Cobicistat is an active pharmaceutical ingredient in the Other Therapeutic Products group (V03AX). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised May 17, 2024[1]
Tybost is indicated as a pharmacokinetic enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of antiretroviral combination therapy in human immunodeficiency virus-1 (HIV-1) infected adults and adolescents aged 12 years and older: • weighing at least 35 kg co-administered with atazanavir or • weighing at least 40 kg co-administered with darunavir.
2.
How to take
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised January 2, 2024[2]
1 INDICATIONS AND USAGE PREZCOBIX is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).
PREZCOBIX is a two-drug combination of darunavir, a human immunodeficiency virus (HIV-1) protease inhibitor, and cobicistat, a CYP3A inhibitor, and is indicated for the treatment of HIV-1 infection in treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).
( 1 )
EUEuropean Union· EMA
1 product
Uses
EUOfficial regulatory label· revised February 14, 2023[3]
Tybost is indicated as a pharmacokinetic enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of antiretroviral combination therapy in human immunodeficiency virus-1 (HIV-1) infected adults and adolescents aged 12 years and older: • weighing at least 35 kg co-administered with atazanavir or • weighing at least 40 kg co-administered with darunavir.
2.
How to take
Drug interactions
Known interactions involving Cobicistat. Select one for details. This list is informational and not a complete interaction checker.
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Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PLGB119720023 · revised May 17, 2024
[2]FDA DailyMed · 16ca460a-3c89-46… · revised January 2, 2024 [PDF]
[3]European Medicines Agency · EMEA/H/C/002572 · revised February 14, 2023
[4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
GBOfficial regulatory label· revised May 17, 2024[1]
Therapy should be initiated by a physician experienced in the management of HIV infection. Posology Tybost is used in combination with atazanavir or darunavir, therefore the atazanavir or darunavir Summary of Product Characteristics should be consulted.
Tybost must be taken orally, once daily with food. The doses of Tybost and the co-administered protease inhibitor, atazanavir or darunavir, are presented in Tables 1 and 2.
Table 1:
Dosing regimens in adults Dose of Tybost Dose of HIV-1 protease inhibitor Atazanavir 300 mg once daily 150 mg once daily Darunavir 800 mg once daily Table 2: Dosing regimens in adolescents aged 12 years and older, weighing ≥ 35 kg Body Weight (kg) Dose of Tybost Dose of HIV-1 protease inhibitor Atazanavir 300 mg once daily ≥ 40 150 mg once daily Darunavir 800 mg once daily 35 to < 40 150 mg once daily Atazanavir 300 mg once daily If the patient misses a dose of Tybost within 12 hours of the time it is usually taken, the patient should take Tybost with food as soon as possible and resume their normal dosing schedule in combination with atazanavir or darunavir.
If a patient misses a dose of Tybost by more than 12 hours, the patient should not take the missed dose and simply resume the usual dosing schedule. 2). Renal impairment No dose adjustment of cobicistat is required for patients with renal impairment, including those with severe renal impairment.
Cobicistat has not been studied in patients receiving dialysis, and, therefore, no recommendation can be made for these patients. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
g. emtricitabine, lamivudine, tenofovir disoproxil, or adefovir) requires dose adjustment based on creatinine clearance. 2. Hepatic impairment No dose adjustment of cobicistat is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B).
Cobicistat has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). 2). Paediatric population The safety and efficacy of cobicistat co-administered with atazanavir in children aged 0 to less than 12 years, or weighing less than 35 kg have not been established.
The safety and efficacy of cobicistat co-administered with darunavir in children aged 0 to less than 12 years, or weighing less than 40 kg have not been established. No data are available. 2). The film-coated tablet should not be chewed or crushed.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised May 17, 2024[1]
Summary of the safety profile Adverse reactions for cobicistat-boosted atazanavir were consistent with the safety profile of ritonavir-boosted atazanavir. The most frequently reported adverse reactions to cobicistat-boosted atazanavir were associated with elevated bilirubin levels (see Table 4).
