Adefovir Dipivoxil
Tablet · Oral
Uses
Adefovir dipivoxil tablets are indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function. For patients 12 to less than 18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg+ chronic hepatitis B virus infection with compensated liver function. Adefovir dipivoxil tablets are a nucleotide analogue indicated for the treatment of chronic hepatitis B in patients 12 years of age and older. ( 1 )
Dosage and administration
One tablet containing 10 mg adefovir dipivoxil once daily orally with or without food. ( 2.1 ) Dose adjustment in renal impairment for adults ( 2.2 ) Creatinine Clearance (mL/min) Creatinine clearance calculated by Cockcroft-Gault method using lean or ideal body weight. Greater than or equal to 50 30 to 49 10 to 29 Hemodialysis Patients Recommended dose and dosing interval 10 mg every 24 hours 10 mg every 48 hours 10 mg every 72 hours 10 mg every 7 days following dialysis No dose recommendations for ( 2.1 ): Non-hemodialysis patients with creatinine clearance less than 10 mL per minute. Adolescent patients with renal impairment. 2.1 Chronic Hepatitis B The recommended dose of adefovir dipivoxil tablets in chronic hepatitis B patients for patients 12 years of age and older with adequate renal function is 10 mg, once daily, taken orally, without regard to food. The optimal duration of treatment is unknown. Adefovir dipivoxil tablets are not recommended for use in children less than 12 years of age. 2.2 Dose Adjustment in Renal Impairment Significantly increased drug exposures were seen when adefovir dipivoxil tablets were administered to adult patients with renal impairment [See Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . Therefore, the dosing interval of adefovir dipivoxil tablets should be adjusted in adult patients with baseline creatinine clearance less than 50 mL per minute using the following suggested guidelines (See Table 1 ). The safety and effectiveness of these dosing interval adjustment guidelines have not been clinically evaluated. Additionally, it is important to note that these guidelines were derived from data in patients with pre-existing renal impairment at baseline. They may not be appropriate for patients in whom renal insufficiency evolves during treatment with adefovir dipivoxil tablets. Therefore, clinical response to treatment and renal function should be closely monitored in these patients. Table 1 Dosing Interval Adjustment of Adefovir Dipivoxil Tablets in Adult Patients with Renal Impairment Creatinine Clearance (mL/min) Creatinine clearance calculated by Cockcroft-Gault method using lean or ideal body weight. Greater than or equal to 50 30 to 49 10 to 29 Hemodialysis Patients Recommended dose and dosing interval 10 mg every 24 hours 10 mg every 48 hours 10 mg every 72 hours 10 mg every 7 days following dialysis The pharmacokinetics of adefovir have not been evaluated in non-hemodialysis patients with creatinine clearance less than 10 mL per minute; therefore, no dosing recommendation is available for these patients. No clinical data are available to make dosing recommendations in adolescent patients with renal insufficiency [See Warnings and Precautions (5.2) ].
