Adefovir

Name: Adefovir

What Is Adefovir?

Adefovir is an antiviral medication. Adefovir prevents viral cells from multiplying in the body and infecting new liver cells.

Adefovir is used to treat chronic hepatitis B in people who are 12 years of age or older. Adefovir is not a cure for chronic hepatitis B.

Adefovir may also be used for purposes not listed in this medication guide.

This medicine may cause a serious condition called lactic acidosis. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Adefovir can also cause serious kidney problems, especially if you have kidney disease or take certain medications.

Tell your doctor if you have been exposed to HIV, or if you have untreated HIV or AIDS. Taking medicines to treat chronic hepatitis B can cause HIV infection to become resistant to the standard HIV and AIDS medications. You may need to be tested for HIV before you start taking adefovir.

You may develop liver symptoms after you stop taking this medication. Your doctor may want to check your liver function for several months after you stop using adefovir.

You should not take adefovir if you are allergic to it.

Do not take adefovir if you also take Atripla, Complera, Stribild, Truvada, or Viread.

Some people taking adefovir develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

Tell your doctor if you have been exposed to HIV, or if you have untreated HIV or AIDS. Taking medicines to treat chronic hepatitis B can cause HIV infection to become resistant to the standard HIV and AIDS medications. You may need to be tested for HIV before you start taking adefovir.

To make sure adefovir is safe for you, tell your doctor if you have:

  • kidney disease; or
  • liver disease.

FDA pregnancy category C. It is not known whether adefovir will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Your name may need to be listed on an antiviral pregnancy registry when you start using this medication.

It is not known whether adefovir passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Adefovir Interactions

Taking this medication will not prevent you from passing hepatitis B to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Adefovir can harm your kidneys. This effect is increased when you also use certain other medicines, including: antivirals, chemotherapy, injected antibiotics, medicine for bowel disorders, medicine to prevent organ transplant rejection, and some pain or arthritis medicines (including aspirin, Tylenol, Advil, and Aleve).

Other drugs may interact with adefovir, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

How should this medicine be used?

Adefovir comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take adefovir at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take adefovir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

What should I do if I forget a dose?

If you remember the missed dose on the day that you were supposed to take it, take the missed dose as soon as you remember it. However, if you do not remember the missed dose until the next day, skip the missed dose and continue your regular dosing schedule. Do not take more than one dose of adefovir on the same day. Do not take a double dose to make up for a missed one.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

  • upset stomach
  • stomach discomfort
  • vomiting
  • gas
  • loose bowel movements
  • loss of appetite

Brand names

  • Hepsera®

Pregnancy & Lactation

Pregnancy Category: C (Pregnancy Registry: 1-800-258-4263)

Lactation: Unknown if excreted in breast milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Commonly used brand name(s)

In the U.S.

  • Hepsera

Available Dosage Forms:

  • Tablet

Therapeutic Class: Antiviral

Pharmacologic Class: Nucleotide Reverse Transcriptase Inhibitor

What are some other side effects of Adefovir?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Loose stools (diarrhea).
  • Gas.
  • Belly pain.
  • Upset stomach or throwing up.
  • Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosing Adult

Hepatitis B (chronic): Oral: 10 mg once daily

Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog-based therapy (eg, adefovir) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016):

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 anaglogues. 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.

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; however, there is insufficient evidence to guide decisions in these patients.

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.

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

Viral breakthrough (AASLD practice guidelines): 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 (AASLD [Terrault 2016]).

