Drugs Information Online
Drugs and diseases reference index

Drugs and diseases reference index
Search
EN

Drugs A-Z List

Diseases & Conditions A-Z List

Herbs & Supplements

Medical Dictionary

Full Article

Popular Drugs

Popular Diseases & Conditions

Drugs reference index «Atazanavir Sulfate»

Atazanavir Sulfate

Pronunciation: (A-ta-ZAN-a-vir SUL-fate)Class: Protease inhibitor

Trade Names:Reyataz- Capsules 100 mg- Capsules 150 mg- Capsules 200 mg- Capsules 300 mg

Pharmacology

Inhibits HIV protease, the enzyme required to form functional proteins in HIV-infected cells.

Pharmacokinetics

Absorption

Rapidly absorbed with a T max of approximately 2.5 h. Mean C max is 3,152 ng/mL. Mean AUC is 22,262 ng•h/mL. Mean C min is 273 ng/mL.

Distribution

Serum protein binding is 86%; distributes into the CSF and semen.

Metabolism

Extensively metabolized. The major pathways are mono-oxygenation and dioxygenation. Minor pathways of metabolism are glucuronidation, N-dealkylation, hydrolysis, and oxygenation with dehydrogenation. In vitro studies using human liver microsomes suggest that atazanavir is metabolized by CYP3A.

Elimination

Elimination is 79% in the feces (20% unchanged) and 13% in the urine (7% unchanged). Mean elimination half-life is 7 h at steady state.

Special Populations

Renal Function Impairment

No data available.

Hepatic Function Impairment

Increased concentrations are expected in patients with moderate to severe hepatic function impairment.

Indications and Usage

In combination with other antiretroviral agents for the treatment of HIV-1 infection.

Contraindications

Drugs that are highly dependent on CYP3A or UGT1A1 for Cl and for which elevated plasma levels are associated with serious and/or life-threatening events (eg, cisapride, ergot derivative, indinavir, irinotecan, lovastatin, midazolam, pimozide, rifampin, simvastatin, St. John's wort, triazolam); hypersensitivity to any component of the product.

Dosage and Administration

Therapy-Naive Adult PatientsAdults

PO The recommended dose is atazanavir 300 mg with ritonavir 100 mg once daily as a single dose with food or for patients who are unable to tolerate ritonavir, the recommended dosage is atazanavir 400 mg, without ritonavir, once daily with food.

Concomitant Therapy

Atazanavir 300 mg with ritonavir 100 mg once daily (all as a single dose with food) if combined with any of the following: tenofovir, H 2 -receptor antagonist, proton-pump inhibitors, or efavirenz.

H 2 -receptor antagonist

The H 2 -receptor antagonist dosage should not exceed a dosage comparable with famotidine 40 mg twice daily. Atazanavir 300 mg and ritonavir 100 mg should be given simultaneously with, and/or at least 10 h after, the dose of the H 2 -receptor antagonist. For patients unable to tolerate ritonavir, atazanavir 400 mg once daily with food should be administered at least 2 h before and at least 10 h after the H 2 -receptor antagonist. For these patients, no single dose of H 2 -receptor antagonist should exceed a dose comparable with famotidine 20 mg, and the total daily dose should not exceed a dose comparable with famotidine 40 mg.

Proton-pump inhibitors

The proton-pump inhibitor dose should not exceed a dose comparable with omeprazole 20 mg and must be taken approximately 12 h prior to the atazanavir 300 mg and ritonavir 100 mg dose.

Efavirenz

If atazanavir is combined with efavirenz, atazanavir 400 mg with ritonavir 100 mg should be administered once daily as a single dose with food, and efavirenz should be administered on an empty stomach, preferably at bedtime.

Therapy-Experienced Adult PatientsAdults

PO The recommended dose is atazanavir 300 mg with ritonavir 100 mg once daily, all as a single dose with food.

Concomitant therapy H 2 -receptor antagonist

Whenever an H 2 -receptor antagonist is given to a patient receiving atazanavir with ritonavir, the H 2 -receptor antagonist dose should not exceed a dose comparable with famotidine 20 mg twice daily, and the atazanavir and ritonavir doses should be given simultaneously with, and/or 10 h after, the dose of H 2 -receptor antagonist. If taken with an H 2 -receptor antagonist, administer atazanavir 300 mg with ritonavir 100 mg once daily, all as a single dose with food. If taken with both an H 2 -receptor antagonist and tenofovir, administer atazanavir 400 mg with ritonavir 100 mg once daily, all as a single dose with food.

Proton-pump inhibitors

Proton-pump inhibitors should not be used in treatment-experienced patients receiving atazanavir.

Efavirenz

Do not coadminister atazanavir with efavirenz in treatment-experienced patients because of decreased atazanavir exposure.