Dosage forms and strengths
Adefovir Dipivoxil Tablets are white to off-white, round, flat-faced bevelled edge tablets, engraved “APO” on one side, “A10” on the other side. Tablets: 10 mg ( 3 )
Contraindications
Adefovir dipivoxil tablets are contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product. Adefovir dipivoxil tablets are contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product. ( 4 )
Warnings and precautions
Severe acute exacerbations of hepatitis: Monitor hepatic function closely at repeated intervals for at least several months in patients who discontinue adefovir dipivoxil. ( 5.1 ) Nephrotoxicity: Monitor renal function during therapy for all patients, particularly those with pre-existing or other risks for renal impairment. Dose adjustment may be required. ( 5.2 ) HIV Resistance: Offer HIV testing to all patients prior to initiating adefovir dipivoxil. Untreated HIV may result in HIV resistance. ( 5.3 ) Lactic acidosis and severe hepatomegaly with steatosis: If suspected, suspend treatment. ( 5.4 ) Coadministration with Other Products: Do not administer adefovir dipivoxil concurrently with VIREAD ® or other tenofovir-containing products. ( 5.5 ) Clinical Resistance: For patients with lamivudine-resistant HBV use adefovir dipivoxil in combination with lamivudine. For all patients, consider modifying treatment in case serum HBV DNA remains above 1000 copies/mL with continued treatment. ( 5.6 ) 5.1 Exacerbation of Hepatitis after Discontinuation of Treatment Severe acute exacerbation of hepatitis has been reported in patients who have discontinued anti-hepatitis B therapy, including therapy with adefovir dipivoxil. Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least several months in patients who discontinue adefovir dipivoxil. If appropriate, resumption of anti-hepatitis B therapy may be warranted. In clinical trials of adefovir dipivoxil, exacerbations of hepatitis (ALT elevations 10 times the upper limit of normal or greater) occurred in up to 25% of patients after discontinuation of adefovir dipivoxil. These events were identified in studies GS-98-437 and GS-98-438 (N=492). Most of these events occurred within 12 weeks of drug discontinuation. These exacerbations generally occurred in the absence of HBeAg seroconversion, and presented as serum ALT elevations in addition to re-emergence of viral replication. In the HBeAg-positive and HBeAg-negative studies in patients with compensated liver function, the exacerbations were not generally accompanied by hepatic decompensation. However, patients with advanced liver disease or cirrhosis may be at higher risk for hepatic decompensation. Although most events appear to have been self-limited or resolved with re-initiation of treatment, severe hepatitis exacerbations, including fatalities, have been reported. Therefore, patients should be closely monitored after stopping treatment. 5.2 Nephrotoxicity Nephrotoxicity characterized by a delayed onset of gradual increases in serum creatinine and decreases in serum phosphorus was historically shown to be the treatment-limiting toxicity of adefovir dipivoxil therapy at substantially higher doses in HIV-infected patients (60 and 120 mg daily) and in chronic hepatitis B patients (30 mg daily). Chronic administration of adefovir dipivoxil (10 mg once daily) may result in delayed nephrotoxicity. The overall risk of nephrotoxicity in patients with adequate renal function is low. However, this is of special importance in patients at risk of or having underlying renal dysfunction and patients taking concomitant nephrotoxic agents such as cyclosporine, tacrolimus, aminoglycosides, vancomycin and non-steroidal anti-inflammatory drugs [See Adverse Reactions (6.2) and Clinical Pharmacology (12.3) ]. It is recommended that creatinine clearance is calculated in all patients prior to initiating therapy with adefovir dipivoxil. It is important to monitor renal function for all patients during treatment with adefovir dipivoxil, particularly for those with pre-existing or other risks for renal impairment. Patients with renal insufficiency at baseline or during treatment may require dose adjustment [See Dosage and Administration (2.2) ]. The risks and benefits of adefovir dipivoxil treatment should be carefully evaluated prior to discontinuing adefovir dipivoxil in a patient with treatment-emergent nephrotoxicity. Pediatric Patients The efficacy and safety of adefovir dipivoxil have not been studied in patients less than 18 years of age with different degrees of renal impairment and no data are available to make dosage recommendations in these patients [See Dosage and Administration (2.2) ]. Caution should be exercised when prescribing adefovir dipivoxil to adolescents with underlying renal dysfunction, and renal function in these patients should be closely monitored. 5.3 HIV Resistance Prior to initiating adefovir dipivoxil therapy, HIV antibody testing should be offered to all patients. Treatment with anti-hepatitis B therapies, such as adefovir dipivoxil, that have activity against HIV in a chronic hepatitis B patient with unrecognized or untreated HIV infection may result in emergence of HIV resistance. Adefovir dipivoxil has not been shown to suppress HIV RNA in patients; however, there are limited data on the use of adefovir dipivoxil to treat patients with chronic hepatitis B co-infected with HIV. 5.4 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 antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with adefovir dipivoxil should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Side effects
