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Journal of Neurology and Clinical Neuroscience | Volume: 03
8th International Conference on
NEUROLOGICAL DISORDERS,
CENTRAL NERVOUS SYSTEM AND STROKE
&
International Conference on
NEUROLOGY AND NEUROSURGERY
December 04-05, Dubai, UAE
Joint event on J Neurol Clin Neurosci, Volume: 03
Reduced anticoagulant effect of Dabigatran in a patient receiving Concomitant
Phenytoin
Shalin Shah
Artemis Institute, India
Reduced Anticoagulant Effect of Dabigatran in a Patient
Receiving Concomitant Phenytoin Objective —
Interaction of dabigatran with phenytoin in a patient with
Cerebral venous thrombosis Introduction Dabigatran,
a direct thrombin inhibitor, is an oral anticoagulant
that was approved for use in the United States in 2010.
It is currently indicated for the prevention of stroke in
patients with Atrial Fibrillation (AF) and for treatment
and prevention of deep vein thrombosis and pulmonary
embolism.[1] It is a pro drug which acts as a substrate for
Permeability Glycoprotein (P-gp). Medications that induce
P-gp (e.g., carbamazepine, rifampin, and phenytoin) can
reduce the bioavailability of medications that are P-gp
substrates. It mainly results in suboptimal anticoagulation
and increases risk of stroke and venous thrombosis. [2]
There are recent studies which supports use of NOACS
in CVT patients.Phenytoin is anti epileptic drug which is
a potent enzyme inducer which reduce efficacy of drugs
metabolized by P 450 enzyme system. P-gp induction by
phenytoin has only been demonstrated in animals (Phase
I studies) [ 3, 4]. Among elderly population , epilepsy
is reported in 30-40% of stroke patients [5] . AEDS can
either reduce or increase absorption of NOAC metabolism
leading to reduced efficacy of this drugs. A reduced NOAC
metabolism can increase significantly the risk of bleeding
in these patients.The clinical relevance of the interaction
between dabigatran and phenytoin has not been well
described. We describe case of interaction between
Dabigatran and phenytoin in a patient with cerebral venous
thrombosis. Case report A 25 years old male patient with
no significant history presented as focal seizures. He was
diagnosed as was started on full dose phenytoin
and enoxaparin . He started gradually improving with
near complete recovery in 2 days. He was discharged
on Dabigatran 150mg twice a day and phenytoin 100mg
three times a day. Around 2 months later he presented
with recurrence of right focal seizures. Repeat MRI brain
showed increase in filling defect in superior sagittal sinus.
He had gradual clinical improvement with no further
seizures and was discharged in next 3 days .So inspite
on full dose NOACS (dabigatran), he had repeat Venous
thrombosis. 3. Discussion Dabigatran does not interact
with the cytochrome P450 system. It acts as a substrate
for Permeability Glycoprotein (P-gp) . So drug interactions
are restricted to absorption across the intestinal wall
only where P gp is present. Drugs that induce cell efflux
transporter P-glycoprotein (P-gp) and/or CYP450 may
decrease DOAC plasma concentrations and increase the
risk for thromboembolic events, while drugs that inhibit
P-gp and/or CYP3A4 may increase DOAC concentrations
and therefore increase bleeding risk. Medications
that induce P-gp (e.g., carbamazepine, rifampin, and
phenytoin) can reduce the bioavailability of medications
that are P gp substrates, such as dabigatran. This can
result in suboptimal anticoagulation, increasing the risk of
stroke and venous thrombosis. [2] In current literature
the relevance of interaction between dabigatran and
phenytoin has not been well described. Few case reports
have been reported. The U.S. labeling for dabigatran are
less clear. The product label for these agents cites only an
example of a P-gp inducer but does not list all of those
that may affect the efficacy of dabigatran. Although it
should be intuitive that phenytoin is an inducer, it is not
specifically listed in the prescribing labeling, which could
easily lead to oversight and subsequent prescribing of
this combination. Conclusion - In conclusion, interaction
between dabigatran and phenytoin is important and
clinicians should be aware of such potential interactions.
Biography
Shalin Shah , has finished his DM neurology last year from prestigious
amrita institute of medical science , kochi ,India. His mentor was Dr.
Anand kumar who is head of department in amrita institute. He had
done work and thesis of vascular headache. At present he is doing his
Stroke and neurointervention fellowship.
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