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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 emtricitabine and tenofovir alafenamide fumarate 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). Discontinuation of emtricitabine and tenofovir alafenamide fumarate 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 emtricitabine and tenofovir alafenamide fumarate 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 emtricitabine and tenofovir alafenamide fumarate in patients with significant underlying liver disorders have not been established (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
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 lifestyle. 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 are often transitory. Late onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour). 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, generalized 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) 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.
Patients with HIV-1 harbouring mutations: Emtricitabine and tenofovir alafenamide fumarate should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R mutation (see Pharmacology: Pharmacodynamics under Actions).
Triple nucleoside therapy: There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when tenofovir disoproxil was combined with lamivudine and abacavir as well as with lamivudine and didanosine as a once daily regimen. Therefore, the same problems may be seen if Emtricitabine and tenofovir alafenamide fumarate is administered with a third nucleoside analogue.
Opportunistic infections: Patients receiving Emtricitabine and tenofovir alafenamide fumarate 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 Pharmacology: Toxicology: Preclinical safety data under Actions).
Patients with end stage renal disease on chronic haemodialysis: Emtricitabine and tenofovir alafenamide fumarate should generally be avoided but may be used in adults with end stage renal disease (estimated CrCl <15 mL/min) on chronic haemodialysis if the potential benefits outweigh the potential risks (see Dosage & Administration). In a study of emtricitabine and tenofovir alafenamide in combination with elvitegravir+cobicistat as a fixed-dose combination tablet (E/C/F/TAF) in HIV-1 infected adults with end stage renal disease (estimated CrCl <15 mL/min) on chronic haemodialysis, efficacy maintained through 48 weeks but emtricitabine expose was significantly higher than in patients with normal renal function. Although there were no new safety issues identified, the implications of increased emtricitabine exposure remain uncertain (see Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
Co-administration of other medicinal products: The co-administration of emtricitabine and tenofovir alafenamide fumarate is not recommended with certain anticonvulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital and phenytoin), antimycobacterials (e.g., rifampicin, rifabutin, rifapentine), boceprevir, telaprevir, St. John's wort and HIV protease inhibitors (PIs) other than atazanavir, lopinavir and darunavir (see Interactions).
Emtricitabine and tenofovir alafenamide fumarate should not be administered concomitantly with medicinal products containing tenofovir alafenamide, tenofovir disoproxil, emtricitabine, lamivudine or adefovir dipivoxil.
Effects on ability to drive and use machines: Patients should be informed that dizziness has been reported during treatment with emtricitabine and tenofovir alafenamide fumarate.
