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Adefovir: Drug information

Adefovir: Drug information
(For additional information see "Adefovir: Patient drug information" and see "Adefovir: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Severe acute exacerbations of hepatitis:

Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti–hepatitis B therapy, including adefovir. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue anti–hepatitis B therapy. If appropriate, resumption of anti–hepatitis B therapy may be warranted.

Nephrotoxicity:

In patients at risk of or having underlying renal dysfunction, long-term administration of adefovir may result in nephrotoxicity. Closely monitor renal function in these patients; they may require dose adjustment.

HIV resistance:

HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with anti–hepatitis B therapies that may have activity against HIV (eg, adefovir).

Lactic acidosis/severe hepatomegaly with steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.

Brand Names: US
  • Hepsera [DSC]
Brand Names: Canada
  • AA-Adefovir;
  • Hepsera [DSC]
Pharmacologic Category
  • Antihepadnaviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HBV)
Dosing: Adult
Chronic hepatitis B

Chronic hepatitis B:

Note: Adefovir is not preferred in the management of chronic hepatitis B due to high rate of resistance with long-term use (Ref); other guidelines do not recommend adefovir therapy (Ref). Other antiviral agents with a high barrier to drug resistance are preferred (eg, tenofovir, entecavir) (Ref).

Oral: 10 mg once daily; may be used as part of a combination regimen (concurrent use with tenofovir should be avoided) (Ref).

Treatment duration: Treatment duration is variable and influenced by hepatitis B e antigen (HBeAg) status, duration of HBV suppression, and presence of cirrhosis/decompensation (Ref):

Patients without cirrhosis:

Hepatitis B e antigen positive (HBeAg-positive) immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion if patient can be closely monitored. An alternative approach is to treat until hepatitis B surface antigen (HBsAg) loss (Ref).

HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg who have achieved long-term (≥3 years) virologic suppression; however, there is insufficient evidence to guide decisions in these patients (Ref).

Patients with cirrhosis:

HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation (Ref).

HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data) (Ref).

Viral breakthrough: Patients with confirmed viral breakthrough (HBV DNA ≥100 IU/mL with previously undetectable levels [<10 IU/mL] or >1 log increase in HBV DNA) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (Ref).

Dosing: Kidney Impairment: Adult

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 49 mL/minute: 10 mg every 48 hours.

CrCl 10 to 29 mL/minute: 10 mg every 72 hours.

CrCl <10 mL/minute (nonhemodyalisis): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Hemodialysis: Dialyzable (~35%): 10 mg every 7 days (following dialysis)

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Adefovir: Pediatric drug information")

Chronic hepatitis B

Chronic hepatitis B: Note: Adefovir is not preferred due to high rate of resistance with long-term use; antivirals with a higher barrier to drug resistance are preferred (Ref).

Children 2 to <7 years: Limited data available: Oral: 0.3 mg/kg/dose once daily; maximum dose: 10 mg/dose (Ref).

Children 7 to <12 years: Limited data available: Oral: 0.25 mg/kg/dose once daily; maximum dose: 10 mg/dose (Ref).

Children ≥12 years and Adolescents: Oral: 10 mg once daily (Ref).

Duration of therapy: Optimal duration of treatment not established; oral antiviral therapy was continued for 1 to 4 years in trials; hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic end point followed by an additional 12 months of consolidation (Ref).

Dosing: Kidney Impairment: Pediatric

Children ≥12 years and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling (has not been studied); based on experience in adults, dosage adjustment should be considered.

Dosing: Hepatic Impairment: Pediatric

Children ≥12 years and Adolescents: No dosage adjustments necessary.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Gastrointestinal: Dyspepsia (3%)

Renal: Increased serum creatinine (≥0.5 mg/dL: 2% to 3%)

Frequency not defined: Renal: Nephrotoxicity

Postmarketing:

Endocrine & metabolic: Hypophosphatemia (Song 2020), lactic acidosis

Gastrointestinal: Pancreatitis

Hepatic: Severe hepatomegaly with steatosis

Neuromuscular & skeletal: Myopathy, osteomalacia (Song 2020)

Renal: Fanconi syndrome (Song 2020), nephrolithiasis (Lin 2017), proximal tubular nephropathy, renal failure syndrome (Xiang 2020)

Contraindications

Hypersensitivity to adefovir or any component of the formulation.

