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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HEPSERA (HEPSERA).
| Breastfeeding | It is not known whether adefovir is excreted in human breast milk. In animal studies, adefovir was detected in rat milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio: not determined in humans. |
| 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. |
■ 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. |
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| 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. |