DrugindexOnline^{2nd edition}

Pronouncation: (Ah-DEF-fah-vihr die-pihv-VOX-ill)
Class: Antiviral agent

Trade Names:
Hepsera
- Tablets 10 mg

Mechanism of Action

Pharmacology

Inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA.

Pharmacokinetics

Absorption

Bioavailability of adefovir is approximately 59%. C _max is approximately 18.4 ng/mL, and T _max is approximately 1.75 h.

Distribution

Up to 4% is protein bound. Vd is approximately 352 to 392 mL/kg (IV doses at steady state).

Metabolism

Adefovir dipivoxil (prodrug) is rapidly converted to adefovir (active).

Elimination

The t _½ is approximately 7.48 h; 45% of dose is recovered as adefovir in the urine over 24 h. Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion.

Special Populations

Renal Function Impairment

The C _max , AUC, and t _½ increased in those with moderate or severe renal function impairment or with end-stage renal disease. Dosing interval modification is recommended.

Indications and Usage

Treatment of chronic hepatitis B in adults with evidence of active viral replication and evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

Contraindications

Standard considerations.

Dosage and Administration

Adults

PO 10 mg daily.

Renal Impairment
Adults

PO For Ccr 50 mL/min or greater, administer 10 mg daily; for Ccr 20 to 49 mL/min, administer 10 mg every 48 h; for Ccr 10 to 19 mL/min, administer 10 mg every 72 h; hemodialysis patients, administer 10 mg every 7 days following dialysis. No dosing recommendations are available for nonhemodialysis patients with Ccr below 10 mL/min.

General Advice

• Administer without regard to food.
• If a dose is missed, take as soon as remembered that day. Do not administer more than 1 dose in a day. Do not administer 2 doses at the same time to catch up.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions

Ibuprofen, drugs that reduce renal function

May increase plasma concentrations of adefovir.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (9%).

Dermatologic

Pruritus; rash (at least 2%).

EENT

Pharyngitis (at least 2%).

GI

Abdominal pain (9%); nausea (5%); flatulence (4%); diarrhea, dyspepsia (3%); vomiting (at least 2%).

Genitourinary

Hematuria (11%); increases in creatinine (7%); renal failure, renal insufficiency (at least 2%); glycosuria (1%).

Hepatic

Increases in ALT (20%); increases in AST (8%); increases in amylase (4%); abnormal liver function, hepatic failure (at least 2%).

Respiratory

Sinusitis (at least 2%); increased cough.

Miscellaneous

Asthenia (13%); fever (at least 2%).

Precautions

Warnings Hepatitis Acute exacerbations have occurred in patients who have discontinued antihepatitis B therapy, including adefovir. Monitor hepatic function closely with clinical and laboratory follow-up for at least several months in patients who discontinue anti hepatitis B therapy. Resumption of antihepatitis B therapy may be warranted. Nephrotoxicity Chronic administration of adefovir in patients at risk of or having underlying renal function impairment may result in nephrotoxicity. Close monitoring required. Dosage adjustment may be necessary. HIV resistance May emerge in unrecognized or untreated HIV infection. Offer HIV antibody testing to all patients prior to initiating therapy. Lactic acidosis/Hepatomegaly Lactic acidosis and hepatomegaly with steatosis (including fatal cases) has been reported with use of nucleoside analogs alone or in combination with other antiretrovirals.

Monitor Monitor renal function in all patients during treatment. Monitor patients for evidence of lactic acidosis and hepatitis.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.

Overdosage

Symptoms

GI side effects.

Patient Information

• Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
• Review dosing schedule with patient.
• Advise patient that tablets can be taken without regard to food but can be taken with food if GI upset occurs.
• Advise patient that if a dose is missed to take it as soon as remembered on that day. Caution patient not to take more than 1 dose of adefovir in a day not to take 2 doses at the same time to catch up.
• Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that stopping therapy may result in severe exacerbation of the hepatitis.
• Advise patient to get an HIV test before starting therapy and anytime after that when there is a chance of exposure to HIV.
• Advise patient that medication will not cure hepatitis B infection or any other viral infection (eg, HIV) and to continue to take other antiviral medications as prescribed.
• Advise patient that this therapy will not prevent transmission of hepatitis B to others and to avoid spreading hepatitis B to others: do not share needles or injection equipment; do not share personal items that have blood or body fluids on them (eg, toothbrushes, razor blades); do not have any kind of sex without protection (eg, condoms, dental dams).
• Advise patient that it is not known if adefovir can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis B infection.
• Instruct patient to immediately report any of the following to health care provider: difficulty breathing, unusual muscle pain, generalized body discomfort, unexplained drowsiness, dizziness, light-headedness, fast or irregular heart beat, stomach pain with nausea and vomiting, cold feeling, especially in arms and legs, yellowing of the skin or eyes, appetite loss, bowel movements turn light in color, or urine turns very dark in color.