atazanavir

Contraindicated in:

Hypersensitivity;
Severe hepatic impairment;
Concurrent use of alfuzosin, amiodarone (when used with ritonavir), apalutamide, carbamazepine, elbasvir/grazoprevir, encorafenib, ergot derivatives, glecaprevir/pibrentasvir, irinotecan, ivosidenib, lomitapide, lovastatin, lurasidone (when used with ritonavir), midazolam (PO), nevirapine, phenobarbital, phenytoin, pimozide, quinidine (when used with ritonavir), rifampin, sildenafil (Revatio), simvastatin, St. John's wort, or triazolam;
Lactation: Breastfeeding should be avoided in women with HIV;
Pedi: ↑risk of kernicterus in infants <3 mo.

Use Cautiously in:

Mild to moderate hepatic impairment;
Pre-existing conduction system disease (marked first-degree AV block or second- or third-degree AV block) or concurrent use of other drugs that prolong the PR interval (especially those metabolized by CYP3A4, including verapamil or diltiazem);
Diabetes mellitus;
Hemophilia (↑ risk of bleeding);
Patients with or at high risk for renal impairment;
Phenylketonuria (oral powder contains aspartame);
OB: Considered a preferred protease inhibitor (when combined with ritonavir) for pregnant females living with HIV who are antiretroviral-naive (as initial therapy), who have had antiretroviral therapy in the past but are restarting, or who require a new antiretroviral regimen (due to poor tolerance or poor virologic response of current regimen).

Adv. Reactions/Side Effects ⬆ ⬇

When used in combination with other antiretrovirals

CV: PR interval prolongation, heart block

Derm: DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, rash, STEVENS-JOHNSON SYNDROME

Endo: Graves' disease, hyperglycemia

GI: nausea, ↑liver enzymes, abdominal pain, autoimmune hepatitis, cholelithiasis, diarrhea, HEPATOTOXICITY, hyperbilirubinemia, jaundice, vomiting