Warnings/Precautions

Disease-related concerns:

• Renal impairment: Dosage adjustment is required in adult patients with renal dysfunction or in patients who develop renal dysfunction during therapy; no data available for use in children ≥12 years of age or adolescents with renal impairment.

Concurrent drug therapy:

• Tenofovir: Do not use concurrently with tenofovir (tenofovir disoproxil fumarate or tenofovir alafenamide) or any tenofovir-containing product.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as dipivoxil:

Hepsera: 10 mg [DSC]

Generic: 10 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Adefovir Dipivoxil Oral)

10 mg (per each): $37.89

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as dipivoxil:

Hepsera: 10 mg [DSC]

Generic: 10 mg

Administration: Adult

Oral: Administer without regard to food.

Administration: Pediatric

Oral: May be administered without regard to food.

Use: Labeled Indications

Hepatitis B, chronic: Treatment of chronic hepatitis B in patients ≥12 years of age with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Note: Adefovir is not preferred in the management of chronic hepatitis B due to high rate of resistance with long-term use (AASLD [Terrault 2018]); other guidelines do not recommend adefovir therapy (EASL 2017). Other antiviral agents with a high barrier to drug resistance are preferred (eg, tenofovir, entecavir) (AASLD [Terrault 2018]; EASL 2017).

Metabolism/Transport Effects

Substrate of OAT1/3; Inhibits MRP2

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ataluren: May increase the serum concentration of Adefovir. Risk C: Monitor therapy

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification

Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy

Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Tacrolimus (Systemic): Adefovir may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination

Tenofovir Products: Adefovir may diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Risk X: Avoid combination

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy

Valproate Products: Pivalate-Conjugated Medications may enhance the adverse/toxic effect of Valproate Products. Specifically, the risk for decreased carnitine concentrations is increased. Risk C: Monitor therapy

Food Interactions

Food does not have a significant effect on adefovir absorption. Management: Administer without regard to meals.

Reproductive Considerations

Treatment for hepatitis B should be evaluated prior to pregnancy. Adefovir is not recommended for use in pregnant patients (AASLD [Terrault 2018]; EASL 2017).

Pregnancy Considerations

Outcome data following maternal or paternal use of adefovir during pregnancy is limited (Funk 2021; Gao 2022; Gu 2014; Yang 2022; Yi 2012). Agents other than adefovir are recommended when hepatitis B treatment is needed in pregnant patients. Patients who become pregnant while taking adefovir should be switched to the preferred agent (AASLD [Terrault 2018]; EASL 2017).

Data collection to monitor pregnancy and infant outcomes following exposure to adefovir is ongoing. Health care providers are encouraged to enroll patients exposed to adefovir during pregnancy in the Hepsera pregnancy registry (800-258-4263).

Breastfeeding Considerations

It is not known if adefovir is present in breast milk.

Patients requiring antivirals for hepatitis B may breastfeed if the infant received immunoprophylaxis at birth; however, recommendations are not specific to adefovir and other agents may be preferred (AASLD [Terrault 2018]; EASL 2017; SMFM 2016). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

HIV status, CrCl (prior to initiation of therapy), HBV DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; if at risk for renal impairment, CrCl, serum phosphate, urine glucose, and urine protein at baseline and at least annually; consider monitoring bone density in patients with risk factors for osteopenia or fracture history (prior to initiation and during therapy); lactic acid levels especially in patients with kidney dysfunction; following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year. Monitor for development of hepatocellular carcinoma as clinically indicated (ie, prolonged viremia, hepatitis C virus co-infection or cirrhosis) (AASLD [Terrault 2018]; EASL 2017; manufacturer’s labeling).

Mechanism of Action

Acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.

Pharmacokinetics (Adult Data Unless Noted)

Note: Pharmacokinetic data reported in pediatric patients (12-18 years) similar to reported adult data.

