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Drugs reference index «Indinavir Sulfate»

Indinavir Sulfate


Indinavir Sulfate

Pronunciation: (in-DIN-ah-veer SULL-fate)Class: Protease inhibitor

Trade Names:Crixivan- Capsules 100 mg- Capsules 200 mg- Capsules 333 mg- Capsules 400 mg

Pharmacology

Inhibits human immunodeficiency virus (HIV) protease, the enzyme that cleaves viral polyprotein precursors into functional proteins in HIV-infected cells. Inhibition of this enzyme by indinavir results in formation of immature noninfectious viral particles.

Pharmacokinetics

Absorption

T max is approximately 0.8 h (fasting). C max is approximately 12,617 nanomolars. The AUC at steady state is approximately 30,691 nanomolars•h. Administration with a high calorie, fat, and protein meal reduced AUC approximately 77% and C max approximately 84%.

Distribution

60% is protein bound.

Metabolism

There are 7 metabolites: 1 glucuronide conjugate and 6 oxidative metabolites. CYP3A4 is major enzyme responsible for formation of oxidative metabolites.

Elimination

The t ½ is approximately 1.8 h. Approximately 83% is excreted in the urine and approximately 19% in the feces.

Special Populations

Hepatic Function Impairment

Mild to moderate: decreased metabolism resulting in an approximate increase in AUC of 60% and increased t ½ to approximately 2.8 h.

Children

AUC and C max slightly increased and trough concentration were considerably lower.

Gender

Females have decreased AUC (13%) and C max (13%).

Indications and Usage

Treatment of HIV infection in combination with other antiretroviral agents.

Contraindications

Concomitant therapy with amiodarone, cisapride, ergot derivatives, midazolam, pimozide, or triazolam; hypersensitivity to any component of product.

Dosage and Administration

Adults

PO 800 mg (two 400 mg capsules) every 8 h.

Dosage Adjustment in Hepatic InsufficiencyAdults

PO Mild-to-moderate hepatic insufficiency caused by cirrhosis: 600 mg every 8 h.

General Advice

  • Administer with water on an empty stomach, 1 h before or 2 h after a meal.
  • If necessary may be administered with skim milk, juice, coffee, tea, or with a light meal. Ensure adequate hydration (48 oz of liquid in 24 h).
  • Do not administer with meal high in calories, fat, or protein.

Storage/Stability

Store in original container with desiccant at controlled room temperature (59° to 86°F). Keep tightly closed. Store unit-dose packages at controlled room temperature. Protect from moisture.

Drug Interactions

Amiodarone, cisapride, ergot derivative (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, triazolam

Because of potential life-threatening reactions, concomitant use with indinavir is contraindicated.

Antiarrhythmic agents (eg, bepridil, quinidine, systemic lidocaine)

Concentrations of these agents may be elevated; monitoring of antiarrhythmic agent concentration is recommended.

Anticonvulsant agents (carbamazepine, phenobarbital, phenytoin)

Indinavir concentrations may be decreased, reducing the therapeutic effect.

Atazanavir

Coadministration with indinavir is not recommended because both agents are associated with indirect hyperbilirubinemia.

Atorvastatin

Atorvastatin concentration may be elevated.

Clarithromycin

Plasma concentration may be elevated by indinavir, increasing the risk of adverse effects.

Clarithromycin, nelfinavir, ritonavir

Indinavir concentrations may be increased; the appropriate dose of indinavir is not known.

Cyclosporine, sirolimus, tacrolimus

Plasma concentrations may be elevated by indinavir, increasing the therapeutic and adverse effects.

Delavirdine, itraconazole, ketoconazole

Indinavir dosage reduction (600 mg every 8 h) should be considered because concentrations may be elevated.

Didanosine

Administration of indinavir and didanosine formulations containing buffer should be separated by at least 1 h and given on an empty stomach.

Dihydropyridine calcium channel blockers (eg, felodipine, nicardipine, nifedipine)

Concentrations of these agents may be increased by indinavir; clinical monitor is recommended.

Efavirenz, nevirapine

Indinavir concentration may be reduced; the optimal dose of indinavir is not known.

HMG-CoA Reductase inhibitors (eg, lovastatin, simvastatin)

Coadministration with indinavir is not recommended because of increased risk of myopathy including rhabdomyolysis.

Rifabutin

When coadministered with indinavir, a dose reduction of rifabutin to 50% the standard dose and an increase of indinavir to 1,000 mg every 8 h is recommended.

Rifampin, St. John's wort

Coadministration is not recommended because indinavir serum levels may be reduced, decreasing the clinical effect and possibly leading resistance to indinavir or the class of protease inhibitors.

Ritonavir, saquinavir

Concentrations of these medications may be increased.

Sildenafil, tadalafil, vardenafil

Indinavir may increase concentrations of these agents; dosage reduction is necessary.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina pectoris, cerebrovascular disorder, MI (postmarketing).

CNS

Headache (5%); dizziness (3%); asthenia/fatigue, malaise, somnolence (2%); oral paresthesia, depression (postmarketing).

Dermatologic

Pruritus (4%); rash (1%); erythema multiforme, Stevens Johnson syndrome, hyperpigmentation, alopecia, ingrown toenails, paronychia (postmarketing).

EENT

Taste perversion (3%).

GI

Abdominal pain (17%); nausea (12%); vomiting (8%); acid regurgitation, anorexia, diarrhea (3%); increased appetite, dyspepsia (2%); abdominal distension (postmarketing).

