BLACK BOX WARNING
- lactic acidosis and severe hepatomegaly with steatosis (class NRTI effect)
- severe acute exacerbation of hepatitis B after discontinuation in HBV-infected patients
tenofovir disoproxil fumarate
Brand: Viread, component of Truvada, Atripla, Stribild, Symfi
⚠ BBW Prototype Drug
Drug Class: nucleotide reverse transcriptase inhibitor (NtRTI)
Drug Family: antiretroviral
Subclass: acyclic nucleotide analog NRTI
Organ Systems: infectious-disease
Mechanism of Action
Prodrug converted to tenofovir diphosphate; competes with deoxyadenosine 5'-triphosphate for incorporation into viral DNA; acts as a chain terminator after incorporation; active against HIV-1, HIV-2, and hepatitis B virus.
HIV reverse transcriptaseHBV DNA polymerase
Indications
- HIV-1 infection (as part of combination ART)
- chronic hepatitis B (HBV) treatment
- HIV pre-exposure prophylaxis (PrEP) in combination with emtricitabine
Contraindications
- tenofovir hypersensitivity
Adverse Effects
Common
- nausea
- diarrhea
- headache
- fatigue
Serious
- nephrotoxicity (Fanconi syndrome, renal tubular acidosis, AKI)
- decreased bone mineral density (osteoporosis)
- lactic acidosis (class NRTI effect)
- severe hepatitis B flare on discontinuation in HBV-coinfected patients
Pharmacokinetics (ADME)
| Absorption | 25% fasting; increases to 39% with food — administer with meal |
| Distribution | widely distributed; low protein binding |
| Metabolism | prodrug hydrolyzed to tenofovir then phosphorylated to active form intracellularly; tenofovir is not a CYP substrate |
| Excretion | renal (70–80% unchanged via glomerular filtration and active tubular secretion); dose adjustment in CKD |
| Half-life | 17 hours (intracellular tenofovir diphosphate: 10–50 hours) |
| Onset | hours to days |
| Peak | 1–2 hours |
| Duration | 24 hours |
| Protein Binding | <0.7% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| atazanavir | tenofovir reduces atazanavir levels by ~25%; always combine with ritonavir boosting | major |
| didanosine | tenofovir increases didanosine levels; increased pancreatitis and peripheral neuropathy risk; avoid combination | major |
| nephrotoxic drugs | additive nephrotoxicity | major |
Nursing Considerations
- Administer with a meal to improve absorption.
- Monitor SCr, eGFR, urine glucose and protein at baseline and every 3–6 months; tenofovir causes proximal tubular toxicity — Fanconi syndrome presents with glycosuria at normal blood glucose, phosphaturia, and aminoaciduria.
- Measure bone mineral density at baseline in patients with risk factors for osteoporosis; tenofovir DF reduces BMD and increases fracture risk.
- If stopping tenofovir in an HBV-coinfected patient, monitor LFTs for 4–6 months; HBV flares can be severe.
Clinical Pearls
- Tenofovir DF has largely replaced older NRTIs (zidovudine, stavudine) in clinical practice due to its superior safety profile and convenient once-daily dosing; its primary toxicities (renal and bone) are generally manageable with monitoring.
- Tenofovir alafenamide (TAF) is a newer prodrug of tenofovir with lower plasma tenofovir levels and equivalent intracellular levels, resulting in significantly less renal and bone toxicity — increasingly preferred over TDF in patients with renal disease or osteoporosis risk.
Safety Profile
Pregnancy safe
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.