adefovir dipivoxil

adefovir dipivoxil,

an antiviral agent used to treat chronic hepatitis B.

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adefovir dipivoxil

Hepsera

Pharmacologic class: Nucleotide reverse transcriptase inhibitor

Therapeutic class: Antiviral

Pregnancy risk category C

FDA Boxed Warning

• Severe acute hepatitis exacerbations have occurred after drug withdrawal. Monitor hepatic function closely for at least several months in patients who discontinue drug or other anti-hepatitis B therapy; if appropriate, resume such therapy.
• Long-term therapy may cause nephrotoxicity in patients with or at risk for underlying renal dysfunction. Monitor renal function closely and adjust dosage as needed.
• Human immunodeficiency virus (HIV) resistance may occur during therapy in patients with chronic hepatitis B infection who have unrecognized or untreated HIV infection.
• Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) may occur with use of drug alone or combined with other antiretrovirals.

Action

Inhibits hepatitis B virus (HBV) DNA polymerase and suppresses HBV replication

Availability

Tablets: 10 mg

⊘Indications and dosages

➣ Chronic HBV with active viral replication plus persistent elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or histologically active disease

Adults: 10 mg P.O. daily

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:
• lactic acidosis, renal or hepatic impairment
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

• Offer HIV testing before starting therapy. (Drug may increase resistance to antiretrovirals in HIV patients.)
• Give with or without food.

Route	Onset	Peak	Duration
P.O.	Rapid	0.6-4 hr	Unknown

Adverse reactions

CNS: headache

GI: nausea, vomiting, diarrhea, abdominal pain, flatulence, dyspepsia, anorexia, pancreatitis

GU: renal dysfunction

Hepatic: severe hepatomegaly with steatosis, hepatitis exacerbation (if therapy is withdrawn)

Metabolic: lactic acidosis

Respiratory: pneumonia

Other: fever, infection, pain, antiretroviral resistance in patients with unrecognized HIV

Interactions

Drug-drug. Acetaminophen, aspirin, indomethacin: granulocytopenia

Acyclovir, adriamycin, amphotericin B, benzodiazepines, cimetidine, dapsone, doxorubicin, experimental nucleotide analogue, fluconazole, flucytosine, ganciclovir, indomethacin, interferon, morphine, phenytoin, probenecid, sulfonamide, trimethoprim, vinblastine, vincristine: increased risk of nephrotoxicity

Drug-diagnostic tests. Amylase, blood glucose, blood urea nitrogen, creatine kinase, hepatic enzymes, lipase: elevated levels

Patient monitoring

• Monitor fluid intake and output.
• Watch for hematuria.
• Assess for signs and symptoms of lactic acidosis, especially in women and overweight patients.
• Check for liver enlargement.
• Monitor liver and kidney function test results.
• After therapy ends, monitor patient for evidence of serious hepatitis exacerbation.

Patient teaching

• Advise patient to take drug with or without food.
• Instruct patient to drink plenty of fluids to ensure adequate urine output.
• Advise patient to monitor urine output and color and to report significant changes.
• Tell patient that drug may cause weakness. Discuss appropriate lifestyle adjustments.
• Caution patient not to take over-the-counter analgesics without prescriber's approval.
• Inform patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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adefovir dipivoxil

Virology A nucleotide analogue effective against the polymerases of hepadnaviruses, retroviruses, herpesviruses, used to treat hepatitis Be antigen in adults with evidence of active viral replication, ↑ LFTs, or histologically active liver disease Adverse effects Renal damage requiring monitoring, diarrhea, nausea; in Pts with HBeAg-positive chronic hepatitis B, 48 wks of adefovir dipivoxil resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and ↑ rates of HBeAg seroconversion. See AIDS, Hepatitis B.