cobicistat (Rx)

Brand and Other Names:Tybost
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 150mg

Pharmacokinetic Enhancer for HIV Treatment

Indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection

Coadministered with atazanavir

  • May use for treatment-naïve or experienced
  • 150 mg PO qDay with atazanavir 300 mg PO qDay

Coadministered with darunavir

  • May use for treatment-naïve or treatment-experienced with no darunavir resistance-associated substitutions
  • 150 mg PO qDay with darunavir 800 mg PO qDay

Dosage Modifications

Refer to prescribing information for darunavir and atazanavir for dosage modifications

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • Coadministered with tenofovir
    • CrCl <70 mL/min: Coadministration with tenofovir not recommended
    • Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: No data

Dosing Considerations

Not interchangeable with ritonavir or recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir, owing to lack of exposure data

Assess CrCl before initiating

  • Assess estimated creatinine clearance (eCrCl)
  • Cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine
  • Does not affect actual renal glomerular function
  • If administering with tenofovir, assess eCrCl, urine glucose, and urine protein at baseline

Testing prior and during treatment

  • Prior to initiation, test patients for hepatitis B infection
  • Assess serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate

Dosage Forms & Strengths

tablet

  • 150mg

Pharmacokinetic Enhancer for HIV Treatment

Indicated to increase systemic exposure of atazanavir in combination with other antiretroviral agents for HIV-1 infected pediatric patients weighing ≥35 kg

<35 kg: Safety and efficacy not established

≥35 kg

  • Combination with atazanavir
    • Cobicistat 150 mg PO qDay in conjunction with atazanavir (300 mg PO qDay) and other antiretroviral agent

Dosage Modifications

Refer to prescribing information for darunavir and atazanavir for dosage modifications

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • Coadministered with tenofovir
    • CrCl <70 mL/min: Coadministration with tenofovir not recommended
    • Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: No data

Dosing Considerations

Not interchangeable with ritonavir or recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir, owing to lack of exposure data

Assess CrCl before initiating

  • Assess estimated creatinine clearance (eCrCl)
  • Cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine
  • Does not affect actual renal glomerular function
  • If administering with tenofovir, assess eCrCl, urine glucose, and urine protein at baseline

Testing prior and during treatment

  • Prior to initiation, test patients for hepatitis B infection
  • Assess serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate
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Interactions

Interaction Checker

and cobicistat

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            Adverse Effects

            Note: Adverse effects listed below are for cobicistat coadministered with atazanavir

            >10%

            Total bilirubin >2.5x ULN (65%)

            Ocular icterus, all grades (15%)

            Jaundice, all grades (13%)

            Nausea, all grades (12%)

            1-10%

            Creatine kinase >10x ULN (5%)

            Jaundice, Grades 2-4 (5%)

            Rash, Grades 2-4 (5%)

            Serum amylase >2x ULN (4%)

            ALT or AST >5x ULN (3%)

            Glycosuria >1000 mg/dL (3%)

            Urine RBC >75 RBC/HPF (3%)

            Ocular icterus Grades 2-4 (3%)

            GGT >5x ULN (2%)

            Nausea, Grades 2-4 (2%)

            <2%

            Gastrointestinal disorders: Diarrhea, vomiting, upper abdominal pain

            General disorders and administration site conditions: Fatigue

            Musculoskeletal and connective-tissue disorders: Rhabdomyolysis

            Nervous system disorders: Headache

            Psychiatric disorders: Depression, abnormal dreams, insomnia

            Renal and urinary disorders: Nephropathy, Fanconi syndrome acquired

            Frequency Not Defined

            Increased triglycerides, +15 from baseline

            Increased LDL-C, +5 from baseline

            Increased total cholesterol, +4 from baseline

            Increased HDL-C, +3 from baseline

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            Warnings

            Contraindications

            Coadministration of with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events

            • Alfuzosin
            • Carbamazepine, phenobarbital, phenytoin
            • Rifampin
            • Lurasidone, pimozide
            • Dihydroergotamine, ergotamine, methylergonovine
            • Cisapride
            • St. John’s wort (Hypericum perforatum)
            • Lomitapide, lovastatin, simvastatin
            • Sildenafil when administered for pulmonary arterial hypertension
            • Triazolam, orally administered midazolam

