Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Be free Epilim® takes care of epilepsy. Life takes care of itself. Bob Peter Okello PAN AFRICAN ASSOCIATION OF NEUROLOGICAL SCIENCE CONGRESS Aficana Hotel Kampala 7th June, 2016 SANOFI AND NEUROLOGY • • • • • • Belief that Epilepsy is still a public health concern Epilepsy not well understood-stigma Treatment areas not well understood. Will not define epilepsy-share experiences with Epilim Epilim-Gaba-transaminase inhibitor Epilim satisfies most of the medical epilepsy treatment goals Achieve Seizure free status Monotherapy preferably Tolerability of treatment of choice 2008 CONSTANT PROOF OF EFFICACY Jedrzejczak J et. al. 2007 Marson AG et. al. Regardless of seizure type or aetiology 1996 De Silva et. al. 1994 Richen et. al. 1985 1967 Carraz et al. First clinical trial to demonstrate VPA efficacy in seizures1 *Valproate Turnbull et. al. First large randomized study showing efficacy of VPA in generalized seizures2 Large randomized Study showing equal efficacy of VPA and CBZ, irrespective of seizure type3 Large long term RCT Comparing VPA,CBZ PHT&PB showed similar Efficacy lower withdrawal for VPA and CBZ4 SANAD study. E effectiveness of VPA, LTG or TPM for generalized seizures and unclassifiable epilepsy: Unblinded RCT5 VIPE study: An observational study of first line VPA monotherapy in partial epilepsy6 VPA: valporate CBZ: carbamazepine LTG: lamotrigine TPM: topiramate PHT: phenytoin PB: phenobarbital Ref: 1. Carraz G, Fau Chateau R et al. Ann Med Psychol.(Paris) 1964;122(Tome 2):557-584 2. Turnbull DM, Howel D, Rawlins MD et al. Br. Med J(Clin Res Ed.) 1985;290(6471)815-819 3.Richens A, Davidson DL, Cartridge NE et al. J Neurol. Neurosurg. Psychiatry. 1994;57(6): 682-6 4. De Silva M,MacArdle B, McGowan M, et al. Lancet: 1996; 347 (9003): 709-713 5. Marson AG, Al-Kharusi AM, Alwaidh M et al. Lancet. 2007 Mar 24; 369 (9566): 1016-1026 6. Jedrzejczak J, Kunikova, M Magureanu S. Eur J Neurol 2008, 15:66-72 should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Monotherapy allowed only after previous treatment failure Spectrum of indications of anti-epileptic drugs Atonic seizures Myoclonic seizures Abscence seizures Epilim®: effective in all types of seizures5,7 Clonic seizures Tonic seizures Tonic-clonic seizures Partial seizures lamotrigine9* topiramate10 ≥2yrs >4yrs *Monotherapy phenytoin11 carbamazepine12 in children under 12 years is not recommended9 Epilim® has a broad spectrum of activity across a wide range of seizure types and epilepsy syndromes7 *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. % of seizure-free adult patients at 2, 3 and 6 months in the intent-to-treat population N= 1192 adults 90 Adapted from Jedrzejczak J, et al. 2008 Epilim® effective first-line in partial seizures6 Percentage of seizure-free patients 100 80 70 60 50 40 30 20 10 0 2 months 3 months 6 months Epilim® provides patients the reassurance of seizure freedom as early as 2 months6 Epilim® effective first-line in partial seizures6 Significant control of seizures6 High retention rate at 6 months6 72.7% remission rate* at 6 months * proportion of seizure-free subjects during the last 3 months of the study; age group >15yrs 88.7% retention rate** ** proportion of subjects remaining on treatment at 6 months of the study; age group >15yrs Favourable tolerance profile6 10.4% reported side-effects (drug related) Epilim® first choice therapy for generalised and unclassified epilepsies5 100 EPILIM® 90 lamotrigine topiramate 80 Adapted from Marson, et al. 2007 *The SANAD Study Percentage of 12-month remission % 12-month remission - per protocol population 70 60 50 40 30 20 10 0 1 2 3 4 5 Time from randomisation (years) Epilim® is more effective than lamotrigine and topiramate in patients with generalised and unclassified epilepsy5 *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. 1.0 lamotrigine p= 0.006 topiramate 0.8 Adapted from Marson, et al. 2007 Epilim® first choice therapy for generalised and unclassified epilepsies5 EPILIM® Probability of remaining on drug *The SANAD Study5 Time to treatment failure for any reason 0.6 0.4 0.2 0 1 2 3 4 5 6 Time from randomisation “Epilim® should remain the drug of first choice for many patients with generalised and unclassified epilepsies”5 *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. *Standard And Newer Antepileptic Drugs 1st-line treatment Endorsed first-line monotherapy14 For all seizure types and most epilepsy syndromes Epilim® is effective & shows acceptable tolerability as first-line monotherapy in partial epilepsy *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Drugs to be avoided Seizure