What it's for (Indications)
- Tenofovir disoproxil (e.
- g.
- , Tenofo-B) is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 17 kg, always used in combination with other antiretroviral agents.
- It is also approved for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients aged 2 years and older with compensated or decompensated liver disease.
- Furthermore, tenofovir disoproxil is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at high risk of HIV-1 infection.
- Its efficacy in these contexts relies on consistent adherence and appropriate medical management, underscoring its role in comprehensive viral disease management strategies.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For the treatment of HIV-1 infection and chronic hepatitis B virus (HBV) infection, the recommended adult oral dosage of tenofovir disoproxil is 300 mg once daily, typically taken with food. In the context of HIV-1 treatment, it must be used as part of a complete antiretroviral regimen to prevent resistance. For pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1, the recommended dosage is also 300 mg once daily. Dosage adjustments are critically important for patients with impaired renal function, based on their estimated creatinine clearance. Specific dosing schedules for renal impairment must be followed as per prescribing information to prevent drug accumulation and potential toxicity, requiring careful physician oversight. Pediatric dosing varies by indication and weight, as detailed in product labeling. |
Safety & Warnings
Common Side Effects
- Common side effects associated with tenofovir disoproxil treatment include gastrointestinal disturbances such as nausea, diarrhea, vomiting, and abdominal pain.
- Patients may also experience asthenia (weakness), headache, rash, and dizziness, which are generally mild to moderate and transient.
- More serious and potentially life-threatening adverse events, though rarer, can occur.
- These include significant renal impairment, which can manifest as Fanconi syndrome or acute renal failure, necessitating close monitoring of kidney function and potentially leading to permanent damage if unaddressed.
- Decreases in bone mineral density, leading to osteopenia or osteoporosis and an increased risk of fractures, have been reported with long-term use.
- A rare but severe complication is lactic acidosis with severe hepatomegaly and steatosis, which requires immediate medical attention due to its high mortality risk.
- Additionally, severe acute exacerbations of hepatitis B can occur in patients coinfected with HIV and HBV after discontinuing tenofovir disoproxil, posing a significant risk of liver decompensation.
Serious Warnings
- Black Box Warning: **WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and SEVERE ACUTE EXACERBATIONS OF HEPATITIS B** **Lactic Acidosis and Severe Hepatomegaly with Steatosis:** Fatal cases of lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate. These conditions are rare but potentially life-threatening. Factors such as obesity and prolonged nucleoside exposure, particularly in women, may increase risk. Treatment with tenofovir disoproxil fumarate should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). Immediate medical evaluation is required to manage these severe adverse reactions. **Severe Acute Exacerbations of Hepatitis B:** Severe acute exacerbations of hepatitis B (HBV) have been reported in patients coinfected with HIV-1 and HBV who have discontinued tenofovir disoproxil fumarate. In some cases, these exacerbations have been associated with hepatic decompensation and liver failure, highlighting the critical need for careful management. Patients with HBV coinfection should be closely monitored for several months after discontinuing tenofovir disoproxil fumarate therapy, including clinical and laboratory assessments of hepatic function (e.g., AST, ALT, bilirubin). Resumption of anti-HBV therapy may be warranted to mitigate the risk of severe hepatic events.
- Patients receiving tenofovir disoproxil should be closely monitored for several critical adverse events.
- **Renal impairment** is a significant concern; baseline and ongoing assessment of renal function (serum creatinine, estimated creatinine clearance, urine glucose, and urine protein) is mandatory, with dosage adjustments or discontinuation as clinically indicated, especially in individuals with pre-existing renal dysfunction or those on concomitant nephrotoxic agents.
- **Decreases in bone mineral density (BMD)** have been observed, particularly in HIV-infected individuals, potentially increasing fracture risk.
- Bone health should be monitored, and calcium/vitamin D supplementation considered for at-risk patients.
- A rare but potentially fatal complication is **lactic acidosis and severe hepatomegaly with steatosis**, which has been reported, often in women and obese individuals; treatment should be suspended immediately if clinical or laboratory signs suggest this condition.
- **Severe acute exacerbations of hepatitis B** can occur in HIV/HBV co-infected patients upon discontinuation of tenofovir disoproxil; hepatic function should be monitored for several months post-cessation, and resumption of anti-HBV therapy may be warranted.
- Before initiating tenofovir disoproxil for PrEP or HBV monotherapy, HIV-1 infection status must be confirmed as negative to prevent the emergence of HIV-1 resistance.
How it Works (Mechanism of Action)
Tenofovir disoproxil fumarate is a prodrug of tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. After oral administration, tenofovir disoproxil fumarate is rapidly absorbed and converted intracellularly into tenofovir, which is then phosphorylated by cellular kinases to the active metabolite, tenofovir diphosphate. Tenofovir diphosphate acts as a competitive inhibitor of both Human Immunodeficiency Virus type 1 (HIV-1) reverse transcriptase and hepatitis B virus (HBV) reverse transcriptase. It competes with the natural substrate, deoxyadenosine triphosphate, for incorporation into viral DNA. Once incorporated, tenofovir diphosphate causes DNA chain termination, thereby preventing the elongation of the viral DNA chain and inhibiting viral replication. This dual inhibitory action against both HIV and HBV reverse transcriptase underpins its therapeutic utility in treating these viral infections and in preventing HIV acquisition, making it a cornerstone of modern antiviral therapy.