Tabulated summary of adverse reactions The safety of cobicistat is based on 144-week data from a phase 3, randomised, active- controlled clinical Study (GS-US-216-0114), in which 692 treatment-naïve patients received at least one dose of cobicistat-boosted atazanavir (n = 344) or ritonavir- boosted atazanavir (n = 348) administered with emtricitabine and tenofovir disoproxil fumarate fixed-dose combination.
Of these 692 patients, 613 (300 atazanavir/cobicistat and 313 atazanavir/ritonavir) and 496 (250 atazanavir/cobicistat and 246 atazanavir/ritonavir) received at least 48 and 144 weeks of treatment, respectively. Adverse reactions to cobicistat-boosted atazanavir during 144 weeks of clinical trial experience from Study GS-US-216-0114 are listed in Table 4, below, by body system organ class and frequency.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated from the available data).
Table 4:
Tabulated summary of adverse reactions to cobicistat-boosted atazanavir based on experience of 144 weeks from phase 3 Study GS-US-216-0114 Frequency Adverse reaction Metabolism and nutrition disorders: Common: hyperglycaemia, increased appetite Psychiatric disorders: Common: insomnia, abnormal dreams Uncommon: depression, sleep disorder Nervous system disorders: Common: headache, dizziness, somnolence, dysgeusia Eye disorders: Very common: ocular icterus Gastrointestinal disorders: Very common: nausea Common: vomiting, diarrhoea, dyspepsia, abdominal pain, abdominal distension, flatulence, dry mouth Hepatobiliary disorders: Very common: jaundice Common: hyperbilirubinaemia Skin and subcutaneous tissue disorders: Common: rash Uncommon: pruritus Musculoskeletal and connective tissue disorders: Uncommon: myalgia Renal and urinary disorders: Uncommon: nephrolithiasis, haematuria, proteinuria General disorders and administration site conditions: Common: fatigue Uncommon: pyrexia, asthenia Description of selected adverse reactions Renal impairment Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
4 mg/dl. In Study GS-US-216-0114, decreases in estimated creatinine clearance occurred early in treatment with cobicistat, after which they stabilised. 8 ml/min in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group.
4% in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group through 144 weeks of treatment. 9%). 0% in the ritonavir-boosted group). 0% in the ritonavir-boosted group. Paediatric population The safety of cobicistat was evaluated in 21 HIV-1 infected virologically suppressed paediatric patients between the ages of 12 to < 18 years through 48 weeks in an open- label clinical study (GS-US-216-0128) of cobicistat-boosted atazanavir (n = 14) or darunavir (n = 7) plus two NRTIs.
In this study, the safety profile of cobicistat was similar to that in adults. Other special population(s) Patients with renal impairment The safety of Tybost in 73 HIV-1 infected treatment-experienced patients with mild to moderate renal impairment (eGFR by Cockcroft-Gault method 50-89 ml/min) who switched pharmacokinetic enhancer from ritonavir to cobicistat was evaluated in an open-label clinical Study (GS-US-236-0118) of cobicistat-boosted atazanavir or darunavir plus two NRTIs.
07 ml/min. The effect of cobicistat on serum creatinine and eGFR in patients switching from ritonavir to cobicistat in Study GS-US-236-0118 was consistent with the effect in treatment-naïve patients in Study GS-US-216-0114. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised May 17, 2024[1]
Co-administration with other medicinal products Cobicistat is a strong mechanism-based CYP3A inhibitor and is a CYP3A substrate. Increased plasma concentrations of medicinal products that are metabolised by CYP3A (including atazanavir and darunavir) are observed on co-administration with cobicistat.
Higher plasma concentrations of co-administered medicinal products can result in increased or prolonged therapeutic effects or adverse reactions. 3). Co-administration of cobicistat with medicinal products that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of therapeutic effect.
5) because decreased plasma concentrations of cobicistat could result in plasma levels that are insufficient to achieve adequate pharmacoenhancement of atazanavir or darunavir. 5). Cobicistat is a weak CYP2D6 inhibitor and is metabolised to a minor extent by CYP2D6.
