Drug points: Pravastatin: interaction with oral anticoagulant?

BMJ 1996; 312 doi: (Published 06 April 1996) Cite this as: BMJ 1996;312:886
  1. None Given,
  2. Thierry Trenque,
  3. Henri Choisy,
  4. Marie-Laure Germain
  1. Centre Regional de Pharmacovigilance, Laboratoire de Pharmacologie, Hopital Maison Blanche, 51092 Reims, France

    Pravastatin is a hydrophilic competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A, the enzyme responsible for the rate limiting step of endogenous cholesterol synthesis. Interaction studies with oral anticoagulants have shown no change in prothrombin time or in the pharmacokinetic variables of pravastatin.1 On the other hand, when lovastatin2 or simvastatin3 and coumarin are administered concomitantly, prothrombin time may be increased in some patients. The clinical safety profiles of these agents are similar.

    After atrial fibrillation, anticoagulants are used to prevent any thromboembolic complications in patients. Moreover, this disorder can be associated with type IIb hypercholesterolaemia. If dietary weight reduction has no effect, treatment with fibric acid derivative or 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors can be started. However, fibrate enhances the effect of anticoagulants,4 and lovatastin or simvastatin given with warfarin increase prothrombin time slightly.5 We report a case of interaction between an oral anticoagulant and pravastatin.

    A 64 year old woman with atrial fibrillation was given 20 mg fluindione (an orally administered indanedione anticoagulant) daily as prophylaxis for any thromboembolic event. Her international normalised ratio was stable between 2.5 and 3.5. Diet and appropriate exercise did not have any effect on her cholesterol (9.03 mmol/l) and triglyceride (5.27 mmol/l) concentrations. Pravastatin 10 mg was given for the control of hypercholesterolaemia; five days later haematuria appeared. Laboratory tests showed an international normalised ratio of 10.2. Treatment was stopped; the bleeding resolved completely over the next 72 hours and international normalised ratio was 3.8.

    In patients with simvastatin or lovastatin added to anticoagulant therapy, monitoring of international normalised ratio must be monitored more frequently during early treatment and should perhaps be extended when patients are given pravastatin in addition to anticoagulants. Unlike other 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, binding interaction does not seem to be implicated since the protein binding of pravastatin is about 50%. The hypothesis of hepatic metabolic interaction may be evoked.


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