Hepsera


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Related to Hepsera: Tyzeka

adefovir dipivoxil

Hepsera

Pharmacologic class: Nucleotide reverse transcriptase inhibitor

Therapeutic class: Antiviral

Pregnancy risk category C

FDA Box 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.

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Hepatic: severe hepatomegaly with steatosis, hepatitis exacerbation (if therapy is withdrawn)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

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.

Adefovir Dipivoxil

A nucleoside analogue antiviral which is effective against viral polymerases (hepadnaviruses, retroviruses—e.g., HIV—herpesviruses—e.g., CMV), and used to treat hepatitis B in adults who have evidence of active viral replication, increased LFTs, histologically active liver disease, and evidence of HBV resistant to other antivirals—e.g., lamivudine.
Benefits 48 weeks of adefovir dipivoxil results in histologic liver improvement, reduces serum HBV DNA and alanine aminotransferase (LFTs), and slows progression of chronic hepatitis B.
Adverse effects Renal toxicity requiring monitoring, asthenia, diarrhoea, dyspepsia, nausea, severe acute exacerbation of hepatitis B after discontinuing.
Mechanism of action Slows progression of chronic hepatitis B by interfering with viral replication and causing DNA chain termination after its incorporation into viral DNA.

Hepsera

A brand name for ADEFOVIR DIPIVOXIL.
References in periodicals archive ?
Gilead submitted a Marketing Authorisation Application (MAA) for Hepsera on March 26, 2002 under the centralized procedure, with the French authorities serving as rapporteur and the Danish authorities acting as co-rapporteur.
After 48 weeks, 53% of hepatitis B e antigen (HbeAg)--positive patients and 64% of HBeAg-negative patients on Hepsera had improved liver histology vs.
Please see full Prescribing Information for Viread, Atripla, Complera, Truvada and Hepsera (including BOXED WARNINGS).
Patients who were randomized to Hepsera and rolled over to Viread at week 48 and received Viread for a subsequent 192 weeks also maintained viral suppression (84 percent and 66 percent for Studies 102 and 103, respectively).
Routinely monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera (adefovir dipivoxil).
Although Chinese-manufactured drugs are generally regarded as inferior to Western branded drugs, many have achieved brand name status among physicians-for example, Tianjin Institute of Pharmaceutical Research's Dai Ding (adefovir) has even higher market share for hepatitis B in China than GlaxoSmithKline's Hepsera.
Truvada, Viread, Hepsera, Emtriva, AmBisome, Letairis, Cayston and Ranexa are registered trademarks of Gilead Sciences, Inc.
Emtriva, Hepsera, Letairis, Truvada and Viread are registered trademarks of Gilead Sciences, Inc.
Based upon prior 24 week treatment results, we are optimistic that clevudine will demonstrate superiority to Hepsera in its ability to suppress HBV DNA and normalize liver enzyme levels after 48 weeks of treatment," stated Dr.
The decrease in other products was due primarily to lower sales volume of Hepsera in the United States and Europe.
The results indicated that patients treated with escalating doses of pradefovir orally, once a day, showed a statistically significant reduction of HBV DNA, a measure of viral load, as compared to Hepsera at all but the lowest dose of pradefovir administered.