Atazanavir / Cobicistat Side Effects

Medically reviewed by Drugs.com. Last updated on Oct 17, 2024.

Applies to atazanavir / cobicistat: oral tablet, tablet oral.

Precautions

Your doctor will want to check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for any unwanted effects.

This medicine should not be used together with alfuzosin (Uroxatral®), carbamazepine (Tegretol®), cisapride (Propulsid®), dronedarone (Multaq®), drospirenone/ethinyl estradiol (Yasmin®, Yaz®), elbasvir/grazoprevir (Zepatier®), glecaprevir/pibrentasvir (Mavyret®), indinavir (Crixivan®), irinotecan (Camptosar®), lomitapide (Juxtapid®), lovastatin (Mevacor®), lurasidone (Latuda®), midazolam (Versed®), nevirapine (Viramune®), phenobarbital (Luminal®), phenytoin (Dilantin®), pimozide (Orap®), ranolazine (Ranexa®), rifampin (Rifadin®, Rimactane®), sildenafil (Revatio®), simvastatin (Zocor®), St. John's wort, triazolam (Halcion®), or ergot medicines (eg, dihydroergotamine, ergotamine, methylergonovine, Cafergot®, Ergomar®, Wigraine®). Do not use this medicine together with colchicine (Colcrys®) if you have kidney or liver disease.

Using this medicine while you are pregnant can harm your unborn baby. It may also cause a rare but serious reaction called lactic acidosis (too much acid in the blood) in pregnant women. Birth control pills may not work as well to prevent pregnancy when used with this medicine. Use another form of birth control (eg, condoms, spermicide) along with your pills. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may cause heart rhythm problems (eg, PR prolongation). Tell your doctor right away if you get dizzy or lightheaded.

Serious allergic and skin reactions (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) can occur with this medicine. Check with your doctor right away if you have any of the following symptoms while using this medicine: severe rash, blistering, peeling, or loosening of the skin, chills, cough, diarrhea, itching, joint or muscle pain, red skin lesions, often with a purple center, skin rash, sore throat, sores, ulcers, or white spots in the mouth or on the lips, or unusual tiredness or weakness.

This medicine may increase your risk for kidney problems, including acute kidney failure, chronic kidney disease, or Fanconi syndrome (when used together with tenofovir DF). Check with your doctor right away if you have changes in how much you urinate, decreased mental sharpness, nausea, vomiting, loss of appetite, or muscle twitches or cramps.

This medicine may increase your risk of having kidney stones or gallstones. Check with your doctor right away if you have blood in your urine, nausea and vomiting, pain in the groin or genitals, or sharp back pain just below the ribs, stomach fullness or pain, recurrent fever, or yellow eyes or skin.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Your immune system may get stronger when you start taking HIV medicines. Tell your doctor right away if you notice any changes in your health. Sometimes the immune system will start to fight infections that were hidden in your body, such as pneumonia, herpes, or tuberculosis. Autoimmune disorders (eg, Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) may also occur.

This medicine may increase blood sugar levels. Check with your doctor if you notice a change in the results of your blood or urine sugar tests.

This medicine does not decrease the risk of transmitting the HIV infection to others through sexual contact or by contaminated blood. Make sure you understand and practice safe sex, even if your partner also has HIV. Avoid sharing needles with anyone.

This medicine may cause you to have excess body fat. Tell your doctor if you notice changes in your body shape, such as an increased amount of fat in the upper back and neck, or around the chest and stomach area. You might also lose fat from the legs, arms, and face.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or non-prescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects

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:

For healthcare professionals

Applies to atazanavir / cobicistat: oral tablet.

General adverse events

In a clinical trial (based on week 144 data), safety of this drug was evaluated in HIV-1-infected, antiretroviral therapy-naive patients using the individual components with other antiretrovirals. In this trial, patients received atazanavir and cobicistat with emtricitabine-tenofovir disoproxil fumarate (DF) (cobicistat-boosted group) or atazanavir and ritonavir with emtricitabine-tenofovir DF (ritonavir-boosted group). In the cobicistat-boosted group, the most commonly reported side effects were associated with elevated bilirubin levels; the most common side effects (grades 2 to 4) were jaundice and rash. Study treatment was discontinued due to side effects in 11% 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

• Very common (10% or more): Hyperbilirubinemia (97.7%), increased total bilirubin (up to 88%), jaundice (up to 13%), increased ALT or AST (12.8%)
• Common (1% to 10%): Increased ALT, increased AST, increased GGT
• Uncommon (0.1% to 1%): Hepatitis
• Rare (0.01% to 0.1%): Hepatosplenomegaly

Atazanavir:

• Very common (10% or more): Elevated indirect (unconjugated) bilirubin/hyperbilirubinemia, 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]

In 1 study through 144 weeks of therapy, hyperbilirubinemia was reported in 97.7% and 97.4% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively; however, more patients in the cobicistat-boosted group had increases in total bilirubin greater than 2 times the upper limit of normal (2 x ULN) than patients in the ritonavir-boosted group (88% versus 80.9%). Study drug was discontinued due to bilirubin-related side effects in 4.9% and 4% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively. Increased ALT or AST greater than 3 x ULN was reported in 12.8% and 9% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.

Increases in total bilirubin greater than 2.5 x ULN was reported in 73% and 66% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively. Increased ALT (greater than 5 x ULN), AST (greater than 5 x ULN), and GGT (greater than 5 x ULN) were reported in 6%, 4%, and 4% of patients in the cobicistat-boosted group, respectively, and 3%, 3%, and 2% of patients in the ritonavir-boosted group, respectively.