For Healthcare Professionals

Applies to adefovir: oral tablet

General

In patients with compensated liver disease, the most commonly reported side effects were asthenia, headache, abdominal pain, and nausea during 48 weeks of therapy. In patients with decompensated liver disease, the most commonly reported side effects were increased creatinine and asthenia during up to 203 weeks of therapy.[Ref]

Renal

Very common (10% or more): Increased serum creatinine
Common (1% to 10%): Renal failure, abnormal renal function
Frequency not reported: Renal toxicity, changes in renal function, renal events, renal insufficiency, renal calculus, renal pain, nephrotoxicity, Fanconi-like syndrome, overall renal function deterioration
Postmarketing reports: Proximal renal tubulopathy, Fanconi syndrome[Ref]

In 125 hepatitis B e antigen (HBeAg)-negative patients with extended therapy (up to 240 weeks), serum creatinine increases of at least 0.5 mg/dL from baseline were confirmed in 4 patients; 1 patient discontinued therapy due to elevated serum creatinine level. In 65 HBeAg-positive patients with extended therapy (up to 234 weeks), serum creatinine increases of at least 0.5 mg/dL from baseline were confirmed in 6 patients; 2 patients discontinued therapy due to elevated serum creatinine level.

Pre- and post-liver transplantation patients (n=226 and 241, respectively) with chronic hepatitis B and lamivudine-resistant hepatitis B were treated for up to 203 weeks; changes in renal function were reported in those with risk factors for renal dysfunction. Serum creatinine increases of at least 0.3 mg/dL from baseline were seen in 37% and 53% of pre-liver transplantation patients by 48 and 96 weeks, respectively; serum creatinine increases of at least 0.5 mg/dL from baseline occurred in 18%, 35%, and 35% of pre-liver transplantation patients by 48, 96, and 144 week, respectively. Serum creatinine increases of at least 0.3 mg/dL from baseline were seen in 32% and 51% of post-liver transplantation patients by 48 and 96 weeks, respectively; serum creatinine increases of at least 0.5 mg/dL from baseline occurred in 12%, 28%, and 30% of post-liver transplantation patients by 48, 96, and 144 weeks, respectively. Serum creatinine elevations at least 0.5 mg/dL from baseline resolved (up to 0.3 mg/dL increase from baseline) in 8 of 39 pre-liver transplantation patients and in 14 of 43 post-liver transplantation patients by last study visit. Serum phosphorus values less than 2 mg/dL were seen in 1.3% and 2.5% of pre- and post-liver transplantation patients, respectively, by last study visit. This drug was discontinued due to renal events in 4% of pre- and post-liver transplant patients. Causality could not be definitely determined because of the presence of multiple risk factors for renal dysfunction.

Fanconi-like syndrome and overall renal function deterioration have been reported at high doses.

Renal failure has also been reported during postmarketing experience.[Ref]

Hepatic

Elevated ALT (greater than 5 times the upper limit of normal [5 x ULN]) and AST (greater than 5 x ULN) were reported in 20% and 8% of patients, respectively, during the first 48 weeks of therapy.

Severe acute exacerbations of hepatitis have been reported in patients who have discontinued this drug. Although most cases appeared self-limited or resolved by restarting therapy, severe hepatitis exacerbations (including fatalities) have been reported.

Clinical and laboratory evidence of exacerbations of hepatitis have been reported after treatment with this drug was discontinued.

Lactic acidosis and severe hepatomegaly with steatosis (including fatalities) have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals.[Ref]

Very common (10% or more): Elevated ALT (20%)
Common (1% to 10%): Elevated AST
Frequency not reported: Hepatic failure, severe acute exacerbations of hepatitis
Postmarketing reports: Clinical and laboratory evidence of exacerbations of hepatitis

Nucleoside analogs:
-Frequency not reported: Severe hepatomegaly with steatosis[Ref]

Other

Very common (10% or more): Asthenia (up to 13%), decreased serum phosphorus
Common (1% to 10%): Decreased carnitine levels
Frequency not reported: Fever, weight loss, influenza-like syndrome, infection, pain, accidental injury[Ref]

Genitourinary

Very common (10% or more): Hematuria (11%)
Common (1% to 10%): Glycosuria

Hematuria (at least 3+) and glycosuria (at least 3+) were reported in 11% and 1% of patients, respectively, during the first 48 weeks of therapy.

