Adefovir dipivoxil
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From MedlinePlus, U.S. National Library of Medicine
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 anti-hepatitis 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 )
Dosing in kidney impairment
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 and Clinical Pharmacology ] . 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. [See table below.] 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 ].
| 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 |
| 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 |
Drug interactions
Check adefovir dipivoxil against a medication listLabel text (2 paragraphs)
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 )
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 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for adefovir dipivoxil. Check the label's hepatic warnings.
Pregnancy and lactation
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…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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