adefovir


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Related to adefovir: telbivudine, Entecavir

adefovir

(a-def-oh-veer) ,

Hepsera

(trade name)

Classification

Therapeutic: antivirals
Pharmacologic: nucleotides
Pregnancy Category: C

Indications

Treatment of chronic hepatitis B in patients with evidence of active viral replication and either evidence of persistently elevated liver function tests or active disease (should be used with lamivudine to ↓ risk of resistance).

Action

Converted to adefovir diphosphate which inhibits viral DNA polymerase (reverse transcriptase). Incorporation into viral DNA causes termination of the DNA chain.

Therapeutic effects

Decreased progression/sequelae of chronic hepatitis B infection.

Pharmacokinetics

Absorption: Rapidly converted from prodrug form (adefovir dipivoxil) to adefovir following oral administration; 59% bioavailable.
Distribution: 0.35–0.39 L/kg.
Metabolism and Excretion: Elimination is primarily renal as unchanged drug.
Half-life: 7.5 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
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Contraindications/Precautions

Contraindicated in: Hypersensitivity; Lactation: Provide formula or discontinue drug.
Use Cautiously in: Unrecognized HIV infection (may foster resistance); Patients with renal impairment or at risk of renal impairment (↑ risk of nephrotoxicity; dose adjustment recommended if CCr <50 mL/min); Liver disease or risk factors for liver disease (↑ risk of hepatotoxicity); Women, obese patients, patients with previous nucleoside exposure (↑ risk of lactic acidosis and hepatotoxicity); Geriatric: Greater risk of side effects due to greater risk of renal or cardiac disorders; Obstetric: Pregnant patients should be enrolled in the pregnancy registry for fetal outcome (1-800-258-4263); Pediatric: Children <12 yr (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • headache

Respiratory

  • cough
  • pharyngitis
  • sinusitis

Gastrointestinal

  • dyspepsia
  • hepatomegaly with steatosis (life-threatening)
  • abdominal pain
  • diarrhea
  • flatulence
  • ↑ liver enzymes
  • nausea
  • vomiting

Genitourinary

  • hematuria
  • nephrotoxicity

Dermatologic

  • pruritus
  • rash

Fluid and Electrolyte

  • lactic acidosis (life-threatening)

Musculoskeletal

  • weakness

Miscellaneous

  • fever
  • HIV resistance

Interactions

Drug-Drug interaction

Drugs that are renally excreted or alter renal function should be used cautiously as they may affect blood levels.Ibuprofen may increase blood levels.Should not be used with tenofovir -containing products.

Route/Dosage

Oral (Adults and Children ≥12 yr) 10 mg once daily.

Renal Impairment

Oral (Adults ) CCr 30–49 mL/min—10 mg every 48 hr; CCr 10–29 mL/min—10 mg every 72 hr; Hemodialysis patients—10 mg every 7 days following dialysis.

Availability (generic available)

Tablets: 10 mg

Nursing implications

Nursing assessment

  • May cause lactic acidosis and severe hepatomegaly with steatosis. Monitor patient for signs (increased serum lactate levels, elevated liver enzymes, liver enlargement on palpation). Therapy should be discontinued if clinical or laboratory signs occur.
  • Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy in patients with HIV infection.Monitor liver function tests and hepatitis B virus levels throughout and following therapy. If therapy is discontinued, may cause severe exacerbation of hepatitis B.
    • Calculate creatinine clearance to determine dose prior to starting therapy.
    • Monitor renal function closely. May cause nephrotoxicity.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: Administer once daily with or without food.

Patient/Family Teaching

  • Instruct patient to take adefovir as directed and not to discontinue medication without consulting health care professional. Take missed dose as soon as it is remembered that day. Do not take more than 1 dose in a day. Consult health care professional if unsure of what to do. Discontinuation may result in exacerbation of hepatitis, usually within 12 wks of stopping. Regular liver function tests and hepatitis B virus levels are required if adefovir is discontinued. Advise the patient that adefovir does not cure hepatitis B, but may lower amount of hepatitis B in the body and decrease the ability of the virus to multiply and infect new liver cells. Instruct patient to read the Patient Information sheet prior to starting therapy.
  • Inform patient that an HIV test should be taken before starting adefovir and anytime when there is a chance patient was exposed to HIV.
  • Inform patient that adefovir does not reduce the risk of transmission of hepatitis B to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles, toothbrushes or razor blades, or donating blood to prevent spreading the hepatitis B virus to others.
  • Instruct patient to notify health care professional immediately if signs of lactic acidosis (weakness or tiredness, unusual muscle pain, dyspnea, stomach pain with nausea and vomiting, feelings of coldness especially in arms or legs, dizziness, lightheadedness, fast or irregular heartbeat) occur.
  • Caution patient to notify health care professional if signs of hepatotoxicity (jaundice, dark urine, light colored bowel movement, anorexia, nausea, bruising, lower stomach pain) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise female patient to avoid breastfeeding and to notify health care professional if pregnancy is planned or suspected.
  • Emphasize the importance of regular blood tests to check hepatitis B virus levels, as well as renal and hepatic function.

Evaluation/Desired Outcomes

  • Decrease in progression of chronic hepatitis B. Patients with serum HBV levels >1000 copies/mL at week 48 of treatment are at greater risk for developing resistance and modification of therapy should be considered.
References in periodicals archive ?
Adefovir meets an urgent, unmet medical need and presents a potential life-saving treatment option for pre- and post-liver transplant patients with lamivudine-resistant HBV who are at high risk for morbidity and mortality," concluded the Adefovir Dipivoxil Study 435 International Investigators in their report published in the December issue of Hepatology.
The rapid completion of the Marketing Authorisation Application for adefovir dipivoxil in Europe, following our U.
The State Food and Drug Administration of China has approved interferon, pegylated interferon, lamivudine, adefovir, telbivudine, and entecavir for the treatment of HBV infection.
In the phase III trial, 375 patients with chronic hepatitis B infection were randomized to either 300 mg/day tenofovir or 10 mg/day adefovir.
Based on the unmet medical needs of patients with chronic hepatitis B, Gilead says it has submitted a request for a priority, or 6-month, review of the adefovir dipivoxil NDA.
Adefovir is a nucleotide analogue associated with a low frequency of resistance; however, its antiviral efficacy is not optimal [8,9].
Interferon alfa may be the treatment of choice for a young, highly motivated patient willing to withstand its significant side effects in order to undergo a relatively short course of therapy with a more durable response and a higher rate of hepatitis B surface antigen loss compared with oral adefovir or entecavir therapy.
The rate of resistance after 4 years on adefovir dipivoxil (Hepsera) monotherapy is 18%.
The following points should be considered when initiating therapy with Viread for the treatment of HBV infection: This indication is based primarily on data from the treatment of nucleoside-treatment-naove patients, and a smaller number of patients who had previously received lamivudine or adefovir.
Supply Adefovir (DOE) and Tenofovir (DOE) as a single agent.
For ALT greater than twice the normal level or for patients with moderate to severe hepatitis on biopsy, consider treatment with interferon-[alpha] (IFN-[alpha]), lamivudine, or adefovir.