Truvada Adverse Reactions

Summary of the safety profile: 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%) in an open-label randomised clinical study in adults (GS-01-934, see Pharmacology: Pharmacodynamics under Actions). The safety profile of emtricitabine and tenofovir disoproxil in this study was consistent with the previous experience with these agents when each was administered with other antiretroviral agents.
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%).
Tabulated summary of adverse reactions: The adverse reactions considered at least possibly related to treatment with the components of Truvada from clinical study and post-marketing experience in HIV-1 infected patients are listed in Table 9, as follows, by body system organ class and frequency. Within each frequency grouping, undesirable effects 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) or rare (≥ 1/10,000 to < 1/1,000). (See Table 9.)

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Description of selected adverse reactions: Renal impairment: As Truvada may cause renal damage monitoring of renal function is recommended (see Precautions). Proximal renal tubulopathy generally resolved or improved after tenofovir disoproxil discontinuation. However, in some HIV-1 infected patients, declines in creatinine clearance did not completely resolve despite tenofovir disoproxil discontinuation. Patients at risk of renal impairment (such as patients with baseline renal risk factors, advanced HIV disease, or patients receiving concomitant nephrotoxic medications) are at increased risk of experiencing incomplete recovery of renal function despite tenofovir disoproxil discontinuation (see Precautions).
Interaction with didanosine: Co-administration of tenofovir disoproxil and didanosine is not recommended as it results in a 40-60% increase in systemic exposure to didanosine that may increase the risk of didanosine-related adverse reactions (see Interactions). Rarely, pancreatitis and lactic acidosis, sometimes fatal, have been reported.
Metabolic parameters: Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see Precautions).
Immune Reactivation Syndrome: In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see Precautions).
Osteonecrosis: Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see Precautions).
Paediatric population: Assessment of adverse reactions related to emtricitabine is based on experience in three paediatric studies (n = 169) where treatment-naïve (n = 123) and treatment-experienced (n = 46) paediatric HIV infected patients aged 4 months to 18 years were treated with emtricitabine in combination with other antiretroviral agents. In addition to the adverse reactions reported in adults, anaemia (9.5%) and skin discolouration (31.8%) occurred more frequently in clinical trials in paediatric patients than in adults (see Tabulated summary of adverse reactions as previously mentioned).
Assessment of adverse reactions related to tenofovir disoproxil is based on two randomised trials (studies GS-US 104-0321 and GS-US-104-0352) in 184 HIV-1 infected paediatric patients (aged 2 to < 18 years) who received treatment with tenofovir disoproxil (n = 93) or placebo/active comparator (n = 91) in combination with other antiretroviral agents for 48 weeks (see Pharmacology: Pharmacodynamics under Actions). The adverse reactions observed in paediatric patients who received treatment with tenofovir disoproxil were consistent with those observed in clinical studies of tenofovir disoproxil in adults (see Tabulated summary of adverse reactions as previously mentioned and Pharmacology: Pharmacodynamics under Actions).
Reductions in BMD have been reported in paediatric patients. In HIV-1 infected adolescents (aged 12 to < 18 years), the BMD Z-scores observed in subjects who received tenofovir disoproxil were lower than those observed in subjects who received placebo. In HIV-1 infected children (aged 2 to 15 years), the BMD Z-scores observed in subjects who switched to tenofovir disoproxil were lower than those observed in subjects who remained on their stavudine- or zidovudine-containing regimen (see Precautions and Pharmacology: Pharmacodynamics under Actions).
In study GS-US-104-0352, 89 HIV-1 infected paediatric patients with a median age of 7 years (range 2 to 15 years) were exposed to tenofovir disoproxil for a median of 331 weeks. Eight of the 89 patients (9.0%) discontinued study drug due to renal adverse events. Five subjects (5.6%) had laboratory findings clinically consistent with proximal renal tubulopathy, 4 of whom discontinued tenofovir disoproxil therapy. Seven patients had estimated glomerular filtration rate (GFR) values between 70 and 90 mL/min/1.73 m². Among them, 3 patients experienced a clinically meaningful decline in estimated GFR during therapy which improved after discontinuation of tenofovir disoproxil.
Other special populations: Individuals with renal impairment: Since tenofovir disoproxil can cause renal toxicity, close monitoring of renal function is recommended in any adults with renal impairment receiving Truvada (see Dosage & Administration, Precautions and Pharmacology: Pharmacokinetics under Actions). The use of Truvada is not recommended in individuals under the age of 18 years with renal impairment (see Dosage & Administration and Precautions).
HIV/HBV or HCV co-infected patients: The adverse reaction profile of emtricitabine and tenofovir disoproxil in a limited number of HIV-infected patients in study GS-01-934 who were co-infected with HBV (n = 13) or HCV (n = 26) was similar to that observed in patients infected with HIV without co-infection. However, as would be expected in this patient population, elevations in AST and ALT occurred more frequently than in the general HIV infected population.
Exacerbations of hepatitis after discontinuation of treatment: In HBV infected patients, clinical and laboratory evidence of hepatitis have occurred after discontinuation of treatment (see Precautions).
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.