ritonavir

ROUTE	ONSET	PEAK	DURATION
PO	rapid	4 hr*	12 hr

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: ↑CK, myalgia

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

Resp: bronchospasm

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

Interactions ⬆ ⬇

Drug-drug:

May significantly ↑ 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 significantly ↑ levels and risk of toxicity of colchicine; concurrent use in patients with renal or hepatic impairment contraindicated; ↓ colchicine dose in patients without renal or hepatic impairment.
Apalutamide may ↓ levels and promote resistance; concurrent use contraindicated.
May ↑ levels and risk of toxicity of maraviroc; ↓ maraviroc dose to 150 mg twice daily.
May ↑ levels and risk of toxicity of clarithromycin; ↓ clarithromycin dose if CCr <60 mL/min.
May ↑ levels and risk of toxicity of rifabutin; ↓ rifabutin dose to 150 mg every other day or 3 times weekly.
May ↑ levels and risk of toxicity of certain opioid analgesics (fentanyl, hydrocodone, oxycodone, tramadol); certain NSAIDs (diclofenac, ibuprofen, indomethacin); certain antiarrhythmics (disopyramide, lidocaine, mexiletine); certain antidepressants (amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, nefazodone, sertraline, trazodone, fluoxetine, paroxetine, venlafaxine); certain antiemetics (dronabinol, ondansetron); certain beta blockers (metoprolol, pindolol, propranolol, timolol); certain calcium channel blockers (amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil); certain immunosuppressants (cyclosporine, tacrolimus); certain antipsychotics (chlorpromazine, haloperidol, perphenazine, risperidone, thioridazine); and also atazanavir, darunavir, fosamprenavir, quinidine, tipranavir, bedaquiline, methamphetamine, and warfarin; may need to ↓ dose.
May ↑ levels and risk of toxicity of vincristine and vinblastine; consider holding or switching to another antiretroviral regimen that does not contain a CYP3A or P-glycoprotein inhibitor.
May ↑ levels and risk of toxicity of dasatinib and nilotinib; may need to ↓ doses of dasatinib and nilotinib.
May ↑ levels and risk of tumor lysis syndrome withvenetoclax and ibrutinib; avoid concurrent use.
May ↑ levels and risk of toxicity of abemaciclib and neratinib; avoid concurrent use.
May ↑ levels and risk of toxicity of glecaprevir/pibrentasvir, sofosbuvir/velpatasvir/voxilaprevir, ombitasvir, and paritaprevir; avoid concurrent use.
May ↑ levels and risk of toxicity of systemic, inhaled, nasal, or ophthalmic corticosteroids (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, triamcinolone); consider alternative corticosteroid such as beclomethasone or prednisolone.
May ↓ levels and effectiveness of hormonal contraceptives, zidovudine, bupropion, and theophylline; dose alteration or alternative therapy may be necessary.
Clarithromycin or fluoxetine may ↑ levels and risk of toxicity.
↑risk of heart block with beta blockers, verapamil, diltiazem, digoxin, or atazanavir.
May ↑ levels and risk of toxicity of phosphodiesterase type 5 inhibitors; ↓ 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.
May ↑ risk of myopathy with atorvastatin or rosuvastatin; use lowest possible statin dose.
May ↑ levels and risk of toxicity of bosentan; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan ≥36 hr before initiation of ritonavir and then restart bosentan ≥10 days later at 62.5 mg once daily or every other day.
May ↑ levels and risk of toxicity of tadalafil (Adcirca); initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) ≥24 hr before initiation of ritonavir and then restart tadalafil (Adcirca) ≥7 days later at 20 mg once daily.
May ↑ levels and risk of toxicity of quetiapine; ↓ quetiapine dose to ⅙ of current dose.
Dexamethasone may ↓ levels and effectiveness; 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, ↓ doses of encorafenib and ivosidenib.
Concurrent use with elagolix may ↑ elagolix levels and ↓ ritonavir levels; do not use with elagolix 200 mg twice daily for >1 mo; do not use with elagolix 150 mg once daily for >6 mo.
May ↑ levels and risk of toxicity of active metabolite of fostamatinib, which can ↑ risk of hepatotoxicity and neutropenia; may need to ↓ fostamatinib dose.

