ADEFOVIR DIPIVOXIL 10 mg Tablet, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Adefovir is used to treat chronic (long-term) hepatitis B infection (swelling of the liver caused by a virus) in adults and children 12 years of age and older. Adefovir is in a class of medications called nucleotide analogs. It works by decreasing the amount of hepatitis B virus (HBV) in the body. Adefovir will not cure hepatitis B and may not prevent complications of chronic hepatitis B such as cirrhosis of the liver or liver cancer. Adefovir may not prevent the spread of hepatitis B to other people.
Read the full MedlinePlus article ↗- Adefovir (sold as Adefovir Dipivoxil or Hepsera) is an antiviral tablet prescribed to treat chronic hepatitis B — a long-term liver infection caused by the hepatitis B virus. Your...
- What exactly is adefovir and why did my doctor prescribe it?
- Please don't stop without talking to your doctor first — this is really important. When people stop adefovir suddenly, hepatitis B can flare back up severely, sometimes to dangerou...
- Can I just stop taking adefovir if I feel better?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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Copovidone is a synthetic polymer made by combining two types of plastic-like molecules. It acts as a binder and film-former to help hold tablet ingredients together and improve how the medicine dissolves in your body.
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UNII 2S7830E561
Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $21.731 | $651.94 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $23.97 | $719.24 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $25.54 | $766.20 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Adefovir Dipivoxil 10 mgthis 42794-0003-08 | Sigmapharm | 30 tablets | $21.731 | AB | Availability likely | — |
| Adefovir dipivoxil 10 mg 60505-3947-03 | Apotex | 30 tablets | $21.731 | AB | Availability likely | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 42794-0003-08 You're viewing this | 1 BOTTLE in 1 CARTON (42794-003-08) / 30 TABLET in 1 BOTTLE | 2016-07-18 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SEVERE ACUTE EXACERBATIONS OF HEPATITIS, NEPHROTOXICITY, HIV RESISTANCE, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-Hepatitis B therapy including Adefovir Dipivoxil Tablets. Hepatic function should be monitored closely 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 [See Warnings and Precautions (5.1) ] .
In patients at risk of or having underlying renal dysfunction, chronic administration of Adefovir Dipivoxil Tablets may result in nephrotoxicity. These patients should be monitored closely for renal function and may require dose adjustment [See Warnings and Precautions (5.2) and Dosage and Administration (2.2) ] . HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated Human Immunodeficiency Virus (HIV) infection treated with antihepatitis B therapies, such as therapy with Adefovir Dipivoxil Tablets, that may have activity against HIV [See Warnings and Precautions (5.3) ] .
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 [See Warnings and Precautions (5 . 4 ) ] . WARNING: SEVERE ACUTE EXACERBATIONS OF HEPATITIS, NEPHROTOXICITY, HIV RESISTANCE, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS See full prescribing information for complete boxed warning.
Severe acute exacerbations of hepatitis may occur in patients who discontinue Adefovir Dipivoxil Tablets. Monitor hepatic function closely in these patients. ( 5.1 ) Chronic use of Adefovir Dipivoxil Tablets may result in nephrotoxicity in patients at risk of renal dysfunction or having underlying renal dysfunction.
Monitor renal function closely in these patients. Dose adjustment may be required. ( 5.2 ) HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection.
( 5.3 ) Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. ( 5.4 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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 nucleotide analogues indicated for the treatment of chronic hepatitis B in patients 12 years of age and older. ( 1 )
⏱️ Dosage and Administration ▾
2 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) a Hemodialysis Patients Greater than or equal to 50 30 - 49 10 - 29 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 a Creatinine clearance calculated by Cockcroft-Gault method using lean or ideal body weight. No dose recommendations for ( 2.1 ): Non-hemodialysis patients with creatinine clearance less than 10 mL per minute.
Adolescent patients with renal impairment.
2.1Chronic 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 is not recommended for use in children less than 12 years of age.
2.2Dose Adjustment in Renal Impairment Significantly increased drug exposures were seen when Adefovir Dipivoxil Tablets was 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) a Hemodialysis Patients Greater than or equal to 50 30 - 49 10 - 29 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 a Creatinine clearance calculated by Cockcroft-Gault method using lean or ideal body weight. 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) ]
2.1Chronic 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 is not recommended for use in children less than 12 years of age.
