Adefovir

Adefovir is a prescription drug used to treat adults with the viral infection chronic hepatitis B. Hepatitis B is a viral infection that causes liver damage. Adefovir belongs to a family of antiviral drugs called nucleotide analog reverse transcriptase inhibitors (NtRTIs). Another member of this family is tenofovir (Viread). The Food and Drug Administration approved adefovir in September 2002. The European Union approved its use in March of 2003. Adefovir is marketed as Hepsera and Preveon by Gilead Sciences.

This electron micrograph shows several hepatitis-B viruses. Source:CDC Public Health Image Library

Uses

Adefovir is indicated for the treatment of chronic hepatitis B in people 12 years of age and older with evidence of active viral replication and one of the following:

• persistent elevations in serum aminotransferases (liver enzymes released into the blood due to liver damage)
• histologically active disease (active viral infection confirmed by microscopically examining an actual tissue sample of the infected liver)

How Adefovir is Taken

Adefovir is available in tablets of 10 mg. The recommended dose is 10 mg taken once daily. The optimal duration of treatment is not known at this time.

How Adefovir Works

Hepatitis B uses an enzyme called reverse transcriptase to replicate. Reverse transcriptase creates DNA strands from ribonucleic acid (RNA). Adefovir is phosphorylated to its active metabolite adefovir diphosphate by cellular kinases and resembles deoxyadenosine triphosphate, a molecule that reverse transcriptase incorporates into the DNA strand. However, adefovir cannot be added to DNA and, instead, it prevents reverse transcriptase from completing the DNA. This prevents the hepatitis B virus from replicating and infecting even more cells.For this reason, adefovir is classified as a nucleotide reverse transcriptase inhibitor.

How the Body Affects Adefovir

Adefovir is poorly absorbed from the gastrointestinal tract and a prodrug called adefovir dipivoxil was synthesized to improve its bioavailability. Oral bioavailability of adefovir after adefovir dipivoxil is about 60% and food has no effect on adefovir absorption.Once absorbed, adefovir dipivoxil is rapidly broken down to adefovir by extracellular enzymes called esterases.Peak circulating levels of adefovir occur 0.5–4 hours post-dosing. Adefovir half-life is 7.48 hours and is excreted by the kidneys by a combination of glomerular filtration adn active tubular secreation.

Side Effects

Side effects seen in clinical studies include the following:

• feelings of weakness
• headache
• abdominal pain
• diarrhea
• nausea
• indigestion
• flatulence
• increased blood creatinine levels, an indicator of slowed kidney function
• low blood phosphate levels

Of these variosu side effects, the most important is kidney dysfunction and all patients on adefovir need their kidney function t be monitored periodically.

Risks and Precautions

• Sudden discontinuation of adefovir may worsen the underlying hepatitis B infection. Discontinuation is supervised by a doctor.
• Routine blood tests and physician visits are required to monitor effectiveness and safety of the drug.
• Adefovir could cause the emergence of strains of HIV that are resistant to treatment. For this reason, HIV tests are performed before starting treatment with adefovir.

• Adefovir can damage the kidney. The risk of kidney damage is increased in people with existing kidney impairment or those taking drugs that also harm the kidney. Cyclosporine (Neoral), tacrolimus (Rapamune), some antibiotics, and non-steroidal anti-inflammatory drugs are some medication that can cause kidney impairment.
• Use of NtRTIs has been associated with development of lactic acidosis (elevated levels of lactic acid) and liver enlargement. The risk is greater in women and during prolonged treatment.

Drug Interactions

Many drugs are pumped into the urine by proteins in the cells lining the kidney tubules. These drugs could slow the excretion of adefovir in the urine. In addition, as mentioned in “Risks and Precautions,” the risk of side effects is increased if adefovir is administered with other drugs that impair kidney function.

History

Adefovir was developed in the Czech Republic as a treatment for HIV/AIDS. The U.S. Food and Drug Administration did not accept a request for approval in 1999, citing a high risk of liver damage and failure at doses needed for HIV/AIDS treatment (60 mg or 120 mg). Without the U.S. market, Gilead Sciences decided to pursue the use of adefovir in hepatitis B, a condition for which lower doses could be used.

Clinical Trials

One study was conducted for 144 weeks to determine the long-term effectiveness of adefovir.^[1] The study’s main findings are as follows:

• 79% of treated patients achieved undetectable levels of viral DNA in their bloodstream
• adefovir also improved liver function–markers of liver damage had disappeared in 88% of patients

References

1. ↑ Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81. Abstract | Full Text | PDF Press Release

External Links

FDA: Patient Information Sheet

Drugs.com

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