epilepsy dan kd sm

Profilaksis Kejang Demam

Presentation TitleDate

2 Company Confidential© 200X Abbott

Pengobatan profilaksis terus menerus diberikan jika:

Pengobatan profilaksis terus menerus diberikan jika:

1. Kejang lama lebih dari 15 menit.

2. Anak mengalami kelainan neurologis yang nyata sebelum atau sesudah kejang, misalnya hemiparesis, paresis Todd, Cerebral Palsy, retardasi mental, hidrosefalus, mikrosefali.

3. Kejang fokal atau parsial



Profilaksis terus Menerus Dipertimbangkan Jika:

1. Kejang berulang dua kali atau lebih dalam 24 jam.

2. Kejang demam terjadi pada bayi kurang dari 12 bulan

3. Kejang demam sering berulang, lebih dari 4x per tahun

Yang dimaksud dipertimbangkan adalah:

Pemberiannya didiskusikan terlebih dahulu dengan orangtuanya



Penatalaksanaan Kejang Demam

FASE

AKUT

PENCEGAHAN INTERMITEN

PENCEGAHAN TERUS MENERUS

Gejala klinis Kejang (+)

Demam (+)

Kejang (–)

Demam (+)

Kejang (–)

Demam (–)

Pengobatan Diazepam

DAN

Antipiretik

Diazepam

DAN

Antipiretik

Valproate DEPAKENE

15-40 mg/kgBB/hari

ATAU

Phenobarbital

Lama terapi Selama kejang Selama demam 1 tahun bebas kejang

Bukti Klinis Valproate untuk Profilaksis Kejang Demam



Depakene® dalam Pencegahan Kejang Demam Kompleks

Well designed, Double blinded, RCT Open,randomized,therapeutic trial

Febrile Seizures, Baram, Shinnar 2002: 278

59

33

4

19

35

0

5

10

15

20

25

30

35

Reccurrence Rate (%)

Ngwane&Bower Mamelle et all

VPAPHBNo Treat

An

gka

rek

ure

nsi

dal

am 1

tah

un



Profilaksis Terus Menerus / Kontinuous (UKK)

Pemberian obat fenobarbital atau asam valproat setiap hari efektif dalam menurunkan risiko berulangnya kejang

Obat yang dipakai untuk profilaksis terus menerus:

1.Asam valproat

Dosis : 15-40 mg/kgBB/hari dibagi 2-3 dosis

2. Phenobarbital

Dosis : 4-5 mg/kgBB/hari dibagi 2 dosis, dengan maksimum 200 mg/hari

Lama pemberian obat 1 tahun bebas kejang



Dosis Depakene

DOSIS UNTUK KEJANG DEMAM:

15-40 mg/kg BB/hari

CARA PENGHENTIAN OBAT:

Harus Tappering off / diturunkan bertahap

1 bulan I 1 bulan-2 1 bulan 3 1 bulan-4

kurangi 25% kurangi 25% kurangi 25% kurangi 25%

Epilepsy

Management Strategies



PRINSIP PENGOBATAN EPILEPSI

Menurut Pedoman Tata Laksana Epilepsi PERDOSSI 2010:

1. Diagnosis epilepsi sudah dipastikan

2. Pastikan faktor pencetus bangkitan dapat dihindari (misalnya : alkohol, kurang tidur, stress, dll)

3. Terdapat minimum 2 kali bangkitan dalam setahun.

4. Setelah penyandang dan atau keluarganya menerima penjelasan tentang tujuan pengobatan

5. Pasien dan /atau keluarganya telah diberitahu tentang kemungkinan efek samping



Selection of the appropriate antiepileptic drug

Epilepsy - Management Guidelines

Partial Tonic-clonic Absence Myoclonic Tonic & Atonic

Myoclonic

Valproic acid

Carbamazepine

Phenytoin

Ethosuximide

Clonazepam

Felbamate

Lamotrigine

GABA

Topiramate

Spectrum of Activity

No Activity

Valproate – The Broad Spectrum Anticonvulsant



Broad Spectrum Anti Epilepsy - Adult

Pedoman Tatalaksana Epilepsi PERDOSSI 2010

* Obat belom tersedia di Indonesia



Broad Spectrum Anti Epilepsy - Pediatric

Pedoman Tatalaksana Epilepsi PERDOSSI 2010

* Obat belom tersedia di Indonesia



Antiepileptic drugs which may WORSEN specific Syndrome

Antiepileptic drug Epileptic syndrome/seizure typeCarbamazepine, Vigabatrin, Tiagabine, Phenytoin

