Genvoya 150 mg/150 mg/200 mg/10 mg film-coated tablets.
Each tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 10 mg of tenofovir alafenamide.
Excipients with known effect
Each tablet contains 60 mg lactose (as monohydrate).
For the full list of excipients, see section 6.1.
Film-coated tablet (tablet).
Green, capsule-shaped, film-coated tablet of dimensions 19 mm x 8.5 mm, debossed with “GSI” on one side of the tablet and “510” on the other side of the tablet.
Genvoya is indicated for the treatment of adults and adolescents (aged 12 years and older with body weight at least 35 kg) infected with human immunodeficiency virus-1 (HIV-1) without any known mutations associated with resistance to the integrase inhibitor class, emtricitabine or tenofovir (see sections 4.2 and 5.1).
Therapy should be initiated by a physician experienced in the management of HIV infection.
Posology
Adults and adolescents aged 12 years and older, weighing at least 35 kg
One tablet to be taken once daily with food.
If the patient misses a dose of Genvoya within 18 hours of the time it is usually taken, the patient should take Genvoya with food as soon as possible and resume the normal dosing schedule. If a patient misses a dose of Genvoya by more than 18 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
If the patient vomits within 1 hour of taking Genvoya another tablet should be taken.
Elderly
No dose adjustment of Genvoya is required in elderly patients (see sections 5.1 and 5.2).
Renal impairment
No dose adjustment of Genvoya is required in adults or adolescents (aged at least 12 years and of at least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 30 mL/min.
Genvoya should not be initiated in patients with estimated CrCl < 30 mL/min as there are no data available regarding the use of Genvoya in this population (see sections 5.1 and 5.2).
Genvoya should be discontinued in patients with estimated CrCl that declines below 30 mL/min during treatment (see sections 5.1 and 5.2).
Hepatic impairment
No dose adjustment of Genvoya is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Genvoya has not been studied in patients with severe hepatic impairment (Child-Pugh Class C); therefore, Genvoya is not recommended for use in patients with severe hepatic impairment (see sections 4.4 and 5.2).
Paediatric population
The safety and efficacy of Genvoya in children younger than 12 years of age, or weighing < 35 kg, have not yet been established. No data are available.
Method of administration
Genvoya should be taken orally, once daily with food (see section 5.2). The film-coated tablet should not be chewed, crushed, or split.
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Co-administration with the following medicinal products due to the potential for serious or life-threatening adverse reactions or loss of virologic response and possible resistance to Genvoya (see section 4.5):
• alpha 1-adrenoreceptor antagonists: alfuzosin
• antiarrhythmics: amiodarone, quinidine
• anticonvulsants: carbamazepine, phenobarbital, phenytoin
• antimycobacterials: rifampicin
• ergot derivatives: dihydroergotamine, ergometrine, ergotamine
• gastrointestinal motility agents: cisapride
• herbal products: St. John's wort (Hypericum perforatum)
• HMG Co-A reductase inhibitors: lovastatin, simvastatin
• neuroleptics: pimozide
• PDE-5 inhibitors: sildenafil for the treatment of pulmonary arterial hypertension
• sedatives/hypnotics: orally administered midazolam, triazolam
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.
Patients co-infected with HIV and hepatitis B or C virus
Patients with chronic hepatitis B or C treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
The safety and efficacy of Genvoya in patients co-infected with HIV-1 and hepatitis C virus (HCV) have not been established. Tenofovir alafenamide is active against hepatitis B virus (HBV), but its clinical efficacy against this virus is under investigation and is not yet fully established.
Discontinuation of Genvoya therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis. Patients co-infected with HIV and HBV who discontinue Genvoya should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
Genvoya should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.
Liver disease
The safety and efficacy of Genvoya in patients with significant underlying liver disorders have not been established.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy (CART) and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Blood lipids and glucose
Levels of blood lipids and glucose may increase during antiretroviral therapy. Such changes may in part be linked to the treatment per se (e.g. increased levels of blood lipids and protease inhibitors [PIs]), and in part to disease control and life style. For monitoring of blood lipids and glucose, reference is made to established HIV treatment guidelines. Lipid and glucose level disorders should be managed as clinically appropriate (see section 4.8).
