Applies to cobicistat: oral tablet.

Serious side effects of Cobicistat

Along with its needed effects, 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 cobicistat:

Less common

• Bloody urine
• chills
• clay-colored stools
• dark urine
• decreased frequency or amount of urine
• dizziness
• fast heartbeat
• fever
• headache
• hives or welts, itching, rash
• hoarseness
• increased thirst
• irritation
• joint pain, stiffness, or swelling
• loss of appetite
• lower back or side pain
• nausea
• pain in the groin or genitals
• redness of the skin
• sharp back pain just below the ribs
• stomach pain
• swelling of the eyelids, face, lips, hands, lower legs, or feet
• tightness in the chest
• trouble breathing or swallowing
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• weight gain
• yellow eyes or skin

Less common

• Muscle pain, stiffness, cramps, or spasms

Other side effects of Cobicistat

Some side effects of cobicistat 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:

Less common

• Diarrhea
• discouragement
• feeling sad or empty
• irritable
• loss of interest or pleasure
• trouble concentrating
• trouble sleeping
• upper abdominal or stomach pain

For Healthcare Professionals

Applies to cobicistat: oral tablet.

General

In a clinical trial, safety of this drug was evaluated in therapy-naive patients using cobicistat-boosted atazanavir with emtricitabine-tenofovir disoproxil fumarate (DF). The most common side effects were jaundice and rash; side effects associated with elevated bilirubin levels were frequently reported.

The manufacturer product information for atazanavir or darunavir should be consulted.^[Ref]

Hepatic

In 1 clinical trial, hyperbilirubinemia (greater than 1 times the upper limit of normal [1 x ULN]) was reported in 97.7% of patients in the cobicistat-boosted atazanavir group and 97.4% in the ritonavir-boosted atazanavir group through 144 weeks of therapy. Increases in total bilirubin greater than 2 x ULN was reported in 88% of patients in the cobicistat-boosted group and 80.9% in the ritonavir-boosted group. Increases in total bilirubin greater than 2.5 x ULN was reported in 73% of patients in the cobicistat-boosted group and 66% in the ritonavir-boosted group. Increased ALT or AST (greater than 3 x ULN) was reported in 12.8% of patients in the cobicistat-boosted group and 9% 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 6%, 4%, and 4% of patients in the cobicistat-boosted group, respectively.^[Ref]

Very common (10% or more): Hyperbilirubinemia, increased total bilirubin, jaundice, increased ALT or AST

Common (1% to 10%): Increased ALT, increased AST, increased GGT^[Ref]

Ocular

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

Gastrointestinal

Increased serum amylase (greater than 2 x ULN) was reported in up to 4% of patients in the cobicistat-boosted group.

If serum amylase was greater than 1.5 x ULN, lipase was also measured. Increased lipase (grades 3 to 4) was reported in up to 7% of patients in the cobicistat-boosted group.^[Ref]

Very common (10% or more): Nausea

Common (1% to 10%): Vomiting, diarrhea, dyspepsia, abdominal pain, abdominal distension, flatulence, dry mouth, increased lipase, increased serum amylase

Frequency not reported: Upper abdominal pain^[Ref]

Musculoskeletal

Increased creatine kinase (at least 10 x ULN) was reported in up to 8% of patients in the cobicistat-boosted group.^[Ref]

Common (1% to 10%): Increased creatine kinase, back pain

Uncommon (0.1% to 1%): Myalgia

Frequency not reported: Rhabdomyolysis^[Ref]

Genitourinary

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

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

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

Hematologic

Decreased neutrophils (less than 750/mm3) has been reported in up to 3% of patients in the cobicistat-boosted group.

Common (1% to 10%): Decreased neutrophils

Nervous system

Common (1% to 10%): Headache, dizziness, somnolence, dysgeusia^[Ref]

Metabolic

Increased serum glucose (greater than 250 mg/dL) has been reported in up to 2% of patients in the cobicistat-boosted group.^[Ref]

Common (1% to 10%): Hyperglycemia/increased serum glucose, increased appetite^[Ref]

Other

Common (1% to 10%): Fatigue

Uncommon (0.1% to 1%): Pyrexia, asthenia

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

Psychiatric

Common (1% to 10%): Insomnia, abnormal dreams, depression

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

Respiratory

Common (1% to 10%): Influenza, bronchitis, upper respiratory tract infection, nasopharyngitis

Renal

Uncommon (0.1% to 1%): Nephrolithiasis

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

In 1 trial, increased serum creatinine and decreased estimated CrCl occurred early in treatment with this drug, after which they stabilized. The mean change in eGFR (by Cockcroft-Gault method) after 144 weeks of therapy was -15.1 mL/min in the cobicistat-boosted group.

In HIV-1-infected therapy-experienced patients with mild to moderate renal dysfunction (eGFR [by Cockcroft-Gault method) 50 to 89 mL/min) who switched pharmacokinetic enhancer from ritonavir to cobicistat, the mean change in serum creatinine was 0.07 mg/dL and the mean change in eGFR (by Cockcroft-Gault method) was -6.2 mL/min at week 96.

Renal impairment (including acute renal failure and Fanconi syndrome) has been reported when this drug was used in regimen containing tenofovir DF.^[Ref]