            Cautions

            Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety; assess CrCl before administering

            New-onset or worsening renal impairment reported when used with antiretroviral regimens containing tenofovir; do not use with tenofovir if CrCl <70 mL/min

            Assess urine glucose and urine protein at baseline and monitor ClCr, urine glucose, and urine protein when using with tenofovir; monitor serum phosphorus in patients with or at risk for renal impairment

            CYP inducers may lower systemic exposure of cobicistat and atazanavir or darunavir, resulting in loss of virologic response

            Cobicistat is an inhibitor of CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3; plasma concentration of drugs that are substrates of the aforementioned isoenzymes or transporters may be increased if coadministered with cobicistat

            Antiretrovirals that are not recommended

            • The following are NOT recommended in combination with cobicistat because dosing recommendations for the combinations have not been established
            • Coadministration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance
            • More than 1 antiretroviral that requires pharmacokinetic enhancement (ie, 2 protease inhibitors or a protease inhibitor in combination with elvitegravir)
            • Darunavir in combination with efavirenz, nevirapine, or etravirine
            • Atazanavir in combination with etravirine
            • Atazanavir in combination with efavirenz in treatment-experienced patients
            • Darunavir 600 mg BID
            • Other HIV-1 protease inhibitors, including fosamprenavir, saquinavir, or tipranavir
            • Stribild fixed-dose combination tablets (elvitegravir, cobicistat, emtricitabine, tenofovir) are not recommended because cobicistat is a component of Stribild
            • Cobicistat in combination with lopinavir/ritonavir or regimens containing ritonavir are not recommended, owing to similar effects of cobicistat and ritonavir on CYP3A
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            Pregnancy & Lactation

            Pregnancy

            Coadministration with darunavir or atazanavir is not recommended during pregnancy

            In a clinical trial of individuals taking cobicistat coadministered with darunavir, exposures of cobicistat and darunavir were substantially lower during the second and third trimesters of pregnancy

            Refer to prescribing information of darunavir and atazanavir about pregnancy

            Animal data

            • In animal reproduction studies in rats and rabbits, no evidence of fetal harm was observed with oral administration of cobicistat during organogenesis at doses that produced exposures up to 1.4x and 3.3x the maximal recommended human dose (MRHD) of 150 mg

            ART pregnancy registry

            • Pregnancy exposure registry that monitors fetal outcomes in individuals exposed to drug during pregnancy
            • Encourage to register patients by calling Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

            Contraception

            • Cobicistat interacts with certain oral contraceptives

            Lactation

            There is no information regarding presence of cobicistat in human milk, the effects on the breastfed infant, or the effects on milk production

            The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants due to potential risk for postnatal transmission of HIV

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            CYP3A4 inhibitor; mechanism-based pharmaco-enhancer, first product to be developed and submitted solely as pharmacokinetic booster for elvitegravir; enhances the systemic exposure of ART CYP3A substrates (ie, atazanavir, darunavir), where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism

            Absorption

            Peak Plasma Time: 3.5 hr

            Peak Plasma Concentration: 0.99 mcg/mL

            Trough Plasma Concentration: 0.03 mcg/mL

            AUC: 7.6 mcg•hr/mL

            Distribution

            Protein bound: 97-98%

            Metabolism

            Metabolized by CYP3A4 and CYP2D6 (minor)

            Inhibits CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3

            Elimination

            Half-life: 3-4 hr

            Excretion: 86.2% feces; 8.2% urine

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            Administration

            Oral Administration

            Must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents

            Coadministration with acid-modifying drugs

            • Atazanavir systemic exposure is decreased if administered comcomitantly with acid modifying drugs
            • Antacids containing aluminum or magnesium hydroxide: Administer antacids at least 2 hr before or after cobicistat with atazanavir
            • H2-receptor antagonists: Administer either at the same time or take cobicistat with atazanavir a minimum of 10 hr after administering H2-receptor antagonists
            • Proton pump inhibitors: Take cobicistat with atazanavir a minimum of 12 hr after administering proton pump inhibitors

            Storage

            Tablets: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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