type Generalised Tonic-clonic Absence Recommended for first-line treatment regardless of seizure type 1st-line (may worsen seizures) Tiagabine Vigabatrin Carbamazepine Gabapentin Oxcarbazepine Tiagabine Vigabatrin Myoclonic Carbamazepine Gabapentin Oxcarbazepine Tiagabine Vigabatrin Tonic Carbamazepine Oxcarbazepine Atomic Carbamazepine Oxcarbazepine Phenytoin NICE Guidelines 201214 Focal with/without Secondary generalisation *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Epilim® effective first-line for the treatment of partial epilepsy in children6 Demonstrates significant efficacy6 83.7% remission rate* at 6 months * proportion of seizure-free subjects during the last 3 months of the study; age group ≥ 15yrs High retention rate at 6 months6 92.0% retention** rate ** proportion of subjects remaining on treatment at 6 months of the study ; age group ≥ 15yrs Epilim® is effective & shows acceptable tolerability as first-line monotherapy in partial epilepsy6 *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Treatment selection for benign childhood epilepsy with centro-temporal spikes13 95% Confidence Intervals (correlated to the length of rectangles) Usually not appropriate Equivocal Usually appropriate N 42 42 41 EPILIM® Carbamazepine oxcarbazepine 1 Epilim® is the gold standard anti-epileptic drug for the treatment of children7 * A survey on paediatric epilepsy and seizures completed by 42 European physicians specialising in paediatric epilepsy 2 3 4 5 6 7 8 9 Paediatric epilepsy survey rating evaluation scale Treatment selection for cryptogenic complex partial seizures 95% Confidence Intervals (correlated to the length of rectangles) Usually not appropriate Equivocal Usually appropriate N 41 41 42 42 carbamazepine oxcarbazepine EPILIM® lamotrigine 1 2 3 4 5 6 7 8 9 Paediatric epilepsy survey rating evaluation scale *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Treatment selection for myoclonic and generalised tonic-clonic Seizures13 95% Confidence Intervals (correlated to the length of rectangles) Usually not appropriate Equivocal Usually appropriate N EPILIM® Lamotrigine Levetiracetam Topiramate clobazam clonazepam 40 40 39 39 40 40 1 Epilim® is the gold standard anti-epileptic drug for the treatment of children7 •A survey on paediatric epilepsy and seizures completed by 42 European physicians specialising in paediatric epilepsy 2 3 4 5 6 7 8 9 Paediatric epilepsy survey rating evaluation scale OpinionEuropean 13Dec 2007Expert Treatment selection for absence epilepsy13 95% Confidence Intervals (correlated to the length of rectangles) Usually not appropriate Equivocal Usually appropriate N Childhood EPILIM® ethosuximide lamotrigine 42 42 42 1 2 3 4 5 6 7 8 9 Paediatric epilepsy survey rating evaluation scale *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Epilepsy/syndrome Usual first-line drug Infantile spasms-west syndrome Vigabatrin, corticosteroids Severe myoclonic epilepsy of infancy - Dravet syndrome Epilim® is recommended as first-line treatment of epilepsy syndromes7 IGE with absences Epilepsy with CSWS Lennox-Gastut and related syndrome IGE with myoclonus with or without GTCS IGE with myoclonus with GTCS Epilim®, topiramate Epilim®, ethosuximide Epilim®, ethosuximide Epilim®, Epilim® + lamotrigine Epilim® Epilim® Focal epilepsy Epilim®, carbamazepine Undetermined epilepsy Epilim® CSWS= Continous Spikes and Waves during Sleep; GTCS=Generalised Tonic-Clonic Seizures; IGE= Idiopathic Generalised Epilepsy * except Status epilepticus *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Epilim® IV vs. phenytoin IV Indicated for all seizure types* Does not cause clinically significant cardiac or respiratory depression Does not cause irritation at site of injection Injectable in less than 5 minutes Generally linear pharmacokinetics, offering a more predictable stable profile Continuous infusion may be used, when repeated doses are needed * except Status epilepticus Percentage of pts with termination of seizures Epilim® IV is effective therapy in seizure Emergency situations15 100 90 96.0% 85.3% 80 70 60 50 40 30 20 10 0 Series of seizures Change of medication/IV switch N = 102 patients; initial Epilim® IV bolus dose varied between 4-16 mg/kg, depending on the severity of the condition, with 74% of patients receiving 15-16 mg/kg, admin. 