5). Cobicistat inhibits the transporters P-gp, BCRP, MATE1, OATP1B1 and OATP1B3. 5). Unlike ritonavir, cobicistat is not an inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or UGT1A1. 5). Contraception requirements Plasma concentrations of ethinyloestradiol are decreased following co-administration of drospirenone/ethinyloestradiol with darunavir/cobicistat.
Alternative or additional contraceptive measures are recommended when oestrogen-based contraceptives are co-administered with darunavir/cobicistat. Plasma concentrations of drospirenone are increased following administration of drospirenone/ethinyloestradiol with atazanavir/cobicistat or with darunavir/cobicistat.
If drospirenone/ethinyloestradiol is co-administered with atazanavir/cobicistat or darunavir/cobicistat clinical monitoring is recommended due to the potential for hyperkalemia. Data are not available to make recommendations on the use of atazanavir/cobicistat or darunavir/cobicistat with other oral contraceptives.
5). 2). Safety and efficacy have not been established for use of cobicistat with either atazanavir or darunavir when used in any other dosing regimen. 2). 2). , another protease inhibitor). Dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of atazanavir, darunavir and/or the other antiretroviral agents that require pharmacoenhancement leading to loss of antiviral activity and development of resistance.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised May 17, 2024[1]
1. Co-administration is contraindicated with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. 5): • alpha 1-adrenoreceptor antagonists: alfuzosin • antiarrhythmics: amiodarone, quinidine • ergot derivatives: dihydroergotamine, ergometrine, ergotamine • HMG Co-A reductase inhibitors: lovastatin, simvastatin • neuroleptics/antipsychotics: pimozide, lurasidone • PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension • sedatives/hypnotics: orally administered midazolam, triazolam Co-administration is contraindicated with medicinal products that are strong inducers of CYP3A due to the potential for loss of therapeutic effect.
This is not medical advice. Consult a qualified healthcare professional.
How to take
USOfficial regulatory label· revised January 2, 2024[2]
2 DOSAGE AND ADMINISTRATION Recommended dosage: One tablet taken once daily with food in adults and pediatric patients weighing at least 40 kg. 1 ) Testing Prior to Initiation: HIV genotypic testing is recommended for antiretroviral treatment experienced patients.
Assess estimated creatinine clearance in all patients prior to starting PREZCOBIX.
When used with tenofovir DF:
Assess urine glucose and urine protein at baseline and monitor creatinine clearance, urine glucose, and urine protein. Monitor serum phosphorus in patients with or at risk for renal impairment. 1 Recommended Dosage PREZCOBIX is a fixed-dose combination product containing 800 mg of darunavir and 150 mg of cobicistat.
In treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions, the recommended dosage of PREZCOBIX is one tablet taken once daily orally with food.
Administer PREZCOBIX in conjunction with other antiretroviral agents. 2 Testing Prior to Initiation of PREZCOBIX HIV Genotypic Testing HIV genotypic testing is recommended for antiretroviral treatment-experienced patients. However, when HIV genotypic testing is not feasible, PREZCOBIX can be used in protease inhibitor-naïve patients, but is not recommended in protease inhibitor-experienced patients.
3) ] . 4) ] . 1) ] . 3) ] . 3) ] . PREZCOBIX should not be initiated in pregnant individuals. An alternative regimen is recommended for those who become pregnant during therapy with PREZCOBIX.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 433 reports total. [4]
Bone Density Decreased 97
Tooth Loss 59
Renal Failure 43
Bone Loss 42
Chronic Kidney Disease 38
Osteonecrosis 38
Renal Injury 33
Skeletal Injury 33
Drug Interaction 28
Multiple Fractures 27
Osteoporosis 25
Adrenal Insufficiency 20
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised January 2, 2024[2]
10) ] The most common adverse reactions to darunavir, a component of PREZCOBIX (incidence greater than or equal to 5%) of at least moderate severity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain, and vomiting.
gov/medwatch . 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 clinical practice.
Clinical Trials in Adults During the darunavir clinical development program, where darunavir was co-administered with ritonavir 100 mg once or twice daily, the most common clinical adverse reactions (incidence greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain, and vomiting.
