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Evotaz Side Effects

Generic Name: atazanavir / cobicistat

Note: This document contains side effect information about atazanavir / cobicistat. Some of the dosage forms listed on this page may not apply to the brand name Evotaz.

In Summary

More frequent side effects include: first degree atrioventricular block. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to atazanavir / cobicistat: oral tablet, tablet oral

Along with its needed effects, atazanavir/cobicistat 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 / cobicistat:

More common

  • Chills
  • clay-colored stools
  • dark urine
  • dizziness
  • fever
  • headache
  • itching, skin rash
  • loss of appetite
  • nausea
  • stomach pain
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vomiting of blood
  • yellow eyes or skin

Incidence not known

  • Black, tarry stools
  • blistering, peeling, or loosening of the skin
  • blood in the urine
  • chest pain
  • decreased appetite
  • diarrhea
  • gaseous abdominal or stomach pain
  • joint or muscle pain
  • pain in the groin or genitals
  • painful or difficult urination
  • recurrent fever
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • sharp back pain just below the ribs
  • sore throat
  • sores, ulcers, or white spots in the mouth or on the lips
  • stomach fullness or tenderness
  • swelling of the feet or lower legs
  • swollen glands
  • unusual bleeding or bruising

For Healthcare Professionals

Applies to atazanavir / cobicistat: oral tablet

General

In clinical trials, safety of this drug was evaluated in HIV-1-infected, antiretroviral therapy-naive patients using the individual components with other antiretrovirals for at least 48 weeks. In 1 trial, atazanavir and cobicistat were used with emtricitabine-tenofovir (cobicistat-boosted group); in another trial, atazanavir and ritonavir were used with emtricitabine-tenofovir (ritonavir-boosted group). In the cobicistat-boosted group, the most common side effects were jaundice, ocular icterus, and nausea; in the ritonavir-boosted group, the most common side effects were jaundice, ocular icterus, nausea, and diarrhea. Study treatment was discontinued due to side effects in 7% of patients in both the cobicistat- and the ritonavir-boosted groups. Most of the side effects included from clinical trials were of at least moderate intensity (grade 2 or higher).

The manufacturer product information for atazanavir and cobicistat should be consulted for additional safety information.[Ref]

Hepatic

Increases in total bilirubin greater than 2.5 times the upper limit of normal (2.5 x ULN) was reported in 65% of patients in the cobicistat-boosted group and 56% in the ritonavir-boosted group. Increased ALT (greater than 5 x ULN), AST (greater than 5 x ULN), and GGT (greater than 5 x ULN) were reported in 3%, 3%, and 2% of patients in the cobicistat-boosted group, respectively, and 2%, 2%, and 1% of patients in the ritonavir-boosted group, respectively.

Jaundice was reported in the cobicistat-boosted group (all grades: 13%; grades 2 to 4: 5%) and the ritonavir-boosted group (all grades: 11%; grades 2 to 4: 3%).

Most patients taking atazanavir experienced asymptomatic elevations in indirect (unconjugated) bilirubin related to inhibition of UGT. This hyperbilirubinemia was reversible upon discontinuation of atazanavir.[Ref]

Very common (10% or more): Increased total bilirubin (65%), jaundice (up to 13%)
Common (1% to 10%): Increased ALT, increased AST, increased GGT

Atazanavir:
-Very common (10% or more): Elevated indirect (unconjugated) bilirubin/hyperbilirubinemia, UDP-glucuronosyl transferase (UGT) inhibited, jaundice, increased total bilirubin
-Common (1% to 10%): Increased ALT, increased AST, increased GGT
-Postmarketing reports: Hepatic function abnormalities, cholelithiasis, cholecystitis, cholestasis[Ref]

Ocular

Ocular icterus was reported in the cobicistat-boosted group (all grades: 15%; grades 2 to 4: 3%) and the ritonavir-boosted group (all grades: 17%; grades 2 to 4: 1%).[Ref]

Very common (10% or more): Ocular icterus (up to 15%)

Atazanavir:
-Very common (10% or more): Ocular icterus[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 12%)
Common (1% to 10%): Increased lipase, increased serum amylase
Frequency not reported: Diarrhea, vomiting, upper abdominal pain

Atazanavir:
-Very common (10% or more): Nausea, diarrhea
-Common (1% to 10%): Increased lipase, increased serum amylase
-Postmarketing reports: Pancreatitis[Ref]

Nausea was reported in the cobicistat-boosted group (all grades: 12%; grades 2 to 4: 2%) and the ritonavir-boosted group (all grades: 11%; grades 2 to 4: 2%). Diarrhea (all grades) was reported in 11% of patients in the ritonavir-boosted group.

