LIQUAMAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIQUAMAR (LIQUAMAR).
Liquamar (phenprocoumon) is a vitamin K antagonist that inhibits the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X in the liver by blocking the reduction of vitamin K to its active hydroquinone form.
| Metabolism | Primarily hepatic metabolism via cytochrome P450 enzymes (CYP2C9, CYP2C8, CYP3A4) to inactive metabolites; enterohepatic recirculation occurs. Long half-life (5-7 days). |
| Excretion | Phenprocoumon is excreted primarily via renal elimination as metabolites (approximately 60-70% of the dose), with about 20% excreted in feces via biliary elimination. Less than 1% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of phenprocoumon is approximately 5 to 7 days (range 3-10 days). This long half-life results in sustained anticoagulant effect over days, requiring careful monitoring and dose adjustments. |
| Protein binding | Phenprocoumon is highly protein-bound, approximately 99% to albumin. |
| Volume of Distribution | The apparent volume of distribution is approximately 0.1-0.2 L/kg, consistent with extensive binding to plasma proteins and limited extravascular distribution. |
| Bioavailability | Phenprocoumon has high oral bioavailability, estimated to be >90% after oral administration, indicating minimal first-pass metabolism. |
| Onset of Action | After oral administration, the onset of action occurs within 24-36 hours, with peak anticoagulant effect (therapeutic INR) typically achieved after 2-3 days due to the need to deplete vitamin K-dependent clotting factors. |
| Duration of Action | The duration of action is prolonged, lasting 5-7 days after a single dose. The anticoagulant effect persists for several days after discontinuation due to the long half-life and slow clearance of the drug. |
Initial: 0.5-1 mg/kg IV (not to exceed 2 mg). Maintenance: 0.5-2 mg IV q8-12h based on INR.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: reduce dose by 25-50%; CrCl <10 mL/min: avoid use or reduce by 50-75%. |
| Liver impairment | Child-Pugh A/B: reduce dose by 30-50%; Child-Pugh C: avoid use or use with extreme caution at 25% of normal dose. |
| Pediatric use | Neonates: 0.1-0.3 mg/kg/dose IV q6-12h; Infants/Children: 0.5-1 mg/kg/dose IV q8-12h; max 2 mg per dose. |
| Geriatric use | Use lower initial doses (0.25-0.5 mg IV) and titrate slowly; monitor INR more frequently due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIQUAMAR (LIQUAMAR).
| Breastfeeding | Phenprocoumon is excreted into breast milk in small amounts (M/P ratio approximately 0.3). No adverse effects in breastfed infants reported with maternal doses up to 12 mg/day. Considered compatible with breastfeeding by the American Academy of Pediatrics. Monitor infant for signs of bruising or bleeding. |
| Teratogenic Risk | LIQUAMAR (phenprocoumon) is a coumarin anticoagulant. First trimester: exposure is associated with warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in 5-10% of cases; risk is dose-dependent. Second and third trimesters: fetal hemorrhage, CNS abnormalities (optic atrophy, microcephaly), and spontaneous abortion. Late third trimester: risk of fetal intracranial hemorrhage during delivery. Avoid use in pregnancy; switch to heparin if anticoagulation required. |
■ FDA Black Box Warning
WARNING: BLEEDING RISK. Phenprocoumon can cause major or fatal bleeding. Patients should be monitored frequently for signs of bleeding. Concomitant use of NSAIDs, aspirin, or other anticoagulants increases risk.
| Serious Effects |
Active bleeding or hemophilia; recent or anticipated surgery (especially CNS/eye); pregnancy (especially first trimester and last weeks); history of warfarin-induced skin necrosis; severe hepatic or renal failure; uncontrolled hypertension; pericarditis; infectious endocarditis; inability to comply with monitoring.
| Precautions | Risk of major bleeding, including intracranial hemorrhage; regular monitoring of INR required; dosing adjustments needed with interacting drugs, dietary vitamin K changes, or hepatic/renal impairment; use with caution in elderly, pregnancy, or patients with bleeding disorders. |
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| Fetal Monitoring | Maternal: frequent INR monitoring (target therapeutic range 2.0-3.0 for most indications). Fetal: serial ultrasound for growth restriction, hydrocephalus, and placental abruption. Consider fetal echocardiography if exposure in first trimester. Neonatal: vitamin K administration at birth, monitor for bleeding (coagulation profile). |
| Fertility Effects | No direct effects on fertility reported. Coumarins may be associated with hormonal contraceptive interference; however, phenprocoumon does not affect fertility in animal studies. |