GU: interstitial nephritis, nephrolithiasis

Metab: fat redistribution

MS: myalgia, polymyositis

Neuro: depression, dizziness, Guillain-Barré syndrome, headache, insomnia

Misc: ANGIOEDEMA, fever, immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels and risk of toxicity of alfuzosin, amiodarone (when used with ritonavir), elbasvir/grazoprevir, ergot derivatives (ergotamine, dihydroergotamine, methylergonovine), glecaprevir/pibrentasvir, irinotecan, lomitapide, lovastatin, lurasidone (when used with ritonavir), midazolam (PO), pimozide, quinidine (when used with ritonavir), sildenafil (Revatio), simvastatin, and triazolam; concurrent use contraindicated.
Levels are significantly ↓ by rifampin and nevirapine; may promote viral resistance; concurrent use is contraindicated.
Carbamazepine, phenytoin, and phenobarbital may significantly ↓ levels and effectiveness. Atazanavir may also ↑ carbamazepine levels and risk of toxicity as well as ↓ phenytoin and phenobarbital levels and effectiveness; concurrent use contraindicated.
Apalutamide may significantly ↓ levels and effectiveness; concurrent use contraindicated.
Encorafenib and ivosidenib may significantly ↓ levels and effectiveness. Atazanavir may also ↑ encorafenib and ivosidenib levels and risk of toxicity; concurrent use contraindicated.
Combination therapy with tenofovir may lead to ↓ virologic response and possible resistance (100 mg ritonavir should be added to boost levels and dose of atazanavir ↓ to 300 mg/day).
Levels and effectiveness are significantly ↓ by omeprazole; do not exceed omeprazole dose of 20 mg/day when used with atazanavir and ritonavir in treatment-naive patients (should be taken at least 12 hr before atazanavir and ritonavir); should not be used in treatment-experienced patients.
Efavirenz↓ levels and may promote viral resistance; 600 mg efavirenz should be given with atazanavir 400 mg/day and ritonavir 100 mg/day to counteract this effect in treatment-naive patients (should not be used with atazanavir in treatment-experienced patients).
Levels are ↑ by ritonavir; ↓ atazanavir dose to 300 mg/day.
Nevirapine may ↓ levels, and atazanavir may ↑ nevirapine levels; avoid concurrent use.
Antacids or buffered medications will ↓ absorption; atazanavir should be given 2 hr before or 1 hr after.
↑levels of lidocaine, amiodarone, or quinidine; blood level monitoring is recommended.
↑risk of bleeding with warfarin; closely monitor INR.
May ↑ levels of and risk of bleeding from dabigatran and edoxaban.
May ↑ levels of and risk of bleeding from rivaroxaban, especially when used with ritonavir; concurrent use of rivaroxaban with atazanavir/ritonavir not recommended.
May ↑ levels of and risk of bleeding from apixaban, especially when used with ritonavir; concurrent use of apixaban with atazanavir/ritonavir not recommended.
↑of tricyclic antidepressants; blood level monitoring is recommended.
↑levels of rifabutin; ↓ rifabutin dose by 75% (150 mg every other day or 3 times weekly).
↑levels of diltiazem and its active metabolite; ↓ diltiazem dose by 50% and ECG monitoring recommended. Similar precautions may be needed with felodipine, nifedipine, nicardipine, and verapamil.
↑levels of fluticasone; consider alternative therapy; should not be used when atazanavir used with ritonavir.
↓levels of voriconazole when atazanavir is used with ritonavir; avoid concurrent use. Voriconazole may also ↑ levels of atazanavir (when used without ritonavir).
↑levels of ketoconazole or itraconazole when atazanavir is used with ritonavir.
↑levels of trazodone; ↓ dose of trazodone.
↑levels of sildenafil, vardenafil, and tadalafil; ↓sildenafil dose to 25 mg every 48 hr; ↓ vardenafil dose to 2.5 mg every 72 hr (when atazanavir used with ritonavir) or 2.5 mg every 24 hr (when atazanavir used alone); ↓ tadalafil dose to 10 mg every 72 hr. Exercise caution and monitor for hypertension, visual changes, and priapism.
↑levels and risk of myopathy from atorvastatin or rosuvastatin; use lowest possible dose of statin; do not exceed rosuvastatin dose of 10 mg/day.
Levels may be ↓ by histamine H2 antagonists, promoting viral resistance; separate doses by at least 10 hr.
↑levels of cyclosporine, sirolimus, and tacrolimus; monitor immunosuppressant levels.
↑levels of clarithromycin; ↓ clarithromycin dose by 50% or consider alternative therapy.
May ↓ levels of some estrogens found in hormonal contraceptives; use alternative nonhormonal method of contraception.
May ↑ levels of buprenorphine; consider ↓ dose of buprenorphine.
Concurrent use of other drugs known to cause PR interval prolongation may ↑ risk of heart block.
May ↑ risk of adverse effects with salmeterol; concurrent use not recommended.
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 atazanavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day; do not use with atazanavir alone (should be used with atazanavir and ritonavir).
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 atazanavir 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.
Concurrent use of lamotrigine with atazanavir and ritonavir results in ↓ lamotrigine levels; concurrent use not recommended.
Concurrent use of voriconazole with atazanavir and ritonavir may result in either ↓ or ↑ voriconazole levels; concurrent use not recommended.
May ↑ quetiapine levels; ↓ quetiapine dose to ⅙ of current dose.
Concurrent use with sofosbuvir/velpatasvir/voxilaprevir may ↑ voxilaprevir levels; concurrent use not recommended.
May ↑ ticagrelor levels and risk of toxicity; concurrent use not recommended.
May ↓ effectiveness of clopidogrel; concurrent use not recommended.
Corticosteroids may ↓ levels and effectiveness. Atazanavir may also ↑ corticosteroid levels and risk of toxicity.
Elagolix may ↓ levels and effectiveness. Atazanavir may also ↑ elagolix levels and risk of toxicity. Limit concurrent use of elagolix 200 mg twice daily with atazanavir for up to 1 mo or limit concurrent use of elagolix 150 mg once daily with atazanavir for up to 6 mo.
May ↑ levels and risk of toxicity of active metabolite of fostamatinib.

Drug-Natural Products:

St. John’s wort significantly ↓ levels and effectiveness; concurrent use contraindicated.

