Primidone Phenytoin

Phenobarbital, primidone, phenytoin and also carbamazepine are inducers of cytochrome P450 enzymes and in combination the effects of substrates... 

Typical inducers include the older anticonvulsants, i.e., barbiturates, primidone, phenytoin, and carba-... 

Herranz, J.L., Armijo, J.A., and Arteaga, R. (1988) Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Epilepsia 29 794-804. 

Approximately doubles widi valproate and decreases by approximately half with carbamazepine/primidone/phenytoin/phenobar-bital/rifampin therefore, initial doses may vary depending on concomitant medications. 

Levonorgestrel is metabolised in the liver and drugs, including primidone, phenytoin, carbamazepine, St John s wort, griseofulvin, rifampicin, rifabutin and ritonavir, that induce liver enzymes will increase its metabolism and may... 

U AntiepileptiCs e.g. carbamazepine [1, 2] primidone, phenytoin, phenylethyl-malonamide, phenobarbital [3] ... 

Concurrent use can be therapeutically valuable. Changes in dosage or the addition or withdrawal of either drug need to be monitored to ensure that toxicity does not occur, or that seizure control is not worsened. The contradictory reports cited here do not provide a clear picture of what is likely to happen. Consider also Primidone + Phenytoin , p.570. 

Detection and result The chromatogram was freed from mobile phase (first dried for 5 min in a stream of cold air, then heated for 10 min at 110°C and allowed to cool), immersed for 5 s in the reagent solution and finally heated for 2 min at 110°C. Grey to grey-blue zones were formed on a light background. The following hRf values were obtained primidone QiR( 10-15) carbamazepine hRf 40 — 45) phenytoin hR( 50 — 55) phenobarbital hRf 60) ethosuximide hRf 75) hexobarbital hRf 90 — 95). 

Fig. 1 Reflectance scan of a blank (A) and of a mixture of antiepileptics with 500 ng substance per chromatogram zone (B). Start (1), primidone (2), carbamazepine (3), phenytoin (4), phenobarbital (5), ethosuximide (6), hexobarbital (7) and solvent front (8).

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

Commonly used drugs that induce liver enzymes (rifampin, phenytoin, carbamazepine, barbiturates, primidone, topiramate) and reduce efficacy of CHC... 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

Phenobarbital, phenytoin, primidone, and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate glucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzyme systems and displaces some drugs from plasma albumin. 

Carbam- azepine Valproic acid, Phenytoin, Clobazam Primidone, Pheno barbital... 

In all this, it should be remembered that the role of regulatory authorities is to protect the public. For entirely justifiable reasons, they will apply very strict criteria to products with a low therapeutic index, non-linear kinetics or imfavour-able physical properties. Digoxin, phenytoin and primidone provide notable examples of drugs where bioinequivalence issues have led to clinical problems. 

While regular monitoring of plasma phenytoin levels can result in improved seizure control, the benefit derived from measuring other commonly prescribed anticonvulsant drugs is difficult to assess. Phenobarbitone, primidone, and carbamazepine will be discussed briefly. 

Primidone has a comparatively short half-life of 10-12 hours (B17). Therefore, the time relationships between blood sampling and dose regimes acquire greater importance when interpreting the results than with either phenobarbitone or phenytoin. 

From the clinical point of view, antiepileptic drugs are primarily divided into two categories those effective in treating major attacks (phenytoin, carbamazepine, mephobarbi-tal, and also primidone), and those effective in treating minor attacks (ethosuximide, acetazolamide, clonazepam, trimethadione, and valproic acid). 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Drugs that may affect methylphenidate include MAOIs. Drugs that may be affected by methylphenidate hydrochloride include guanethidine, anticonvulsants (eg, phenytoin, phenobarbital, primidone), selective serotonin reuptake inhibitors, coumarin anticoagulants, and tricyclic antidepressants. 

Epilepsy, monotherapy Indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). 

The apparent clearance of lamotrigine is affected by the coadministration of AEDs. Lamotrigine is eliminated more rapidly in patients who have been taking hepatic enzyme inducing antiepileptic drugs (ElAEDs), including carbamazepine, phenytoin, phenobarbital, and primidone. 

Lamotrigine Added to Carbamazepine, Phenytoin, Phenobarbital, or Primidone (Without Valproic Acid) in Patients >12 Years of Age ... 

Discontinuing carbamazepine, phenytoin, phenobarbital, or primidone should prolong the half-life of lamotrigine discontinuing valproate should shorten the half-life of lamotrigine. 

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