See the darunavir full prescribing information for additional information on adverse reactions reported with darunavir co-administered with ritonavir. See cobicistat full prescribing information for clinical trial information on adverse reactions reported with cobicistat.
One single arm clinical trial was conducted with darunavir and cobicistat administered as single entities in 313 subjects with HIV-1 infection. Adverse reactions evaluated through Week 24 did not differ substantially from those reported in clinical trials with darunavir co-administered with ritonavir.
Clinical Trials in Pediatric Patients No clinical trials with PREZCOBIX were performed in pediatric patients. However, the safety of the components of PREZCOBIX, darunavir and cobicistat, co-administered with two nucleoside reverse transcriptase inhibitors, was evaluated in pediatric subjects of 12 to less than 18 years of age with HIV-1 infection through clinical trial GS-US-216-0128 (virologically-suppressed, N=7 with weight ≥40 kg) through Week 48.
2) ] . 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of darunavir. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
2) ] .
USOfficial regulatory label· Warnings and precautions· revised January 2, 2024[2]
, acute hepatitis, cytolytic hepatitis), liver injury, including some fatalities can occur with PREZCOBIX. Monitor liver function before and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases.
1 ) Skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis, can occur with PREZCOBIX.
Discontinue treatment if severe reaction develops. 2 ) When PREZCOBIX is used in combination with a tenofovir disoproxil fumarate (tenofovir DF) containing regimen, cases of acute renal failure and Fanconi syndrome have been reported.
4 ) PREZCOBIX is not recommended in combination with other antiretroviral drugs that require pharmacokinetic boosting. 6 ) Monitor in patients with a known sulfonamide allergy. 9 ), and immune reconstitution syndrome. 10 ) Patients with hemophilia may develop increased bleeding events.
5% of subjects. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse reactions. Post-marketing cases of liver injury, including some fatalities, have also been reported with darunavir co-administered with ritonavir.
These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having co-morbidities including hepatitis B or C co-infection, and/or developing immune reconstitution syndrome. A causal relationship with darunavir co-administered with ritonavir has not been established.
Appropriate laboratory testing should be conducted prior to initiating therapy with PREZCOBIX and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of PREZCOBIX treatment.
Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZCOBIX should prompt consideration of interruption or discontinuation of treatment.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised January 2, 2024[2]
4 CONTRAINDICATIONS Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. PREZCOBIX should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life threatening events (narrow therapeutic index).
Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Co-administration of PREZCOBIX with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance.
3) ] are listed below. g. dihydroergotamine, ergotamine, methylergonovine Herbal product: St. John's wort ( Hypericum perforatum ) Hepatitis C direct acting antiviral: elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam PREZCOBIX is contraindicated in patients receiving certain co-administered drugs for which altered plasma concentrations are associated with serious and/or life-threatening events or loss of therapeutic effect.
2 )
This is not medical advice. Consult a qualified healthcare professional.
EUOfficial regulatory label· revised February 14, 2023[3]
Therapy should be initiated by a physician experienced in the management of HIV infection. Posology Tybost is used in combination with atazanavir or darunavir, therefore the atazanavir or darunavir Summary of Product Characteristics should be consulted.
Tybost must be taken orally, once daily with food. The doses of Tybost and the co-administered protease inhibitor, atazanavir or darunavir, are presented in Tables 1 and 2.
Table 1:
Dosing regimens in adults Dose of Tybost Dose of HIV-1 protease inhibitor 150 mg once daily Atazanavir 300 mg once daily Darunavir 800 mg once daily 3 Table 2: Dosing regimens in adolescents aged 12 years and older, weighing ≥ 35 kg Body Weight (kg) Dose of Tybost Dose of HIV-1 protease inhibitor ≥ 40 150 mg once daily Atazanavir 300 mg once daily Darunavir 800 mg once daily 35 to < 40 150 mg once daily Atazanavir 300 mg once daily If the patient misses a dose of Tybost within 12 hours of the time it is usually taken, the patient should take Tybost with food as soon as possible and resume their normal dosing schedule in combination with atazanavir or darunavir.