Availability ⬆ ⬇

(Generic available)

Capsules: 150 mg; 200 mg; 300 mg
Oral powder: 50 mg/packet
In combination with: cobicistat (Evotaz). See Appendix [not included in this PDA edition].

Route/Dosage ⬆ ⬇

PO (Adults ): Therapy-naive: 400 mg once daily or 300 mg once daily with ritonavir 100 mg once daily (must be used with ritonavir in pregnancy); should be used at a dose of 300 mg once daily with ritonavir 100 mg once daily if used concomitantly with tenofovir, H₂ receptor antagonist, or proton pump inhibitor; should be used at a dose of 400 mg once daily with ritonavir 100 mg once daily if used concomitantly with efavirenz. Therapy-experienced: 300 mg once daily with ritonavir 100 mg once daily; should be used at dose of 400 mg once daily with ritonavir 100 mg once daily if used with tenofovir and a H₂ receptor antagonist; in pregnant patients in 2nd or 3rd trimester, should be used at a dose of 400 mg once daily with ritonavir 100 mg once daily if used with tenofovir or a H₂ receptor antagonist.
PO (Capsules)(Children ≥6 yr): Therapy-naive or therapy-experienced (15–34.9 kg): 200 mg once daily with ritonavir 100 mg once daily; Therapy-naive or therapy-experienced (≥35 kg): 300 mg once daily with ritonavir 100 mg once daily; Therapy-naive, ≥13 yr, ≥40 kg and unable to tolerate ritonavir: 400 mg once daily.
PO (Oral Powder)(Children ≥3 mo and ≥5 kg): Therapy-naive or therapy-experienced (5–14.9 kg): 200 mg once daily with ritonavir 80 mg once daily; Therapy-naive or therapy-experienced (15–24.9 kg): 250 mg once daily with ritonavir 80 mg once daily.

Renal Impairment

PO (Adults ): Therapy-naive and hemodialysis: 300 mg once daily with ritonavir 100 mg once daily; Therapy-experienced and hemodialysis: contraindicated.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 300 mg once daily (do not use with ritonavir).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits the action of HIV protease, preventing maturation of virions.

Therapeutic effects:

↑CD4 cell counts and ↓ viral load with subsequent slowed progression of HIV and its sequelae.

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly absorbed (↑ by food).

Distribution: Enters CSF and semen.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme; 13% excreted unchanged in urine.

Half-Life: 7 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2.5 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking atazanavir with food as directed. Advise patient to read the Patient Information before taking and with each Rx refill in case of changes. Atazanavir must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; then return to regular dose schedule. If within 6 hr of next dose, omit dose and take next dose at regular time. Do not double doses.
Instruct patient that atazanavir should not be shared with others.
Inform patient that atazanavir does not cure HIV or prevent associated or opportunistic infections. Atazanavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading HIV to others.
Instruct 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; interactions may be fatal.
May cause dizziness. Caution patient to notify health care professional if this occurs and to avoid driving and other activities requiring alertness until response to medication is known.
Instruct patient to notify health care professional immediately if signs and symptoms of hepatitis (flu-like symptoms, tiredness, nausea, lack of appetite, yellow skin or eyes, dark urine, pale stools, pain or sensitivity to touch on right side below ribs), skin reactions with symptoms (flu-like symptoms, fever, muscle aches, conjunctivitis, blisters, mouth sores, swelling of face, tiredness), gallbladder disorder (right or middle upper stomach pain, fever, nausea, vomiting, yellowing of skin and whites of eyes), kidney stones (side pain, blood in urine, pain upon urination), change in heart rhythm, high blood sugar, or signs of immune reconstitution syndrome (signs and symptoms of an infection) occur.
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 females of reproductive potential to avoid pregnancy and breastfeeding during therapy. Instruct females using hormonal contraceptives to use an effective alternative nonhormonal method of contraception. Advise patient to notify health care professional immediately if pregnancy is planned or suspected and to avoid breastfeeding. If pregnant patient is exposed to atazanavir, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Monitor neonates exposed to atazanavir in utero for development of severe hyperbilirubinemia during first few days of life.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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Indications ⬇

Contraind./Precautions ⬆ ⬇