Tenvir (Tenofovir Disoproxil Fumarate)

TDF and chronic hepatitis B

The World Health Organization (WHO) estimates that about 254 million people were living with chronic hepatitis B (CHB) in 2022. Chronic HBV infection can lead to long-term complications such as cirrhosis, liver failure and a higher risk of hepatocellular carcinoma (HCC). Over the past decade, HBV management has improved, and effective antiviral treatment options include tenofovir disoproxil fumarate (TDF).

TDF is an oral prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor that works against both hepatitis B virus (HBV) and HIV-1. For HIV-1, TDF is used only in combination with other antiretroviral medicines. For chronic hepatitis B, TDF is used as an antiviral treatment option; in Australian patients, HIV-1 testing is recommended before starting TDF for HBV.

Clinical trial data show that TDF can help suppress HBV DNA in many patients during long-term treatment. In adult trials, ongoing follow-up included long-term treatment for up to 384 weeks in extension phases. In the treatment of chronic hepatitis B, the optimal length of treatment is unknown.

Important safety note: severe acute flare-ups of hepatitis B have been reported after stopping anti-hepatitis B treatment, including TDF. Liver function should be monitored with clinical and laboratory follow-up for at least several months after stopping treatment; in Australia, restarting treatment may be warranted if appropriate.

Indications

VIREAD (tenofovir disoproxil fumarate, TDF) is indicated for the treatment of chronic hepatitis B virus (HBV) in adults and paediatric patients 2 years of age and older weighing at least 10 kg.

Drug interactions

TDF is mainly cleared by the kidneys. Taking it with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the other medicine; drugs that reduce kidney function may increase tenofovir concentrations. In the treatment of chronic hepatitis B, TDF should not be used together with adefovir dipivoxil.

• Coadministration decreases atazanavir concentrations. When it is coadministered with TDF, atazanavir should be given with ritonavir. Certain HIV-1 protease inhibitors, including lopinavir/ritonavir, and some HCV regimens can increase tenofovir concentrations, so in Australian clinical practice patients should be monitored for signs of tenofovir toxicity, including renal adverse effects.
• TDF increases didanosine concentrations. Dose reduction and close monitoring for didanosine toxicity are warranted.
• Examples of drugs eliminated by active tubular secretion include acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs. If used together, monitor kidney function as clinically appropriate.

Possible side effects

Along with its intended effect, this medicine may cause side effects. Evaluation of side effects in CHB with compensated liver disease is based on controlled clinical trials in 641 subjects who received treatment during a 48-week double-blind period.

In these trials, the most common side effect (all grades) was nausea (9%). Other treatment-emergent side effects reported in more than 5% of subjects included abdominal pain, diarrhoea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.

It should be noted that in Australia, stopping treatment can lead to a flare-up (worsening) of hepatitis B. During follow-up after discontinuation, monitor liver function with clinical and laboratory parameters for at least several months in Australian practice. If appropriate, it may be advisable to restart treatment.

Storage

Store TDF tablets at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Keep the bottle tightly closed and dispense only in the original container. Do not use if the seal over the bottle opening is broken or missing. Keep out of reach of children.