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CP-066 Decreased inr after acenocoumarol and ombitasvir/paritaprevir/ritonavir co-administration
  1. A De Lorenzo-Pinto,
  2. CG Rodríguez-González,
  3. A Giménez-Manzorro,
  4. S Manrique-Rodríguez,
  5. S Ibáñez-García,
  6. V Escudero-Vilaplana,
  7. B Marzal-Alfaro,
  8. A Herranz-Alonso,
  9. JL Revuelta-Herrero,
  10. M Sanjurjo-Sáez
  1. Hospital General Universitario Gregorio Marañon, Pharmacy Department, Madrid, Spain

Abstract

Background Limited data are available regarding co-administration of acenocoumarol with direct acting antiviral agents.

Purpose We report a case of a patient who required a significant increase in the acenocoumarol weekly dose when co-administered with ombitasvir/paritaprevir/ritonavir.

Material and methods Data on international normalised ratio (INR), acenocumarol dosing and concomitant medications were obtained from the general practitioner. Potential drug-drug interactions were checked using Lexi-Comp, SPC and www.hep-druginteractions.org

Results A 61-year-old-male with treatment naïve genotype 1a chronic hepatitis C was examined in the gastroenterology department. His baseline viral load was 2 893 236 IU/mL and he had compensated liver cirrhosis.

His medical record included rheumatic valvulopathy that required double valve replacement and anticoagulation with acenocoumarol 8 mg/week (target INR 2.5–3.5). His INR had been stable on a dose of 8–9.5 mg/week over the past 2 years. Concomitant medications included omeprazole 20 mg/24 h, lisinopril 5 mg/24 h, digoxin 0.125 mg/24 h, bisoprolol 2.5 mg/24 h and furosemide as needed. Omeprazole interacts with acenocoumarol but increases its effect. Concomitant medications had not been modified for several months.

He started antiviral treatment in April 2015 with ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg/24 h, dasabuvir 250 mg/12 h and ribavirin 400 mg/12 h for 24 weeks. His baseline INR was 3. After evaluating potential interactions, the gastroenterologist recommended close digoxin and INR monitoring.

At week 4, the INR became subtherapeutic at 1.4. Therefore, the acenocoumarol dose was increased to 11 mg/week and enoxaparin 100 mg/24 h was started.

At week 6, the INR was 1.6 and the dose was titrated to 13 mg/week. Enoxaparin was reduced to 60 mg/24 h.

At week 9, the INR was 1.9 and the dose was increased to 16.5 mg/week.

At week 12, the INR was 2.1 and the dose was increased to 19.5 mg/week. Enoxaparin was withheld.

At week 16, the INR was 2.3 and the dose was titrated to 20.5 mg/week.

At week 24,the INR was 3.8 and the dose was decreased to 19 mg/week.

At the end of treatment, the acenocoumarol dose had been increased by 137.5%.

During the 24 week period, the patient reported no compliance problems, treatment modifications or dietary changes. He did not experience any thrombotic or bleeding event.

A causality assessment was conducted according to the Naranjo algorithm and the score obtained was 5 (adverse drug reaction classified as probable).

Conclusion There is a possibility of decreased INR after concomitant use of acenocoumarol and ombitasvir/paritaprevir/ritonavir.

No conflict of interest.

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