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Hepsera Side Effects

Generic Name: adefovir

Note: This page contains information about the side effects of adefovir. Some of the dosage forms included on this document may not apply to the brand name Hepsera.

For the Consumer

Applies to adefovir: oral tablet

In addition to its needed effects, some unwanted effects may be caused by adefovir (the active ingredient contained in Hepsera). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking adefovir:

More common:
  • Dark urine
  • general tiredness and weakness
  • light-colored stools
  • nausea and vomiting
  • upper right abdomen or stomach pain
  • yellow eyes and skin
Less common:
  • Blood in the urine
  • change in frequency of urination or amount of urine
  • difficult breathing
  • drowsiness
  • increased thirst
  • loss of appetite
  • swelling of the feet or lower legs
  • weakness
  • Fast, shallow breathing
  • general feeling of discomfort
  • muscle pain or cramping
  • shortness of breath
  • sleepiness
  • unusual tiredness or weakness
Incidence not known:
  • Bloating
  • bone fractures, especially of the thigh bone
  • bone pain
  • chills
  • cloudy urine
  • constipation
  • convulsions
  • darkened urine
  • decreased frequency or amount of urine
  • fast heartbeat
  • fever
  • increase in the amount of urine
  • increased blood pressure
  • indigestion
  • lower back or side pain
  • muscular pain, tenderness, wasting, or weakness
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • swelling of the face, fingers, or lower legs
  • weight gain

Minor Side Effects

Some of the side effects that can occur with adefovir may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:
  • Abdominal or stomach pain
  • headache
  • lack or loss of strength
Less common:
  • Acid or sour stomach
  • belching
  • bloated or full feeling
  • diarrhea
  • excess air or gas in the stomach or intestines
  • heartburn
  • passing gas
  • stomach discomfort, upset, or pain

For Healthcare Professionals

Applies to adefovir: oral tablet


In patients with chronic hepatitis B, the incidence of side effects increased slightly with increased duration of treatment.[Ref]


Other side effects have included asthenia (13%), abdominal pain (9%), fever (greater than or equal to 2%), weight loss, influenza-like syndrome, infection, back pain, pain, and accidental injury.[Ref]


Renal side effects have included hematuria (greater than or equal to 3+, 11% ), increases in serum creatinine (greater than or equal to 0.3 mg/dL, 4% to 37%; greater than or equal to 0.5 mg/dL, 2% to 31%), decreases in serum phosphorus (4% to 6%), renal failure (greater than or equal to 2%), renal insufficiency (greater than or equal to 2%), glycosuria (greater than or equal to 3+, 1%), renal calculus, and renal pain. Adefovir was discontinued due to renal side effects in 1% of pre- and post-liver transplant patients. Causality could not be definitely determined because of the presence of multiple risk factors for renal dysfunction. A rare potential risk of adefovir (the active ingredient contained in Hepsera) includes nephrotoxicity. Fanconi-like syndrome and overall renal function deterioration have been reported at high doses. Renal failure, proximal renal tubulopathy, and Fanconi syndrome have been reported during postmarketing experience.[Ref]

Nervous system

Nervous system side effects have included headache (9%), dizziness, and insomnia.[Ref]


Gastrointestinal side effects have included abdominal pain (9%), nausea (5%), flatulence (4%), diarrhea (3%), dyspepsia (3%), vomiting (2%), and anorexia. Pancreatitis has been reported during postmarketing experience.[Ref]


Hepatic side effects have included hepatic failure (greater than or equal to 2%), and laboratory abnormalities with increases in ALT (greater than 5 times ULN), AST (greater than 5 times ULN), creatine kinase (greater than 4 times ULN), and amylase (greater than 2 times ULN). Nucleoside analogs alone or in combination with antiretrovirals have been associated with lactic acidosis and severe hepatomegaly with steatosis.