Childhood absence epilepsy, Juvenille absence epilepsy, Juvenille myoclonic epilepsy

Vigabatrin Absences & Absences status

ClonazepamGeneralized Tonic-Status in Lennox - Gestaut Syndrome

LamotrigineDravet̀ s syndrome

Juvenille myoclonic epilepsySource: SIGN, Diagnosis & Management Epilepsies in Children & Young people - March 2005

Bukti Klinis Valproate untuk Epilepsi



Depakote in Generalized SeizureSummary of Key Studies Evaluating Valproate Monotherapy in Patients with Primary Generalized Seizures:

Authors Patients Receiving

VPA Monotherapy

Seizure Free Patients

N %

Burgeois et al 118 98 83%

Covanis et al 240 200 83%

Turnbull et al 37 27 73%

Wilder et al 34 25 73%

Wilder BJ, Polypharmacy to Monotherapy in the Treatment of Epilepsy, Nindermere communications Inc, 1987

Profil Produk Depakene / Depakote



Struktur Kimia Depakene / Depakote



Mekanisme Kerja Depakene / Depakote

GABA synthesis

activates GABA synthesising enzyme GAD

GABA Turnover

Inhibits Succinic semi-aldehyde dehydrogenase

Gamma hydroxy butyric acid

Inhibits aldehyde reductase



Farmakokinetik Depakene / Depakote

• T1/2: 6-16 jam, rata-rata 10.6 jam

• Absorpsi cepat dan komplit melalui sal. pencernaan dari oral.

• Metabolisme di hepar

• Ekskresi di urin (metabolit)

• Jika diberikan bersamaan atau sesudah makan akan sedikit memperlambat penyerapan tapi tidak mempengaruhi jumlah dan efektivitas

• plasma binding protein 90%. (McNamara 1996, Dollery 1990)



Farmakokinetik Depakene / Depakote

Depakene DepakoteKonsentrasi plasma puncak

1 - 2 jam setelah pemberian

2 - 4 jam setelah pemberian

Depakote diubah --> btk aktif Depakene

Melewati plasenta & ASI 10% 10%

Tingkat terapeutik total plasma

50 - 100 ug/ml (Epilepsi)

50 - 100 ug/ml (Epilepsi)

Msk otak & cairan serebrospinal Cepat Cepat

Valproate in Once Daily dose

When Once-daily Dosing May be Useful1,2

:

• When administering medication is time and labor intensive

• When patients are likely to refuse medication

• When multiple doses per day are inconvenient

1. Zlotnick S, Prince T, Frenchman IB. Cost analysis of immediate- versus controlled-release medication administration in long-term care.The Consultant Pharmacist. 1996;11(7):689-692. 2. Stahl SM. At long last, long-lasting psychiatric medications: an overview ofcontrolled-release technologies. J Clin Psych. 2003 April;64.

Once-daily Dosing May Enhance Patient Convenience and Simplify TreatmentOnce-daily Dosing May Enhance Patient Convenience and Simplify Treatment

Please see slides 8-10 for dosing considerations.

DEPAKOTE ER Provides Once-daily Dosing1-5

DEPAKOTE ER features a hydrophilic polymer matrix controlled-release tablet system to provide more consistent blood levels over 24 hours. This system of polymer wetting, polymer hydration, drug diffusion, and polymer erosion results in the release of drug in the stomach, small intestine, and large intestine over an 18- to 24-hour period of time.

1. DEPAKOTE ER package insert, Abbott Laboratories. 2. Data on file, Abbott Laboratories. 3. Stahl SM. At long last, long-lasting psychiatric medications: an overview of controlled-release technologies. J Clin Psych. 2003 April;64. 4. Valesco M, et al. Influence of drug: hydroxypropyl methylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets. Journal of Controlled Release.1999;57:75-85. 5. Ford J, et al. Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropyl methylcellulose matrix tablets. International Journal of Pharmaceutics. 1987;40:223-234.

0 hours 24 hours



Relationship between formulation, plasma concentration and risk of side effects and loss of efficacy

Preparations

Depakote® 250mg

Film coated tablet

250 mg sodium hydrogen divalproate

Depakene® syrup

5 ml = 250 mg valproic acid

ASKES



Depakote ER® 250 mg

250 mg divalproex sodium Extended Release

Depakote ER® 500 mg

500 mg divalproex sodium Extended Release

Preparations

ASKES

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epilepsy dan kd sm

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