The following adverse reactions are discussed in other sections of the labeling: Severe acute exacerbations of Hepatitis [ S ee Boxed Warning , Warnings and Precautions (5.1) ] Nephrotoxicity [See Boxed Warning , Warnings and Precautions (5.2) ] Most common adverse reaction (incidence greater than 5%) in compensated liver disease patients were asthenia, headache, abdominal pain and nausea. ( 6.1 ) The most common adverse reaction in pre- and post- transplantation lamivudine-resistant liver disease patients was increased creatinine. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with adefovir dipivoxil. Adverse reactions to adefovir dipivoxil identified from placebo-controlled and open label studies include the following: asthenia, headache, abdominal pain, diarrhea, nausea, dyspepsia, flatulence, increased creatinine, and hypophosphatemia. The incidence of these adverse reactions in studies 437 and 438, where 522 patients with chronic hepatitis B and compensated liver disease received double-blind treatment with adefovir dipivoxil (N=294) or placebo (N=228) for 48 weeks is presented in Table 2. Patients who received open-label adefovir dipivoxil for up to 240 weeks in Study 438 reported adverse reactions similar in nature and severity to those reported in the first 48 weeks. Table 2 Adverse Reactions (Grades 1 to 4) Reported in ≥3% of All Adefovir Dipivoxil-Treated Patients in Pooled Studies 437 to 438 Studies (0 to 48 Weeks) In these studies, the overall incidence of adverse reactions with adefovir dipivoxil was similar to that reported with placebo. The incidence of adverse reactions is derived from treatment-related events as identified by the study investigators. Adverse Reaction Adefovir Dipivoxil 10 mg (N=294) Placebo (N=228) Asthenia 13% 14% Headache 9% 10% Abdominal Pain 9% 11% Nausea 5% 8% Flatulence 4% 4% Diarrhea 3% 4% Dyspepsia 3% 2% No patients treated with adefovir dipivoxil developed a confirmed serum creatinine increase greater than or equal to 0.5 mg/dL from baseline or a confirmed phosphorus decrease to 2 mg/dL or less by Week 48. By Week 96, 2% of adefovir dipivoxil-treated patients, by Kaplan-Meier estimate, had increases in serum creatinine greater than or equal to 0.5 mg/dL from baseline (no placebo-controlled results were available for comparison beyond Week 48). For patients who chose to continue adefovir dipivoxil for up to 240 weeks in Study 438, 4 of 125 patients (3%) had a confirmed increase of 0.5 mg/dL from baseline. The creatinine elevation resolved in 1 patient who permanently discontinued treatment and remained stable in 3 patients who continued treatment. For 65 patients who chose to continue adefovir dipivoxil for up to 240 weeks in Study 437, 6 had a confirmed increase in serum creatinine of greater than or equal to 0.5 mg/dL from baseline with 2 patients discontinuing from the study due to the elevated serum creatinine concentration. See Adverse Reactions (6.2) for changes in serum creatinine in patients with underlying renal insufficiency at baseline. 6.2 Special Risk Patients Pre- and Post-Liver Transplantation Patients Additional adverse reactions observed from an open-label study (Study 435) in pre- and post-liver transplantation patients with chronic hepatitis B and lamivudine-resistant hepatitis B administered adefovir dipivoxil once daily for up to 203 weeks include: abnormal renal function, renal failure, vomiting, rash, and pruritus. Changes in renal function occurred in pre-and post-liver transplantation patients with risk factors for renal dysfunction, including concomitant use of cyclosporine and tacrolimus, renal insufficiency at baseline, hypertension, diabetes, and on-study transplantation. Therefore, the contributory role of adefovir dipivoxil to these changes in renal function is difficult to assess. Increases in serum creatinine greater than or equal to 0.3 mg/dL from baseline were observed in 37% and 53% of pre-liver transplantation patients by Weeks 48 and 96, respectively, by Kaplan-Meier estimates. Increases in serum creatinine greater than or equal to 0.3 mg/dL from baseline were observed in 32% and 51% of post-liver transplantation patients by Weeks 48 and 96, respectively, by Kaplan-Meier estimates. Serum phosphorus values less than 2 mg/dL were observed in 3/226 (1.3%) of pre-liver transplantation patients and in 6/241 (2.5%) of post-liver transplantation patients by last study visit. Four percent (19 of 467) of patients discontinued treatment with adefovir dipivoxil due to renal adverse events. 6.3 Pediatric Patients Assessment of adverse reactions is based on a placebo-controlled study (Study 518) in which 173 pediatric patients aged 2 to less than 18 years with chronic hepatitis B and compensated liver disease received double-blind treatment with adefovir dipivoxil (N=115), or placebo (N=58) for 48 weeks [See Clinical Studies (14.4) and Use In Specific Populations (8.4) ] . The safety profile of adefovir dipivoxil in patients 12 to less than 18 years of age (N=56) was similar to that observed in adults. No pediatric patients treated with adefovir dipivoxil developed a confirmed serum creatinine increase greater than or equal to 0.5 mg/dL from baseline or a confirmed phosphorus decrease to less than 2 mg/dL by Week 48. 6.4 Post-Marketing Experience In addition to adverse reaction reports from clinical trials, the following possible adverse reactions have also been identified during post-approval use of adefovir dipivoxil.