Increased serum amylase (greater than 2 x ULN) was reported in 4% and 2% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.

If serum amylase was greater than 1.5 x ULN, lipase was also measured. Increased lipase (grades 3 to 4) was reported in 9% and 6% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.[Ref]

Dermatologic

Common (1% to 10%): Rash (rash events included allergic dermatitis, drug hypersensitivity, generalized pruritus, eosinophilic pustular folliculitis, rash, generalized rash, macular rash, maculopapular rash, morbilliform rash, papular rash, urticaria)

Atazanavir:
-Common (1% to 10%): Rash events
-Frequency not reported: Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, mild-to-moderate maculopapular skin eruptions
-Postmarketing reports: Alopecia, maculopapular rash, pruritus, angioedema[Ref]

Rash events (grades 2 to 4) were reported in 5% and 4% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.[Ref]

Musculoskeletal

Common (1% to 10%): Increased creatine kinase
Frequency not reported: Rhabdomyolysis

Atazanavir:
-Common (1% to 10%): Increased creatine kinase
-Postmarketing reports: Arthralgia[Ref]

Increased creatine kinase (at least 10 x ULN) was reported in 5% and 6% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.[Ref]

Renal

Nephrolithiasis has been reported with atazanavir. In clinical trials, nephrolithiasis was reported in 2% of patients in the cobicistat-boosted group and no patients in the ritonavir-boosted group. Onset of nephrolithiasis was about 24 weeks in the cobicistat-boosted group.

In clinical trials, serum creatinine increased and estimated CrCl decreases occurred early during therapy in the cobicistat-boosted group after which they stabilized. After 48 weeks of therapy, eGFR (based on CrCl) change averaged -13.4 mL/min in the cobicistat-boosted group and -9.1 mL/min in the ritonavir-boosted group.

Renal impairment (including acute renal failure and Fanconi syndrome) has been reported when cobicistat was used in a regimen containing tenofovir.

In clinical trials over 48 weeks (n=771), 6 (1.5%) patients using atazanavir, cobicistat, and tenofovir discontinued therapy due to a renal side effect; 5 patients had laboratory findings consistent with proximal renal tubulopathy. None of the 5 patients had baseline renal dysfunction (e.g., estimated CrCl less than 70 mL/min). Laboratory findings in these 5 patients improved but did not completely resolve in all patients when therapy was stopped. No patients required renal replacement therapy.[Ref]

Common (1% to 10%): Nephrolithiasis
Frequency not reported: Decreased estimated CrCl, increased serum creatinine, decreased estimated glomerular filtration rate (eGFR; based on CrCl), nephropathy, Fanconi syndrome, laboratory findings consistent with proximal renal tubulopathy

Atazanavir:
-Frequency not reported: Decreased eGFR
-Postmarketing reports: Nephrolithiasis, interstitial nephritis

Cobicistat:
-Frequency not reported: Decreased estimated CrCl, increased serum creatinine, tubular secretion of creatinine inhibited (actual renal glomerular function not affected), decreased eGFR, renal impairment (including acute renal failure, Fanconi syndrome)[Ref]

Genitourinary

Increased urine RBC (greater than 75 RBC/high power field) and urine glucose (at least 1000 mg/dL) have been reported in 3% and 3% of patients in the cobicistat-boosted group, respectively, and 2% and 1% of patients in the ritonavir-boosted group, respectively.[Ref]

Common (1% to 10%): Hematuria (increased urine RBC), glycosuria (increased urine glucose)

Atazanavir:
-Common (1% to 10%): Increased urine RBC, increased urine glucose[Ref]

Metabolic

Frequency not reported: Increased fasted total cholesterol, increased fasted high-density lipoprotein cholesterol, increased fasted low-density lipoprotein cholesterol, increased fasted triglycerides

Atazanavir:
-Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, diabetic ketoacidosis

Combination antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")[Ref]

Nervous system

Frequency not reported: Headache[Ref]

Other

Frequency not reported: Fatigue

Atazanavir:
-Postmarketing reports: Edema[Ref]

Psychiatric

Frequency not reported: Depression, abnormal dreams, insomnia[Ref]

Cardiovascular

Atazanavir:
-Common (1% to 10%): First-degree atrioventricular (AV) block
-Frequency not reported: Prolongation of the PR interval, abnormalities in AV conduction, other conduction abnormalities
-Postmarketing reports: Second-degree AV block, third-degree AV block, left bundle branch block, QTc prolongation[Ref]

Immunologic

Atazanavir:
-Frequency not reported: Immune reconstitution syndrome

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

Hematologic

Protease inhibitor therapy:
-Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs[Ref]

References

1. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb, Princeton, NJ.

2. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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