Adefovir dipivoxil is an orally administered nucleotide analog reverse transcriptase inhibitor used to treat chronic active hepatitis B infection.

It is recommended for the treatment of actively replicating Hepatitis B in patients with compensated liver disease, histologically proven active liver inflammation, fibrosis, and decompensated liver disease when used in conjunction with another antiviral medication.

It was initially developed for the treatment of HIV (Human immunodeficiency infection), however, the doses required to treat HIV infection was associated with severe adverse effects.

Thus the FDA refused to approve it for HIV infection.

Adefovir dipivoxil 10 mg dose in Adults:

• 10 mg tablets once a day

Adefovir duration of Treatment:

Hepatitis Be antigen (HBeAg) positive chronic hepatitis:

• Once HBeAg seroconversion and undetectable serum HBV DNA have occurred, treatment should be continued for at least another year.

• Continue treatment for additional six months after HBeAg seroconversion.

HBeAg negative chronic hepatitis:

• Treat >1 year until hepatitis B surface antigen (HBsAg) clearance

Note: Patients not achieving a <2 log decrease in serum HBV DNA after at least 6 months of therapy should be switched to alternative therapy.

Avoid using it with tenofovir!

Adepovir dipivoxil dose in children:

Children 2 to <7 years:

• Oral: 0.3 mg/kg/dose once daily; maximum dose: 10 mg

Children ≥7 to <12 years:

• Oral: 0.25 mg/kg/dose once daily; maximum dose: 10 mg

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

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Adefovir duration of treatment for chronic hepatitis B:

• Optimal duration of treatment has not been established, however, therapy should continue for at least 6 months after seroconversion.
• Prolonged therapy of up to 4 years has been reported to be safe and well-tolerated. 

Pregnancy Risk Factor:  C

• Adefovir should be used in pregnancy only when clearly indicated.

Adefovir use during breastfeeding.

• Adefovir should not be used during lactation, as excretion in breast milk is not known.

Adefovir dipivoxil dose in kidney disease:

Cl cr ≥50 mL/minute:

• No dosage adjustment necessary

Cl cr 20-49 mL/minute:

• 10 mg every 48 hours

Cl cr 10-19 mL/minute:

• 10 mg every 72 hours

Hemodialysis:

• 10 mg every 7 days (following dialysis)

Adefovir in liver disease:

• No dose adjustment required in liver disease.

Adefovir dipivoxil Side effects:

• Central nervous system:
  • Headache

• Gastrointestinal:

  • Abdominal pain
  • Diarrhea
  • vomiting
  • pancreatitis
  • flatulence
  • dyspepsia
  • nausea

• Genitourinary:

  • Hematuria

• Dermatologic:

  • Pruritis
  • Skin rash

• Hepatic:

  • Exacerbation of liver injury upon discontinuation
  • hepatitis

• Neuromuscular:

  • Asthenia and weakness
  • back pain
  • myopathy

• Endocrine:

  • Hypophosphatemia
  • osteomalacia

• Respiratory:

  • Cough
  • rhinitis

• Renal:

  • Increased serum creatinine
  • Renal failure
  • tubular nephropathy

Contraindications & warnings:

Adefovir dipivoxil is contraindicated in patients with hypersensitivity to the drug.

U.S. Boxed Warnings

• Lactic acidosis:

  • Patients with liver disease, particularly if they are pregnant, may be at risk of severe hepatomegaly and severe lactic acidosis.

• Exacerbations severe after discontinuation

  • 25% of patients, especially those with cirrhosis may experience severe exacerbations upon discontinuation.
  • This usually occurs within 12 weeks. However, it is possible to self-limit the symptoms once the treatment is resumed.
  • After discontinuing treatment, liver function tests must be monitored for several months.

• HIV resistance:

  • HIV status should be determined prior to initiating the treatment with adefovir as HIV resistance in untreated or unrecognized HIV may develop.

• Renal dysfunction:

  • Use with caution in patients with renal dysfunction and in patients at risk of renal toxicity including patients on nephrotoxic drugs as renal impairment may occur with the chronic use of adefovir.

How to monitor a patient taking Adefovir tablets?