Genitourinary

Nephrolithiasis/urolithiasis (9%); dysuria (2%); renal insufficiency, acute renal failure, pyelonephritis with or without bacteremia, interstitial nephritis sometimes with indinavir crystal deposits, crystalluria, dysuria (postmarketing).

Hematologic-Lymphatic

Anemia (1%); increased spontaneous bleeding in patients with hemophilia (postmarketing).

Hepatic

Jaundice (2%); liver function abnormalities, hepatitis, hepatic failure, pancreatitis (postmarketing).

Hypersensitivity

Anaphylactoid reactions, urticaria, vasculitis (postmarketing).

Lab Tests

Increased serum bilirubin (12%); increased ALT (5%); increased AST (4%); decreased neutrophils, increased serum amylase (2%); decreased hemoglobin, decreased platelet count, increased glucose (1%); increased serum cholesterol and triglycerides (postmarketing).

Metabolic-Nutritional

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia (postmarketing).

Musculoskeletal

Back pain (8%); arthralgia (postmarketing).

Respiratory

Cough (2%).

Miscellaneous

Fever (2%); redistribution/accumulation of body fat (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined. HIV-infected mothers should not breast-feed to avoid risking potential transmission of HIV to infant.

Children

Safety and efficacy not established.

Elderly

Dose selection should be cautious, reflecting greater frequency of decreased hepatic, renal, or cardiac function.

Fat redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance have been reported.

Hemolytic anemia

Acute hemolytic anemia, including cases resulting in death, have been reported. Discontinue indinavir and treat appropriately if hemolytic anemia occurs.

Hemophilia

Spontaneous bleeding and increased need for factor VIII has been reported in patients with hemophilia A and B treated with protease inhibitors.

Hepatic insufficiency/Cirrhosis

Lower indinavir doses may be required because indinavir is hepatically metabolized.

Hepatitis

Hepatitis, including cases resulting in death, have been reported during treatment with indinavir.

Hyperbilirubinemia

Indirect hyperbilirubinemia has occurred frequently during treatment with indinavir; increases in serum transaminases has occurred infrequently.

Hyperglycemia

New onset diabetes mellitus, exacerbation of preexisting diabetes, and hyperglycemia have been reported in patients receiving protease inhibitor therapy.

Immune reconstitution syndrome

Has been reported in patients treated with combination antiretroviral therapy.

Nephrolithiasis/Urolithiasis

Has occurred, more commonly in pediatric than adult patients. Temporarily interrupt therapy (eg, 1 to 3 days) if signs or symptoms of nephrolithiasis/urolithiasis occur (flank pain, with or without hematuria or microscopic hematuria).

Tubulointerstitial nephritis

Tubulointerstitial nephritis with medullary calcification and cortical atrophy have been reported in patients with asymptomatic severe leukocyturia (greater than 100 cells/high power field). Follow patients closely, frequently monitor with urinalysis, and consider discontinuing indinavir in patients who develop asymptomatic severe leukocyturia.

Overdosage

Symptoms

Nephrolithiasis/urolithiasis, flank pain, hematuria, nausea, vomiting, diarrhea.

Patient Information

  • Explain name, dose, action, potential side effects of drug, and special storage requirements (store in original container with desiccant and keep tightly closed).
  • Advise patient or caregiver to read the Patient Information leaflet before starting therapy and with each refill.
  • Warn patient that this drug is not to be used by itself but is combined with other antiviral agents and not to change the dose or stop taking any other antiviral agents, unless advised by their health care provider.
  • Instruct patient to take indinavir exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
  • Advise patient to take prescribed dose with water on an empty stomach 1 h before or 2 h after meals. Advise patient that if stomach upset occurs medication may be taken with other liquids (eg, skim milk, juice, coffee or tea), or with a light meal (eg, dry toast with jelly, skim milk, juice, coffee with skim milk and sugar; or corn flakes with skim milk and sugar) Caution patient that taking indinavir with a meal high in calories, fat, and protein reduces absorption and effectiveness of indinavir.
  • Advise patient that if a dose is missed to take the dose as soon as possible and then return to the normal schedule. However, if a dose is skipped caution patient not to double the dose to catch up but to continue with their normal schedule.
  • Advise patient to maintain good hydration and that adults should drink at least 48 oz of liquids every day.
  • Advise patient that indinavir may cause changes in body fat distribution (eg, increased amount of fat in upper back and neck, breasts, and around the back, chest and stomach area; or loss of fat from arms, legs and face) and that the cause and long-term health effects of these changes are not know at this time. Advise patient to report changes in body fat distribution to health care provider.
  • Inform patient that indinavir does not completely eliminate HIV virus and therefore does not reduce risk of transmitting HIV to others. Appropriate precautions (eg, practice safer sex using a latex or polyurethane condom to lower chance of sexual contact with semen, vaginal secretions, or blood; not using or sharing dirty needles) must still be followed.
  • Advise patient that indinavir is not a cure for HIV infection and illnesses associated with HIV infection, including opportunistic infections, may continue to be acquired. Patient should remain under a physician's care.
  • Instruct patient to not take any prescription or OTC medications, herbal preparations, or dietary supplements, particularly St. John's wort, unless advised by health care provider. Caution patient not to start any new medication or dietary supplement without talking to health care provider first.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding. Caution HIV-infected mother that breastfeeding could cause HIV infection in the baby.
  • Remind patient that examinations and laboratory tests will be required to monitor therapy and to keep appointments.

Copyright © 2009 Wolters Kluwer Health.

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