Adefovir Dipivoxil

Name: Adefovir Dipivoxil

Warnings

Black Box Warnings

Severe acute exacerbations of hepatitis reported following discontinuing drug; monitor hepatic function

Chronic use may result in nephrotoxicity in patients with renal impairment or in those at risk of renal dysfunction; dose adjustment may be required

Resistance to HIV NRTIs may emerge in patients with chronic hepatitis B in whom HIV infection is unrecognized or untreated

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogs alone or in combination with other antiretrovirals; obesity and prolonged nucleoside exposure may be risk factors

Contraindications

Hypersensitivity

Cautions

Discontinuation may result in severe acute exacerbation of hepatitis B

Patients who discontinue treatment: Monitor hepatic function for several months

Patients with renal dysfunction: Risk of nephrotoxicity (monitor and adjust dose accordingly)

Coadministration with drugs that reduce renal function may increase adefovir serum concentration

Do not administer with tenofovir (additive toxicity)

May increase HIV resistance in untreated patients who are HIV+

Risk of lactic acidosis, severe hepatomegaly with steatosis

To monitor fetal outcomes, Pregnancy Registry established: 1-800-258-4263

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Introduction

Antiviral; acyclic nucleotide.1

Actions and Spectrum

  • Adefovir available as adefovir dipivoxil, a diester prodrug that is inactive until converted in vivo to adefovir and phosphorylated to adefovir diphosphate.1

  • An acyclic nucleotide antiviral.1

  • Active in vitro and in vivo against HBV.1 2

  • Also has some in vitro activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), HIV-1 and HIV-2, human papillomavirus (HPV), Epstein-Barr virus, and varicella zoster virus, but has not been shown to be effective in clinical infections caused by these viruses.2 15 22

  • HBV with reduced susceptibility to adefovir can develop in some patients during long-term use.1 9 12 16 17

  • Cross-resistance can occur among the nucleoside antivirals used for treatment of HBV.26 28

  • Some strains of HBV may be cross-resistant to both adefovir and lamivudine,26 27 28 but some lamivudine-resistant HBV may be susceptible to adefovir and some adefovir-resistant isolates may be susceptible to lamivudine.1 9 16 19 21 26

  • In vitro studies indicate that some HBV with mutations associated with adefovir resistance may have decreased susceptibility to entecavir.24

Advice to Patients

  • Advise patient of the risks and benefits of adefovir and other alternatives for treatment of HBV infection and importance of reading the adefovir patient package insert before starting treatment.1

  • Importance of remaining under the care of a clinician while taking adefovir and not discontinuing the drug without first informing a clinician.1

  • Importance of following a regular dosage schedule and avoiding missed doses.1

  • Risk of exacerbations of hepatitis when adefovir is discontinued and importance of close monitoring of liver function and HBV levels for several months or longer after the drug is stopped.1

  • Risk of nephrotoxicity and importance of monitoring renal function during treatment, especially in those with preexisting renal impairment or other risks for renal impairment.1

  • Importance of immediately reporting to clinicians any signs or symptoms of lactic acidosis (e.g., weakness/fatigue, unusual muscle pain, trouble breathing, stomach pain with nausea and vomiting, cold intolerance especially in the arms and legs, dizziness or feeling light-headed, fast or irregular heart beat) or any signs or symptoms of hepatotoxicity (e.g., jaundice, dark urine, bowel movements light in color, anorexia, nausea, stomach pain).1 Importance of reporting any other unusual symptoms or if any known symptom persists or worsens.1

  • Risk of emergence of HIV resistance in patients with unrecognized or untreated HIV infection; importance of HIV antibody testing prior to initiation of adefovir therapy and anytime during therapy if possible exposure to HIV occurs.1

  • Advise patients with lamivudine-resistant HBV that they should receive adefovir in conjunction with lamivudine and should not receive adefovir monotherapy.1

  • Advise patients that it is not known whether adefovir will prevent transmission of HBV to others and that appropriate measures should be taken to prevent sexual or other transmission of the virus.1

  • Advise patients that the optimal duration of treatment and the relationship between treatment response and long-term outcomes (hepatocellular carcinoma, decompensated cirrhosis) are not known.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Drug Interactions

Since adefovir is eliminated by the kidney, coadministration of Adefovir Dipivoxil Tablets with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either adefovir and/or these co-administered drugs [See Clinical Pharmacology (12.3)].

Patients should be monitored closely for adverse events when Adefovir Dipivoxil Tablets is co-administered with drugs that are excreted renally or with other drugs known to affect renal function [See Warnings and Precautions (5.2)].