• Before you start therapy with adefovir check your HIV status and kidney function.
• Every 3 months, monitor liver function tests
• Monitor viral markers for hepatitis B (HBV DNA every 3-6 months during treatment (continue monitoring for at least 1 year after discontinuation--recurrent hepatitis may occur on discontinuation).
• Monitoring renal function is important before starting treatment. This should be done every three months.
• Patients who have received nephrotoxic medications are more likely to experience this problem.

• Chronic Hepatitis B

  • HBV DNA should be monitored 3 times per month until it is undetectable, and then every 3 to 6 months.
  • Anti-HBe status and HBeAg status in HBeAg positive patient to monitor seroconversion and HBsAg
  • Creatinine clearance
  • Patients at high risk for renal dysfunction should be monitored for serum phosphate, urine glucose, or urine protein before initiating treatment. Also, monitor them annually thereafter.
  • Patients with osteopenia or fracture risk should keep an eye on their bone density.
  • Check the amount of lactic acid if necessary.
  • Every three months for at least a year, check for recurrences of viremia, ALT flares, and seroreversion.
  • Patients at high risk for developing hepatocellular carcinoma should be closely watched.

How to take Adefovir tablets?

• It may be administered without regard to meals. 

Adefovir dipivoxil Mechanism of Action:

• It is an acyclic nuclear nucleotide reverse transcriptionase inhibitor (adenosine analog) that interferes with HBV viralRNA-dependent DNA polymerase, resulting in inhibitions of viral replication.
• Half-life elimination: up to 7.5 hours, but prolonged in renal impairment
• Time to peak action: 1.75 hours

Adefovir dipivoxil Brands (International):

• Adepact
• Adepam
• Adeptin
• Adesera
• Adesil
• Adevir
• Afoliva
• Everhepa
• Hepcure
• Hepovir
• Hepsera
• Hepssel

Adefovir cost in US:

• Adefovir Dipivoxil tablets

  • 10 mg (per each): $37.89

• Hepsera tablets

  • 10 mg (per each): $59.37

Adefovir cost and brands in Pakistan:

ADEFASS (FASSGEN PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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Adefo ( SHROOQ PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 3510

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ADEWEL (WELMARK PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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ADGEN (GENE-TECH LABORATORIES)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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ADROWIN (WNS FIELD PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack ; Rs. 6000

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ADVIR (AMSON VACCINES & PHARMA (PVT) LTD)

Tablets : 10 mg :

30 tablets pack : Rs. 3000

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ANOVIR (CARAWAY PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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Adefo (SCILIFE PHARMA (PRIVATE) LTD)

Tablets : 10 mg :

30 tablets pack : Rs.3000

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B-AD (DANAS PHARMACEUTICALS (PVT) LTD)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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EFFO-B (NIMRALL LABORATORIES)

Tablets : 10 mg :

30 tablets pack  : Rs. 6000

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HAPOTIN (GENOME PHARMACEUTICALS (PVT) LTD)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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HAPTIC (PANACEA PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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HEPBI (SAFFRON PHARMACEUTICAL (PRIVATE)LIMITED)

Tablets : 10 mg :

30 tablets pack : Rs. 3000

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HEPIRAL (PHARMIX LABORATORIES (PRIVATE) LIMITED )

Tablets : 10 mg :

30 tablets pack : Rs. 3000‘

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HEPOVIR (SJ. 8. G. FAZUL ELLAHI (PVT) LTD)

Tablets : 10 mg :

30 tablets pack : Rs. 351

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HEPSERA (EVEREST PHARMACEUTICALS)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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HEPTROL (MACTER INTERNATIONAL (PVT) LTD)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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HI-VIR (LINEAR PHARMA)

Tablets : 10 mg :

30 tablets pack : Rs. 6000

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TONAVIR (ROTEX MEDICA PAKISTAN (PVT) LTD)

Tablets : 10 mg :

30 tablets pack ; Rs. 6000

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VADEFO (VALOR PHARMACEUTICALS)

Tablets : 10 mg: 

30 tablets pack ; Rs. 6000

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VIRGOCIL (GOODMAN INTERNATIONAL)

Tablets : 10 mg :

30 tablets pack : Rs. 5000