If a patient misses a dose of Tybost by more than 12 hours, the patient should not take the missed dose and simply resume the usual dosing schedule. 2). Renal impairment No dose adjustment of cobicistat is required for patients with renal impairment, including those with severe renal impairment.
Cobicistat has not been studied in patients receiving dialysis, and, therefore, no recommendation can be made for these patients. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
g. emtricitabine, lamivudine, tenofovir disoproxil, or adefovir) requires dose adjustment based on creatinine clearance. 2. Hepatic impairment No dose adjustment of cobicistat is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B).
Cobicistat has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). 2). Paediatric population The safety and efficacy of cobicistat co-administered with atazanavir in children aged 0 to less than 12 years, or weighing less than 35 kg have not been established.
The safety and efficacy of cobicistat co-administered with darunavir in children aged 0 to less than 12 years, or weighing less than 40 kg have not been established. No data are available. 2). The film-coated tablet should not be chewed or crushed.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised February 14, 2023[3]
Summary of the safety profile Adverse reactions for cobicistat-boosted atazanavir were consistent with the safety profile of ritonavir- boosted atazanavir. The most frequently reported adverse reactions to cobicistat-boosted atazanavir were associated with elevated bilirubin levels (see Table 4).
Tabulated summary of adverse reactions The safety of cobicistat is based on 144-week data from a phase 3, randomised, active-controlled clinical Study (GS-US-216-0114), in which 692 treatment-naïve patients received at least one dose of cobicistat-boosted atazanavir (n = 344) or ritonavir-boosted atazanavir (n = 348) administered with emtricitabine and tenofovir disoproxil fumarate fixed-dose combination.
Of these 692 patients, 613 (300 atazanavir/cobicistat and 313 atazanavir/ritonavir) and 496 (250 atazanavir/cobicistat and 246 atazanavir/ritonavir) received at least 48 and 144 weeks of treatment, respectively. Adverse reactions to cobicistat-boosted atazanavir during 144 weeks of clinical trial experience from Study GS-US-216-0114 are listed in Table 4, below, by body system organ class and frequency.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 17 Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated from the available data).
Table 4:
Tabulated summary of adverse reactions to cobicistat-boosted atazanavir based on experience of 144 weeks from phase 3 Study GS-US-216-0114 Frequency Adverse reaction Metabolism and nutrition disorders: Common: hyperglycaemia, increased appetite Psychiatric disorders: Common: insomnia, abnormal dreams Uncommon: depression, sleep disorder Nervous system disorders: Common: headache, dizziness, somnolence, dysgeusia Eye disorders: Very common: ocular icterus Gastrointestinal disorders: Very common: nausea Common: vomiting, diarrhoea, dyspepsia, abdominal pain, abdominal distension, flatulence, dry mouth Hepatobiliary disorders: Very common: jaundice Common: hyperbilirubinaemia Skin and subcutaneous tissue disorders: Common: rash Uncommon: pruritus Musculoskeletal and connective tissue disorders: Uncommon: myalgia Renal and urinary disorders: Uncommon: nephrolithiasis, haematuria, proteinuria General disorders and administration site conditions: Common: fatigue Uncommon: pyrexia, asthenia Description of selected adverse reactions Renal impairment Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
4 mg/dl. In Study GS-US-216-0114, decreases in estimated creatinine clearance occurred early in treatment with cobicistat, after which they stabilised. 8 ml/min in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group.
4% in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group through 144 weeks of treatment. 9%). 0% in the ritonavir-boosted group). 0% in the ritonavir-boosted group. Paediatric population The safety of cobicistat was evaluated in 21 HIV-1 infected virologically suppressed paediatric patients between the ages of 12 to < 18 years through 48 weeks in an open-label clinical study (GS-US-216-0128) of cobicistat-boosted atazanavir (n = 14) or darunavir (n = 7) plus two NRTIs.