Distribution: 0.35 to 0.39 L/kg

Protein binding: ≤4%

Metabolism: Prodrug; rapidly converted to adefovir (active metabolite) in intestine

Bioavailability: 59%

Half-life elimination: 7.5 hours; prolonged in renal impairment

Time to peak: Median: 1.75 hours (range: 0.58 to 4 hours)

Excretion: Urine (45% as active metabolite within 24 hours); Dialysis: ~35% of dose (10 mg) removed during 4 hours hemodialysis session

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Cmax and AUC increased in those with moderate or severe renal function impairment or with end-stage renal disease.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Hepsera | Revervir;
  • (AT) Austria: Hepsera;
  • (AU) Australia: Apo-adefovir | Hepsera;
  • (BD) Bangladesh: Infovir;
  • (BE) Belgium: Hepsera;
  • (BG) Bulgaria: Hepsera;
  • (BR) Brazil: Hepsera;
  • (CH) Switzerland: Hepsera;
  • (CL) Chile: Hepsera;
  • (CN) China: A gan ding | Dai ding | He wei li | Hepsera | Li fu zhi | Yi lai fen | You he ding | Yue bao;
  • (CO) Colombia: Hepsera | Virofagon;
  • (DE) Germany: Hepsera;
  • (DO) Dominican Republic: Hepsera;
  • (EG) Egypt: Civirus | Dovocare | Fodavir | Hepsera;
  • (FI) Finland: Hepsera;
  • (FR) France: Adefovir dipivoxyl | Hepsera;
  • (GB) United Kingdom: Hepsera;
  • (GR) Greece: Hepsera;
  • (HK) Hong Kong: Hepsera;
  • (ID) Indonesia: Hepsera;
  • (IE) Ireland: Hepsera;
  • (IL) Israel: Hepsera;
  • (IN) India: Adesera | Adfovir | Adheb;
  • (IT) Italy: Hepsera;
  • (JO) Jordan: Hepsera;
  • (JP) Japan: Hepsera;
  • (KR) Korea, Republic of: Adecis | Adefor | Adefora | Adefosil | Adefovil | Adefovir | Adefovir b.r | Adepact | Adepam | Adepsera | Adeptin | Adesera | Adesil | Adesis | Adeva | Adevir | Afoliva | Aforiva | Afovil | Afovir | Apovir | Aprogen adefovir | Asevira | Austin adefovir | Baihepa | Boryung adefovir | Everhepa | Hepasera | Hepavir | Hepcetovi | Hepcevir | Hepcure | Heppure | Hepsa | Hepsava | Hepsedefo | Hepsedepo | Hepsel | Hepsera | Hepseron | Hepserusa | Hepses | Hepsevir | Hepsk | Hepssel | Heptec | Hepxa | Hevir | Inist adefovir | Liversera | Sunsera | Uniliver | Wonderhepa;
  • (LB) Lebanon: Adesera;
  • (LT) Lithuania: Hepsera;
  • (LU) Luxembourg: Hepsera;
  • (LV) Latvia: Hepsera;
  • (MY) Malaysia: Hepsera;
  • (NL) Netherlands: Hepsera;
  • (NO) Norway: Hepsera;
  • (NZ) New Zealand: Hepsera;
  • (PE) Peru: Hepsera;
  • (PH) Philippines: Hepsera;
  • (PK) Pakistan: Adeday | Adefo | Hepbi | Hepovir | Hepsera | Medfir | Zurax;
  • (PL) Poland: Hepsera;
  • (PR) Puerto Rico: Hepsera;
  • (PT) Portugal: Hepsera;
  • (QA) Qatar: Hepsera;
  • (RO) Romania: Hepsera;
  • (SA) Saudi Arabia: Hepsera;
  • (SE) Sweden: Hepsera;
  • (SG) Singapore: Hepsera;
  • (SI) Slovenia: Hepsera;
  • (TH) Thailand: Hepsera;
  • (TN) Tunisia: Hepsera;
  • (TR) Turkey: Hepsera;
  • (TW) Taiwan: Hepsera
  1. Adefovir dipivoxil tablet [prescribing information]. Bensalem, PA: Sigmapharm Laboratories, LLC; June 2019.
  2. American Academy of Pediatrics (AAP). In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021.
  3. Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed, Philadelphia, PA: American College of Physicians; 2007.
  4. European Association for the Study of the Liver (EASL). European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398. doi:10.1016/j.jhep.2017.03.021 [PubMed 28427875]