Mitochondrial dysfunction
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues. The main adverse reactions reported are haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactataemia, hyperlipasaemia). These events are often transitory. Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour). Whether the neurological disorders are transient or permanent is currently unknown. Any child exposed in utero to nucleoside and nucleotide analogues, even HIV negative children, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in case of relevant signs or symptoms. These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Immune Reactivation Syndrome
In HIV infected patients treated with CART, including with emtricitabine, immune reactivation syndrome has been reported. In HIV infected patients with severe immune deficiency at the time of institution of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples include cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be eva luated and treatment instituted when necessary.
Autoimmune disorders (such as Graves' disease) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable, and these events can occur many months after initiation of treatment.
Opportunistic infections
Patients receiving Genvoya or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases.
Osteonecrosis
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to CART. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Nephrotoxicity
A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to dosing with tenofovir alafenamide cannot be excluded (see section 5.3).
Co-administration of other medicinal products
Some medicinal products should not be co-administered with Genvoya (see sections 4.3 and 4.5).
Other antiretroviral medicinal products
Genvoya should not be co-administered with other antiretroviral medicinal products (see section 4.5).
Contraception requirements
Female patients of childbearing potential should use either a hormonal contraceptive containing at least 30 µg ethinylestradiol and containing norgestimate as the progestagen or should use an alternative reliable method of contraception (see sections 4.5 and 4.6). The effect of co-administration of Genvoya with oral contraceptives containing progestagens other than norgestimate is not known and, therefore, should be avoided.
Excipients
Genvoya contains lactose monohydrate. Consequently, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
Genvoya should not be co-administered with other antiretroviral medicinal products. Therefore, information regarding drug-drug interactions with other antiretroviral products (including PIs and non-nucleoside reverse transcriptase inhibitors [NNRTIs]) is not provided (see section 4.4). Interaction studies have only been performed in adults.
Genvoya should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.
Elvitegravir
Elvitegravir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A may affect the exposure of elvitegravir. Co-administration of Genvoya with medicinal products that induce CYP3A may result in decreased plasma concentrations of elvitegravir and reduced therapeutic effect of Genvoya (see “Concomitant use contraindicated” and section 4.3). Elvitegravir may have the potential to induce CYP2C9 and/or inducible uridine diphosphate glucuronosyltransferase (UGT) enzymes; as such it may decrease the plasma concentration of substrates of these enzymes.
Cobicistat
Cobicistat is a strong mechanism-based inhibitor of CYP3A and is also a CYP3A substrate. Cobicistat is also a weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6. Medicinal products that inhibit CYP3A may decrease the clearance of cobicistat, resulting in increased plasma concentrations of cobicistat.
Medicinal products that are highly dependent on CYP3A metabolism and have high first pass metabolism are the most susceptible to large increases in exposure when co-administered with cobicistat (see “Concomitant use contraindicated” and section 4.3).
Cobicistat is an inhibitor of the following transporters: P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration with medicinal products that are substrates of P-gp, BCRP, OATP1B1 and OATP1B3 may result in increased plasma concentrations of these products.
Emtricitabine
In vitro and clinical pharmacokinetic drug-drug interaction studies have shown that the potential for CYP-mediated interactions involving emtricitabine with other medicinal products is low. Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product. Medicinal products that decrease renal function may increase concentrations of emtricitabine.
Tenofovir alafenamide
Tenofovir alafenamide is transported by P-gp and BCRP. Medicinal products that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. However, upon co-administration with cobicistat in Genvoya, near maximal inhibition of P-gp by cobicistat is achieved leading to increased availability of tenofovir alafenamide with resulting exposures comparable to tenofovir alafenamide 25 mg administered alone. As such, tenofovir alafenamide exposures following administration of Genvoya are not expected to be further increased when used in combination with another P-gp inhibitor (e.g., ketoconazole). It is not known whether the co-administration of Genvoya and xanthine oxidase inhibitors (e.g., febuxostat) would increase systemic exposure to tenofovir. In vitro and clinical pharmacokinetic drug-drug interaction studies have shown that the potential for CYP-mediated interactions involving tenofovir alafenamide with other medicinal products is low. Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. Tenofovir alafenamide is not an inhibitor of CYP3A4 in vivo. Tenofovir alafenamide is a substrate of OATP in vitro. Inhibitors of OATP and BCRP include ciclosporin.