In this study, the safety profile of cobicistat was similar to that in adults. Other special population(s) Patients with renal impairment The safety of Tybost in 73 HIV-1 infected treatment-experienced patients with mild to moderate renal impairment (eGFR by Cockcroft-Gault method 50-89 ml/min) who switched pharmacokinetic enhancer from ritonavir to cobicistat was evaluated in an open-label clinical Study (GS-US-236-0118) of cobicistat-boosted atazanavir or darunavir plus two NRTIs.
07 ml/min. The effect of cobicistat on serum creatinine and eGFR in patients switching from ritonavir to cobicistat in Study GS-US-236-0118 was consistent with the effect in treatment- naïve patients in Study GS-US-216-0114. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised February 14, 2023[3]
Co-administration with other medicinal products Cobicistat is a strong mechanism-based CYP3A inhibitor and is a CYP3A substrate. Increased plasma concentrations of medicinal products that are metabolised by CYP3A (including atazanavir and darunavir) are observed on co-administration with cobicistat.
Higher plasma concentrations of co-administered medicinal products can result in increased or prolonged therapeutic effects or adverse reactions. 3). Co-administration of cobicistat with medicinal products that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of therapeutic effect.
5) because decreased plasma concentrations of cobicistat could result in plasma levels that are insufficient to achieve adequate pharmacoenhancement of atazanavir or darunavir. 5). Cobicistat is a weak CYP2D6 inhibitor and is metabolised to a minor extent by CYP2D6.
5). Cobicistat inhibits the transporters P-gp, BCRP, MATE1, OATP1B1 and OATP1B3. 5). Unlike ritonavir, cobicistat is not an inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or UGT1A1. 5). Contraception requirements Plasma concentrations of ethinyloestradiol are decreased following co-administration of drospirenone/ethinyloestradiol with darunavir/cobicistat.
Alternative or additional contraceptive 5 measures are recommended when oestrogen-based contraceptives are co-administered with darunavir/cobicistat. Plasma concentrations of drospirenone are increased following administration of drospirenone/ethinyloestradiol with atazanavir/cobicistat or with darunavir/cobicistat.
If drospirenone/ethinyloestradiol is co-administered with atazanavir/cobicistat or darunavir/cobicistat clinical monitoring is recommended due to the potential for hyperkalemia. Data are not available to make recommendations on the use of atazanavir/cobicistat or darunavir/cobicistat with other oral contraceptives.
5). 2). Safety and efficacy have not been established for use of cobicistat with either atazanavir or darunavir when used in any other dosing regimen. 2). 2). , another protease inhibitor). Dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of atazanavir, darunavir and/or the other antiretroviral agents that require pharmacoenhancement leading to loss of antiviral activity and development of resistance.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised February 14, 2023[3]
1. Co-administration is contraindicated with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. 5): • alpha 1-adrenoreceptor antagonists: alfuzosin • antiarrhythmics: amiodarone, quinidine • ergot derivatives: dihydroergotamine, ergometrine, ergotamine 4 • HMG Co-A reductase inhibitors: lovastatin, simvastatin • neuroleptics/antipsychotics: pimozide, lurasidone • PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension • sedatives/hypnotics: orally administered midazolam, triazolam Co-administration is contraindicated with medicinal products that are strong inducers of CYP3A due to the potential for loss of therapeutic effect.
Tybost should not be used in combination with other medicinal products containing cobicistat or with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A. Effects on estimated creatinine clearance Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
This effect on serum creatinine, leading to a decrease in the estimated creatine clearance, should be taken into consideration when cobicistat is administered to patients in whom the estimated creatinine clearance is used to guide aspects of their clinical management, including adjusting doses of co-administered medicinal products.
g. emtricitabine, lamivudine, tenofovir disoproxil or adefovir). 2. There are currently inadequate data to determine whether co-administration of tenofovir disoproxil and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil without cobicistat.
Liver disease Cobicistat has not been studied in patients with severe hepatic […]
4% of subjects. 1%) reported during the clinical development program. During post-marketing experience toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported.
