Adefovir, Hepsera

U.S. BRAND NAMES — Hepsera™
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — Hepatitis B (chronic): Oral: 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 20-49 mL/minute: 10 mg every 48 hours
Clcr 10-19 mL/minute: 10 mg every 72 hours
Hemodialysis: 10 mg every 7 days (following dialysis)
DOSING: HEPATIC IMPAIRMENT — No adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as dipivoxil: Hepsera®: 10 mg
DOSAGE FORMS: CONCISE Tablet: Hepsera®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to food.
USE — Treatment of chronic hepatitis B with evidence of active viral replication (based on persistent elevation of ALT/AST or histologic evidence), including patients with lamivudine-resistant hepatitis B
ADVERSE REACTIONS SIGNIFICANT — For a majority of adverse reactions, the incidence in adefovir-receiving patients was similar to or less than that observed with placebo treatment.
>10%: Hepatic: ALT increased (>5 x ULN: 20%) Neuromuscular & skeletal: Weakness (13%) Renal: Hematuria (grade 3: 11%)
1% to 10%: Central nervous system: Headache (9%) Dermatologic: Rash, pruritus Endocrine & metabolic: Hypophosphatemia (1% to 2%) Gastrointestinal: Abdominal pain (9%), nausea (5%), amylase increased (grade 3: 4%), flatulence (4%), diarrhea (3%), dyspepsia (3%), vomiting Hepatic: AST increased (>5 x ULN: 8%), abnormal liver function, hepatic failure Neuromuscular & skeletal: Creatine kinase increased (7%) Renal: Serum creatinine increased (2% to 3%), glycosuria (grade 3: 1%), renal failure, renal insufficiency Note: In liver transplant patients with baseline renal dysfunction, frequency of increased serum creatinine has been observed to be as high as 32% to 53% at 48 and 96 weeks post-transplantation, respectively; considering the concomitant use of other potentially nephrotoxic medications, baseline renal insufficiency, and predisposing comorbidities, the role of adefovir in these changes could not be established.
Postmarketing and/or case reports: Hepatitis, nephrotoxicity
CONTRAINDICATIONS — Hypersensitivity to adefovir or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: See "Disease-related concerns" below. Human immunodeficiency virus (HIV): See "Disease-related concerns" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Renal impairment: See "Disease-related concerns" below.
Concerns related to adverse effects: Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required. HIV: [U.S. Boxed Warning]:May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir. Renal impairment: [U.S. Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. Dosage adjustment is required in patients with renal dysfunction or in patients who develop renal dysfunction during therapy.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Ganciclovir, valganciclovir: May increase the adverse effects/toxicity of reverse transcriptase inhibitors; monitor.
Nephrotoxic agents (eg, aminoglycosides, immunosuppressants, NSAIDs, vancomycin): May increase the risk of renal toxicity with adefovir.
Ribavirin: Concomitant use of ribavirin and nucleoside analogues may increase the risk of developing hepatic decompensation or other signs of mitochondrial toxicity, including pancreatitis or lactic acidosis.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Should be avoided in hepatitis B infection due to potential hepatic toxicity.
Food: Does not have a significant effect on adefovir absorption.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy only when clearly needed. Pregnant women exposed to adefovir should be registered with the pregnancy registry (800-258-4263).
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken without regard to food.
PRICING — (data from drugstore.com)Tablets (Hepsera) 10 mg (30): $670.52
MONITORING PARAMETERS — HIV status (prior to initiation of therapy); serum creatinine (prior to initiation and during therapy); viral load; LFTs for several months following discontinuation of adefovir
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Limited experience in acute overdose. Chronic overdose may be associated with renal toxicity and gastrointestinal adverse effects. Hemodialysis may be effective in the removal of adefovir (35% of a 10 mg dose removed in 4 hours).
INTERNATIONAL BRAND NAMES — Adesera (IN); Hepsera (AR, AT, AU, BE, BG, CH, CL, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, HK, HN, HU, ID, IE, IL, IT, KR, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PT, RU, SE, SG, SV, TH, TR, TW)
MECHANISM OF ACTION — Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS Distribution: 0.35-0.39 L/kg
Protein binding: 4%
Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine
Bioavailability: 59%
Half-life elimination: 7.5 hours; prolonged in renal impairment
Time to peak: 1.75 hours
Excretion: Urine (45% as active metabolite within 24 hours)
PATIENT INFORMATION — Not a cure for hepatitis B, nor will it reduce the risk of transmission. Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Do not discontinue unless instructed by prescriber; additional monitoring is required after discontinuation to ensure the disease does not recur.
(For additional information see "Adefovir: Patient drug information")