Adefovir Dipivoxil

Pronunciation: a-DEF-oh-vir dye-piv-OX-il
Class: Antiviral agent

Trade Names

Hepsera
- Tablets 10 mg

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.

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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 terminal elimination half-life 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

C max , AUC, and half-life increased in those with moderate or severe renal function impairment or with end-stage renal disease. Dosing interval modification is recommended.

Hepatic Function Impairment

No changes in pharmacokinetics were observed in patients with moderate and severe hepatic function impairment. No dosage adjustment is required.

Elderly

Pharmacokinetics have not been studied.

Children

Pharmacokinetics in children 12 to 18 yr of age are comparable with those observed in adults.

Indications and Usage

Treatment of chronic hepatitis B in patients 12 yr of age and older 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 and Children 12 yr of age and older

PO 10 mg daily.

Renal Function Impairment
Adults

PO For CrCl 50 mL/min or more, 10 mg daily; for CrCl 30 to 49 mL/min, 10 mg every 48 h; for CrCl 10 to 29 mL/min, 10 mg every 72 h; for hemodialysis patients, 10 mg every 7 days following dialysis. No dosing recommendations are available for nonhemodialysis patients with CrCl below 10 mL/min. No clinical data are available for dosing recommendations in adolescent patients with renal function impairment.

General Advice

  • Administer without regard to food.

Storage/Stability

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

Drug Interactions

Drugs that reduce renal function, ibuprofen

May increase plasma concentrations of adefovir.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Asthenia (13%); headache (9%).

GI

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

Genitourinary

Fanconi syndrome, proximal renal tubulopathy, renal failure (postmarketing).

Lab Tests

Decreased serum phosphorous, increased serum creatinine.

Metabolic-Nutritional

Hypophosphatemia (postmarketing).

Musculoskeletal

Myopathy, osteomalacia (postmarketing).

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 antihepatitis B therapy. Resumption of antihepatitis B therapy may be warranted.

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) have been reported with use of nucleoside analogs alone or in combination with other antiretrovirals.

Nephrotoxicity

Chronic administration of adefovir in patients at risk of or having underlying renal function impairment may result in nephrotoxicity. Close monitoring is required. Dosage adjustment may be necessary.


Monitor

Monitor renal function in all patients during treatment, especially those with preexisting or other risk factors for renal impairment. Monitor patients for evidence of lactic acidosis or pronounced hepatotoxicity and steatosis; suspend therapy in patients who develop clinical or laboratory findings suggestive of these conditions. Monitor hepatic function at repeated intervals with both clinical and laboratory follow-up for at least several months in patients discontinuing therapy; closely monitor patients after stopping therapy. Prior to starting therapy, offer HIV antibody testing to all patients.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 12 yr of age.

Elderly

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

Renal Function

Dosage adjustments may be necessary. No data are available for making dosing recommendations in patients younger than 18 yr of age with renal function impairment.

Clinical resistance

Resistance to adefovir can result in viral load rebound, which may result in exacerbation of hepatitis B and, in patients with hepatic function impairment, may lead to liver decompensation and possible death. To reduce the risk of resistance in patients with lamivudine-resistant HBV, use adefovir dipivoxil combined with lamivudine; do not use adefovir dipivoxil monotherapy. To reduce the risk of resistance in patients receiving adefovir dipivoxil monotherapy, consider modifying treatment if serum HBV DNA levels remain above 1,000 copies/mL with continued treatment.

Overdosage

Symptoms

GI adverse reactions.

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, and 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 hepatitis.
  • Advise patient to get an HIV test before starting therapy and any time 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: appetite loss; cold feeling, especially in arms and legs; difficulty breathing; dizziness; fast or irregular heart beat; generalized body discomfort; light-colored bowel movements or very dark-colored urine; light-headedness; stomach pain with nausea and vomiting; unexplained drowsiness; unusual muscle pain; yellowing of the skin or eyes.

Copyright © 2009 Wolters Kluwer Health.

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