Applies to atazanavir: oral capsule, oral powder.

Serious side effects of Atazanavir

Along with its needed effects, atazanavir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking atazanavir:

Incidence not known

• Bloating
• blood in the urine
• blurred vision
• chest pain or discomfort
• chills
• clay-colored stools
• constipation
• dark urine
• decreased appetite
• diarrhea
• dizziness or lightheadedness
• dry mouth
• fainting
• fast heartbeat
• fast, shallow breathing
• fever
• flushed, dry skin
• fruit-like breath odor
• gaseous abdominal or stomach pain
• general feeling of discomfort
• headache
• hives, itching, or skin rash
• increased hunger
• increased thirst
• increased urination
• indigestion
• irregular heartbeat
• loss of appetite
• loss of consciousness
• muscle pain or cramping
• nausea
• pain in the groin or genitals
• pain in the stomach, side, or abdomen, possibly radiating to the back
• recurrent fever
• severe nausea or vomiting
• sharp back pain just below the ribs
• sleepiness
• slow or irregular heartbeat
• stomach discomfort or fullness
• sweating
• swelling
• tightness in the chest
• trouble with breathing
• unexplained weight loss
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• yellow eyes or skin

Other side effects of Atazanavir

Some side effects of atazanavir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Back pain
• cough, increased
• discouragement
• extra body fat
• feeling sad or empty
• irritability
• loss of interest or pleasure
• trouble concentrating
• trouble sleeping

Less common

• Burning, numbness, tingling, or painful sensations
• difficulty with moving
• muscle stiffness
• pain
• pain in the joints
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

Incidence not known

• Hair loss or thinning of the hair
• rash with flat lesions or small raised lesions on the skin

For Healthcare Professionals

Applies to atazanavir: oral capsule, oral powder for reconstitution.

General

The most common side effects reported in therapy-naive patients during clinical trials were nausea, jaundice/scleral icterus, and rash. The most common side effects reported in therapy-experienced patients during clinical trials were jaundice/scleral icterus and myalgia.^[Ref]

Hepatic

Very common (10% or more): Elevated indirect (unconjugated) bilirubin (up to 87%), elevated total bilirubin (up to 53%), elevated ALT (up to 25%), jaundice (up to 19%)

Common (1% to 10%): Elevated AST, jaundice/scleral icterus

Uncommon (0.1% to 1%): Hepatitis

Rare (less than 0.1%): Hepatosplenomegaly

Frequency not reported: Hepatomegaly, liver damage, acute hepatic cytolysis, biliary lithiasis, choledocholithiasis

Postmarketing reports: Hepatic function abnormalities, cholelithiasis, cholecystitis, cholestasis^[Ref]

Elevated total bilirubin (at least 2.6 times the upper limit of normal [2.6 x ULN]), ALT (at least 5.1 x ULN), and AST (at least 5.1 x ULN) have been reported in up to 53%, up to 25%, and up to 10% of patients, respectively.

Most patients taking this drug experienced asymptomatic elevations in indirect (unconjugated) bilirubin related to inhibition of UDP-glucuronosyl transferase. This hyperbilirubinemia was reversible upon discontinuation of this drug.^[Ref]

Other

Elevated total cholesterol (at least 240 mg/dL) and triglycerides (at least 751 mg/dL) have been reported in up to 25% and up to 8% of patients, respectively.^[Ref]

Very common (10% or more): Elevated total cholesterol (up to 25%)

Common (1% to 10%): Elevated triglycerides, fever/pyrexia, pain, fatigue, asthenia, lipodystrophy syndrome

Uncommon (0.1% to 1%): Chest pain, malaise, gait disturbances, decreased weight, weight gain

Rare (less than 0.1%): Edema

Frequency not reported: Elevated low-density lipoprotein cholesterol, elevated high-density lipoprotein cholesterol, burning sensation, dysplasia, facial atrophy, generalized edema, heat sensitivity, infection, overdose, pallor, peripheral edema, substernal chest pain, sweating, semicircular canal lithiasis^[Ref]

Dermatologic

Very common (10% or more): Rash (up to 20%)

Common (1% to 10%): Lipodystrophy

Uncommon (0.1% to 1%): Alopecia, pruritus, urticaria

Rare (less than 0.1%): Vesiculobullous rash, eczema

Frequency not reported: Photosensitivity

Postmarketing reports: Maculopapular rash, erythema multiforme, toxic skin eruptions, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, angioedema, Stevens-Johnson syndrome^[Ref]

Gastrointestinal

Elevated amylase (at least 2.1 x ULN) and lipase (at least 2.1 x ULN) have been reported in up to 14% and up to 11% of patients, respectively.^[Ref]

Very common (10% or more): Nausea (up to 20%), elevated amylase (up to 14%), elevated lipase (up to 11%)

Common (1% to 10%): Abdominal pain, diarrhea, vomiting, dyspepsia

Uncommon (0.1% to 1%): Dry mouth, flatulence, gastritis, pancreatitis, abdominal distension, aphthous stomatitis

Frequency not reported: Acholia, colitis, constipation, dental pain, esophageal ulcer, gastrointestinal disorder, peptic ulcer, sialolithiasis/parotid gland lithiasis^[Ref]