Drug interactions
Since adefovir is eliminated by the kidney, coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either adefovir and/or these coadministered drugs [See Clinical Pharmacology ( 12.3) ]. Patients should be monitored closely for adverse events when adefovir dipivoxil is coadministered with drugs that are excreted renally or with other drugs known to affect renal function [ See Warnings and Precautions (5.2) ] . Adefovir dipivoxil should not be administered in combination with VIREAD [ See Warnings and Precautions (5.5)] . Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of adefovir or the coadministered drug. Monitor for adefovir dipivoxil associated adverse events. ( 7 )
Use in specific populations
• Pediatrics: Not recommended in children less than 12 years of age. ( 2.1 , 8.4 , 14.4 ) Renal Impairment: Dose adjustment may be required. ( 2.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adefovir dipivoxil during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258- 4263. Risk Summary Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects, miscarriage or adverse maternal or fetal outcomes. Adefovir disoproxil (ADV) use during pregnancy has been evaluated in a limited number of individuals reported to the APR and the number of exposures to adefovir is insufficient to make a risk assessment compared to a reference population. The estimated background rate for major birth defects is 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). The estimated rate of miscarriage is not reported in the APR. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background rate of miscarriage in the U.S. general population is 15–20%. In animal reproduction studies with oral ADV, no adverse developmental effects were observed at exposures (C max ) 23 times higher in rats and 40 times higher in rabbits than those at the recommended human dose (RHD) of adefovir dipivoxil (see Data). Data Animal Data In an embryo-fetal development study, ADV was administered orally to pregnant rabbits (at 1, 5, or 20 mg/kg/day) during organogenesis (on gestation day 6 through 18). No adverse developmental effects were observed at up to the highest dose tested, at systemic exposure (C max ) 40 times that in humans at the RHD of adefovir dipivoxil. In a pre/post-natal development study, ADV was administered orally to pregnant rats (at 2.5, 10, or 40 mg/kg/day) from organogenesis, through late gestation, delivery, and lactation (gestation day 7 to lactation/postpartum day 20). Reduced body weight of the offspring due to maternal toxicity was observed at systemic exposure 23 times that in humans at the RHD of adefovir dipivoxil. In an embryo-fetal development study, ADV was administered intravenously to pregnant rats (at 2.5, 10, and 20 mg/kg/day) during organogenesis (gestation day 6 through 15). Embryo-fetal toxicity including malformations (anasarca, depressed eye bulge, umbilical hernia and kinked tail) and skeletal variations (reduction of ossified metacarpal bones, increases in thoracic vertebrae and decreases in lumbar vertebrae) occurred at systemic exposure (Cmax) 38 times that in humans at the RHD of adefovir dipivoxil. No adverse developmental effects were observed at an exposure (Cmax) 12 times that in humans at the RHD of adefovir dipivoxil. 8.2 Lactation Risk Summary It is not known whether adefovir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for adefovir dipivoxil and any potential adverse effects on the breastfed infant from adefovir dipivoxil or from the underlying maternal condition. 