Concomitant use contraindicated
Co-administration of Genvoya and some medicinal products that are primarily metabolised by CYP3A may result in increased plasma concentrations of these products, which are associated with the potential for serious or life-threatening adverse reactions such as peripheral vasospasm or ischaemia (e.g., dihydroergotamine, ergotamine, ergometrine), or myopathy, including rhabdomyolysis (e.g., simvastatin, lovastatin), or prolonged or increased sedation or respiratory depression (e.g., orally administered midazolam or triazolam). Co-administration of Genvoya and other medicinal products primarily metabolised by CYP3A such as amiodarone, quinidine, cisapride, pimozide, alfuzosin and sildenafil for pulmonary arterial hypertension is contraindicated (see section 4.3).
Co-administration of Genvoya and some medicinal products that induce CYP3A such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital, and phenytoin may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance (see section 4.3).
Other interactions
Cobicistat and tenofovir alafenamide are not inhibitors of human UGT1A1 in vitro. It is not known whether cobicistat, emtricitabine, or tenofovir alafenamide are inhibitors of other UGT enzymes.
Interactions between the components of Genvoya and potential co-administered medicinal products are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”). The interactions described are based on studies conducted with Genvoya, or the components of Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide), as individual agents and/or in combination, or are potential drug-drug interactions that may occur with Genvoya.
Table 1: Interactions between the individual components of Genvoya and other medicinal products
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Medicinal product by therapeutic areas
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Effects on medicinal product levels.
Mean percent change in AUC, Cmax, Cmin1
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Recommendation concerning co-administration with Genvoya
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ANTI-INFECTIVES
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Antifungals
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Ketoconazole (200 mg twice daily)/ Elvitegravir (150 mg once daily)2
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Elvitegravir:
AUC: ↑ 48%
Cmin: ↑ 67%
Cmax: ↔
Concentrations of ketoconazole and/or cobicistat may increase with co-administration of Genvoya.
|
When administering with Genvoya, the maximum daily dose of ketoconazole should not exceed 200 mg per day. Caution is warranted and clinical monitoring is recommended during the co-administration.
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|
Itraconazole3
Voriconazole3
Posaconazole3
Fluconazole
|
Interaction not studied with any of the components of Genvoya.
Concentrations of itraconazole, fluconazole and posaconazole may be increased when co-administered with cobicistat.
Concentrations of voriconazole may increase or decrease when co-administered with Genvoya.
|
Clinical monitoring should be made upon co-administration with Genvoya. When administering with Genvoya, the maximum daily dose of itraconazole should not exceed 200 mg per day.
An assessment of benefit/risk ratio is recommended to justify use of voriconazole with Genvoya.
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Antimycobacterials
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Rifabutin (150 mg every other day)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)
|
Co-administration of rifabutin, a potent CYP3A inducer, may significantly decrease cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.
Rifabutin:
AUC: ↔
Cmin: ↔
Cmax: ↔
25-O-desacetyl-rifabutin
AUC: ↑ 525%
Cmin: ↑ 394%
Cmax: ↑ 384%
Elvitegravir:
AUC: ↓ 21%
Cmin: ↓ 67%
Cmax: ↔
Cobicistat:
AUC: ↔
Cmin: ↓ 66%
Cmax: ↔
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Co-administration of Genvoya and rifabutin is not recommended.
If the combination is needed, the recommended dose of rifabutin is 150 mg 3 times per week on set days (for example Monday-Wednesday-Friday).
Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is warranted due to an expected increase in exposure to desacetyl-rifabutin. Further dose reduction of rifabutin has not been studied. It should be kept in mind that a twice weekly dose of 150 mg may not provide an optimal exposure to rifabutin thus leading to a risk of rifamycin resistance and a treatment failure.
