Topiramate BNF 73 (HAL 309-310)

INDICATIONS AND DOSE

Monotherapy of generalised tonic-clonic seizures or focal

seizures with or without secondary generalisation

▶ BY MOUTH

▶ Child 6–17 years: Initially 0.5–1 mg/kg once daily (max.

per dose 25 mg) for 1 week, dose to be taken at night,

then increased in steps of 250–500 micrograms/kg

twice daily, dose to be increased by a maximum of

25mg twice daily at intervals of 1–2 weeks; usual dose

50 mg twice daily (max. per dose 7.5 mg/kg twice daily),

if child cannot tolerate titration regimens

recommended above then smaller steps or longer

interval between steps may be used; maximum 500 mg

per day

▶ Adult: Initially 25 mg once daily for 1 week, dose to be

taken at night, then increased in steps of 25–50 mg

every 1–2 weeks, dose to be taken in 2 divided doses;

usual dose 100–200 mg daily in 2 divided doses,

adjusted according to response, doses of 1 g daily have

been used in refractory epilepsy; maximum 500 mg per

day continued→

BNF 73 Epilepsy and other seizure disorders 309

Nervous system
4

Adjunctive treatment of generalised tonic-clonic seizures

or focal seizures with or without secondary

generalisation | Adjunctive treatment for seizures

associated with Lennox-Gastaut syndrome

▶ BY MOUTH

▶ Child 2–17 years: Initially 1–3 mg/kg once daily (max.

per dose 25 mg) for 1 week, dose to be taken at night,

then increased in steps of 0.5–1.5 mg/kg twice daily,

dose to be increased by a maximum of 25mg twice

daily at intervals of 1–2 weeks; usual dose

2.5–4.5 mg/kg twice daily (max. per dose 7.5 mg/kg

twice daily), if child cannot tolerate recommended

titration regimen then smaller steps or longer interval

between steps may be used; maximum 400 mg per day

▶ Adult: Initially 25–50 mg once daily for 1 week, dose to

be taken at night, then increased in steps of 25–50 mg

every 1–2 weeks, dose to be taken in 2 divided doses;

usual dose 200–400 mg daily in 2 divided doses;

maximum 400 mg per day

Migraine prophylaxis

▶ BY MOUTH

▶ Adult: Initially 25 mg once daily for 1 week, dose to be

taken at night, then increased in steps of 25 mg every

week; usual dose 50–100 mg daily in 2 divided doses;

maximum 200 mg per day

l CAUTIONS Avoid in acute porphyrias p. 930 . risk of

metabolic acidosis . risk of nephrolithiasis—ensure

adequate hydration (especially in strenuous activity or

warm environment)

l INTERACTIONS → Appendix 1 (topiramate).

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . aggression .

agitation . alopecia . anaemia . anxiety . appetite changes .

arthralgia . cognitive impairment . confusion . constipation

. depression . diarrhoea . dizziness . drowsiness . dry mouth

. dyspepsia . dyspnoea . epistaxis . gastritis . impaired

attention . impaired coordination . irritability . malaise .

mood changes . movement disorders . muscle spasm .

muscular weakness . myalgia . nausea . nephrolithiasis .

nystagmus . paraesthesia . pruritus . rash . seizures . sleep

disturbance . speech disorder . taste disturbance . tinnitus .

tremor . urinary disorders . visual disturbances . vomiting

▶ Uncommon Abdominal distension . altered sense of smell .

blepharospasm. blood disorders . bradycardia . dry eye .

flatulence . flushing . gingival bleeding . glossodynia .

haematuria . halitosis . hearing loss . hypokalaemia .

hypotension . increased lacrimation . influenza-like

symptoms . leucopenia . metabolic acidosis . mydriasis .

neutropenia . palpitation . pancreatitis . panic attack .

peripheral neuropathy . photophobia . postural

hypotension . psychosis . reduced sweating . salivation .

sexual dysfunction . skin discoloration . suicidal ideation .

thirst . thrombocytopenia . urinary calculus

▶ Rare Abnormal skin odour . calcinosis . hepatic failure .

hepatitis . periorbital oedema . Raynaud’s syndrome .

Stevens-Johnson syndrome . unilateral blindness

▶ Very rare Angle-closure glaucoma

▶ Frequency not known Encephalopathy . hyperammonaemia

. maculopathy . toxic epidermal necrolysis

SIDE-EFFECTS, FURTHER INFORMATION

▶ Acute myopia with secondary angle-closure

glaucoma Topiramate has been associated with acute

myopia with secondary angle-closure glaucoma, typically

occurring within 1 month of starting treatment. Choroidal

effusions resulting in anterior displacement of the lens

and iris have also been reported. If raised intra-ocular

pressure occurs:

. seek specialist ophthalmological advice;

. use appropriate measures to reduce intra-ocular

pressure;

. stop topiramate as rapidly as feasible

l PREGNANCY Increased risk of cleft palate if taken in the

first trimester of pregnancy.

