Adefovir

Name: Adefovir

Adefovir Dosage

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take adefovir with a full glass of water. Adefovir may be taken with or without food.

Use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. You should not stop using adefovir without your doctor's advice.

While using adefovir, you may need frequent blood tests. Your kidney or liver function may also need to be checked. You must remain under the care of a doctor while you are using adefovir. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What is the most important information I should know about adefovir?

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.

Adefovir dosing information

Usual Adult Dose for Chronic Hepatitis B:

10 mg orally once a day, without regard to food

Usual Pediatric Dose for Chronic Hepatitis B:

Less than 12 years: Not recommended.
12 years or older: 10 mg orally once a day, without regard to food

What other drugs will affect adefovir?

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.

Uses For adefovir

Adefovir is used to treat chronic (long-term) hepatitis B virus (HBV) infection in patients who are at least 12 years of age. Adefovir is not a cure for the hepatitis B virus, but it may lower the amount of virus in your body. It may also lower the ability of the virus to multiply in your body.

adefovir is available only with your doctor's prescription.

adefovir Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

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
Rare
  • 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

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

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

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Brand Names U.S.

  • Hepsera

Pharmacology

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

Distribution

0.35 to 0.39 L/kg

Metabolism

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

Excretion

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

Time to Peak

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

Half-Life Elimination

7.5 hours; prolonged in renal impairment

Protein Binding

≤4%

ALERT U.S. 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.

Warnings/Precautions

Concerns related to adverse effects:

• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Fatal cases of lactic acidosis and severe hepatomegaly with steatosis have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Exacerbations may occur in up to 25% of patients and usually within 12 weeks and may be self-limited or resolve upon resuming treatment; risk may be increased with advanced liver disease or cirrhosis. Monitor liver function several months after stopping treatment; reinitiation of antihepatitis B therapy may be required. Ethanol should be avoided in hepatitis B infection due to potential hepatic toxicity.

• HIV: [US Boxed Warning]: May cause the development of HIV resistance in chronic hepatitis B patients with unrecognized or untreated HIV infection. Determine HIV status prior to initiating treatment with adefovir.

• Renal impairment: [US Boxed Warning]: Use with caution in patients with renal dysfunction or in patients at risk of renal toxicity (including concurrent nephrotoxic agents or NSAIDs). Chronic administration may result in nephrotoxicity. 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 or adolescents with renal impairment. Calculation of creatinine clearance in all patients is recommended prior to initiating therapy.

Concurrent drug therapy:

• Tenofovir: Do not use concurrently with tenofovir (Viread®) or any product containing tenofovir (eg, Truvada, Atripla, Complera).

Other warnings/precautions:

• Appropriate use: Current clinical hepatitis B practice guidelines do not recommend adefovir for initial use in the management of chronic HBV due to high rate of resistance with long-term use; other antiviral agents with a high barrier to drug resistance are preferred (eg, tenofovir or entecavir). In the setting of lamivudine-resistant HBV, adefovir (including when combined with lamivudine) is also not a preferred strategy to manage antiviral resistance; consult current clinical practice guidelines for recommendations (AASLD [Terrault 2016]). If used, combination therapy with lamivudine should be used to decrease the risk of resistance in patients with lamivudine-resistant HBV.

Renal Dose Adjustments

CrCl 30 to 49 mL/min: 10 mg orally every 48 hours
CrCl 10 to 29 mL/min: 10 mg orally every 72 hours
CrCl less than 10 mL/min, non-hemodialysis: Data not available

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