ADEFOVIR DIPIVOXIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADEFOVIR DIPIVOXIL (ADEFOVIR DIPIVOXIL).
Adefovir dipivoxil is a prodrug of adefovir, an acyclic nucleotide analog of adenosine monophosphate. It is phosphorylated intracellularly to adefovir diphosphate, which inhibits hepatitis B virus (HBV) DNA polymerase by competing with the natural substrate deoxyadenosine triphosphate and causing DNA chain termination after incorporation into viral DNA.
| Metabolism | Adefovir dipivoxil is rapidly converted to adefovir by esterases. Adefovir is not significantly metabolized; it is eliminated renally by a combination of glomerular filtration and active tubular secretion. No CYP450-mediated metabolism. |
| Excretion | Renal (90% as unchanged drug via active tubular secretion); biliary/fecal (<5%) |
| Half-life | Terminal elimination half-life is 7.5 hours (range 5–10 h); clinically, supports once-daily dosing with dose adjustment for renal impairment. |
| Protein binding | ≤4% (low binding; negligible affinity for serum proteins) |
| Volume of Distribution | 0.4 L/kg (392 L in adults); indicates extensive tissue distribution (including liver). |
| Bioavailability | Oral: 59% (range 40–70%); prodrug adefovir dipivoxil is rapidly converted to adefovir. |
| Onset of Action | Oral: Not applicable for immediate effect; virologic response (HBV DNA reduction) observed within 2–4 weeks of daily dosing. |
| Duration of Action | Sustained virologic suppression with daily dosing; no single-dose duration defined due to chronic therapy. On discontinuation, viral rebound may occur within weeks. |
| Molecular Weight | 501.47 |
10 mg orally once daily on an empty stomach.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥50 mL/min: 10 mg every 24 hours; CrCl 30-49 mL/min: 10 mg every 48 hours; CrCl 10-29 mL/min: 10 mg every 72 hours; Hemodialysis: 10 mg every 7 days after dialysis. |
| Liver impairment | No adjustment required for mild-moderate hepatic impairment (Child-Pugh A or B). Not studied in severe (Child-Pugh C). |
| Pediatric use | Approved for age ≥12 years: 10 mg orally once daily. For age <12 years, use is not established. |
| Geriatric use | Monitor renal function; adjust dose based on CrCl. No specific dose adjustment solely for age. |
| 1st trimester | Adefovir dipivoxil is not recommended during the first trimester due to potential teratogenicity based on animal studies; human data limited. |
| 2nd trimester | Use only if potential benefit justifies risk; no adequate well-controlled studies in pregnant women. |
| 3rd trimester | Same as second trimester; caution advised. |
Clinical note
Comprehensive clinical and safety monograph for ADEFOVIR DIPIVOXIL (ADEFOVIR DIPIVOXIL).
| Placental transfer | Crosses the placenta in humans; evidence from cord blood samples shows detectable levels. |
| Breastfeeding | Adefovir is excreted into human milk in low concentrations; limited data suggest no adverse effects in nursing infants, but caution is advised due to potential for serious adverse reactions. |
■ FDA Black Box Warning
WARNING: SEVERE ACUTE EXACERBATION OF HEPATITIS B, NEPHROTOXICITY, HIV RESISTANCE, and LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS. See full prescribing information for complete boxed warning.
| Serious Effects |
Hypersensitivity to adefovir or any component of the formulation
| Precautions | Severe acute exacerbation of hepatitis B upon discontinuation of therapy, Nephrotoxicity: monitor renal function, especially in patients at risk or with pre-existing renal impairment, HIV resistance: test for HIV before initiation in patients with unknown HIV status, Lactic acidosis and severe hepatomegaly with steatosis, Use with caution in elderly, renal impairment, or concomitant nephrotoxic agents |
| Food/Dietary | No clinically significant food interactions; can be taken with or without food. Avoid high-fat meals if gastrointestinal intolerance occurs. |
Loading safety data…
| Lactation Rating |
| L3 - Moderately Safe |
| Teratogenic Risk | Adefovir dipivoxil is an FDA Pregnancy Category C drug. Animal studies have shown teratogenicity (malformations, embryo-fetal toxicity) at doses 23 times the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. In first trimester, risk cannot be excluded; use only if benefit outweighs risk. In second and third trimesters, potential for fetal harm exists; consider alternative therapy. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN) and liver function tests monthly during pregnancy. Also monitor for lactic acidosis and hepatomegaly. Fetal assessment via ultrasound may be considered if exposure occurs. |
| Fertility Effects | In animal studies, adefovir had no effect on fertility at doses up to 19 times the human dose. Human data are lacking; effects on fertility are unknown. Use with caution in patients planning pregnancy. |
| Clinical Pearls | Monitor renal function closely; dose adjust for CrCl <50 mL/min. Check LFTs and HBV DNA every 3 months. Avoid in decompensated cirrhosis. HIV co-infected patients require concomitant antiretroviral therapy due to risk of HIV resistance. Prolonged therapy may lead to adefovir-resistant HBV mutations (rtA181V/T, rtN236T). |
| Patient Advice | Take with or without food at the same time daily. · Do not stop taking without consulting your doctor; stopping may cause severe hepatitis flare. · Report any signs of kidney problems (decreased urination, swelling) or lactic acidosis (unusual muscle pain, trouble breathing). · Regular blood tests are required to monitor liver and kidney function. · Use effective contraception during treatment if you or your partner can become pregnant. · Avoid alcohol and other medications that can damage the liver or kidneys without medical advice. |