Discontinue PREZCOBIX immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
Mild-to-moderate rash was also reported and often occurred within the first four weeks of treatment and resolved with continued dosing. 3 Effects on Serum Creatinine Cobicistat 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 PREZCOBIX, particularly in patients with medical conditions or receiving drugs needing monitoring with estimated creatinine clearance.
2) ] . 2) ] . Consider alternative medications that do not require dosage adjustments in patients with renal impairment. 4 mg/dL from baseline should be closely monitored for renal safety. 4 New Onset or Worsening Renal Impairment When Used With Tenofovir Disoproxil Fumarate Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported when cobicistat, a component of PREZCOBIX, was used in an antiretroviral regimen that contained tenofovir DF.
3) ] . 2) ] and perform routine monitoring of estimated creatinine clearance, urine glucose, and urine protein during treatment when PREZCOBIX is used with tenofovir DF. Measure serum phosphorus in patients with or at risk for renal impairment when used with tenofovir DF.
Co-administration of PREZCOBIX and tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended. See cobicistat full prescribing information for additional information regarding cobicistat. 5 Risk of Serious Adverse Reactions or Loss of Virologic Response Due to Drug Interactions Initiation of PREZCOBIX, which inhibits CYP3A, in patients receiving medications metabolized by CYP3A, or initiation of medications metabolized by CYP3A in patients already receiving PREZCOBIX may increase plasma concentrations of medications metabolized by CYP3A and reduce plasma concentrations of active metabolite(s) formed by CYP3A.
Initiation of medications that inhibit or induce CYP3A may respectively increase or decrease concentrations of PREZCOBIX. These interactions may lead to: clinically significant adverse reactions, potentially leading to severe, life threatening, or fatal events from higher exposures of concomitant medications.
clinically significant adverse reactions from higher exposures of PREZCOBIX. loss of therapeutic effect of the concomitant medications from lower exposures of active metabolite(s). loss of therapeutic effect of PREZCOBIX and possible development of resistance from lower exposures of PREZCOBIX.
See Table 1 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during PREZCOBIX therapy; review concomitant medications during PREZCOBIX therapy; and monitor for the adverse reactions associated with concomitant medications [see Contraindications (4) and Drug Interactions (7) ] .
When used with concomitant medications, PREZCOBIX may result in different drug interactions than those observed or expected with darunavir co-administered with ritonavir. 3) ] . , another protease inhibitor or elvitegravir) because dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance.
PREZCOBIX is not recommended in combination with products containing the individual components of PREZCOBIX (darunavir and cobicistat) or with ritonavir. For additional recommendations on use of PREZCOBIX with other antiretroviral agents, [see Drug Interactions (7) ] .
7 Sulfa Allergy Darunavir contains a sulfonamide moiety. Monitor patients with a known sulfonamide allergy after initiating PREZCOBIX. In clinical studies with darunavir co-administered with ritonavir, the incidence and severity of rash were similar in subjects with or without a history of sulfonamide allergy.
8 Diabetes Mellitus/Hyperglycemia New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in patients with HIV-1 infection receiving HIV protease inhibitor (PI) therapy.
Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued PI therapy, hyperglycemia persisted in some cases.
Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and causal relationships between HIV PI therapy and these events have not been established. 9 Fat Redistribution Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.
The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. 10 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including PREZCOBIX.
During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of antiretroviral treatment.
11 Hemophilia There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis in patients with hemophilia type A and B treated with HIV PIs. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with HIV PIs was continued or reintroduced if treatment had been discontinued.
A causal relationship between PI therapy and these episodes has not been established.
Tybost should not be used in combination with other medicinal products containing cobicistat or with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A. Effects on estimated creatinine clearance Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine.
This effect on serum creatinine, leading to a decrease in the estimated creatine clearance, should be taken into consideration when cobicistat is administered to patients in whom the estimated creatinine clearance is used to guide aspects of their clinical management, including adjusting doses of co-administered medicinal products.
g. emtricitabine, lamivudine, tenofovir disoproxil or adefovir). 2. There are currently inadequate data to determine whether co-administration of tenofovir disoproxil and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil without cobicistat.
Liver disease Cobicistat has not been studied in patients with severe hepatic […]