Jaundice (grades 2 to 4) was reported in 6% and 3% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.

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]

Gastrointestinal

• Very common (10% or more): Nausea (up to 12%)
• Common (1% to 10%): Increased lipase, increased serum amylase, diarrhea, vomiting, dyspepsia, abdominal pain, abdominal distension, flatulence, dry mouth
• Uncommon (0.1% to 1%): Pancreatitis, gastritis, aphthous stomatitis
• Frequency not reported: 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 and diarrhea were reported in 2% and 2% of patients in the cobicistat-boosted group, respectively, and 2% and 1% of patients in the ritonavir-boosted group, respectively.

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 7% and 3% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.^[Ref]

Ocular

• Very common (10% or more): Ocular icterus^[Ref]

Ocular icterus (grades 2 to 4) was reported in 4% and 2% 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)
• Uncommon (0.1% to 1%): Pruritus, urticaria, alopecia
• Rare (0.01% to 0.1%): Vesiculobullous rash, eczema, vasodilatation

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
• Uncommon (0.1% to 1%): Myalgia, muscle atrophy, arthralgia
• Rare (0.01% to 0.1%): Myopathy
• Frequency not reported: Rhabdomyolysis, osteonecrosis

Atazanavir:

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

Increased creatine kinase (at least 10 x ULN) was reported in 8% and 9% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.^[Ref]

Renal

• Uncommon (0.1% to 1%): Interstitial nephritis
• Rare (0.01% to 0.1%): Kidney pain
• Frequency not reported: Decreased estimated CrCl, increased serum creatinine, decreased estimated glomerular filtration rate (eGFR; by Cockcroft-Gault method), nephropathy, Fanconi syndrome acquired, nephrolithiasis, laboratory findings consistent with proximal renal tubulopathy

Atazanavir:

• Frequency not reported: Decreased eGFR
• Postmarketing reports: Nephrolithiasis, interstitial nephritis, granulomatous interstitial nephritis, chronic kidney disease

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]

In 1 study, serum creatinine increases and estimated CrCl decreases occurred early during therapy in the cobicistat-boosted group, after which they stabilized. After 144 weeks of therapy, eGFR (by Cockcroft-Gault method) change averaged -15.1 mL/min in the cobicistat-boosted group and -8 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 DF.

In clinical trials over 144 weeks (n=692), 10 (2.9%) patients using atazanavir, cobicistat, and tenofovir DF discontinued therapy due to a renal side effect; 7 patients had laboratory findings consistent with proximal renal tubulopathy. One patient had baseline renal dysfunction (e.g., estimated CrCl less than 70 mL/min). Laboratory findings in these 7 patients improved but did not completely resolve in all patients when therapy was stopped. No patients required renal replacement therapy.

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

Genitourinary

• Common (1% to 10%): Hematuria (increased urine RBC), glycosuria (increased urine glucose)
• Uncommon (0.1% to 1%): Proteinuria, pollakiuria

Atazanavir:

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

Increased urine RBC (greater than 75 RBC/high power field) and urine glucose (at least 1000 mg/dL) were reported in 6% and 3% of patients in the cobicistat-boosted group, respectively, and 3% and 3% of patients in the ritonavir-boosted group, respectively.^[Ref]

Metabolic

• Common (1% to 10%): Hyperglycemia (increased serum glucose), increased appetite
• Uncommon (0.1% to 1%): Anorexia

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")

Antiretroviral therapy:

• Frequency not reported: Increased glucose levels^[Ref]

Increased serum glucose (at least 250 mg/dL) was reported in 2% and 2% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.^[Ref]

Nervous system

• Common (1% to 10%): Headache, dizziness, somnolence, dysgeusia
• Uncommon (0.1% to 1%): Peripheral neuropathy, syncope, amnesia^[Ref]

Headache (grades 2 to 4) was reported in 2% and 1% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.^[Ref]

Other

• Common (1% to 10%): Fatigue
• Uncommon (0.1% to 1%): Decreased weight, weight gain, pyrexia, asthenia, chest pain, malaise
• Rare (0.01% to 0.1%): Edema, gait disturbance
• 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: Edema

Antiretroviral therapy:

• Frequency not reported: Increased weight, increased blood lipid levels^[Ref]

Psychiatric

• Common (1% to 10%): Abnormal dreams, insomnia
• Uncommon (0.1% to 1%): Depression, sleep disorder, disorientation, anxiety^[Ref]

Hematologic

• Common (1% to 10%): Decreased neutrophils

Atazanavir:

• Common (1% to 10%): Decreased neutrophils

Protease inhibitor therapy:

• Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs^[Ref]

Decreased neutrophils (less than 750/mm3) were reported in 3% and 2% of patients in the cobicistat-boosted and ritonavir-boosted groups, respectively.^[Ref]

Cardiovascular

• Uncommon (0.1% to 1%): Hypertension
• Rare (0.01% to 0.1%): Palpitation

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, torsades de pointes^[Ref]

Hypersensitivity

• Uncommon (0.1% to 1%): Hypersensitivity

Respiratory

• Uncommon (0.1% to 1%): Dyspnea

Endocrine

• Uncommon (0.1% to 1%): Gynecomastia

Immunologic

Atazanavir:

• Frequency not reported: Immune reconstitution syndrome

Combination antiretroviral therapy:

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

See also:

Further information

Atazanavir/cobicistat side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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