5-10 mins followed by a continuous infusion of 0.5-4.0 mg/kg/h maintenance dose within 2 hrs to 10 days Epilim® IV represents an effective alternative to phenytoin in all seizure emergency situations with no evidence of sedation, cardiorespiratory disturbances and hypotension15 Epilim® has over 45 years of clinical experience in millions of patients worldwide1 Epilim® is distinguished by its broad spectrum of efficacy against seizures7 Epilim® remains the mainstay for treatment of epilepsy in all age groups7 Epilim® is the gold standard AED for the treatment of children7 Epilim® has a low risk of causing paradoxical seizure aggravation7 *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Epilim® Adult Dosing Guidelines8 Epilim® Adult Dosing Guidelines8 Starting dose * 600 mg/day* *Increasing by 200 mg/day at 3 day intervals until control is achieved. Maximum dose is 2500mg /day • Epilim® should preferably be taken with or after food • The tablets should be swallowed whole and not crushed or chewed, and not taken with aerated mineral water • Epilim® Chrono is a controlled-release formulation and may be given once or twice daily *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Children under 20 kg • 20 mg/kg/day given in divided doses Epilim® Paediatric Dosing Guidelines8 Weight (kg) 5 10 Average Daily Dose 100 mg In mg 2.5 ml In ml 200 mg 5 ml 15 20 300 mg 7.5 ml 400 mg 10 ml Children 20 kg and over • 20-30 mg/kg/day given in divided doses Weight (kg) Average Daily Dose In mg 20 400 to 600 mg 40 800 to 1200 mg • Initial dose: 400 mg/day, irrespective of body mass Epilim® IV Dosage Guidelines8 1. Reconstitute with the solvent provided 2. Loading Dose: 400-800 mg IV over 3-5 minutes 3. Maintenance Dose: continuous or repeated infusion up to a maximum of 2 500 mg/day *Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. IMPORTANT Children exposed in utero to valproate are at a high risk of serious developmental disorders (in up to 30-40% of cases) and/or congenital malformations (in approximately 10% of cases). Valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated. Valproate treatment must be started and supervised by a doctor experienced in managing epilepsy or bipolar disorder. Carefully balance the benets of valproate treatment against the risks when prescribing valproate for the rst time, at routine treatment reviews, when a female child reaches puberty and when a woman plans a pregnancy or becomes pregnant. Prescriber must ensure that all female patients are informed of and understand: - risks associated with valproate during pregnancy; - need to use eective contraception; - need for regular review of treatment; - the need to rapidly consult if she is planning a pregnancy or becomes pregnant. REFERENCES: 1. Carraz G, Fau R, Chateau R, et al. Ann Med Psychol (Paris) 1964;122(Tome 2):577-584.2. Turnbull DM, Howel D, Rawlins MD, et al. Br Med J (Clin Res Ed) 1985; 290(6471): 815819. 3). Richens A, Davidson DL, Cartlidge NE, et al. J Neurol Neurosurg Psychiatry 1994; 57(6): 682-687. 4. De Silva M, MacArdle B, McGowan M, et al. Lancet 1996;347(9003):709-713. 5. Marson AG, et al. The SANAD Study of Effectiveness of Valproate, Lamotrigine, or Topiramate for Generalised & UnclassifiableEpilepsy: An Unblinded Randomised Controlled Trial. The Lancet 2007;369:1016-26. 6. Jedrzejczak J, et al. An Observational Study of First-line Valproate Monotherapy in Focal Epilepsy. Eur Jnl of Neurology 2008(15): 66-72. 7. Guerrini R, et al. Paediatric Drugs. 2006;8(2):113-129. 8. Epilim® Package Insert; sanofi-aventis south africa (Pty) Ltd. 9. Lamotrigine Package Insert; GlaxoSmithKline South Africa (Pty) Ltd. 10. Topiramate Package Insert; Janssen Pharmaceutica (Pty) Ltd. 11. Phenytoin Package Insert; Pfizer Laboratories (Pty) Ltd. 12. Carbamazepine Package Insert; Novartis South Africa (Pty) Ltd. 13. Wheless JW, et al. Treatment of Paediatric Epilepsy: European Expert Opinion 2007. Epileptic Disorders 2007;9:S1-S62. 14. National Institute for Clinical Excellence (NICE) Clinical Guideline 20. The Epilepsies: The Diagnosis and Management of Epilepsies in Adults and Children in Primary and Secondary care. October 2004. (www.nice.org.uk/CG020NICEguideline). 15. Peters CNA, et al. IV Valproate as an Innovative Therapy in Seizure Emergency Situations Including Status Epilepticus Experience in 102 Adult Patients. Seizure 2005(1):164-169. 16. Morton LD, et al.Treatment Options for Acute Seizure Acre. CNS Drugs 1998;10(6)405-416. Abbreviated Prescribing Information. Please read full package insert carefully before prescribing. Epilim® REGISTRATION NUMBERS: Epilim® Liquid Sugar-free: J/2.5/148; Epilim® CR 200: 27/2.5/0322; Epilim® CR 300: Y/2.5/286; Epilim® CR 500: 27/2.5/0323; Epilim® 100 Crushable: 27/2.5/0500. Epilim® Intravenous: Y/2.5/43;Water for Injection - Epilim®: Y/34/156. NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION: sanofi-aventis south africa (pty) ltd., sanofiaventis House, 2 Bond Street, Midrand, 1685. ZASE.VPA.13.10.02