Overview
Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor used for the treatment of HIV-1 infection and chronic hepatitis B virus infection. It works by inhibiting viral replication through incorporation into viral DNA, leading to chain termination. The drug is also used in combination with emtricitabine for HIV-1 pre-exposure prophylaxis (PrEP) in at-risk individuals.
Mechanism of Action
Tenofovir disoproxil fumarate is a prodrug that is converted to tenofovir, which is then phosphorylated to tenofovir diphosphate. Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and HBV polymerase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, causes chain termination.
Indications
- Treatment of HIV-1 infection in combination with other antiretroviral agents
- Treatment of chronic hepatitis B virus infection
- HIV-1 pre-exposure prophylaxis (PrEP) in combination with emtricitabine for at-risk individuals
Common Doses
- 300 mg
- 200 mg/300 mg (combination with emtricitabine)
Dosage
For HIV-1 treatment: 300 mg once daily. For chronic hepatitis B: 300 mg once daily. For HIV-1 PrEP (with emtricitabine): 200 mg/300 mg once daily. Dosage adjustments required for renal impairment.
Contraindications
- Use in individuals with unknown or positive HIV-1 status when prescribed for HIV-1 PrEP
- Severe renal impairment (creatinine clearance <30 mL/min) without dose adjustment
Side Effects
- Nausea
- Diarrhea
- Headache
- Fatigue
- Renal impairment
- Decreased bone mineral density
- Lactic acidosis
- Hepatomegaly with steatosis
- Exacerbation of hepatitis B upon discontinuation
Interactions
- Drugs that reduce renal function may increase tenofovir concentrations
- Concomitant use with other nephrotoxic drugs increases risk of renal toxicity
- Didanosine coadministration may increase didanosine concentrations
Counseling Points
- Take exactly as prescribed, typically once daily with or without food
- For HIV-1 PrEP, must have confirmed negative HIV-1 status before initiation and every 3 months during therapy
- Report symptoms of lactic acidosis (nausea, vomiting, abdominal pain, weakness)
- Monitor for signs of kidney problems (changes in urine output, swelling)
- Do not stop medication without consulting healthcare provider, especially if HBV-infected
- Use additional barrier protection methods for HIV prevention during PrEP therapy
- Regular monitoring of renal function and bone density recommended