pharmacopeia
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Mechanism of action

Sourced from openFDA

Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Inhibition of CYP3A-mediated metabolism by cobicistat increases the systemic exposure of CYP3A substrates atazanavir and darunavir.

Breast Cancer Resistance ProteinCytochrome P450 2D6Cytochrome P450 3AMultidrug and Toxin Extrusion Transporter 1Organic Anion Transporting Polypeptide 1B1Organic Anion Transporting Polypeptide 1B3P-Glycoprotein

Indications

Sourced from openFDA
  • TYBOST is a CYP3A inhibitor 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 in adults and in pediatric patients weighing at least 14 kg. ( 1.1 ) Limitations of Use : TYBOST is not interchangeable with ritonavir to increase systemic exposure of darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data.ICD-10: B20

Contraindications

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  • The concomitant use of TYBOST with atazanavir or darunavir and the following drugs is contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ] . Alpha 1-adrenoreceptor antagonist: alfuzosin Antianginal: ranolazine Antiarrhythmic: dronedarone Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine Antimycobacterial: rifampin Antineoplastics: irinotecan These contraindications apply only to TYBOST coadministered with atazanavir Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St.contraindicated

Dosage & administration

Sourced from openFDA

TYBOST must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents. ( 2.1 , 2.2 ) Recommended dosage in adults: ( 2.1 ) Adult Patient Populations Coadministered Agent Dosage TYBOST Dosage Treatment-naïve or treatment-experienced atazanavir 300 mg orally once daily 150 mg orally once daily Treatment-naïve or treatment-experienced with no darunavir resistance-associated substitutions darunavir 800 mg orally once daily Recommended dosage in pediatric patients: TYBOST 150 mg or TYBOST 90 mg orally once daily based on body weight. For dosage recommendations for TYBOST and the coadministered protease inhibitor atazanavir or darunavir in pediatric patients, refer to Table 2 and Table 3 of the full prescribing information respectively. ( 2.2 ) Prior to starting TYBOST, assess estimated creatinine clearance. ( 2.3 ) Coadministration with tenofovir disoproxil fumarate (TDF): assess estimated creatinine clearance, urine glucose, and urine protein at baseline. ( 2.3 ) TYBOST coadministered with TDF is not recommended in patients who have an estimated creatinine clearance below 70 mL/min because dose adjustment of TDF is required below 50 mL/min and such dose adjustments have not been established for coadministration with TYBOST. ( 2.4 ) 2.1 Recommended Dosage in Adults Administer TYBOST in conjunction with atazanavir or darunavir and other antiretroviral agents in the treatment of adults with HIV-1 infection.

Warnings & precautions

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Assess creatinine clearance (CLcr) before initiating treatment. ( 5.1 ) When TYBOST is used in combination with a TDF-containing regimen, cases of acute renal failure and Fanconi syndrome have been reported. ( 5.2 ) Use with TDF: Assess urine glucose and urine protein at baseline and monitor CLcr, urine glucose, and urine protein. Monitor serum phosphorus in patients with or at risk for renal impairment. ( 5.2 ) TYBOST in combination with more than one antiretroviral that requires pharmacokinetic enhancement (i.e., two protease inhibitors or elvitegravir in combination with a protease inhibitor) is not recommended. ( 5.4 ) Use with HIV-1 protease inhibitors other than atazanavir or darunavir administered once daily is not recommended. ( 5.4 ) Coadministration with drugs or regimens containing ritonavir is not recommended. ( 5.4 ) 5.1 Effects on Serum Creatinine TYBOST decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. This effect should be considered when interpreting changes in estimated creatinine clearance in patients initiating TYBOST, particularly in patients with medical conditions or receiving drugs needing monitoring with estimated creatinine clearance. Prior to initiating therapy with TYBOST, assess estimated creatinine clearance [see Dosage and Administration (2.3) ] .

Adverse reactions

Sourced from openFDA

The following adverse reaction is described in greater detail in another section of the labeling: New Onset or Worsening Renal Impairment When Used with Tenofovir Disoproxil Fumarate [see Warnings and Precautions (5.2) ]. The most common adverse drug reactions observed with TYBOST in combination with atazanavir (incidence greater than 5%, Grades 2−4) are jaundice and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from Clinical Trials Experience in Adults The safety of TYBOST is based on Week 144 data from a Phase 3 trial, Trial 114, in which 692 antiretroviral treatment-naïve participants with HIV-1 received: TYBOST coadministered with atazanavir and TDF/emtricitabine (administered as TRUVADA) (N=344) or ritonavir coadministered with atazanavir and TDF/emtricitabine (administered as TRUVADA) (N=348). The most common adverse reactions (Grades 2−4) and reported in >5% of participants in the TYBOST group were jaundice (6%) and rash (5%). The proportion of participants who discontinued study treatment due to adverse events, regardless of severity, was 11% in both the TYBOST and ritonavir groups.

