HEPSERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HEPSERA (HEPSERA).
Acyclic nucleotide analog of adenosine monophosphate; inhibits hepatitis B virus (HBV) DNA polymerase by competing with the natural substrate dATP, causing DNA chain termination after incorporation into viral DNA.
| Metabolism | Not significantly metabolized; eliminated unchanged in urine via glomerular filtration and active tubular secretion. No significant CYP450 involvement. |
| Excretion | Primarily renal; 70-90% of an oral dose is excreted unchanged in urine via active tubular secretion and glomerular filtration. Biliary/fecal elimination accounts for <5%. |
| Half-life | Terminal elimination half-life is approximately 6-9 hours in patients with normal renal function. In renal impairment, half-life is prolonged (up to 18 hours in moderate impairment, >30 hours in severe impairment). Steady-state is achieved within 5-7 days. |
| Protein binding | ≤4% bound to plasma proteins (albumin). Negligible binding ensures high free fraction available for pharmacological activity. |
| Volume of Distribution | Apparent Vd is approximately 0.5 L/kg (range 0.3-0.7 L/kg), indicating distribution into total body water with minimal tissue binding. |
| Bioavailability | Oral bioavailability is approximately 59% (range 40-70%) in healthy adults. Food decreases absorption; take on an empty stomach. |
| Onset of Action | Oral administration: Clinical effect (reduction in HBV DNA) begins within 2-4 weeks of dosing; maximal suppression typically seen by 12-24 weeks. |
| Duration of Action | Duration of antiviral effect: 24 hours at steady state. Once-daily dosing maintains therapeutic plasma concentrations. Dose adjustments required in renal impairment to prolong dosing interval. |
| Molecular Weight | 501.47 |
10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl >=50 mL/min: 10 mg every 24 hours; CrCl 30-49 mL/min: 10 mg every 48 hours; CrCl 10-29 mL/min: 10 mg every 72 hours; Hemodialysis: 10 mg every 7 days after dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Safety and efficacy not established in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in children below 12 years of age. For adolescents 12-17 years weighing >=10 kg: 10 mg orally once daily. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal impairment and monitor renal function regularly. |
| 1st trimester | Adefovir dipivoxil (Hepsera) is classified as FDA pregnancy category C. Animal studies have shown teratogenicity at high doses. Use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | Limited human data; animal studies suggest risk. Use only if clearly needed. |
| 3rd trimester | No adequate human studies; use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for HEPSERA (HEPSERA).
| Placental transfer | Adefovir crosses the placenta in rats; human data not available. |
| Breastfeeding | It is not known whether adefovir is excreted in human milk. Because many drugs are excreted in milk, caution should be exercised when Hepsera is administered to a nursing woman. |
| Lactation Rating |
■ FDA Black Box Warning
Severe acute exacerbation of hepatitis B has been reported in patients who have discontinued anti-hepatitis B therapy, including HEPSERA. Hepatic function should be monitored closely for at least several months after stopping treatment.
| Serious Effects |
Hypersensitivity to adefovir dipivoxil or any component of the formulation
| Precautions | Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases; nephrotoxicity (increased serum creatinine and decreased serum phosphate); HIV resistance in patients with unrecognized or untreated HIV infection; exacerbation of hepatitis after discontinuation; use with caution in renal impairment. |
| Food/Dietary | Avoid high-fat meals as they may delay absorption; take on an empty stomach if possible. No specific food restrictions, but maintain adequate hydration. |
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| L3 (Limited Data) or Probably Compatible? |
| Teratogenic Risk | HEPSERA (adefovir dipivoxil) is FDA Pregnancy Category C. In animal studies, adefovir was teratogenic in rats at doses 23 times the human therapeutic exposure. There are no adequate and well-controlled studies in pregnant women. First trimester: unknown risk. Second and third trimesters: unknown risk but potential for fetal harm based on animal data. Use only if clearly needed. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN, urine protein) and hepatic function (ALT, AST, bilirubin) periodically during therapy. In pregnant women, monitor for signs of hepatic flare upon discontinuation. Fetal monitoring: routine prenatal care including ultrasound for fetal growth and anatomy. |
| Fertility Effects | In animal fertility studies, adefovir did not impair fertility in male or female rats at doses up to 250 mg/kg/day (approximately 35 times the human dose). No human data on fertility effects are available. |
| Clinical Pearls | Monitor renal function closely; dose adjustment required for CrCl <50 mL/min. Consider nephrotoxicity risk, especially in decompensated cirrhosis with ascites. Perform HIV antibody testing before initiation due to risk of HIV resistance if tenofovir is used later. Assess for lactic acidosis and hepatomegaly with steatosis, rare but potentially fatal. |
| Patient Advice | Take exactly as prescribed; do not stop without doctor's advice as hepatitis may worsen. · Report any muscle pain, weakness, or dark urine (possible myopathy). · Avoid alcohol and NSAIDs to reduce kidney stress. · Use effective contraception if applicable; safety in pregnancy not established. · Attend regular blood tests for kidney function and hepatitis B markers. |