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Anti-hepatitis C virus medicinal products
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Telaprevir (750 mg three times daily)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)4
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Telaprevir:
AUC: ↔
Cmin: ↔
Cmax: ↔
Elvitegravir:
AUC: ↔
Cmin: ↑ 29%
Cmax: ↔
Cobicistat:
AUC: ↔
Cmin: ↑ 232%
Cmax: ↔
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Co-administration with telaprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide, therefore co-administration of Genvoya and telaprevir is not recommended.
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Ledipasvir (90 mg once daily)/ Sofosbuvir (400 mg once daily)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)/ Emtricitabine (200 mg once daily)/ Tenofovir alafenamide (10 mg once daily)
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Ledipasvir:
AUC: ↑ 79%
Cmin: ↑ 93%
Cmax: ↑ 65%
Sofosbuvir:
AUC: ↑ 47%
Cmin: N/A
Cmax: ↑ 28%
Sofosbuvir metabolite GS-566500:
AUC: ↔
Cmin: ↔
Cmax: ↔
Sofosbuvir metabolite GS-331007:
AUC: ↑ 48%
Cmin: ↑ 66%
Cmax: ↔
Elvitegravir:
AUC: ↔
Cmin: ↑ 46%
Cmax: ↔
Cobicistat:
AUC: ↑ 53%
Cmin: ↑ 225%
Cmax: ↔
Emtricitabine:
AUC: ↔
Cmin: ↔
Cmax: ↔
Tenofovir alafenamide:
AUC: ↔
Cmin: N/A
Cmax: ↔
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No dose adjustment of ledipasvir/sofosbuvir and Genvoya is warranted upon co-administration.
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Boceprevir
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Interaction not studied with any of the components of Genvoya.
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Co-administration with boceprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide, therefore co-administration of Genvoya and boceprevir is not recommended.
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Macrolide antibiotics
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Clarithromycin
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Interaction not studied with any of the components of Genvoya.
Concentrations of clarithromycin and/or cobicistat may be altered with co-administration of Genvoya.
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Clarithromycin dosing should be based on the patient's CrCl, taking into consideration the effect of cobicistat on CrCl and serum creatinine (see section 4.8).
Patients with CrCl greater than or equal to 60 mL/min:
No dose adjustment of clarithromycin is required.
Patients with CrCl between 30 mL/min and 60 mL/min:
The dose of clarithromycin should be reduced by 50%.
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Telithromycin
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Interaction not studied with any of the components of Genvoya.
Concentrations of telithromycin and/or cobicistat may be altered with co-administration of Genvoya.
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Clinical monitoring is recommended upon co-administration of Genvoya.
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ANTICONVULSANTS
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Carbamazepine (200 mg twice daily)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)
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Co-administration of carbamazepine, a potent CYP3A inducer, may significantly decrease cobicistat plasma concentrations.
Elvitegravir:
AUC: ↓ 69%
Cmin: ↓ 97%
Cmax: ↓ 45%
Cobicistat:
AUC: ↓ 84%
Cmin: ↓ 90%
Cmax: ↓ 72%
Carbamazepine:
AUC: ↑ 43%
Cmin: ↑ 51%
Cmax: ↑ 40%
Carbamazepine-10,11-epoxide:
AUC: ↓ 35%
Cmin: ↓ 41%
Cmax: ↓ 27%
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Carbamazepine decreases plasma concentrations of elvitegravir and cobicistat, which may result in loss of therapeutic effect and development of resistance. Co-administration of Genvoya with carbamazepine is contraindicated (see section 4.3).
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GLUCOCORTICOIDS
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Inhaled/Nasal corticosteroids
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Fluticasone
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Interaction not studied with any of the components of Genvoya.
Concomitant use of inhaled or nasal fluticasone propionate and Genvoya may increase plasma concentrations of fluticasone, resulting in reduced serum cortisol concentrations.
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Caution is warranted and clinical monitoring is recommended upon co-administration of Genvoya.
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ANTACIDS
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Magnesium/aluminium-containing antacid suspension (20 mL single dose)/ Elvitegravir (50 mg single dose)/ Ritonavir (100 mg single dose)
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Elvitegravir (antacid suspension after ± 2 hours):
AUC: ↔
Cmin: ↔
Cmax: ↔
Elvitegravir (simultaneous administration):
AUC: ↓ 45%
Cmin: ↓ 41%
Cmax: ↓ 47%
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Elvitegravir plasma concentrations are lower with antacids due to local complexation in the gastrointestinal tract and not to changes in gastric pH. It is recommended to separate Genvoya and antacid administration by at least 4 hours.
