Aptiom | Pharmacology Mentor

Generic Name

Aptiom (tenofovir alafenamide fumarate)

Mechanism

Tenofovir alafenamide is a lipophilic prodrug of tenofovir.
1. After oral absorption, it is rapidly converted to tenofovir in plasma via a deamidation pathway.
2. Inside hepatocytes or lymphocytes, tenofovir is phosphorylated to tenofovir diphosphate (TFV-DP).
3. TFV-DP competes with natural deoxyadenosine triphosphate and is incorporated into viral DNA by the reverse transcriptase/viral polymerase, causing premature chain termination.
*Result:* Selective inhibition of HBV DNA polymerase and HIV‑1 reverse transcriptase with minimal effect on host DNA polymerases.

Pharmacokinetics

Parameter	Typical Value
Absorption	Rapid; Cmax at ~1 h post‑dose; >90 % bioavailability in fasting state.
Distribution	Highly lipophilic; ~95 % protein binding.
Metabolism	Primarily deamidation to tenofovir; minor CYP3A4 oxidation.
Elimination	Renal excretion of tenofovir (≈25 % renal clearance). Half‑life of TFV‑DP in PBMCs ~100 h.
Food Effect	Food delays absorption but does not alter AUC; use with or without food.

Indications

Chronic Hepatitis B Virus (HBV) infection – monotherapy or in combination.
HIV‑1 Pre‑Exposure Prophylaxis (PrEP) in combination with emtricitabine (as part of Truvada or Descovy).

*Guideline reference:* American Association for the Study of Liver Diseases (AASLD) 2023 Guidelines.

Contraindications

Contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) or on dialysis.
Warnings:
Renal toxicity (rare, but monitor eGFR).
Osteopenia/osteoporosis (mild, less risk than tenofovir disoproxil fumarate).
Hepatic dysfunction: not recommended in decompensated cirrhosis.
Pregnancy: limited data; use only if benefits outweigh risks.

Dosing

Chronic HBV: 25 mg orally once daily, independent of meals.
HIV‑PrEP (once‑daily regimen): 25 mg of tenofovir alafenamide + 200 mg emtricitabine daily.
Patients with mild renal impairment (CrCl ≥ 50 mL/min): standard dose.
Patients with moderate renal impairment (CrCl 30–49 mL/min): consider dose adjustment; expert panel recommends close monitoring or alternative therapy.

Adverse Effects

Category	Examples
Common	Headache, nausea, diarrhea, fatigue, arthralgia, insomnia, mild increase in serum creatinine.
Serious	Acute kidney injury, bone loss (decrease in bone mineral density), hypersensitivity rash, drug‑induced liver injury.
Potential for resistance	Occurs rarely when monotherapy is used; monitor viral load in HBV.

Monitoring

Baseline & every 3–6 months:
Serum creatinine/eGFR.
Liver function tests (ALT, AST, bilirubin).
Complete blood count.
Quantitative HBV DNA or HIV RNA (as applicable).
Bone health: DEXA scan if risk factors or prolonged therapy (>2 years).
Adherence support: counseling, pill counts.
Drug interactions: Monitor concomitant CYP3A4 inducers/inhibitors; adjust dose if needed.

Clinical Pearls

Reduced nephro‑toxicity: Tenofovir alafenamide delivers 10–20 × lower plasma tenofovir concentrations than tenofovir disoproxil fumarate, markedly diminishing renal and bone side‑effects.
PrEP efficacy: Studies (e.g., HPTN 083) show >90 % protection when taken daily or as a single‑dose “on‑demand” strategy (first dose then 2 h later).
Avoid concomitant nephrotoxic drugs: NSAIDs, ACE inhibitors, or diuretics can exacerbate subtle eGFR declines; dose monitoring is advised.
Pregnancy caution: While data are limited, the drug crosses the placenta; use only if no safer alternative.
Patient education: Stress adherence; missed doses can lead to breakthrough infection and resistance.
Drug‑drug interactions: Rifampin and other strong CYP3A4 inducers reduce TFV‑DP levels; consider alternative antiviral per guidelines.

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• Reference Highlights
• AASLD Hepatitis B Treatment Guidelines 2023.
• WHO Guidelines on HIV PrEP.
• FDA Summary of Product Characteristics for Aptiom (2018).

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