Download ORIGINAL AND GENERIC AEDs IN THE TREATMENT OF EPILEPSY

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ORIGINAL AND GENERIC AEDs IN THE TREATMENT OF EPILEPSY
– BIOPHARMACEUTICAL, PHARMACOKINETIC,
PHARMACOLOGICAL, CLINICAL AND ECONOMIC PROBLEMS
Jerzy Majkowski1, Władysław Lasoń2, Władysława Daniel2, Joanna Jędrzejczak3,
Danuta Ryglewicz4, Zbigniew Stelmasiak5, Beata Majkowska-Zwolińska6,
Ewa Motta7, Sergiusz Jóźwiak8, Janusz Wendorff9
1
Centrum Diagnostyki i Leczenia Padaczki, Fundacja Epileptologii, Warszawa; 2 Instytut
Farmakologii PAN, Kraków; 3Klinika Neurologii i Epileptologii, CMKP, Warszawa; 4Instytut
Psychiatrii i Neurologii, Warszawa; 5Klinika Neurologii AM, Lublin; 6Klinika Neurochirurgii
AM, Warszawa; 7 Katedra i Klinika Neurologii Śl. AM, Katowice; 8Klinika Neurologii
i Epileptologii CZD, Warszawa; 9Klinika Neurologii CZMP, Łódź
Summary
Objective. This article presents the state-of-the-art concerning the possible consequences of substitution of original drugs with generic drugs (and vice versa) and substitution of one generic drug
with another generic drug in the treatment of epilepsy (exchange of pharmaceutical preparations).
Review of the literature and personal experience. Pharmacokinetic and biopharmaceutical foundations for the prediction of the risk involved in substituting one preparation with another one in
some groups of patients are available. The literature does not address the possible consequences
of such exchange for high risk groups. If we consider the differences in bioavailability of original and
generic drugs and the differences in their therapeutic equivalence, we must conclude that preparation substitution is counter-indicated in three groups of chronic epileptic patients. Group one comprises patients with optimally controlled seizures, receiving maximal or near maximal drug doses. In
this group difference in bioavailability (±20%) may provoke seizures or toxicity (reduced or increased
bioavailability, respectively). Group two comprises patients with long-term seizure remission on
small doses of AEDs or undergoing dose reduction. In this group reduced AED concentration may
provoke a seizure. Group three consists of patients with altered pharmacokinetics in whom change
of preparation may lead to toxicity or provoke seizures (newborn babies, young children, patients
over 65, pregnant women and patients with abnormal absorption, metabolism or elimination).
Conclusions. 1. Drug substitution is counter-indicated in patients with increased risk of deterioration of the course of epilepsy. 2. Pharmacists should not substitute one drug for another drug without the doctor's permission and doctors should inform patients about possible negative consequences of substitution. 3. A national system monitoring the adverse effects of AEDs should be
introduced. 4. Multi-centre comparative research on drug substitution from the point of view of its
effectiveness and financial consequences is recommended. 5. Better control of seizures means
lower cost of treatment. 6. To reduce the cost of treatment it is necessary to ensure that doctors are
systematically and comprehensively trained and that a specialisation course ending in a final examination is introduced for neurologists-epileptologists.
Key words: AED bioavailability – Bioequivalence and therapeutic equivalence – Risk of AED substitution – Cost of treatment of epilepsy – Original drugs and generics
Recived December 4, 2004
SUMMARY
Epileptologia 2004, 12: 365-389