For information on other acid reducing agents (e.g., H2-receptor antagonists and proton pump inhibitors), see “Studies conducted with other medicinal products”.
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FOOD SUPPLEMENTS
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Multivitamin supplements
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Interaction not studied with any of the components of Genvoya.
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As the effect of cationic complexation of elvitegravir cannot be excluded when Genvoya is co-administered with multivitamin supplements, it is recommended to separate Genvoya and multivitamin supplements dosing by at least 4 hours.
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ORAL ANTI-DIABETICS
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Metformin
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Interaction not studied with any of the components of Genvoya.
Cobicistat reversibly inhibits MATE1, and concentrations of metformin may be increased when co-administered with Genvoya.
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Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking Genvoya.
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NARCOTIC ANALGESICS
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Methadone (80-120 mg)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)
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Methadone:
AUC: ↔
Cmin: ↔
Cmax: ↔
Cobicistat:
AUC: ↔
Cmin: ↔
Cmax: ↔
Elvitegravir:
AUC: ↔
Cmin: ↔
Cmax: ↔
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No dose adjustment of methadone is required.
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Buprenorphine/Naloxone (16/4 to 24/6 mg)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)
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Buprenorphine:
AUC: ↑ 35%
Cmin: ↑ 66%
Cmax: ↑ 12%
Naloxone:
AUC: ↓ 28%
Cmax: ↓ 28%
Cobicistat:
AUC: ↔
Cmin: ↔
Cmax: ↔
Elvitegravir:
AUC: ↔
Cmin: ↔
Cmax: ↔
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No dose adjustment of buprenorphine/naloxone is required.
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ORAL CONTRACEPTIVES
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Norgestimate (0.180/0.215 mg once daily)/ Ethinylestradiol (0.025 mg once daily)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)4
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Norgestimate:
AUC: ↑ 126%
Cmin: ↑ 167%
Cmax: ↑ 108%
Ethinylestradiol:
AUC: ↓ 25%
Cmin: ↓ 44%
Cmax: ↔
Elvitegravir:
AUC: ↔
Cmin: ↔
Cmax: ↔
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Caution should be exercised when co-administering Genvoya and a hormonal contraceptive. The hormonal contraceptive should contain at least 30 µg ethinylestradiol and contain norgestimate as the progestagen or patients should use an alternative reliable method of contraception (see sections 4.4 and 4.6).
The long-term effects of substantial increases in progesterone exposure are unknown. The effect of co-administration of Genvoya with oral contraceptives containing progestagens other than norgestimate is not known and therefore should be avoided.
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ANTIARRHYTHMICS
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Digoxin (0.5 mg single dose)/ Cobicistat (150 mg multiple doses)
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Digoxin:
AUC: ↔
Cmax: ↑ 41%
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It is recommended that digoxin levels be monitored when digoxin is combined with Genvoya.
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Disopyramide
Flecainide
Systemic lidocaine
Mexiletine
Propafenone
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Interaction not studied with any of the components of Genvoya.
Concentrations of these antiarrhythmic drugs may be increased when co-administered with cobicistat.
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Caution is warranted and clinical monitoring is recommended upon co-administration with Genvoya.
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ANTI-HYPERTENSIVES
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Metoprolol
Timolol
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Interaction not studied with any of the components of Genvoya.
Concentrations of beta-blockers may be increased when co-administered with cobicistat.
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Clinical monitoring is recommended and a dose decrease may be necessary when these agents are co-administered with Genvoya.
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Amlodipine
Diltiazem
Felodipine
Nicardipine
Nifedipine
Verapamil
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Interaction not studied with any of the components of Genvoya.
Concentrations of calcium channel blockers may be increased when co-administered with cobicistat.
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Clinical monitoring of therapeutic effects and adverse reactions is recommended when these medicinal products are concomitantly administered with Genvoya.
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ENDOTHELIN RECEPTOR ANTAGONISTS
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Bosentan
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Interaction not studied with any of the components of Genvoya.