Adefovir Dipivoxil Tablets should not be administered in combination with VIREAD [See Warnings and Precautions (5.5)].

Patient Counseling Information

Instructions for Safe Use

See FDA-approved patient labeling (Patient Information)

  • Physicians should inform patients of the potential risks and benefits of Adefovir Dipivoxil Tablets and of alternative modes of therapy.
  • Physicians should instruct their patients to:
    • Read the Patient Package Insert before starting Adefovir Dipivoxil Tablets therapy.
    • Follow a regular dosing schedule to avoid missing doses.
    • Immediately report any severe abdominal pain, muscle pain, yellowing of the eyes, dark urine, pale stools, and/or loss in appetite.
    • Inform their doctor or pharmacist if they develop any unusual symptom(s), or if any known symptom persists or worsens.
  • Patients should remain under the care of a physician when using Adefovir Dipivoxil Tablets.
  • Patients should be advised that:
    • The optimal duration of Adefovir Dipivoxil Tablets treatment and the relationship between treatment response and long-term outcomes such as hepatocellular carcinoma or decompensated cirrhosis are not known.
    • Patients should not discontinue Adefovir Dipivoxil Tablets without first informing their physician [See Warnings and Precautions (5.1)].
    • Routine laboratory monitoring and follow-up with a physician is important during Adefovir Dipivoxil Tablets therapy.
    • Obtaining HIV antibody testing prior to starting Adefovir Dipivoxil Tablets is important [See Warnings and Precautions. (5.3)]
    • Adefovir Dipivoxil Tablets should not be administered concurrently with ATRIPLA or COMPLERA or STRIBILD or TRUVADA or VIREAD [See Warnings and Precautions (5.5)].
    • Lamivudine-resistant patients should use Adefovir Dipivoxil Tablets in combination with lamivudine and not as Adefovir Dipivoxil Tablets monotherapy [See Warnings and Precautions. (5.6)]

Pregnancy and Breastfeeding

  • Physicians should inform women of childbearing age about the risks associated with exposure to Adefovir Dipivoxil Tablets during pregnancy.
  • Patients should inform their physician if they become pregnant while using Adefovir Dipivoxil Tablets.
  • Pregnant patients using Adefovir Dipivoxil Tablets should be informed about the Adefovir Dipivoxil Tablets pregnancy registry and offered the opportunity to enroll.
  • Patients should be informed that it is not known whether Adefovir Dipivoxil Tablets is excreted into human milk or if it can harm a nursing infant. Therefore, a decision should be made whether to discontinue breastfeeding or drug.

Manufactured by:

Sigmapharm Laboratories, LLC
Bensalem, PA 19020

OS003-06 REV.0913 

PRINCIPAL DISPLAY PANEL- Adefovir Dipivoxil 10 mgBottle Label

Sigmapharm Laboratories, LLC

NDC 42794-003-08

Adefovir Dipivoxil Tablets

10 mg

PHARMACIST: DISPENSE THE PATIENT INFORMATION LEAFLET WITH DRUG PRODUCT

Rx Only

30 Tablets

PRINCIPAL DISPLAY PANEL- Adefovir Dipivoxil 10 mg Carton Label

Sigmapharm Laboratories, LLC

NDC 42794-003-08

Adefovir Dipivoxil Tablets

10 mg

PHARMACIST: DISPENSE THE PATIENT INFORMATION LEAFLET WITH DRUG PRODUCT

Rx Only

30 Tablets

Adefovir Dipivoxil 
Adefovir Dipivoxil tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:42794-003
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Adefovir Dipivoxil (ADEFOVIR) Adefovir Dipivoxil 10 mg
Inactive Ingredients
Ingredient Name Strength
ANHYDROUS LACTOSE  
CROSPOVIDONE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
SILICON DIOXIDE  
COPOVIDONE  
Product Characteristics
Color white (white to off-white) Score no score
Shape ROUND (Flat faced beveled edged tablets, debossed on one side and plain on the other side) Size 10mm
Flavor Imprint Code 3
Contains     
Packaging
# Item Code Package Description
1 NDC:42794-003-08 1 BOTTLE in 1 CARTON
1 30 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA202051 09/03/2013
Labeler - Sigmapharm Laboratories, LLC (556234636)
Registrant - Sigmapharm Laboratories, LLC (556234636)
Establishment
Name Address ID/FEI Operations
Sigmapharm Laboratories, LLC 556234636 analysis(42794-003), manufacture(42794-003), api manufacture(42794-003)
Revised: 06/2016   Sigmapharm Laboratories, LLC
  • Hepatitis B (HBV, Hep B)
  • Sexually Transmitted Diseases in Women (STD)
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