2.2Dose Adjustment in Renal Impairment Significantly increased drug exposures were seen when Adefovir Dipivoxil Tablets was 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 Dipiv…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Adefovir Dipivoxil is available as tablets. Each tablet contains 10 mg of adefovir dipivoxil. The tablets are white, round, flat faced beveled edged tablets, debossed Σ 3 on one side and plain on the other side. Tablets: 10 mg ( 3 )
⛔ Contraindications ▾
4 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 Cautions ▾
5 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 Tablets. ( 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 Tablets. 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 Tablets 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 )
5.1Exacerbation 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 Tablets. 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 Tablets. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
In clinical trials of Adefovir Dipivoxil Tablets, 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 Tablets. 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.
5.2Nephrotoxicity 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 Tablets (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 Tablets. It is important to monitor renal function for all patients during treatment with Adefovir Dipivoxil Tablets, 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 Tablet…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe acute exacerbations of Hepatitis [See 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 reacion in pre- and post-transplantation lamivudine-resistant liver disease patients was increased creatinine.
( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Sigmapharm Laboratories at (1-215-352-6655 ) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 Tablets. Adverse reactions to Adefovir Dipivoxil Tablets 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 Tablets (N=294) or placebo (N=228) for 48 weeks is presented in Table 2. Patients who received open-label Adefovir Dipivoxil Tablets 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 1–4) Reported in ≥3% of All Adefovir Dipivoxil Tablets-Treated Patients in Pooled Studies 437–438 Studies (0–48 Weeks) a Adverse Reaction Adefovir Dipivoxil Tablets 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% a In these studies, the overall incidence of adverse reactions with Adefovir Dipivoxil Tablets was similar to that reported with placebo.
The incidence of adverse reactions is derived from treatment-related events as identified by the study investigators. No patients treated with Adefovir Dipivoxil Tablets developed a confirmed serum creatinine increase greater than or equal to 0.5 mg/dL from baseline or confirmed phosphorus decrease to 2 mg/dL or less by Week 48. By Week 96, 2% of Adefovir Dipivoxil Tablets-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 Tablets 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 Tablets 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.
6.2Special 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 Tablets once daily for up to 203 weeks include: abnormal ren…
🔄 Drug Interactions ▾
7 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 coadministered drugs [See Clinical Pharmacology (12.3) ] . Patients should be monitored closely for adverse events when Adefovir Dipivoxil Tablets are coadministered 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) ]. 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 Tablets associated adverse events.
( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATION 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 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Adefovir Dipivoxil Tablets 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 Tablets ( 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 Tablets. 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 Tablets. 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 (C max ) 38 times that in humans at the RHD of Adefovir Dipivoxil Tablets.
No adverse developmental effects were observed at an exposure (C max ) 12 times that in humans at the RHD of Adefovir Dipivoxil Tablets.
8.2Lactation 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 Tablets and any potential adverse effects on the breastfed infant from Adefovir Dipivoxil Tablets or from the underlying maternal condition.
8.4Pediatric Use Pediatric patients 12 to less than 18 years: The safety, efficacy, and pharmacokinetics of Adefovir Dipivoxil Tablets 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 Tablets 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 si…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Adefovir Dipivoxil Tablets 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 Tablets ( 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 Tablets. 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 Tablets. 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 (C max ) 38 times that in humans at the RHD of Adefovir Dipivoxil Tablets.
No adverse developmental effects were observed at an exposure (C max ) 12 times that in humans at the RHD of Adefovir Dipivoxil Tablets.
🧒 Pediatric Use ▾
8.4Pediatric Use Pediatric patients 12 to less than 18 years: The safety, efficacy, and pharmacokinetics of Adefovir Dipivoxil Tablets 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 Tablets 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%) [ See Clinical Studies (14.4) , Dosage and 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 ▾
8.5Geriatric Use Clinical studies of Adefovir Dipivoxil Tablets 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 ▾
10 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 Tablets, a four-hour hemodialysis session removed approximately 35% of the adefovir dose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Adefovir is an antiviral drug [See Microbiology (12.4) ].
12.3Pharmacokinetics Adult Subjects The pharmacokinetics of adefovir have been evaluated in healthy volunteers and patients with chronic hepatitis B. Adefovir pharmacokinetics are similar between these populations. Absorption Adefovir dipivoxil is a diester prodrug of the active moiety adefovir.
