Tenofovir disoproxil fumarate

Oral
Chronic hepatitis B
Adult: 300 mg once daily.
Child: ≥2 years weighing ≥10 kg: 8 mg/kg once daily. Max: 300 mg daily.
Renal impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hours of dialysis.

CrCl (ml/min)	Dosage Recommendation
10-29	300 mg 72-96 hourly.
30-49	300 mg 48 hourly.

Oral
HIV infection
Adult: In combination with other antiretrovirals: 300 mg once daily.
Child: ≥2 years weighing ≥10 kg: 8 mg/kg once daily. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Renal impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hours of dialysis.

CrCl (ml/min)	Dosage Recommendation
10-29	300 mg 72-96 hourly.
30-49	300 mg 48 hourly.

Hypersensitivity. Lactation.

Patient with risk factors for liver disease; coinfection with HIV and HBV. Renal and hepatic impairment. Pregnancy. Patient Counselling This drug may cause dizziness, if affected, do not drive or operate machinery. Monitoring Parameters Monitor renal function and serum phosphate concentrations before the start of therapy, within the first 4 weeks of treatment, after 3 months of treatment, and every 3-6 months thereafter; bone density at baseline and during treatment; LFT every 3 months during therapy and for several months following discontinuation. Determine HIV status in all hepatitis B virus (HBV) infected patients prior to treatment.

Significant: Decreased bone mineral density, immune reconstitution syndrome, osteomalacia with proximal renal tubulopathy, acute renal failure and/or Fanconi syndrome. Gastrointestinal disorders: Diarrhoea, vomiting, nausea, abdominal pain, abdominal distention, flatulence. General disorders and administration site conditions: Asthenia, fatigue, fever. Metabolism and nutrition disorders: Hypophosphataemia. Nervous system disorders: Dizziness, headache. Psychiatric disorders: Insomnia, depression. Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus.
Potentially Fatal: Lactic acidosis, severe hepatomegaly with steatosis.

May decrease the plasma concentrations of atazanavir and increased plasma concentration of tenofovir disoproxil fumarate when given concomitantly. May increase the plasma concentrations of didanosine. Increased risk of nephrotoxicity with drugs that reduce renal function (e.g. cidofovir, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin). Decreased therapeutic effect with adefovir.

High fat meals may increase bioavailability of tenofovir.

Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir. It interferes with DNA synthesis of HIV through competitive inhibition of reverse transcriptase and incorporation into viral DNA. It also inhibits hepatitis B virus polymerase, resulting in inhibition of viral replication.
Absorption: Rapidly absorbed from the gastrointestinal tract. Increased bioavailability when taken with a high fat meal. Bioavailability: Approx 25%. Time to peak plasma concentration: 36-84 minutes (fasting); 96-144 minutes (with high fat meal).
Distribution: Widely distributed into body tissues, particularly the kidneys and liver. Volume of distribution: 1.2-1.3 L/kg. Plasma protein binding: <7%.
Metabolism: Tenofovir disoproxil fumarate is rapidly converted intracellularly to tenofovir via hydrolysis, and subsequently phosphorylated to the active form, tenofovir diphosphate.
Excretion: Via urine (70-80%, as unchanged drug). Elimination half-life: 17 hours.

Oral: Store at 25°C.

Antivirals