Truvada

/ Gilead

Treatment or prevention of HIV in adults: One tablet, once daily.
Separate preparations of emtricitabine and tenofovir disoproxil are available for treatment of HIV-1 infection if it becomes necessary to discontinue or modify the dose of one of the components of Truvada. Please refer to the Summary of Product Characteristics for these medicinal products.
If a dose of Truvada is missed within 12 hours of the time it is usually taken, Truvada should be taken as soon as possible and the normal dosing schedule should be resumed. If a dose of Truvada is missed by more than 12 hours and it is almost time for the next dose, the missed dose should not be taken and the usual dosing schedule should be resumed.
If vomiting occurs within 1 hour of taking Truvada, another tablet should be taken. If vomiting occurs more than 1 hour after taking Truvada a second dose should not be taken.
Elderly: No dose adjustment is required.
Renal impairment: Emtricitabine and tenofovir are eliminated by renal excretion and the exposure to emtricitabine and tenofovir increases in individuals with renal dysfunction.
Truvada should only be used in individuals with creatinine clearance (CrCl) <80 mL/min if the potential benefits are considered to outweigh the potential risks. Dosing recommendations in individuals with renal impairment
Mild renal impairment (CrCl 50-80 mL/min):
Treatment of HIV-1 infection: Limited data from clinical studies support once daily dosing. 
Pre-exposure prophylaxis: Limited data from clinical studies support once daily dosing in HIV-1 uninfected individuals with CrCl 60-80 mL/min. Use is not
recommended for use in HIV-1 uninfected individuals with CrCl < 60 mL/min as it has not been studied in this population.
Moderate renal impairment (CrCl 30-49 mL/min):
Treatment of HIV-1 infection: Administration of Truvada every 48 hours is recommended based on modelling of single-dose pharmacokinetic data for
emtricitabine and tenofovir disoproxil in non-HIV infected subjects with varying degrees of renal impairment.
Pre-exposure prophylaxis: Truvada is not recommended for use in this population.
Severe renal impairment (CrCl < 30 mL/min) and haemodialysis patients:
Treatment of HIV-1 infection: Not recommended because appropriate dose reductions cannot be achieved with the combination tablet.
Pre-exposure prophylaxis: Truvada is not recommended for use in this population.
Hepatic impairment: No dose adjustment is required in patients with hepatic impairment.
Paediatric population: The safety and efficacy of Truvada in children under the age of 18 years have not yet been established.
Method of administration: Oral administration. It is preferable that Truvada is taken with food. The film coated tablet can be disintegrated in approximately 100 mL of water, orange juice or grape juice and taken immediately.

Treatment of HIV-1 infection: Truvada is a fixed dose combination of emtricitabine and tenofovir disoproxil fumarate. It is indicated in combination with other anti-retroviral medicinal products for the treatment of HIV-1 infected adults over 18 years of age.
Pre-exposure prophylaxis (PrEP): Truvada is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.

Hypersensitivity to the active substances or to any of the excipients.
Use for pre-exposure prophylaxis in individuals with unknown or positive HIV-1 status.

Patients with HIV-1 harbouring mutations: Truvada should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R mutation.
Patients with hepatitis B or C virus infection: Discontinuation of Truvada therapy in patients infected with HBV may be associated with severe acute exacerbations of hepatitis. Patients infected with HBV who discontinue Truvada should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of hepatitis B therapy may be warranted. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.
Renal insufficiency: Exposure to emtricitabine and tenofovir may be significantly increased when administered to patients with moderate to severe renal impairment. Dosing interval adjustment is required in patients with moderate renal impairment (creatinine clearance between 30 and 49 ml/min), according to the following: Creatinine clearance >50 ml/minute: Every 24 hours; creatinine clearance 30-49 ml/min: Every 48 hours. Clinical response to treatment and renal function should be closely monitored in these patients. Not recommended for patients with severe renal impairment.
If patients have difficulty in swallowing, Truvada can be disintegrated in approximately 100 ml of water, orange juice or grape juice and taken immediately. Should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil (as fumarate) or other cytidine analogs, such as lamivudine and zalcitabine.
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 are 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: HIV-1 infected patients receiving Truvada 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.
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 fumarate was combined with lamivudine and abacavir as well as with lamivudine and didanosine as a once daily regimen.
See prescribing information for full details.

HIV-1 infection: The most frequently reported adverse reactions considered possibly or probably related to emtricitabine and/or tenofovir disoproxil were nausea (12%) and diarrhoea (7%).
Pre-exposure prophylaxis: No new adverse reactions to Truvada were identified from two randomised placebo-controlled studies (iPrEx, Partners PrEP) in which 2,830 HIV-1 uninfected adults received Truvada once daily for pre-exposure prophylaxis. Patients were followed for a median of 71 weeks and 87 weeks, respectively. The most frequent adverse reaction reported in the Truvada group in the iPrEx study was headache (1%).
See prescribing information for full details.

Concomitant use not recommended: Truvada should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil, tenofovir alafenamide or other cytidine analogues, such as lamivudine. Truvada should not be administered concomitantly with
adefovir dipivoxil.
Didanosine: The co-administration of Truvada and didanosine is not recommended.
Increased systemic exposure to didanosine may increase
didanosine-related adverse reactions. Rarely, pancreatitis and
lactic acidosis, sometimes fatal, have been reported.
Co-administration of tenofovir disoproxil and didanosine at a
dose of 400 mg daily has been associated with a significant
decrease in CD4 cell count, possibly due to an intracellular
interaction increasing phosphorylated (i.e. active) didanosine.
A decreased dosage of 250 mg didanosine co-administered with tenofovir disoproxil therapy has been associated with reports of high rates of virological failure within several tested combinations for the Didanosine/Emtricitabine Interaction not studied. treatment of HIV-1 infection.
Renally eliminated medicinal products: Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of Truvada with medicinal products that reduce renal function or compete for active tubular secretion (e.g. cidofovir) may increase serum concentrations of emtricitabine, tenofovir and/or the co-administered medicinal products.
Use of Truvada should be avoided with concurrent or recent use of a nephrotoxic medicinal product.
Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2.
Other interactions: Interactions between Truvada or its individual component(s) and other medicinal products are listed in Table 2 at the attached doctor’s leaflet (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, twice daily as “b.i.d.” and once daily as “q.d.”). If available, 90% confidence intervals are shown in parentheses.
See prescribing information for full details.

Pregnancy: A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil.
Animal studies on emtricitabine and tenofovir disoproxil do not indicate reproductive toxicity. Therefore the use of Truvada may be considered during pregnancy, if necessary.
Breast-feeding: Emtricitabine and tenofovir have been shown to be excreted in human milk. There is insufficient information on the effects of emtricitabine and tenofovir in newborns/infants. Therefore Truvada should not be used during breast-feeding.
As a general rule, it is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV to the infant.

If overdose occurs the individual must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Up to 30% of the emtricitabine dose and approximately 10% of the tenofovir dose can be removed by haemodialysis. It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis.

Sodium content: This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.