  5. Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21(1):70-84. doi:10.1016/S1473-3099(20)30586-7 [PubMed 32805200]
  6. Gao X, Duan X, Cai H, et al. Pregnancy outcomes for pregnant women with chronic hepatitis B exposing to entecavir or adefovir dipivoxil therapy before or in early pregnancy. J Matern Fetal Neonatal Med. 2022;35(3):476-480. doi:10.1080/14767058.2020.1723540 [PubMed 32019360]
  7. Gu Y, Ru T, Zhou YH, Hu Y. Adefovir as a possible teratogen: evidence from paternal exposure. Dig Liver Dis. 2014;46(12):1134-1135. doi:10.1016/j.dld.2014.08.035 [PubMed 25174874]
  8. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al Adefovir Dipivoxil 438 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B [published correction appears in: N Engl J Med. 2003;348(12):1192]. N Engl J Med. 2003;348(9):800-807. [PubMed 12606734]
  9. Hepsera (adefovir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; November 2012.
  10. Hepsera (adefovir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; December 2018.
  11. Jonas MM, Kelly D, Pollack H, et al. Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B. Hepatology. 2008;47(6):1863-1871. doi: 10.1002/hep.22250 [PubMed 18433023]
  12. Jonas MM, Kelly D, Pollack H, et al. Efficacy and safety of long-term adefovir dipivoxil therapy in children with chronic hepatitis B infection. Pediatr Infect Dis J. 2012;31(6):578-582. doi: 10.1097/INF.0b013e318255ffe7 [PubMed 22466329]
  13. Komatsu H, Inui A, Fujisawa T. Pediatric hepatitis B treatment. Ann Transl Med. 2017;5(3):37. doi:10.21037/atm.2016.11.52 [PubMed 28251116]
  14. Lin J, Zhuo Y, Zhang D. Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B. BMC Nephrol. 2017;18(1):275. doi:10.1186/s12882-017-0693-4 [PubMed 28851305]
  15. Marcellin P, Chang TT, Lim SG, et al; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348(9):808-816. doi: 10.1056/NEJMoa020681 [PubMed 12606735]
  16. Refer to manufacturer's labeling.
  17. Society for Maternal-Fetal Medicine (SMFM), Dionne-Odom J, Tita AT, Silverman NS. #38: hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6-14. doi:10.1016/j.ajog.2015.09.100 [PubMed 26454123]
  18. Song K, Yan Q, Yang Y, et al. Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review. J Int Med Res. 2020;48(10):300060520954713. doi:10.1177/0300060520954713 [PubMed 33100076]
  19. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800 [PubMed 29405329]
  20. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283. doi: 10.1002/hep.28156 [PubMed 26566064]
  21. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-pediatric-opportunistic-infections/whats-new. Updated September 14, 2023. Accessed October 2023.
  22. Yang R, Yin N, Zhao Y, et al. Adverse events during pregnancy associated with entecavir and adefovir: new insights from a real-world analysis of cases reported to FDA adverse event reporting system. Front Pharmacol. 2022;12:772768. doi:10.3389/fphar.2021.772768 [PubMed 35046808]
  23. Xiang Q, Liu Z, Yu Y, et al. Osteomalacia and renal failure due to Fanconi syndrome caused by long-term low-dose adefovir dipivoxil: a case report. BMC Pharmacol Toxicol. 2020;21(1):43. doi:10.1186/s40360-020-00421-6 [PubMed 32503675]
  24. Yi W, Liu M, Cai HD. Safety of lamivudine treatment for chronic hepatitis B in early pregnancy. World J Gastroenterol. 2012;18(45):6645-6650. doi: 10.3748/wjg.v18.i45.6645. [PubMed 23236240]
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