Drug-Natural Products:

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

Drug-Food:

Food↑ absorption.

Route/Dosage ⬆ ⬇

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).

Availability ⬆ ⬇

(Generic available)

Tablets: 100 mg
Oral powder: 100 mg/pkt

Assessment ⬆ ⬇

Assess for change in severity of HIV symptoms and for signs/symptoms of opportunistic infections during therapy.
Assess for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). Monitor patients for development of severe cutaneous adverse reactions, such as SJS and TEN, including signs and symptoms of prodrome of fever, malaise, mucosal lesions, progressive skin rash, blisters, lymphadenopathy, conjunctivitis, myalgias, hepatitis, or eosinophilia. If a severe cutaneous adverse reaction is suspected, hold ritonavir until etiology of reaction is determined. Consultation with a dermatologist is recommended. If a severe cutaneous adverse reaction is confirmed, permanently discontinue ritonavir.
Assess cardiac history and ECG at baseline; monitor for PR interval prolongation and 2nd- and 3rd-degree atrioventricular block.

Lab Test Considerations:

Monitor viral load at baseline and with modification of antiretroviral treatment, at 2–8 wk, then every 4–8 wk until values are below the limit of detection (<200 copies/mL), and then every 3–4 mo; if viral loads suppressed for >2 yr, monitoring may be extended to every 6 mo.
Monitor CD4 cell counts at baseline and with modification of antiretroviral treatment and then every 3–6 mo during the 1st 2 yr of treatment and if the CD4 counts are <300 cells/mm³ or viremia develops; if viral loads suppressed for >2 yr, monitoring may be extended to every 12 mo.
- Monitor CBC with differential at baseline then every 3–6 mo or when CD4 testing is done.
Perform hepatitis B and C screening at baseline and with modification of antiretroviral treatment; may repeat screening every 12 mo in high-risk patients if results are negative at baseline.
Monitor ALT, AST, GGT, and total bilirubin at baseline and with modification of antiretroviral treatment and then every 3–4 mo or more frequently if signs of hepatotoxicity develop. May ↑ AST, ALT, GGT, and total bilirubin.
Monitor serum triglycerides and total cholesterol at baseline and then every 6–12 mo during therapy. May ↑ triglycerides.
Monitor fasting blood glucose and A1c at baseline and with modification of antiretroviral treatment and then every 3–6 mo in patients with abnormal values or every 12 mo in patients with normal values. May cause hyperglycemia.
Monitor basic chemistry, uric acid, and CK at baseline and with modification of antiretroviral treatment, at 2–8 wk, and then every 3–6 mo. May CK and uric acid.

Implementation ⬆ ⬇

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 ↓ 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, and 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.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of ritonavir. Emphasize the importance of taking as directed, at evenly spaced times during day. Do not take more than prescribed amount, and do not stop taking without consulting health care provider. Take missed doses as soon as remembered; do not double doses. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
Because of potential for numerous drug interactions with ritonavir, advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider 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 ↓ 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.
Inform patient that ritonavir may cause hyperglycemia. Advise patient to notify health care provider if ↑ thirst or hunger; unexplained weight loss; ↑ urination; fatigue; or dry, itchy skin occurs.
Warn patient to report symptoms of arrhythmias and PR prolongation (fast heartbeat, skipped beats, palpitations, dizziness, light-headedness, trouble breathing, faintness).
Instruct patient to notify health care provider 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.
Rep: Advise women of reproductive potential taking oral contraceptives to use a nonhormonal method of birth control during ritonavir therapy. If pregnancy is suspected, notify health care provider promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise women of reproductive potential to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