed with applesauce, vanilla pudding, water, chocolate milk, or infant formula to reduce the bitter flavor. Administer within 2 hr of preparation or discard.
  • May be administered via feeding tubes compatible with ethanol and propylene glycol, such as silicone and polyvinyl chloride; do not use with polyurethane feeding tubes due to potential incompatibility.
  • If nausea occurs on dose of 600 mg twice daily, may titrate by 300 mg twice daily for 1 day, then 400 mg twice daily for 2 days, then 500 mg twice daily for 1 day, then 600 mg twice daily thereafter.
  • Patients initiating concurrent therapy with nucleoside analogues may have less GI intolerance by initiating ritonavir for 2 wk and then adding the nucleoside analogue.

• Emphasize the importance of taking ritonavir as directed, at evenly spaced times during day. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; do not double doses.
• Instruct patient that ritonavir should not be shared with others.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Inform patient that ritonavir does not cure HIV or prevent associated or opportunistic infections. Ritonavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of ritonavir are unknown at this time.
• Inform patient that ritonavir may cause hyperglycemia. Advise patient to notify health care professional if increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin occurs.
• Instruct patient to notify health care professional immediately if rash occurs.
• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
• Advise patient taking oral contraceptives to use a nonhormonal method of birth control during ritonavir therapy. If pregnancy is suspected notify health care professional promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
• Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

• Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
• Decrease in viral load and improvement in CD4 cell counts.

Norvir