What are the side effects of Tenofovir (antiretroviral medication)?

Side Effects of Tenofovir

Tenofovir causes kidney and bone toxicities as its most clinically significant adverse effects, with the disoproxil fumarate (TDF) formulation carrying substantially higher risk than tenofovir alafenamide (TAF), particularly when used with pharmacokinetic boosters. 1

Major Serious Adverse Effects

Renal Toxicity

• Kidney dysfunction is the most concerning adverse effect, manifesting as proximal tubular dysfunction (Fanconi syndrome), acute kidney injury, or chronic kidney disease 1, 2
• Fanconi syndrome presents with urinary wasting of low molecular weight proteins, phosphate, uric acid, and glucose, which is slowly progressive and worsens with longer duration of TDF use 3
• Distal renal tubular acidosis has been reported, though rare, presenting with non-anion-gap metabolic acidosis 4
• Risk is especially elevated when TDF is combined with ritonavir-boosted protease inhibitors or in patients with preexisting renal disease 1, 5
• TAF formulation achieves lower plasma tenofovir concentrations and causes significantly less renal toxicity compared to TDF 1

Bone Toxicity

• Decreased bone mineral density occurs with TDF, leading to bone pain, softening, or thinning that may result in fractures 1, 2
• Bone loss is partially explained by hyperphosphaturia secondary to tubular dysfunction, which alters the interplay between bone, kidney, and regulatory hormones 3
• TAF is associated with less bone toxicity than TDF 1
• Bone mineral density shows rapid improvement after TDF discontinuation 3

Lactic Acidosis and Hepatic Toxicity

• Lactic acidosis is a rare but serious medical emergency that can lead to death, presenting with weakness, unusual muscle pain, shortness of breath, stomach pain with nausea/vomiting, cold or blue extremities, dizziness, or fast heartbeat 1, 2
• Severe liver problems can occur rarely, potentially leading to death, with symptoms including jaundice, dark urine, light-colored stools, prolonged loss of appetite, nausea, or abdominal pain 2

Common Adverse Effects

Gastrointestinal Symptoms

• Nausea is the most frequently reported side effect, occurring in 8-18.5% of patients (significantly higher than placebo at 5-7.1%) 1, 2, 6, 7
• Diarrhea and vomiting are common, with vomiting reported in 11.3% versus 7.1% in placebo groups 1, 2
• Abdominal pain and flatulence occur in more than 3% of patients 7

Neurological Symptoms

• Headache is commonly reported 1, 2
• Dizziness occurs in 15.1% versus 11.0% in placebo groups 1
• Fatigue and weakness are frequent complaints 1, 2

Other Common Effects

• Depression 2
• Rash 2
• Sleep disorders and insomnia 1
• Fever and itching (particularly in patients with advanced HBV infection) 2

Laboratory Abnormalities

• Elevated creatinine occurs in approximately 2% of patients (versus 1% with placebo) 1
• Decreased phosphorus levels in less than 1% of patients 1
• Elevated creatine kinase (>2% incidence) 7
• Elevated triglycerides, amylase, AST, and ALT (>2% incidence for grade III/IV abnormalities) 7
• Hyperglycemia and glucosuria (>2% incidence) 7
• TAF may be associated with higher blood lipid levels than TDF 1

Important Clinical Considerations

Monitoring Requirements

• Baseline and periodic renal function testing (eGFR, urinalysis for glycosuria, proteinuria) is essential before and during treatment 5, 2
• Monitor electrolytes closely, particularly phosphate, potassium, and bicarbonate 5
• Bone density assessment may be needed in high-risk patients 2

Tolerability Profile

• Most adverse events are mild and self-limited, particularly gastrointestinal symptoms which typically lessen after the first month 1
• Serious adverse events leading to discontinuation are infrequent (5%), similar to placebo (8%) 7
• Completion rates for TAF-containing regimens range from 82-96% in clinical studies 1

Drug Interactions

• Didanosine levels increase by 44-60% when coadministered with tenofovir, requiring monitoring for didanosine toxicity 6, 8
• Atazanavir requires dosage modification when used with tenofovir 8
• Tenofovir is not metabolized by cytochrome P450 enzymes, resulting in fewer drug interactions than many other antiretrovirals 8