8.4 Pediatric Use Pediatric patients 12 to less than 18 years : The safety, efficacy, and pharmacokinetics of adefovir dipivoxil in pediatric patients (aged 12 to less than 18 years) were evaluated in a double-blind, randomized, placebo-controlled study (GS-US-103-518, Study 518) in 83 pediatric patients with chronic hepatitis B and compensated liver disease. The proportion of patients treated with adefovir dipivoxil who achieved the primary efficacy endpoint of serum HBV DNA less than 1,000 copies/mL and normal ALT levels at the end of 48 weeks blinded treatment was significantly greater (23%) when compared to placebo-treated patients (0%) [ S ee Clinical Studies ( 14.4) , Dosage a nd Administration ( 2) and Adverse Reactions ( 6.3) ] . Pediatric patients 2 to less than 12 years : Patients 2 to less than 12 years of age were also evaluated in Study 518. The efficacy of adefovir dipivoxil was not significantly different from placebo in patients less than 12 years of age. Adefovir dipivoxil tablets are not recommended for use in children below 12 years of age. 8.5 Geriatric Use Clinical studies of adefovir dipivoxil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, caution should be exercised when prescribing to elderly patients since they have greater frequency of decreased renal or cardiac function due to concomitant disease or other drug therapy. 8.6 Patients with Impaired Renal Function It is recommended that the dosing interval for adefovir dipivoxil be modified in adult patients with baseline creatinine clearance less than 50 mL per minute. The pharmacokinetics of adefovir have not been evaluated in non-hemodialysis patients with creatinine clearance less than 10 mL per minute or in adolescent patients with renal insufficiency; therefore, no dosing recommendations are available for these patients [See Dosage a nd Administration ( 2.2) and Warning s a nd Precautions ( 5.2) ] .
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adefovir dipivoxil during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258- 4263. Risk Summary Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects, miscarriage or adverse maternal or fetal outcomes. Adefovir disoproxil (ADV) use during pregnancy has been evaluated in a limited number of individuals reported to the APR and the number of exposures to adefovir is insufficient to make a risk assessment compared to a reference population. The estimated background rate for major birth defects is 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). The estimated rate of miscarriage is not reported in the APR. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background rate of miscarriage in the U.S. general population is 15–20%. In animal reproduction studies with oral ADV, no adverse developmental effects were observed at exposures (C max ) 23 times higher in rats and 40 times higher in rabbits than those at the recommended human dose (RHD) of adefovir dipivoxil (see Data). Data Animal Data In an embryo-fetal development study, ADV was administered orally to pregnant rabbits (at 1, 5, or 20 mg/kg/day) during organogenesis (on gestation day 6 through 18). No adverse developmental effects were observed at up to the highest dose tested, at systemic exposure (C max ) 40 times that in humans at the RHD of adefovir dipivoxil. In a pre/post-natal development study, ADV was administered orally to pregnant rats (at 2.5, 10, or 40 mg/kg/day) from organogenesis, through late gestation, delivery, and lactation (gestation day 7 to lactation/postpartum day 20). Reduced body weight of the offspring due to maternal toxicity was observed at systemic exposure 23 times that in humans at the RHD of adefovir dipivoxil. In an embryo-fetal development study, ADV was administered intravenously to pregnant rats (at 2.5, 10, and 20 mg/kg/day) during organogenesis (gestation day 6 through 15). Embryo-fetal toxicity including malformations (anasarca, depressed eye bulge, umbilical hernia and kinked tail) and skeletal variations (reduction of ossified metacarpal bones, increases in thoracic vertebrae and decreases in lumbar vertebrae) occurred at systemic exposure (Cmax) 38 times that in humans at the RHD of adefovir dipivoxil. No adverse developmental effects were observed at an exposure (Cmax) 12 times that in humans at the RHD of adefovir dipivoxil.
