What are the potential drug interactions with Nicoumalone (Acenocoumarol)?

Nicoumalone (Acenocoumarol) Drug Interactions

Acenocoumarol requires careful management of drug interactions, particularly with CYP2C9 inhibitors and inducers, antiplatelet agents, NSAIDs, and amiodarone, which can significantly alter anticoagulant effect and bleeding risk.

Critical Interactions Requiring Dose Adjustment

Amiodarone - High Risk Interaction

• Amiodarone potentiates acenocoumarol effect in all patients, requiring an immediate 50% dose reduction when initiating concurrent therapy 1, 2
• The acenocoumarol sensitivity index decreases from 13.2 to 4.2 micrograms/kg/day after amiodarone initiation, representing a greater than 3-fold increase in anticoagulant effect 1
• Severe bleeding diathesis developed in 7 of 36 patients (19%) receiving both medications without appropriate dose adjustment 1
• After amiodarone discontinuation, acenocoumarol requirements increase substantially (sensitivity index rises from 6.2 to 28.1 micrograms/kg/day), necessitating dose adjustments for 2-4 weeks post-discontinuation 1, 2
• Monitor INR daily initially, then every 2-3 days until stable when adding or removing amiodarone 1

CYP2C9 Inhibitors

• Strong CYP2C9 inhibitors require 25-33% acenocoumarol dose reduction with intensified INR monitoring 3
• Fluconazole and amiodarone (dual CYP2C9 and CYP3A4 inhibitors) warrant 25% dose reduction 3
• Metronidazole necessitates 20% dose reduction 3
• Azole antifungals (except nystatin as alternative) require close monitoring or dose adjustment 3

CYP3A4 and CYP2C9 Inducers

• Rifampicin, phenytoin, carbamazepine, and phenobarbital significantly reduce acenocoumarol effect 3
• Full enzyme induction occurs over 2-4 weeks and persists 2-4 weeks after discontinuation 3
• Increase INR monitoring frequency to every 3-5 days during initiation and discontinuation periods 3

Bleeding Risk Interactions

Antiplatelet Agents and NSAIDs

• Concomitant use of antiplatelet agents increases bleeding risk by at least 60%, similar to other vitamin K antagonists 3
• Aspirin, clopidogrel, ticlopidine, prasugrel, and ticagrelor all substantially increase hemorrhagic complications 3
• NSAIDs compound bleeding risk through both antiplatelet effects and gastric mucosal injury 3
• Add proton pump inhibitor when antiplatelet or NSAID co-administration is clinically necessary 3
• Reassess regularly whether antiplatelet/NSAID combination remains appropriate 3

Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs increase bleeding risk through platelet dysfunction 3
• Consider alternative antidepressants or add gastroprotection when combination is unavoidable 3

Monitoring Strategy

Routine Management

• Establish baseline INR before initiating interacting medications 3
• Screen for all antiplatelet and NSAID use at each visit 3
• Perform medication reconciliation at every encounter to identify new potential interactions 3
• Increase monitoring frequency (every 3-5 days) when adding or removing interacting drugs 3

High-Risk Situations

• Polypharmacy patients require enhanced surveillance for cumulative interaction effects 3
• Renal or hepatic impairment may exacerbate drug interactions, though amiodarone-acenocoumarol interaction occurs independent of organ function 1

Practical Dosing Considerations

Conversion Between Vitamin K Antagonists

• When switching from acenocoumarol to warfarin, multiply acenocoumarol dose by 1.85 to estimate warfarin maintenance dose 4
• When switching from acenocoumarol to phenprocoumon, multiply acenocoumarol dose by 0.84 4
• These transitions require INR monitoring every 2-3 days until therapeutic stability achieved 4

Common Pitfalls to Avoid

• Never assume acenocoumarol's shorter half-life (10 hours) provides protection against interactions - factor VII levels fluctuate based on vitamin K intake rather than drug half-life 5
• Do not delay dose reduction when initiating amiodarone - the interaction is immediate and universal 1, 2
• Avoid assuming stability after enzyme inducer discontinuation - effects persist for weeks 3
• Do not overlook herbal medications, particularly St. John's wort, which acts as a potent CYP3A4 inducer 3