Therapy-Naive ChildrenChildren 6 to younger than 18 yr of age

PO Dosage should not exceed the recommended adult dosage. For treatment-naive patients who are 13 yr of age and older and at least 39 kg who are unable to tolerate ritonavir, the recommended dosage is atazanavir 400 mg, without ritonavir, once daily with food.

15 to less than 25 kg

Administer atazanavir 150 mg with ritonavir 80 mg once daily with food.

25 to less than 32 kg

Administer atazanavir 200 mg with ritonavir 100 mg once daily with food.

32 to less than 39 kg

Administer atazanavir 250 mg with ritonavir 100 mg once daily with food.

At least 39 kg

Administer atazanavir 300 mg with ritonavir 100 mg once daily with food.

Therapy-Experienced ChildrenChildren 6 to younger than 18 yr of age

PO Dosage should not exceed the recommended adult dosage.

25 to less than 32 kg

Administer atazanavir 200 mg with ritonavir 100 mg once daily with food.

32 to less than 39 kg

Administer atazanavir 250 mg with ritonavir 100 mg once daily with food.

At least 39 kg

Administer atazanavir 300 mg with ritonavir 100 mg once daily with food.

Renal ImpairmentAdults

PO Treatment-naive patients with end-stage renal disease managed with hemodialysis should receive atazanavir 300 mg with ritonavir 100 mg. No dosage adjustment is needed in patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis.

Hepatic Function ImpairmentAdults

PO Use with caution in patients with mild to moderate hepatic function impairment. Consider a dosage reduction to 300 mg/day in patients with moderate hepatic function impairment. Do not use in patients with severe hepatic function impairment. Atazanavir with ritonavir use is not recommended in patients with hepatic function impairment.

General Advice

  • Must be taken with food.
  • Data are insufficient to recommend atazanavir without ritonavir in patients younger than 13 yr of age.
  • In children, data are insufficient to recommend atazanavir in treatment-experienced patients with body weight less than 25 kg.
  • Atazanavir should not be administered to treatment-experienced patients with end-stage renal failure managed with hemodialysis.

Storage/Stability

Store capsules at 59° to 86°F.

Drug Interactions

Alfentanyl, antiarrhythmic agents (eg, amiodarone, quinidine, systemic lidocaine), buprenorphine, calcium channel blockers (eg, bepridil, diltiazem, felodipine), carbamazepine, fentanyl, fluticasone, HMG-CoA reductase inhibitors (ie, atorvastatin, lovastatin, simvastatin), immunosuppressive agents (ie, cyclosporine, sirolimus, tacrolimus), irinotecan, itraconazole, ixabepilone, ketoconazole, oral contraceptives (eg, ethinyl estradiol, norethindrone), protease inhibitors, rifabutin, rosuvastatin, saquinavir, sildenafil, sufentanil, tadalafil, tenofovir, trazodone, tricyclic antidepressants, vardenafil, warfarin

Atazanavir may increase plasma levels of these agents, increasing the risk of toxicity and, in some instances, life-threatening reactions. Up to a 75% reduction in the rifabutin dose is recommended. Consider a 50% reduction in the diltiazem dose and titrate the dose of other calcium channel blockers. Use sildenafil with caution and at a reduced dosage of 25 mg every 48 h and monitor for adverse reactions. Concomitant use of atazanavir is not recommended with lovastatin, simvastatin, and irinotecan.

Antacids and buffered medications (eg, didanosine buffered preparation), efavirenz, H 2 -receptor antagonists, nevirapine, proton pump inhibitors (eg, omeprazole), tenofovir

May reduce atazanavir plasma levels, decreasing the therapeutic effect. Coadministration of nevirapine or proton pump inhibitors with atazanavir is not recommended. Do not coadminister atazanavir without ritonavir with efavirenz or tenofovir.

Azole antifungal agents, clarithromycin, ritonavir

Atazanavir plasma levels are increased.

Cisapride, ergot derivatives (eg, ergotamine), indinavir, irinotecan, lovastatin, midazolam, pimozide, rifampin, simvastatin, St. John's wort, triazolam

Coadministration with atazanavir is contraindicated because of serious or life-threatening adverse reactions.

Clarithromycin

Plasma levels of clarithromycin may be elevated by atazanavir, which may result in QTc prolongation. Use a 50% reduction in clarithromycin dose. In addition, levels of the active metabolite (14-OH clarithromycin) may be reduced. Use alternative therapy for indications other than Mycobacterium avium complex.

Didanosine

Atazanavir and didanosine should not be administered at the same time. Give atazanavir with food 2 h before or 1 h after didanosine buffered formulation. Administration of didanosine enteric-coated capsule simultaneously with atazanavir with food will decrease didanosine exposure; therefore, give atazanavir and didanosine enteric-coated capsules at different times.

