What are the contraindications for tenofovir (Antiretroviral medication)?

Contraindications of Tenofovir

Tenofovir has no absolute contraindications listed in its FDA labeling 1. However, there are critical clinical situations where tenofovir should be avoided or used with extreme caution to prevent serious morbidity and mortality.

Clinical Situations Where Tenofovir Should Be Avoided

Severe Renal Impairment

• Tenofovir disoproxil fumarate (TDF) should be avoided or dose-adjusted in patients with creatinine clearance below 60 mL/min 2
• Tenofovir alafenamide (TAF) is not recommended in patients with creatinine clearance below 30 mL/min 2
• TDF should be discontinued immediately if renal function worsens, particularly with evidence of proximal tubular dysfunction 2, 3
• TDF is not recommended for patients with osteopenia or osteoporosis due to bone mineral density effects 2

Active Fanconi Syndrome

• Discontinue TDF immediately upon diagnosis of Fanconi syndrome, as continued exposure leads to worsening renal function and irreversible damage 3
• For patients with active TDF-associated proximal tubulopathy, TAF should ideally be initiated only after tubulopathy has resolved 3

High-Risk Renal Toxicity Scenarios

• Avoid TDF in patients with concurrent or recent use of nephrotoxic drugs 1
• Use extreme caution when combining TDF with ritonavir-boosted protease inhibitors (atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir) or cobicistat-containing regimens, as these increase tenofovir concentrations and require frequent renal monitoring 2
• Patients taking tenofovir with efavirenz-containing regimens require caution due to increased tenofovir levels 2

Specific Drug Combinations to Avoid

Absolute Contraindications for Co-administration

• Do not use tenofovir with other tenofovir-containing products (ATRIPLA, COMPLERA, DESCOVY, GENVOYA, ODEFSEY, STRIBILD, TRUVADA, or VEMLIDY) 1
• Do not administer TDF in combination with adefovir (HEPSERA) 1
• Sofosbuvir-based regimens are contraindicated in patients being treated with amiodarone due to risk of life-threatening arrhythmias 2

Combinations Requiring Extreme Caution

• When ledipasvir/sofosbuvir is used with tenofovir plus rilpivirine or efavirenz, tenofovir levels increase, raising renal toxicity risk; monitor renal function every 2-4 weeks in high-risk patients 2
• Concomitant use with didanosine increases didanosine concentrations by 44-60%; monitor for pancreatitis and neuropathy 1, 4

Monitoring Requirements to Prevent Toxicity

Before Initiating TDF

• Assess estimated creatinine clearance before starting treatment 1
• In patients at risk for renal dysfunction, assess estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein before initiating and periodically during treatment 1

During Treatment

• Monitor for development of kidney disease with estimated glomerular filtration rate, urinalysis, and testing for glycosuria and albuminuria or proteinuria when ART is initiated or changed and every 6 months once HIV RNA is stable 2
• More frequent monitoring (every 2-4 weeks) is required in patients with creatinine clearance 30-60 mL/min or pre-existing Fanconi syndrome when using tenofovir with ritonavir-boosted protease inhibitors 2

Special Populations

Hepatitis B Co-infection

• HIV antibody testing should be offered to all HBV-infected patients before initiating tenofovir 1
• Tenofovir should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection 1
• Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who discontinued tenofovir; hepatic function must be monitored closely, and resumption of anti-hepatitis B therapy may be warranted 1

Pregnancy and Pediatrics

• HIV-infected pregnant women should initiate ART for their own health and to reduce HIV transmission 2
• Tenofovir is approved for pediatric patients 2 years and older for HIV treatment and 12 years and older for hepatitis B treatment 1

Common Pitfalls to Avoid

• Do not assume tenofovir is safe in all patients with "normal" baseline renal function—risk factors include hypertension, diabetes, HIV-associated kidney disease, hepatitis B or C co-infection, and concurrent use with ritonavir-boosted protease inhibitors 5
• Do not rely solely on serum creatinine—assess for glycosuria, phosphaturia, and proteinuria to detect early tubular dysfunction 6
• Do not continue TDF when rapid decline in kidney function occurs (eGFR drops by more than 25% and decreases to <50 mL/min/1.73 m² from baseline) 5