Presentation and Status in Health Basket
Film Coated Tablets
One tablet to be taken once daily with/without food.
Missed doses: If the patient misses a dose within 18 hours of the time it is usually taken, the patient should take the drug as soon as possible and resume the normal dosing schedule. If a patient misses a dose 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 the drug another tablet should be taken. If a patient vomits more than 1 hour after taking the drug they do not need to take another dose of the drug until the next regularly scheduled dose.
Renal impairment: No dose adjustment is required in patients with estimated creatinine clearance (CrCl) ≥ 30 mL/min. Initiation of this drug is not recommended in patients with estimated CrCl below 30 mL/min, as there are insufficient data available regarding the use of this medication in this population.
Hepatic impairment: No dose adjustment is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. This medication has not been studied in patients with severe hepatic impairment (Child-Pugh Class C), therefore this drug is not recommended for use in patients with severe hepatic impairment.
Paediatric population: The safety and efficacy of this drug in children under the age of 18 years have not yet been established. No data are available.
Elderly: There are limited data on the use of this drug in patients aged 65 years and over. No dose adjustment of this drug is required in elderly patients.
Method of administration: Oral use. Biktarvy can be taken with or without food.
The film-coated tablets should not be chewed, crushed or split.
Treatment of adults infected with human immunodeficiency virus-1 (HIV-1) without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir.
Hypersensitivity to the active substances or to any of the excipients.
Co-administration with rifampicin and St John’s Wort (Hypericum perforatum).
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.
There are limited safety and efficacy data for this medication in patients co-infected with HIV-1 and hepatitis C virus (HCV).
This medication contains tenofovir alafenamide, which is active against hepatitis B virus (HBV).
Discontinuation of this medication 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 this medication should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
Liver disease: The safety and efficacy of this medication 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.
Weight and metabolic parameters: An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.
Mitochondrial dysfunction following exposure in utero: Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia). These events have often been transitory. Late onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behavior). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical findings of unknown etiology, particularly neurologic findings. 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 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 evaluated and treatment instituted when necessary.
Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) 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 should be advised that this medication or any other antiretroviral therapy does not cure HIV infection and that they may still develop opportunistic infections and other complications of HIV infection. Therefore patients 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 of other medicinal products.
This medication should not be co-administered simultaneously with magnesium/aluminium-containing antacids or iron supplements under fasted conditions. This medication should be administered at least 2 hours before, or with food 2 hours after antacids containing magnesium and/or aluminium. This medication should be administered at least 2 hours before iron supplements, or taken together with food.
See prescribing information for full details.
Depression, abnormal dreams, headache, dizziness, diarrhea, nausea, fatigue.
See prescribing information for full details.
Interaction studies have only been performed in adults.
The drugs should not be administered concomitantly with medicinal products containing tenofovir alafenamide, tenofovir disoproxil, lamivudine or adefovir dipivoxil used for the treatment of HBV infection.
Bictegravir: Bictegravir is a substrate of CYP3A and UGT1A1. Co-administration of bictegravir and medicinal products that potently induce both CYP3A and UGT1A1, such as rifampicin or St. John’s wort, may significantly decrease plasma concentrations of bictegravir, which may result in a loss of therapeutic effect of this agent and development of resistance, therefore co-administration is contraindicated.
Co-administration of bictegravir with medicinal products that potently inhibit both CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of bictegravir, therefore co-administration is not recommended.
Bictegravir is both a P-gp and a BCRP substrate. The clinical relevance of this feature is not established. Therefore, caution is recommended when bictegravir is combined with medicinal products known to inhibit P-gp and/or BCRP (e.g. macrolides, ciclosporin, verapamil, dronedarone, glecaprevir/pibrentasvir) (see also table below).
Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Co-administration of this medication with the OCT2 and MATE1 substrate metformin did not result in a clinically significant increase in metformin exposure. The drug may be co-administered with substrates of OCT2 and MATE1.
Bictegravir is not an inhibitor or inducer of CYP in vivo.
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-glycoprotein (P –gp) and breast cancer resistance protein (BCRP). Co-administration of this agent with medicinal products that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. Medicinal products that induce P-gp activity (e.g. rifabutin, carbamazepine, phenobarbital) are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide, which may lead to loss of therapeutic effect of the drug and development of resistance. Co-administration of this medication with other medicinal products that inhibit P-gp and BCRP may increase the absorption and plasma concentration of tenofovir alafenamide.
Interactions between this drug or its individual component(s) and other medicinal products: See prescribing information for full details.
Pregnancy and Lactation
Pregnancy: There are no or limited data (less than 300 pregnancy outcomes) from the use of bictegravir or tenofovir alafenamide in pregnant women. A large amount of data on pregnant women (more than 1,000 exposed outcomes) indicate no malformative nor foetal/neonatal toxicity associated with emtricitabine.
Lactation: It is not known whether bictegravir or tenofovir alafenamide is excreted in human milk. Emtricitabine is excreted in human milk. In animal studies, bictegravir was detected in the plasma of nursing rat 11 pups likely due to the presence of bictegravir in milk, without effects on nursing pups. In animal studies it has been shown that tenofovir is excreted in milk.
If overdose occurs the patient must be monitored for evidence of toxicity.
Treatment of overdose with this drug consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.
There is no specific antidote for overdose with this drug. As bictegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Emtricitabine can be removed by hemodialysis, which removes approximately 30% of the emtricitabine dose over a 3 hour dialysis period starting within 1.5 hours of emtricitabine dosing.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis.
Storage: Store in the original package in order to protect from moisture. No special storage conditions are required. Storage at room temperature is recommended.