ritonavir


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ritonavir

 [rĭ-ton´ah-vir]
an HIV protease inhibitor that causes the human immunodeficiency virus to form noninfectious particles; used to treat HIV infection and AIDS, administered orally.

ritonavir

Pharmacologic class: Protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category B

FDA Box Warning

• Coadministration with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloids may cause potentially serious or life-threatening adverse events.

Action

Inhibits human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase by binding directly to reverse transcriptase and blocking RNA-dependent and DNA-dependent polymerase activity

Availability

Capsules: 100 mg

Oral solution: 80 mg/ml

Tablets: 100 mg

Indications and dosages

HIV in combination with other antiretrovirals

Adults: Initially, 300 mg P.O. b.i.d.; increase by 100 mg b.i.d. q 2 to 3 days, up to a usual maintenance dosage of 600 mg b.i.d.

Children age 1 month and older: 350 to 400 mg/m2 P.O. b.i.d., not to exceed 600 mg b.i.d. Start with 250 mg/m2 P.O. b.i.d.; increase by 50 mg/m2 P.O. b.i.d. q 2 to 3 days, up to a usual maintenance dosage of 400 mg P.O. b.i.d. If patient doesn't tolerate 400 mg/m2b.i.d. due to adverse reactions, the highest tolerated dose may be used for maintenance therapy, or alternative therapy should be considered.

Children ages 2 and older: 400 mg/m2 b.i.d., not to exceed 600 mg b.i.d. Start with 250 mg/m2 to minimize nausea.

Dosage adjustment

• Concurrent use of other protease inhibitors

Off-label uses

• Chronic hepatitis B

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of alfuzosin, amiodarone, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, lovastatin, methylergonovine, oral midazolam, pimozide, propafenone, quinidine, sildenavir (Revatio, when used for pulmonary arterial hypotension), simvastatin, triazolam, voriconazole, or St. John's wort

Precautions

Use cautiously in:
• hepatic disease, diabetes mellitus, hemophilia types A and B
• underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, cardiomyopathies
• concurrent use with drugs that prolong PR interval (including calcium channel blockers, beta-adrenergic blockers, digoxin, atazanavir)
• concurrent use with drugs for erectile dysfunction (such as sildenafil, tadalafil, vardenafil)
• concurrent use with fluticasone, atorvastatin, lovastatin, simvastatin, and St. John's wort (use not recommended)
• pregnant or breastfeeding patients.

Administration

• Give with meals to increase absorption.
• Mix oral solution with chocolate milk or liquid nutritional supplement to mask taste.
• Know that drug is usually given with other antiretrovirals.

Don't give concurrently with amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, midazolam, pimozide, propafenone, quinidine, terfenadine, or triazolam. Serious interactions may occur.

Adverse reactions

CNS: headache, dizziness, depression, insomnia, drowsiness, asthenia, paresthesia, syncope, malaise

CV: vasodilation, prolonged PR interval

EENT: pharyngitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, flatulence, abdominal pain, anorexia, pancreatitis

Musculoskeletal: myalgia

Skin: diaphoresis, mild skin eruptions, Stevens-Johnson syndrome (rare)

Respiratory: bronchospasm

Other: abnormal taste, fever, pain, allergic reactions including anaphylaxis (rare), immune reconstitution syndrome

Interactions

Drug-drug.Amiodarone, bepridil, cisapride, flecainide, midazolam, pimozide, propafenone, quinidine, triazolam: inhibited metabolism of these drugs, leading to life-threatening reactions (such as arrhythmias, prolonged sedation, and respiratory depression) Amitriptyline, anticoagulants, atovaquone, carbamazepine, clozapine, cyclosporine, desipramine, diltiazem, disopyramide, divalproex, dofetilide, dronabinol, ethinyl estradiol, lamotrigine, phenytoin, sulfamethoxazole, theophylline, zidovudine: increased risk of toxicity of these drugs

Amprenavir: increased amprenavir blood level

Astemizole, cisapride, encainide: increased risk of arrhythmias

Atorvastatin, cerivastatin, lovastatin, simvastatin, terfenadine: increased blood levels of these drugs, increased risk of rhabdomyolysis

Barbiturates, nevirapine, phenytoin, rifamycins: decreased ritonavir blood level

Bupropion: increased risk of seizures

Clarithromycin, efavirenz: increased blood levels of both drugs

Dihydroergotamine, ergonovine, ergotamine, methylergonovine: ergot toxicity

Fluconazole: increased ritonavir blood level

Fluticasone: increased fluticasone exposure resulting in decreased cortisol concentration

Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase, cholesterol, creatine kinase, gamma-glutamyltransferase, triglycerides, uric acid: increased levels

Hematocrit, hemoglobin, neutrophils, red blood cells, white blood cells: decreased levels

Drug-herbs.St. John's wort: decreased ritonavir blood level

Patient monitoring

• Monitor CBC, liver function tests, electrolyte levels, and lipid panel.
• Assess neurologic status closely. Stay alert for depression.
• Monitor bone mineral density in patients with history of pathologic fractures or who are at risk for osteopenia.

Monitor for signs and symptoms of immune reconstitution syndrome, especially during initial phase of combination antiretroviral treatment when patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalo virus, Pneumocystis jiroveci pneumonia, or tuberculosis), which may necessitate further evaluation and treatment.
• Monitor vital signs and watch for syncope.
• Closely monitor nutritional and hydration status.

