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. |
| Molecular Weight | 330.31 |
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 | Avoid due to teratogenic risk; may cause fetal warfarin embryopathy (nasal hypoplasia, stippled epiphyses) if exposure between 6-12 weeks. |
| 2nd trimester | Use only if benefits outweigh risks; increased risk of hemorrhage and placental abruption. |
| 3rd trimester | Avoid near term; risk of fetal hemorrhage and neonatal anticoagulation; consider switching to heparin. |
Clinical note
Comprehensive clinical and safety monograph for LIQUAMAR (LIQUAMAR).
| Placental transfer | Crosses placenta; warfarin is highly protein-bound but still reaches fetal circulation; associated with fetal hemorrhage and embryopathy. |
| Breastfeeding | Excreted into breast milk in small amounts; generally considered compatible with breastfeeding, but monitor infant for bleeding signs. Avoid if infant has vitamin K deficiency or bleeding disorder. |
■ 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 |
Hemorrhagic tendencies or blood dyscrasiasRecent or impending surgery of the central nervous system or eyeThreatened abortionUncontrolled hypertensionLack of reliable laboratory monitoring for INRSevere hepatic or renal impairmentPericardial effusion or pericarditisMalignant hypertensionKnown hypersensitivity to warfarin
| 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. |
| Food/Dietary | Avoid large amounts of foods high in vitamin K (e.g., kale, spinach, broccoli, Brussels sprouts, parsley, green tea) as they can reduce anticoagulant effect. Maintain consistent intake of vitamin K-rich foods; do not binge or drastically change diet. Cranberry juice and alcohol may potentiate effect; limit alcohol to moderate use. Grapefruit juice may also interact; avoid excessive consumption. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | Liquamar (phenprocoumon) is a long-acting oral anticoagulant with a half-life of 5-6 days, requiring less frequent dose adjustments than warfarin. INR monitoring is essential; therapeutic range typically 2.0-3.0 for most indications. Avoid concurrent use of NSAIDs, aspirin, and antiplatelet agents to reduce bleeding risk. Vitamin K reversal is effective but may require higher doses due to prolonged action. |
| Patient Advice | Take exactly as prescribed; do not skip or double doses. · Report any signs of bleeding: unusual bruising, blood in urine/stool, coughing up blood, excessive menstrual bleeding. · Avoid activities with high risk of injury; use soft toothbrush and electric razor. · Keep all appointments for INR blood tests. · Inform all healthcare providers you are taking this anticoagulant. · Do not start or stop any medications (including over-the-counter) without consulting your doctor. · Wear a medical alert bracelet or carry a card indicating you take an anticoagulant. |