Co-administration with Genvoya may lead to decreased elvitegravir and/or cobicistat exposures and loss of therapeutic effect and development of resistance.
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Alternative endothelin receptor antagonists may be considered.
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ANTICOAGULANTS
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Warfarin
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Interaction not studied with any of the components of Genvoya.
Concentrations of warfarin may be affected upon co-administration with Genvoya.
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It is recommended that the international normalised ratio (INR) be monitored upon co-administration of Genvoya. INR should continue to be monitored during the first weeks following ceasing treatment with Genvoya.
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Dabigatran
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Interaction not studied with any of the components of Genvoya.
Concentrations of dabigatran may be increased upon co-administration with Genvoya.
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Clinical monitoring is recommended when dabigatran is co-administered with P-gp inhibitors. A coagulation test helps to identify patients with an increased bleeding risk due to increased dabigatran exposure.
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INHALED BETA AGONIST
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Salmeterol
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Interaction not studied with any of the components of Genvoya.
Co-administration with Genvoya may result in increased plasma concentrations of salmeterol, which is associated with the potential for serious or life-threatening adverse reactions.
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Concurrent administration of salmeterol and Genvoya is not recommended.
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HMG CO-A REDUCTASE INHIBITORS
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Rosuvastatin (10 mg single dose)/ Elvitegravir (150 mg once daily)/ Cobicistat (150 mg once daily)
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Elvitegravir:
AUC: ↔
Cmin: ↔
Cmax: ↔
Rosuvastatin:
AUC: ↑ 38%
Cmin: N/A
Cmax: ↑ 89%
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Concentrations of rosuvastatin are transiently increased when administered with elvitegravir and cobicistat. Dose modifications are not necessary when rosuvastatin is administered in combination with Genvoya.
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Atorvastatin
Pitavastatin
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Interaction not studied with any of the components of Genvoya.
Concentrations of atorvastatin and pitavastatin may be increased when administered with elvitegravir and cobicistat.
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Co-administration of atorvastatin with Genvoya is not recommended. If the use of atorvastatin is considered strictly necessary, the lowest possible dose of atorvastatin should be administered with careful safety monitoring.
Caution should be exercised when co-administering Genvoya with pitavastatin.
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Pravastatin
Fluvastatin
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Interaction not studied with any of the components of Genvoya.
Concentrations of these HMG Co-A reductase inhibitors are expected to transiently increase when administered with elvitegravir and cobicistat.
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Dose modifications are not necessary when administered in combination with Genvoya.
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Lovastatin
Simvastatin
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Interaction not studied with any of the components of Genvoya.
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Co-administration of Genvoya and lovastatin and simvastatin is contraindicated (see section 4.3).
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PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITORS
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Sildenafil
Tadalafil
Vardenafil
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Interaction not studied with any of the components of Genvoya.
PDE-5 inhibitors are primarily metabolised by CYP3A. Co-administration with Genvoya may result in increased plasma concentrations of sildenafil and tadalafil, which may result in PDE-5 inhibitor-associated adverse reactions.
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Co-administration of Genvoya and sildenafil for the treatment of pulmonary arterial hypertension is contraindicated.
Caution should be exercised, including consideration of dose reduction, when co-administering Genvoya with tadalafil for the treatment of pulmonary arterial hypertension.
For the treatment of erectile dysfunction, it is recommended that a single dose of sildenafil no more than 25 mg in 48 hours, vardenafil no more than 2.5 mg in 72 hours, or tadalafil no more than 10 mg in 72 hours be co-administered with Genvoya.
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ANTIDEPRESSANTS
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Sertraline (50 mg single dose)/ Genvoya (150/150/200/10 mg once daily)
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Elvitegravir:
AUC: ↔
Cmin: ↔
Cmax: ↔
Tenofovir alafenamide:
AUC: ↔
Cmin: ↔
Cmax: ↔
Sertraline:
AUC: ↔
Cmin: ↔
Cmax: ↔
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Concentrations of sertraline are not affected upon co-administration with Genvoya. No dose adjustment is required upon co-administration.
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Tricyclic antidepressants (TCAs)
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