Tenofovir Disoproxil
Tenofovir disoproxil is a nucleotide analogue reverse transcriptase inhibitor. Its FDA label states it is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection, and separately for the treatment of chronic hepatitis B. MedlinePlus explains that it works by decreasing the amount of HIV and hepatitis B virus in the blood.
Key points
- Tenofovir disoproxil is indicated, in combination with other antiretroviral agents, for HIV-1 infection, and separately for chronic hepatitis B.
- It works by decreasing the amount of HIV and hepatitis B virus in the blood.
- Before starting treatment, the label calls for HIV antibody testing to be offered to all patients with hepatitis B virus infection.
How tenofovir moves through the body
After a single oral dose, tenofovir has a terminal elimination half-life of approximately 17 hours. It is also a substrate of the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters, so an inhibitor of either transporter can raise how much of the drug is absorbed.
The hepatitis B boxed warning
Tenofovir disoproxil’s label carries a boxed warning: severe acute exacerbations of hepatitis B virus have been reported in patients with chronic hepatitis B who have discontinued anti-hepatitis B therapy, including this medicine. The label calls for patients who stop treatment to be monitored closely, with clinical and laboratory follow-up for at least several months, and states that resuming anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since a post-treatment flare can lead to liver decompensation and liver failure. MedlinePlus states the same warning in patient-facing terms: a person with hepatitis B virus infection who takes tenofovir disoproxil may find their condition suddenly worsens after they stop taking it.
The label separately warns that lactic acidosis and severe liver enlargement with fatty change, including fatal cases, have been reported with nucleoside analogues such as tenofovir disoproxil, alone or combined with other antiretrovirals.
The kidney and the bone
Tenofovir is principally eliminated by the kidney, and the label states that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with its use.
Bone effects follow from the same place. The label reports cases of osteomalacia associated with proximal renal tubulopathy, showing as bone pain or pain in the extremities and capable of contributing to fractures, and it asks that hypophosphataemia and osteomalacia secondary to proximal renal tubulopathy be considered in anyone at risk of renal dysfunction who develops persistent or worsening bone or muscle symptoms during treatment. That is the practical link a reader needs: bone pain on this medicine is a reason to look at the kidneys.
Separately, in clinical trials in adults with HIV-1, tenofovir disoproxil was associated with slightly greater decreases in bone mineral density and increases in biochemical markers of bone metabolism, suggesting increased bone turnover. The label asks that assessment of bone mineral density be considered in patients with a history of pathologic fracture, or other risk factors for osteoporosis or bone loss.