Nervous system

Very common (10% or more): Headache (up to 14%)

Common (1% to 10%): Peripheral neurological symptoms, dizziness

Uncommon (0.1% to 1%): Syncope, peripheral neuropathy, amnesia, somnolence, dysgeusia

Frequency not reported: Paresthesias^[Ref]

Musculoskeletal

Very common (10% or more): Elevated creatine kinase (up to 11%)

Common (1% to 10%): Back pain, myalgia, arthralgia

Uncommon (0.1% to 1%): Muscle atrophy

Rare (less than 0.1%): Myopathy

Frequency not reported: Bone pain, extremity pain, myasthenia, osteonecrosis^[Ref]

Elevated creatine kinase (at least 5.1 x ULN) has been reported in up to 11% of patients.^[Ref]

Hematologic

Decreased neutrophils (less than 750 cells/mm3), hemoglobin (less than 8 g/dL), and platelets (less than 50,000 cells/mm3) have been reported in up to 8%, up to 5%, and up to 5% of patients, respectively.^[Ref]

Common (1% to 10%): Decreased neutrophils, decreased hemoglobin, decreased platelets

Rare (less than 0.1%): Spontaneous bleeding in hemophiliacs^[Ref]

Metabolic

Common (1% to 10%): Elevated glucose

Uncommon (0.1% to 1%): Anorexia, increased appetite

Rare (less than 0.1%): Ketoacidosis

Frequency not reported: Hyperkalemia, lactic acidosis, hyperlactatemia, redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), hypertriglyceridemia, hypercholesterolemia, insulin resistance

Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia^[Ref]

Elevated glucose (at least 251 mg/dL) has been reported in 5% of patients.^[Ref]

Psychiatric

Common (1% to 10%): Depression, insomnia

Uncommon (0.1% to 1%): Anxiety, disorientation, sleep disorder, abnormal dream^[Ref]

Ocular

Common (1% to 10%): Scleral icterus/ocular icterus^[Ref]

Respiratory

Common (1% to 10%): Increased cough

Uncommon (0.1% to 1%): Dyspnea^[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Hypertension

Rare (less than 0.1%): Palpitation, vasodilatation

Frequency not reported: Prolongation of the PR interval, abnormalities in atrioventricular (AV) conduction, first-degree AV block, prolonged QT interval, ventricular tachycardia, increased QRS interval, heart arrest, heart block, myocarditis

Postmarketing reports: Second-degree AV block, third-degree AV block, left bundle branch block, QTc prolongation, torsades de pointes^[Ref]

In healthy volunteers and patients, abnormalities in AV conduction were asymptomatic and generally limited to first-degree AV block.

A 59-year-old HIV-infected woman with congestive heart failure and an ejection fraction of 30% started lamivudine, zidovudine, and atazanavir. One month later, the patient presented with syncope and complained of nausea, which had begun 5 days prior. During the month after therapy initiation, the patient experienced slowly progressive shortness of breath. An ECG showed a QTc interval prolongation of 619 min. Prior to starting antiretroviral therapy, an ECG showed a QTc interval of 398 min for the patient. The patient developed continuous ventricular tachycardia and was defibrillated to sinus bradycardia, which worsened her QT interval prolongation. The patient developed torsades de pointes, which reverted after further defibrillation. Treatment to increase her heart rate and decrease her QT interval was started. The patient's antiretroviral therapy was discontinued during her hospitalization and was not restarted due to concerns regarding QT prolongation. The patient's QTc interval decreased to 394 min and she had no additional ventricular tachyarrhythmias. The patient was restarted on lamivudine, zidovudine, and atazanavir and within 2 days, ECG showed QTc interval prolongation to 571 min. The atazanavir was concluded to be the cause of the prolonged QT interval and torsades de pointes. The patient's QT interval returned to normal following discontinuation of her antiretroviral therapy.^[Ref]

Renal

An analysis of a ureteral stone determined it was 60% atazanavir metabolite and 40% calcium phosphate (carbonate apatite). The stone was not metabolites adsorbed into the apatite but contained atazanavir crystals. Analysis of renal calculi from additional patients determined concentrations of atazanavir ranging from 40% to 100%.

Postmarketing reports of chronic kidney disease in HIV-infected patients using this drug (with or without ritonavir) included biopsy-proven cases of granulomatous interstitial nephritis associated with deposition of atazanavir crystals in renal parenchyma.^[Ref]

Uncommon (0.1% to 1%): Interstitial nephritis

Rare (less than 0.1%): Acute interstitial nephritis, renal colic, reversible acute renal failure, urolithiasis, kidney pain

Postmarketing reports: Nephrolithiasis, hydronephrosis, renal insufficiency, granulomatous interstitial nephritis, chronic kidney disease^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity

Frequency not reported: Allergic reaction^[Ref]

Genitourinary

Uncommon (0.1% to 1%): Hematuria, frequency of micturition/pollakiuria, proteinuria, gynecomastia

Frequency not reported: Decreased male fertility^[Ref]

Immunologic

Frequency not reported: Immune reconstitution syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)^[Ref]