VIREAD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIREAD (VIREAD).
Tenofovir disoproxil fumarate is a nucleotide analog reverse transcriptase inhibitor (NtRTI) that undergoes intracellular phosphorylation to tenofovir diphosphate, which incorporates into viral DNA and terminates chain elongation.
| Metabolism | Tenofovir disoproxil is rapidly hydrolyzed to tenofovir; tenofovir is minimally metabolized by CYP450 enzymes. Approximately 70-80% is excreted unchanged in urine via combination of glomerular filtration and active tubular secretion. |
| Excretion | Renal: 70-80% unchanged via glomerular filtration and tubular secretion; fecal: <1% |
| Half-life | Terminal half-life: 17 hours (intracellular active metabolite tenofovir diphosphate: 60-100 hours); supports once-daily dosing |
| Protein binding | <7.2% bound to plasma proteins (negligible binding) |
| Volume of Distribution | 1.2 L/kg (independent of body weight); indicates distribution into total body water |
| Bioavailability | Oral: 25% (fasting); increased with high-fat meal (around 40%) |
| Onset of Action | Oral: Not applicable for acute effect; antiviral effect begins within days, maximal HIV RNA suppression by 4-6 weeks |
| Duration of Action | 24 hours after single dose; requires daily dosing due to intracellular half-life; duration of suppression correlates with intracellular tenofovir diphosphate |
| Molecular Weight | 635.52 |
| Action Class | Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) |
| Brand Substitutes | Tavin Tablet, Tenvir Tablet, Tenarica Tablet, Ricovir 300mg Tablet, Synflovir Tablet |
300 mg orally once daily with food.
| Dosage form | POWDER |
| Renal impairment | Creatinine clearance (CrCl) ≥50 mL/min: 300 mg every 24 hours. CrCl 30–49 mL/min: 300 mg every 48 hours. CrCl 10–29 mL/min: 300 mg every 72–96 hours. Hemodialysis: 300 mg every 7 days (after dialysis). |
| Liver impairment | No dose adjustment required for mild to severe hepatic impairment (Child-Pugh A, B, or C). |
| Pediatric use | For patients 2 to <12 years (≥10 kg): 8 mg/kg (maximum 300 mg) orally once daily. For patients ≥12 years (≥35 kg): 300 mg orally once daily. |
| Geriatric use | Select dose based on renal function; monitor renal function regularly due to age-related decline in CrCl. |
| 1st trimester | Limited data; no increased risk of major malformations based on registry studies. Use only if clearly needed. |
| 2nd trimester | No evidence of fetal harm in animal studies; human data limited. Use if benefit outweighs risk. |
| 3rd trimester | No known adverse fetal effects; may be used for maternal HIV or HBV treatment. |
Clinical note
Comprehensive clinical and safety monograph for VIREAD (VIREAD).
| Placental transfer | Tenofovir crosses the placenta; cord blood concentrations are similar to maternal plasma concentrations, indicating extensive transfer. |
| Breastfeeding | Tenofovir disoproxil fumarate is excreted into human milk at low levels. In HIV-infected mothers, breast milk can contain HIV virus, so breastfeeding is not recommended. For HBV, consider the risk of infant exposure against benefit of maternal treatment. |
■ FDA Black Box Warning
Lactic acidosis/severe hepatomegaly with steatosis; post-treatment exacerbation of hepatitis B.
| Serious Effects |
Hypersensitivity to tenofovir or any component of the formulation
| Precautions | New onset or worsening renal impairment (monitor creatinine clearance and urine glucose/protein); Fanconi syndrome; risk of nephrotoxicity with concurrent or recent use of nephrotoxic agents; decreased bone mineral density; immune reconstitution syndrome; redistribution/accumulation of body fat; hepatic decompensation in patients with cirrhosis and hepatitis B. |
| Food/Dietary | High-fat meals increase absorption of tenofovir DF; take with food. No specific food restrictions, but consistent timing with meals recommended. |
Loading safety data…
| Lactation Rating | L2 (probably compatible) |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; however, a large prospective cohort study (Antiretroviral Pregnancy Registry) shows no increased risk of major birth defects. First trimester exposure: not associated with increased malformations. Second/third trimester: no fetal risks identified. Monitor for mitochondrial toxicity in neonates. |
| Fetal Monitoring | Monitor renal function (serum creatinine, urine protein) and bone density in pregnant women receiving tenofovir. Check liver function tests if concurrent hepatotoxicity risk. Fetal monitoring includes standard prenatal ultrasound for growth and anatomy. In neonates, monitor for bone mineral density if prolonged in utero exposure. |
| Fertility Effects | Animal studies: no effect on fertility. Human data: limited. Tenofovir does not impair spermatogenesis in men or ovulation in women. No evidence of reduced fertility in women on antiretroviral therapy. Clinically, no significant impact on male or female reproductive function. |
| Clinical Pearls | Monitor renal function before and during therapy, especially in patients with renal impairment or those taking nephrotoxic drugs. Dose adjustment required for CrCl < 50 mL/min. Tenofovir DF may cause Fanconi syndrome, bone mineral density loss, and renal tubular dysfunction. Use with caution in HIV/HBV coinfection as abrupt discontinuation can cause severe HBV exacerbation. Tenofovir alafenamide (TAF) is a prodrug with lower renal and bone toxicity compared to tenofovir disoproxil fumarate (TDF). |
| Patient Advice | Take VIREAD with food to improve absorption. · Do not miss doses; adherence is critical to prevent resistance. · Report severe or persistent bone pain, muscle pain, or kidney pain. · If you have hepatitis B, do not stop VIREAD without medical supervision due to risk of flare-up. · May cause dizziness; avoid driving if affected. · Use effective contraception during treatment (not recommended during pregnancy unless clearly needed). |