Severe acute exacerbations of hepatitis have been reported in patients who have discontinued adefovir (the active ingredient contained in Hepsera) dipivoxil. Although most events appear to have been self-limited, fatalities have been reported. Patients who discontinue adefovir dipivoxil should have close monitoring of hepatic function at repeated intervals over a period of time. If appropriate, resumption of antihepatitis B therapy may be warranted.[Ref]


Dermatologic side effects reported in pre- and post-liver transplantation patients have included pruritus and rash in greater than or equal to 2% of patients.[Ref]


Respiratory side effects reported in pre- and post-liver transplantation patients have included increased cough, pharyngitis, and sinusitis in greater than or equal to 2% of patients. Bronchitis and rhinitis have also been reported.[Ref]


Cardiovascular side effects have included myocardial infarction at high doses.[Ref]


Musculoskeletal side effects have included arthralgia. Hypophosphatemic osteomalacia (in the context of Fanconi syndrome) has been reported. Myopathy and osteomalacia (manifested as bone pain and may contribute to fractures), both associated with proximal renal tubulopathy, have been reported during postmarketing experience.[Ref]


Metabolic side effects have included hypophosphatemia during postmarketing experience.[Ref]


Ocular side effects have included amblyopia at high doses.[Ref]


1. "Product Information. Hepsera (adefovir dipivoxil)." Gilead Sciences, Foster City, CA.

2. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B." N Engl J Med 352 (2005): 2673-81

3. Fontaine H, Vallet-Pichard A, Chaix ML, et al. "Efficacy and safety of adefovir dipivoxil in kidney recipients, hemodialysis patients, and patients with renal insufficiency." Transplantation 80 (2005): 1086-92

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5. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. "Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B." N Engl J Med 348 (2003): 800-7

6. Marcellin P, Chang TT, Lim SG, et al. "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B." N Engl J Med 348 (2003): 808-16

7. Sun DQ, Wang HS, Ni MY, Wang BJ, Guo RC "Pharmacokinetics, safety and tolerance of single- and multiple-dose adefovir dipivoxil in healthy Chinese subjects." Br J Clin Pharmacol 63 (2007): 15-23

8. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. "Long-Term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years." Gastroenterology (2006):

9. Gish RG "Clinical trial results of new therapies for HBV: implications for treatment guidelines." Semin Liver Dis 25 Suppl 1 (2005): 29-39

10. Wong T, Girgis CM, Ngu MC, et al. "Hypophosphatemic osteomalacia after low-dose adefovir dipivoxil therapy for hepatitis B." J Clin Endocrinol Metab 95 (2010): 479-80

11. Perazella MA "Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity." Am J Med Sci 325 (2003): 349-62

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13. de Silva HJ, Dassanayake AS, Manamperi A, de Silva AP "Treatment of Lamivudine-resistant hepatitis B infection in post-renal transplant patients with adefovir dipivoxil: premiminary results." Transplant Proc 38 (2006): 3118-20

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15. Lok AS "The maze of treatments for hepatitis B." N Engl J Med 352 (2005): 2743-6

16. Tanji N, Tanji K, Kambham N, Markowitz GS, Bell A, D'agati VD "Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion." Hum Pathol 32 (2001): 734-40

17. Roling J, Schmid H, Fischereder M, Draenert R, Goebel FD "HIV-Associated Renal Diseases and Highly Active Antiretroviral Therapy-Induced Nephropathy." Clin Infect Dis 42 (2006): 1488-95

18. Garcia A, Mazuecos A, Gonzalez P, et al. "Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and Lamivudine-resistant hepatitis B infection." Transplant Proc 37 (2005): 1462-3

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21. Delaney WE 4th "Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil." J Antimicrob Chemother (2007):

22. Sims KA, Woodland AM "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection." Pharmacotherapy 26 (2006): 1745-57

23. Izzedine H, Launay-Vacher V, Deray G "Renal tubular transporters and antiviral drugs: an update." AIDS 19 (2005): 455-62

24. Robinson DM, Scott LJ, Plosker GL "Entecavir: a review of its use in chronic hepatitis B." Drugs 66 (2006): 1605-22

25. Bendele RA, Richardson FC "Adefovir nephrotoxicity and mitochondrial DNA depletion." Hum Pathol 33 (2002): 574

26. Szczech LA "Hypertension and medication-related renal dysfunction in the HIV-infected patient." Semin Nephrol 21 (2001): 386-93

27. Falloon J "Salvage antiretroviral therapy." Aids 14 (2000): s209-17

28. Izzedine H, Hulot JS, Launay-Vacher V, et al. "Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: Two double-blind, randomized, placebo-controlled studies." Kidney Int 66 (2004): 1153-8

Not all side effects for Hepsera may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.