What are the potential adverse reactions of Truvada (emtricitabine/tenofovir disoproxil fumarate)?

Truvada Adverse Reactions

Truvada (emtricitabine/tenofovir disoproxil fumarate) most commonly causes gastrointestinal symptoms (diarrhea, nausea), headache, fatigue, and dizziness, with serious but less common risks including renal impairment, bone mineral density loss, and lactic acidosis. 1

Common Adverse Reactions (≥10% incidence)

In HIV-1 infected patients, the most frequently reported adverse reactions include: 1

• Diarrhea (9% in clinical trials) 1
• Nausea (9%) 1
• Fatigue (9%) 1
• Headache (6%) 1
• Dizziness (8%) 1
• Depression (9%) 1
• Insomnia (5%) 1
• Abnormal dreams 1
• Rash (7%) 1

In HIV-uninfected adults using Truvada for PrEP, adverse reactions reported by more than 2% of participants and more frequently than placebo included: 1

• Headache 1
• Abdominal pain 1
• Weight decrease 1

Serious Renal Adverse Reactions

Renal toxicity represents one of the most clinically significant concerns with Truvada. 1

• New onset or worsening renal impairment can occur, including acute renal failure and Fanconi syndrome 1
• Proximal renal tubulopathy has been reported, manifesting as bone pain, pain in extremities, hypophosphatemia, and osteomalacia 1
• Elevated creatinine was observed as a laboratory abnormality in PrEP studies 2
• Case reports of TDF-induced Fanconi's syndrome exist in the postexposure prophylaxis literature 2
• Approximately 80% of sofosbuvir (when combined with TDF) is renally excreted, and TDF may accumulate in tubular cells causing decreased GFR and phosphate loss 2

Avoid administering Truvada with concurrent or recent use of nephrotoxic drugs, and monitor renal function closely 1

Bone Mineral Density Effects

TDF is associated with decreases in bone mineral density and increased bone turnover. 1

• Bone mineral density decreases and increases in biochemical markers of bone metabolism suggest increased bone turnover 1
• Osteomalacia associated with proximal renal tubulopathy has been reported, manifested as bone pain or pain in extremities that may contribute to fractures 1
• Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk who present with persistent or worsening bone or muscle symptoms 1
• Assessment of BMD should be considered for patients with a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss 1

Hepatic Adverse Reactions

Severe hepatomegaly with steatosis and lactic acidosis are rare but potentially fatal complications: 1

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs including FTC and TDF 1
• Treatment should be suspended in any individual who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity 1
• Severe acute exacerbations of hepatitis B can occur in HBV-coinfected patients who discontinue Truvada 1

Dermatologic Reactions

• Skin discoloration (hyperpigmentation) occurred in 3% of subjects taking FTC+TDF, generally mild and asymptomatic 1
• Rash occurred in 7% of patients in clinical trials 1

Mitochondrial Toxicity

As an NRTI-containing regimen, Truvada carries class-specific mitochondrial toxicity risks: 2

• May manifest as peripheral neuropathy, myopathy, pancreatitis, lipoatrophy, hepatic steatosis, and lactic acidosis 2
• This hallmark toxicity of the NRTI class is less common with newer NRTIs but remains a consideration 2

Immune Reconstitution Syndrome

In HIV-infected patients starting treatment, immune reconstitution syndrome may occur: 1

• Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have been reported in the setting of immune reconstitution 1
• Time to onset is variable and can occur many months after initiation of treatment 1

Drug Discontinuation Rates

• Adverse events leading to discontinuation occurred in approximately 1-2% of participants in clinical trials 1, 3
• In the DISCOVER trial comparing emtricitabine/tenofovir alafenamide to Truvada, 49 (2%) of 2693 participants discontinued due to adverse events 3

Weight Changes

• Weight gain has been observed, though this was more pronounced with tenofovir alafenamide formulations compared to TDF 4
• In PrEP trials, weight decrease was reported more frequently than placebo 1

Important Clinical Monitoring

Regular monitoring is essential to detect and manage adverse reactions: 1

• Creatinine clearance should be checked at 3 months after initiation, then every 6 months while on Truvada 2
• HIV testing every 2-3 months for PrEP patients to detect breakthrough infections 2
• Hepatitis B screening before initiation, as discontinuation can cause severe exacerbations 2
• Bone mineral density assessment in patients with risk factors for osteoporosis 1