Pediatric use
8.4 Pediatric Use Pediatric patients 12 to less than 18 years : The safety, efficacy, and pharmacokinetics of adefovir dipivoxil in pediatric patients (aged 12 to less than 18 years) were evaluated in a double-blind, randomized, placebo-controlled study (GS-US-103-518, Study 518) in 83 pediatric patients with chronic hepatitis B and compensated liver disease. The proportion of patients treated with adefovir dipivoxil who achieved the primary efficacy endpoint of serum HBV DNA less than 1,000 copies/mL and normal ALT levels at the end of 48 weeks blinded treatment was significantly greater (23%) when compared to placebo-treated patients (0%) [ S ee Clinical Studies ( 14.4) , Dosage a nd Administration ( 2) and Adverse Reactions ( 6.3) ] . Pediatric patients 2 to less than 12 years : Patients 2 to less than 12 years of age were also evaluated in Study 518. The efficacy of adefovir dipivoxil was not significantly different from placebo in patients less than 12 years of age. Adefovir dipivoxil tablets are not recommended for use in children below 12 years of age.
Geriatric use
8.5 Geriatric Use Clinical studies of adefovir dipivoxil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, caution should be exercised when prescribing to elderly patients since they have greater frequency of decreased renal or cardiac function due to concomitant disease or other drug therapy.
Overdosage
Doses of adefovir dipivoxil 500 mg daily for 2 weeks and 250 mg daily for 12 weeks have been associated with gastrointestinal side effects. If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. Following a 10 mg single dose of adefovir dipivoxil, a four-hour hemodialysis session removed approximately 35% of the adefovir dose.
Description
Adefovir dipivoxil is a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The chemical name of adefovir dipivoxil is 9-[2-[[bis[(pivaloyloxy)methoxy]-phosphinyl]-methoxy]ethyl]adenine. It has a molecular formula of C 20 H 32 N 5 O 8 P, a molecular weight of 501.47 g/mol and the following structural formula: Adefovir dipivoxil is a white to off-white powder with an aqueous solubility of 19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2. It has an octanol/aqueous phosphate buffer (pH 7) partition coefficient (log p) of 1.91. Adefovir dipivoxil tablets are for oral administration. Each tablet contains 10 mg of adefovir dipivoxil and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, starch and talc. adefovir-dipivoxil
Mechanism of action
12.1 Mechanism of Action Adefovir is an antiviral drug [See Microbiology ( 12.4 )].
How supplied
Adefovir Dipivoxil Tablets are white to off-white, round, flat-faced bevelled edge tablets, engraved “APO” on one side, “A10” on the other side. They are supplied as follows: Bottles of 30s (NDC-60505-3947-3) Store in original container at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not use if seal over bottle opening is broken or missing.
Storage
Store in original container at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not use if seal over bottle opening is broken or missing.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Inform patients of the potential risks and benefits of adefovir dipivoxil tablets and of alternative modes of therapy. Instruct patients to: 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. Advise patients 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 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 )]. Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to adefovir dipivoxil [see Use in Specific Populations ( 8.1 )].
Label text from the FDA structured product label by Apotex Corp. (revised Jul 22, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Adefovir Dipivoxil in 2 products
Adefovir Dipivoxil NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60505-3947 | Adefovir Dipivoxil 10 mg/1 Tablet | Apotex Corp. | ANDA |
| 42794-003 | Adefovir Dipivoxil 10 mg/1 Tablet | Sigmapharm Laboratories, LLC | ANDA |
Frequently asked questions
What is Adefovir Dipivoxil used for?
Adefovir dipivoxil tablets are indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with…
What are the side effects of Adefovir Dipivoxil?
The following adverse reactions are discussed in other sections of the labeling: Severe acute exacerbations of Hepatitis [ S ee Boxed Warning , Warnings and Precautions (5.1) ] Nephrotoxicity [See Boxed Warning , Warnings and Precautions (5.2) ] Most common adverse reaction (incidence greater than 5%) in compensated liver disease patients were asthenia, headache, abdominal pain and nausea. ( 6.1… See the full label for the complete list.
Who makes Adefovir Dipivoxil?
Adefovir Dipivoxil is listed by 2 labelers in the FDA NDC directory, including Apotex Corp., Sigmapharm Laboratories, LLC.