Use in specific populations

Sourced from openFDA

Pregnancy: TYBOST coadministered with darunavir or atazanavir is not recommended during pregnancy. TYBOST coadministered with darunavir or atazanavir should not be initiated in pregnant individuals. ( 2.5 , 8.1 , 12.3 ) Pediatrics: Not recommended for patients weighing less than 14 kg. ( 8.4 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors fetal outcomes in individuals exposed to TYBOST during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263. Risk Summary TYBOST coadministered with darunavir or atazanavir is not recommended during pregnancy [see Dosage and Administration (2.5) ] . 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 [see Data and Clinical Pharmacology (12.3) ] . TYBOST use during pregnancy has been evaluated in a limited number of individuals as reported by the APR, and available data show no significant difference in the rate of overall birth defects for cobicistat compared with the background rate for major defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) ( see Data ). The rate of miscarriage is not reported in the APR.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption In a trial where participants were instructed to take coadministered TYBOST and darunavir with food, median cobicistat peak plasma concentrations were observed approximately 3.5 hours postdose. Steady-state cobicistat C max , AUC tau, and C tau (mean ± SD) values were 0.99 ± 0.3 mcg/mL (n=60), 7.6 ± 3.7 mcg∙hr/mL (n=59), and 0.03 ± 0.1 mcg/mL (n=59), respectively.

Overdosage

Sourced from openFDA

If overdose occurs, the patient must be monitored for evidence of toxicity. Treatment of overdose with TYBOST consists of general supportive measures including monitoring of vital signs, as well as observation of the clinical status of the patient. As cobicistat is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis.

Approval history

Sourced from openFDA
  • Aug 27, 2012NDANDA203100Gilead Sciences Inc
  • Sep 24, 2014NDANDA203094Gilead Sciences Inc
  • Jan 29, 2015NDANDA205395Janssen Prods
  • Jan 29, 2015NDANDA206353Bristol
  • Nov 5, 2015NDANDA207561Gilead Sciences Inc
  • Jul 17, 2018NDANDA210455Janssen Prods

FDA shortages

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Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

  • Evotaz, Tablet, 300 mg; 150 mg (NDC 0003-3641-11)To be discontinued
    Sponsor: Bristol Myers Squibb Co.
    Updated
  • Tybost, Tablet, 150 mg (NDC 61958-1401-1)To be discontinued
    Sponsor: Gilead Sciences, Inc.
    Updated

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
20,686 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Bone Density Decreased8,07539%
  2. 2Chronic Kidney Disease4,72823%
  3. 3Renal Injury4,57522%
  4. 4Tooth Loss4,16020%
  5. 5Bone Loss4,09520%
  6. 6Skeletal Injury4,07720%
  7. 7Osteonecrosis4,04720%
  8. 8Renal Failure3,84919%
  9. 9Multiple Fractures3,71218%
  10. 10Pain3,51217%
  11. 11Emotional Distress3,40616%
  12. 12Osteoporosis3,36216%
  13. 13Anxiety3,17715%
  14. 14Anhedonia3,01915%
  15. 15Osteopenia2,06510.0%

Literature

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Recent PubMed references pinned to Cobicistat as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 169 ClinicalTrials.gov registrations naming Cobicistat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Cobicistat work?
Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Inhibition of CYP3A-mediated metabolism by cobicistat increases the systemic exposure of CYP3A substrates atazanavir and darunavir.
What is Cobicistat used for?
According to FDA labeling, Cobicistat carries indications including: TYBOST is a CYP3A inhibitor 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 in adults and in pediatric patients weighing at least 14 kg. ( 1.1 ) Limitations of Use : TYBOST is not interchangeable with ritonavir to increase systemic exposure of darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Cobicistat?
Cobicistat is classified as Other therapeutic products, Cytochrome P450 3A Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A Inhibitors, Multidrug and Toxin Extrusion Transporter 1 Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, P-Glycoprotein Inhibitors.
What are the brand names for Cobicistat?
Cobicistat is marketed under brand names including Evotaz, Genvoya, Prezcobix, Stribild, Symtuza, Tybost.
What are the contraindications for Cobicistat?
Cobicistat labeling lists contraindications including: The concomitant use of TYBOST with atazanavir or darunavir and the following drugs is contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ] . Alpha 1-adrenoreceptor antagonist: alfuzosin Antianginal: ranolazine Antiarrhythmic: dronedarone Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine Antimycobacterial: rifampin Antineoplastics: irinotecan These contraindications apply only to TYBOST coadministered with atazanavir Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St.. Always consult the full prescribing information and a clinician.
Note. Data for cobicistat is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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