Lapatinib

Avoid coadministration.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Left bundle branch block, QTc prolongation, second-degree AV block, third-degree AV block (postmarketing).

CNS

Headache (7%); peripheral neurologic symptoms (4%); insomnia (3%); depression, dizziness (2%).

Dermatologic

Rash (14%); alopecia, maculopapular rash, pruritus (postmarketing).

GI

Nausea (14%); diarrhea, vomiting (8%); abdominal pain (4%); pancreatitis (postmarketing).

Genitourinary

Nephrolithiasis (postmarketing).

Hepatic

Jaundice/scleral icterus (13%); cholecystitis, cholelithiasis, cholestasis, hepatic function abnormalities (postmarketing).

Lab Tests

Altered laboratory tests, including ALT, amylase, AST, creatine kinase, glucose, HDL and LDL cholesterol, hemoglobin, lipase, neutrophils, platelets, total bilirubin, total cholesterol, and triglycerides.

Metabolic-Nutritional

Diabetes mellitus, hyperglycemia (postmarketing).

Musculoskeletal

Myalgia (4%); arthralgia (postmarketing).

Respiratory

Cough (21%); rhinorrhea (6%).

Miscellaneous

Fever (19%); edema (postmarketing).

Precautions

Monitor

Monitor ECG at baseline and periodically thereafter. Monitor glucose, lipids, and LFTs. Monitor CD4+ cell count and HIV RNA load. Monitor patient for signs and symptoms of lactic acidosis.

Pregnancy

Category B .

Lactation

Undetermined. HIV-infected mothers should not breast-feed their infants.

Children

Safety and efficacy not established in children younger than 3 mo of age.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Renal Function

Atazanavir should not be administered to HIV-treatment–experienced patients with end-stage renal disease managed with hemodialysis.

Hepatic Function

Use with caution (see Administration and Dosage).

CV

Prolongation of the PR interval in the ECG has been reported. Use with caution in patients with preexisting conduction system disease (eg, marked first-degree AV block or second- or third-degree AV block).

Diabetes mellitus/hyperglycemia

New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitor therapy.

Fat redistribution

Redistribution and accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, have occurred in patients receiving antiretroviral therapy.

Hemophilia

Increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B has occurred in patients treated with protease inhibitors.

Hyperbilirubinemia

Asymptomatic elevations in indirect bilirubin occur in most patients.

Immune reconstitution syndrome

Has been reported; patients may develop an inflammatory response to indolent or residual opportunistic infections during initial phase of combination antiretroviral treatment.

Resistance/Cross-resistance

Various degrees of cross-resistance between protease inhibitors have been observed.

Overdosage

Symptoms

Asymptomatic bifascicular block, hyperbilirubinemia, jaundice, PR interval prolongation.

Patient Information

  • Advise patient 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 health care provider.
  • Instruct patient to take atazanavir exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
  • Advise patient to take prescribed dose once daily, at about the same time each day, and to swallow capsules whole. Caution patient not to crush, chew, or open capsules.
  • Advise patient to take each dose with food or snack to increase absorption and effectiveness.
  • Advise patient that if a dose is missed to take it as soon as possible and then return to the normal schedule. However, if it is within 6 h of the next dose, advise patient to skip the missed dose and take the next dose at the regular time. If a dose is skipped, caution patient not to double the dose to catch up but to continue with the normal schedule.
  • Instruct patient taking antacids or didanosine chewable/dispersible buffered tablets to take atazanavir 2 h before or 1 h after these medicines.
  • Instruct patient to report the following symptoms immediately to health care provider: dizziness, light-headedness, palpitations (pounding in the chest), persistent nausea or vomiting, profound weakness or tiredness, unexpected stomach discomfort, trouble breathing, yellowing of the skin or eyes.
  • Advise patient that medication 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 known at this time. Advise patient to report changes in body fat distribution to health care provider.
  • Inform patient that drug does not completely eliminate HIV virus and therefore does not reduce risk of transmitting HIV to others. Appropriate precautions (eg, practicing safe 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 drug is not a cure for HIV infection, and illnesses associated with HIV infection, including opportunistic infections, may still be acquired. Advise patient to remain under care of health care provider.
  • Instruct patient not to 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.
  • Patient using a phosphodiesterase type 5 (PDE5) inhibitor (eg, sildenafil, tadalafil, vardenafil) may be at greater risk of experiencing PDE5-associated adverse reactions; advise patients to promptly report low BP, visual changes, or prolonged penile erection to health care provider.
  • Instruct patients with diabetes 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.
  • Instruct HIV-infected mothers not to breast-feed. Caution HIV-infected mother that breast-feeding could cause HIV infection in the baby.

Copyright © 2009 Wolters Kluwer Health.

Comment «Atazanavir Sulfate»