Patient teaching

• Advise patient to take with meals to increase absorption.
• Encourage patient or caregiver to mix oral solution with chocolate milk or liquid nutritional supplement to mask taste. Tell caregiver that oral solution is recommended for children older than age 1 month who can't swallow capsules or tablets and, when possible, to administer dose using a calibrated dosing syringe.
• Tell patient to swallow tablets whole and not to chew, break, or crush them.
• Tell patient drug may cause numbness, tingling, weakness, and other CNS effects that increase his injury risk. Urge him to use appropriate safety precautions.
• Instruct patient to report depression.
• Advise patient not to take nonprescription drugs or herbal products, particularly St. John's wort, without consulting prescriber.
• Tell female patient not to breastfeed because of risk of serious adverse reactions and possible HIV transmission to infant.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

ritonavir

/ri·to·na·vir/ (rĭ-to´nah-vir) an HIV protease inhibitor used in treatment of HIV infection and AIDS.

ritonavir

(rĭ-tŏn′ə-vîr)
n.
A protease-inhibiting drug usually used in combination with other drugs to suppress the replication of HIV.

ritonavir

a protease inhibitor.
indications It is prescribed in the treatment of acquired immunodeficiency syndrome, as part of a multidrug regimen including at least three antiretroviral drugs.
contraindications Hypersensitivity to ritonavir precludes its use. Concurrent use of any of several other drugs is either contraindicated or warrants caution, including ergot derivatives, benzodiazepine sedative-hypnotics, some antiarrhythmic medications, some HMG-CoA reductase inhibitors (statins), some erectile dysfunction medicines, and some analgesics.
adverse effects Protease inhibitors cause problems with lipid metabolism and lead to hyperlipidemia, hyperglycemia and redistribution of body fat (e.g., buffalo hump), central obesity, breast enlargement, and facial atrophy. Additional side effects often reported include nausea, vomiting, diarrhea, and numbness about the lips.

ritonavir

An HIV-1 protease inhibitor which carves functional proteins from a large precursor molecule. When administered to HIV-infected individuals, HIV load decreases by 2 orders of magnitude; CD4-T cells increase 3-fold.

Mechanism of action
Ritonavir is prescribed with Highly Active Antiretroviral Therapy (HAART) because it inhibits the host enzyme that metabolises other protease inhibitors.

Adverse effects
Asthenia, malaise, diarrhoea, nausea, vomiting, abdominal pain.

ritonavir

Norvir® AIDS A potent HIV protease inhibitor which is combined with reverse transcriptase inhibitors, nucleoside analogues to manage AIDS Adverse effects GI tract complaints–nausea, diarrhea, perioral paresthesiae, ↑ liver function tests, lipodystrophy–↑ glucose, ↑ fat, ↑ abdominal girth, ↓ fatty tissue from face, arms, legs, ↑ TGs, paresthesias. See AIDS, Antiretroviral, Protease inhibitor; Cf Reverse transcriptase inhibitor.

ritonavir

A PROTEASE INHIBITOR drug used in combination with other drugs to treat AIDS. The drug is on the WHO official list. A brand name for ritonavor with lopinavir is Kaletra.
References in periodicals archive ?
Recommended drug combinations in the private sector (8) Dose PI-naive patient PIs Nevirapine Efavirenz Atazanavir/ Not 400 mg/100 mg ritonavir recommended once a day Darunavir/ SD SD ritonavir Lopinavir/ SD SD ritonavir Saquinavir/ SD SD ritonavir Dose PI-experienced patient PIs Nevirapine Efavirenz Atazanavir/ Not 400 mg/100 mg ritonavir recommended Darunavir/ SD SD ritonavir Lopinavir/ 600 mg/150 mg 600 mg/150 mg ritonavir twice daily twice daily Saquinavir/ SD SD ritonavir PI = protease inhibitor; SD = standard dose.
Results from this study revealed that ritonavir 800 mg was administered with saquinavir 800 mg.
I think the gastrointestinal and lipid side effects from ritonavir are not related to inhibition of cytochrome P450 3A4.
Several small studies have evaluated once-daily dosing with 1400mg fosamprenavir and 100mg ritonavir and demonstrated no loss of virological potency or durability and a trend towards improved lipid parameters.
A stock solution containing indinavir sulfate, nelfinavir mesylate, ritonavir, and saquinavir mesylate was prepared in methanol.
Although earlier intervention with combination therapy may provide much more effective treatment, ritonavir in patients with advanced disease and extensive previous antiretroviral use is safe and effective, lowers the risk of Aids complications, and prolongs survival," Dr William Cameron, of Ottawa General Hospital in Canada, said in The Lancet medical journal.
Trial participants were randomized (1:1) to receive a once-daily regimen of cobicistat 150 mg, atazanavir 300 mg and Truvada (n=344) or ritonavir 100 mg, atazanavir 300 mg and Truvada (n=348).
VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin, dosed twice daily.
Fluticasone, a corticosteroid used in children, is known to interact with ritonavir, resulting in high levels of corticosteroids, suppression of the adrenocortical axis and Cushing's syndrome.
The PI atazanavir and its ritonavir booster both are labeled category B.
The FDA approves the PIs ritonavir (Norvir) and indinavir (Crixivan).
New labeling for Desyrel (trazodone hydrochloride) alerts health care professionals to potential drug interactions with ketoconazole, ritonavir, and indinavir.