Oxcarbazepine

OXCARBAZEPINE
• Bioavailability < 100 %• Reduced in liver to the active metabolite, • 27 % excreted unchanged by kidneys• Peak serum drug level 4 – 6 hours• Peak serum metabolite level 8 hours• Elimination half life 8 – 10 hours• Time to steady state – 2 days• Protein binding 38 % • Partial seizures in adults• All indications of Carbamazepine including • Trigeminal neuralgia• Mood stabiliser in affective disorders • Hypersensitivity to Carbamazepine• Pregnancy, Lactation• Renal dysfunction, hepatic dysfunction• Hyponatremia (25 – 50 % of patients on chronic therapy have Na levels below 135 but this is usually asymptomatic. Hyponatremia is due to anti diuretic effect and consumption of large volumes of fluid is to be discouraged) (Serum sodium level should be monitored regularly during therapy) • Starting dose 300 mg bd• Increase dose by 600 mg / day at weekly • Maximum 1200 mg bd• Dosing interval twice daily 8. Name some proprietary preparations.
• Oxep (Nicholas Piramal)• Oxrate (Merind Pharma)• Oxetal (Sun Pharma)• Oxeptal (Stedman)• Oxcarb (Cipla)• Selzic (Solus Pharma)• Zenoxa (Intas)• Trioptal (Novartis) • Better than Carbamazepine• Milder side effects• Fewer idiosyncratic reactions• Fewer interactions with other drugs • Moderately high cost• May render hormonal contraceptive • May increase plasma level of Phenytoin and Phenobarbitone and these drugs may decrease oxcarbazepine level CLONAZEPAM
• It is a benzodiazepine• GABA – A receptor agonist • Oral bioavailability – 80 %• Time to peak levels – 1 – 8 hours• Time to steady state – 4 – 10 days• Biotransformation • Reduction, Hydroxylation, Acetylation, Nitration in liver • Elimination half life – 20 – 80 hours• Protein binding – 86 %• Active metabolite - none • Sleep apnea• Respiratory depression Renal dysfunction (can be used with caution) 7. What is the dose, available formulations and cost ? • Start with 0.25 mg hs. Can go upto 2 mg bd 8. What are the available market preparations ? Wide spectrum of activity including many • Sedation• Probable teratogenecity• Withdrawal symptoms – Sudden withdrawal – may even lead to status– Moderately slow withdrawal • Increased seizure frequency• Anxiety, Insomnia, Restlessness, Confusion – Withdrawal rate should not exceed 0.5 mg per month LAMOTRIGINE
• Inhibits release of excitatory aminoacids • Blocks voltage dependant sodium channel • Bioavailability 98 %• Oral dose rapidly and completely absorbed• Peak serum level 1 – 3 hours (adults) and 1 – 6 hours (children)• Plasma half life 12 – 60 hours• Time to steady state 3 – 15 days• Protein binding 55 %• 85 % metabolised by conjugation in liver and excreted as glucuronide• Active metabiolite – none• 10 % excreted by kidneys unchanged• Eliminated more rapidly in patients on hepatic enzyme inducing drugs like phenytoin, phenobarbitone and carbamazepine • Starting dose 12.5 to 25 mg / day• Increase dose by 50 mg every 1 – 2 weeks• Maintenance dose 200 – 500 mg / day in 2 divided doses• Clearance of lamotrigine is reduced by 50 % in presence of valproate – so dose in patient already getting valproate – 25 mg on alternate days for 2 weeks– Then 25 mg / day for 2 weeks– Increase by 25 mg / day every 1 – 2 weeks– Maximum dose 75 mg bd • Dose reduction should be 50 % per week over 2 – 3 weeks unless safety concerns require rapid withdrawal • Preferably II line drug, rarely I line drug• Partial seizures • Absences• Atonic seizures• Lennox Gastaut Syndrome• Drug may increase frequency of myoclonic • Rash especially if valproate is also given, if starting dose is high or if dose escalation is rapid (Rash may disappear despite continued medication) • Headache, fever, arthralgia, asthenia• Tremor, eosinophilia, blood dyscrasias, Steven Johnson syndrome• Nausea, dyspepsia, vomiting• Confusion, agitation, hallucination, psychosis• Insomnia, drowsiness• Blurred vision, diplopia• Rhinitis, pharyngitis, bronchitis, cough• Hepatic dysfunction• Unsteadiness especially if carbamazepine is also given • Lactation – as considerable amount is excreted in • Renal dysfunction• Hepatic dysfunction• Concomitant valproate therapy (a few cases have been reported when patients who had sexual dysfunction while on AED improved with Lamotrigine) • Lamitor (Torrent)• Lamepil (Innova)• Lamidus (Zydus)• Lametec (Cipla)• Lamez (Intaz)• Lamosyn (Sun) TOPIRAMATE
• Multiple actions contributing to its antiepileptic • Actions on sodium conductance, GABA - A receptor activity, glutamate receptor activity, calcium channel activity and carbonic anhydrase • Bioavailability 100 %• Plasma elimination half life 18 – 30 hours• Time to steady state 4 – 5 days• Protein binding 15 %• 80 % drug eliminated unchanged in urine• Rest metabolised to inactive compounds in • Topiramate levels decreased by concomitant administration of carbamazepine, phenytoin and phenobarbital • Phenytoin level increased by topiramate • Start with 25 mg / day• Increase dose by 25 – 50 mg every fortnight• Maximum dose 200 mg bd (rarely 300 mg bd) – Partial seizures– Secondary generalised seizures– GTCS– Atonic seizures– Lennox Gastaut syndrome • Renal dysfunction• History of presence of renal calculi• Pregnancy• Glaucoma (ensure adequate fluid intake to decrease risk • Confusion, impaired concentration, memory difficulty, • Fatigue, somnolence, headache• Agitation, emotional lability, depression, paresthesiae• Anorexia, nausea, diarrhea, weight loss• Leucopenia• Nystagmus, ataxia, diplopia, tremor• Renal stones• Adverse effects reduced by slow titration of drug • Epitome (Triton)• Topiram (Zydus)• Topaz (Intaz)• Topiral (Symbiosis)• Topirate (Stimulus)• Topamate (Cipla)• Nextop (Torrent) • Weight loss (especially when valproate • Powerful antiepileptic effect, sometimes effective when all other AED’s are ineffective ZONISAMIDE
It is a sulfonamide derivative chemically – Inhibits voltage gated sodium channel– Affects T type calcium currents– Affects excitatory glutaminergic transmission– Binds to benzodiazepine GABA – A receptor • Partial seizures• Generalised seizures• Lennox Gastaut Syndrome• Infantile spasm• Atypical absences• Progressive myoclonic epilepsy (Licenced for monotherapy and adjunct therapy in JapanLicenced for adjunct therapy in refractory partial epilepsy 4. What are the formulations and brands ? • Oral bioavailability < 100 %• Time to peak levels 2 – 4 hours• Elimination half life 50 – 70 hours• Protein binding 30 – 60 %• Biotransformation: Acetylation, Reduction, – Initial 25 mg bd– Maintenance 100 – 400 / day– Maximum 600 mg / day – Initial 2 – 4 mg / kg / day– Maintenance 4 – 8 mg / kg / day • Half life is long on monotherapy but considerably reduced in • Renal failure• Pregnancy• Lactation • Broad spectrum of action• Specially useful in Lennox Gastaut syndrome, infantile spasms, progressive myoclonic epilepsy

Source: http://www.anuradhaclinic.com/ppt/AEDs.pdf