Based on a cross study comparison, the approximate oral bioavailability of adefovir from Adefovir Dipivoxil Tablets is 59%. Following oral administration of a 10 mg single dose of Adefovir Dipivoxil Tablets to chronic hepatitis B patients (N=14), the peak adefovir plasma concentration (C max ) was 18.4 ± 6.26 ng/mL (mean ± SD) and occurred between 0.58 and 4.00 hours (median=1.75 hours) post dose. The adefovir area under the plasma concentration-time curve (AUC 0–∞ ) was 220 ± 70.0 ng·h/mL.
Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours. The pharmacokinetics of adefovir in subjects with adequate renal function were not affected by once daily dosing of 10 mg Adefovir Dipivoxil Tablets over seven days. The impact of long-term once daily administration of 10 mg Adefovir Dipivoxil Tablets on adefovir pharmacokinetics has not been evaluated.
Effects of Food on Oral Absorption Adefovir exposure was unaffected when a 10 mg single dose of Adefovir Dipivoxil Tablets was administered with food (an approximately 1000 kcal high-fat meal). Adefovir Dipivoxil Tablets may be taken without regard to food. Distribution In vitro binding of adefovir to human plasma or human serum proteins is less than or equal to 4% over the adefovir concentration range of 0.1 to 25 µg/mL.
The volume of distribution at steady-state following intravenous administration of 1.0 or 3.0 mg/kg/day is 392 ± 75 and 352 ± 9 mL/kg, respectively. Metabolism and Elimination Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses of Adefovir Dipivoxil Tablets.
Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion [ See Drug Interactions (7) and Clinical Pharmacology (12.3) ]. Assessment of Drug Interactions Adefovir dipivoxil is rapidly converted to adefovir in vivo. At concentrations substantially higher (greater than 4000-fold) than those observed in vivo, adefovir did not inhibit any of the common human CYP450 enzymes, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.
Adefovir is not a substrate for these enzymes. However, the potential for adefovir to induce CYP450 enzymes is unknown. Based on the results of these in vitro experiments and the renal elimination pathway of adefovir, the potential for CYP450 mediated interactions involving adefovir as an inhibitor or substrate with other medicinal products is low.
The pharmacokinetics of adefovir have been evaluated in healthy adult volunteers following multiple dose administration of Adefovir Dipivoxil Tablets (10 mg once daily) in combination with lamivudine (100 mg once daily) (N=18), trimethoprim/sulfamethoxazole (160/800 mg twice daily) (N=18), acetaminophen (1000 mg four times daily) (N=20), ibuprofen (800 mg three times daily) (N=18), and enteric coated didanosine (400 mg) (N=21). The pharmacokinetics of adefovir have also been evaluated in post-liver transplantation patients following multiple dose administration of Adefovir Dipivoxil Tablets (10 mg once daily) in combination with tacrolimus (N=16).
The pharmacokinetics of adefovir have been evaluated in healthy volunteers following single dose pegylated interferon α-2a (PEG-IFN) (180 mcg) (N=15). Adefovir did not alter the pharmacokinetics of lamivudine, trimethoprim/sulfamethoxazole, acetaminophen, ibuprofen, enteric coated didanosine (didanosine EC), or tacrolimus. The evaluation of the effect of…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Adefovir is an antiviral drug [See Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED / STORAGE AND HANDLING Adefovir Dipivoxil is available as tablets. Each tablet contains 10 mg of adefovir dipivoxil. The tablets are white, round, flat faced beveled edged tablets, debossed ∑3 on one side and plain on the other side.
They are packaged as follows: Bottles of 30 tablets (NDC 42794-003-08) containing polyester and desiccant and closed with a child-resistant closure. Store in original container at 25 °C (77 °F), excursions permitted to 15° - 30 °C (59° - 86 °F) (See USP Controlled Room Temperature). Do not use if seal over bottle opening is broken or missing.
📦 Storage and Handling ▾
Store in original container at 25 °C (77 °F), excursions permitted to 15° - 30 °C (59° - 86 °F) (See USP Controlled Room Temperature). Do not use if seal over bottle opening is broken or missing.
📋 Description ▾
11 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 501.48 and the following structural formula: Adefovir dipivoxil is a white to off-white crystalline 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: copovidone, anhydrous lactose, microcrystalline cellulose, silicon dioxide, crospovidone and magnesium stearate. chemical structure
💬 Information for Patients ▾
17 PATIENT COUNSELING 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 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) ].
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) ] . Manufactured by: Sigmapharm Laboratories, LLC Bensalem, PA 19020 OS003-09 REV.0821