Gastrointestinal

Common (1% to 10%): Abdominal pain, nausea, flatulence, diarrhea, dyspepsia, vomiting, increased amylase
Postmarketing reports: Pancreatitis[Ref]

Increased amylase (greater than 2 x ULN) was reported in 4% of patients during the first 48 weeks of therapy.[Ref]

Nervous system

Common (1% to 10%): Headache
Frequency not reported: Dizziness[Ref]

Musculoskeletal

Increased creatine kinase (greater than 4 x ULN) was reported in 7% of patients during the first 48 weeks of therapy.

Osteomalacia and myopathy, both associated with proximal renal tubulopathy, have been reported.[Ref]

Common (1% to 10%): Increased creatine kinase
Frequency not reported: Arthralgia, back pain, hypophosphatemic osteomalacia (in the context of Fanconi syndrome)
Postmarketing reports: Myopathy, osteomalacia (manifested as bone pain and infrequently contributing to fractures)[Ref]

Dermatologic

Common (1% to 10%): Pruritus, rash[Ref]

Metabolic

Common (1% to 10%): Hypophosphatemia
Frequency not reported: Anorexia

Nucleoside analogs:
-Frequency not reported: Lactic acidosis[Ref]

Hypophosphatemia has also been reported during postmarketing experience.

Lactic acidosis and severe hepatomegaly with steatosis (including fatalities) have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals.[Ref]

Psychiatric

Frequency not reported: Insomnia

Respiratory

Frequency not reported: Increased cough, pharyngitis, sinusitis, bronchitis, rhinitis[Ref]

Cardiovascular

Myocardial infarction has been reported at high doses.[Ref]

Frequency not reported: Myocardial infarction[Ref]

Ocular

Frequency not reported: Amblyopia[Ref]

Amblyopia has been reported at high doses.[Ref]

Some side effects of adefovir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Precautions

Severe acute exacerbations of hepatitis, including fatalities, have been reported in patients who have discontinued antihepatitis B therapy, including therapy with adefovir dipivoxil. Patients who discontinue adefovir dipivoxil should have close monitoring of hepatic function at repeated intervals with both clinical and laboratory follow-up for at least several months. If appropriate, resumption of antihepatitis B therapy may be warranted.

Exacerbation of hepatitis B may result from resistance to adefovir dipivoxil and may lead to liver decompensation and possible fatal outcome. To reduce the risk of resistance, adefovir dipivoxil should be administered with lamivudine and should not be used as monotherapy in patients with lamivudine-resistant hepatitis B. To reduce the risk of resistance, treatment modification should be considered in patients using adefovir dipivoxil monotherapy if serum hepatitis B DNA remains over 1000 copies/mL with continued therapy.

The use of adefovir dipivoxil in patients at risk of or having underlying renal dysfunction, and patients taking other nephrotoxic agents may result in nephrotoxicity. Creatinine clearance should be calculated prior to initiating adefovir therapy. Close clinical and laboratory monitoring of all patients' renal function is recommended and appropriate dosage adjustments should be made if indicated. The risks and benefits of treatment should be carefully evaluated before discontinuing adefovir due to treatment-emergent nephrotoxicity.

HIV resistance may occur in patients treated with antihepatitis B therapies, including adefovir dipivoxil, that have activity against HIV in a chronic hepatitis B patient with unrecognized or untreated HIV infection. HIV antibody testing should be offered to all patients prior to the start of adefovir dipivoxil therapy.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. Risk factors may include female gender, obesity, and prolonged nucleoside exposure. Caution is recommended in patients with risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatomegaly.

Adefovir dipivoxil should not be administered concomitantly with tenofovir or tenofovir-containing products including emtricitabine-tenofovir, efavirenz/emtricitabine/tenofovir, cobicistat/elvitegravir/emtricitabine/tenofovir, and emtricitabine/rilpivirine/tenofovir.

Adefovir dipivoxil use is not recommended in pediatric patients less than 12 years of age.

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