The dose should be monitored carefully during

pregnancy and after birth, and adjustmentsmade on a

clinical basis.

It is recommended that the fetal growth should be

monitored.

l BREAST FEEDING Manufacturer advises avoid—present in

milk.

l HEPATIC IMPAIRMENT Use with caution in moderate to

severe impairment—clearancemay be reduced.

l RENAL IMPAIRMENT

▶ In adults Half usual starting and maintenance dose if eGFR

less than 70 mL/minute/1.73m2—reduced clearance and

longer time to steady-state plasma concentration.

▶ In children Half usual starting and maintenance dose if

estimated glomerular filtration less than

70 mL/minute/1.73m2—reduced clearance and longer time

to steady-state plasma concentration. Use with caution.

l DIRECTIONS FOR ADMINISTRATION

TOPAMAX® CAPSULES Swallow whole or sprinkle contents

of capsule on soft food and swallow immediately without

chewing.

l PRESCRIBING AND DISPENSING INFORMATION

Switching between formulations Care should be taken when

switching between oral formulations in the treatment of

epilepsy. The need for continued supply of a particular

manufacturer’s product should be based on clinical

judgement and consultation with the patient or their

carer, taking into account factors such as seizure

frequency and treatment history.

Patients being treated for epilepsymay need to be

maintained on a specific manufacturer’s branded or

generic topiramate product.

l PATIENT AND CARER ADVICE

Medicines for Children leaflet: Topiramate for preventing

seizures www.medicinesforchildren.org.uk/topiramate-forpreventing-

seizures

TOPAMAX® CAPSULES Patients or carers should be given

advice on how to administer Topamax ® capsules.

TRANSLATE
Topiramate

l INDIKASI DAN DOSIS

Monoterapi kejang tonik-klonik umum atau fokal

kejang dengan atau tanpa generalisasi sekunder

▶ OLEH MULUT

▶ Anak 6-17 tahun: Awalnya 0,5-1 mg / kg sekali sehari (maks.

per dosis 25 mg) selama 1 minggu, dosis yang akan diambil pada malam hari,

kemudian meningkat dalam langkah 250-500 mikrogram / kg

dua kali sehari, dosisnya harus ditingkatkan maksimal

25mg dua kali sehari pada interval 1-2 minggu; Dosis biasa

50 mg dua kali sehari (maks. Per dosis 7,5 mg / kg dua kali sehari),
jika anak tidak dapat mentolerir rejimen titrasi

disarankan di atas maka langkahnya lebih kecil atau lebih lama

interval antar langkah dapat digunakan; maksimal 500 mg

per hari

▶ Dewasa: Awalnya 25 mg sekali sehari selama 1 minggu, dosisnya

diambil pada malam hari, kemudian meningkat dalam langkah 25-50 mg

setiap 1-2 minggu, dosis yang harus diambil dalam 2 dosis terbagi;

Dosis biasa 100-200 mg setiap hari dalam 2 dosis terbagi,

disesuaikan menurut respon, dosis 1 g sehari miliki

telah digunakan pada epilepsi refrakter; maksimum 500 mg per

hari terus →

BNF 73 Epilepsi dan gangguan kejang lainnya 309

Sistem saraf 4

Pengobatan adjunctive untuk kejang tonik klonik umum

atau kejang fokal dengan atau tanpa sekunder

generalisasi | Pengobatan adjunctive untuk kejang

terkait dengan sindrom Lennox-Gastaut

▶ OLEH MULUT

▶ Anak 2-17 tahun: Awalnya 1-3 mg / kg sekali sehari (maks.

per dosis 25 mg) selama 1 minggu, dosis yang akan diambil pada malam hari,

kemudian meningkat dalam langkah 0,5-1,5 mg / kg dua kali sehari,

Dosis harus ditingkatkan maksimal 25mg dua kali

setiap hari dengan interval 1-2 minggu; Dosis biasa

2,5-4,5 mg / kg dua kali sehari (maks. Per dosis 7,5 mg / kg

dua kali sehari), jika anak tidak bisa mentolerir yang dianjurkan

regimen titrasi maka langkahnya lebih kecil atau interval yang lebih lama

antara langkah-langkah yang bisa digunakan; maksimal 400 mg per hari

▶ Dewasa: Awalnya 25-50 mg sekali sehari selama 1 minggu, dosis ke

diminum di malam hari, kemudian meningkat dalam langkah 25-50 mg

setiap 1-2 minggu, dosis yang harus diambil dalam 2 dosis terbagi;

Dosis biasa 200-400 mg setiap hari dalam 2 dosis terbagi;

maksimal 400 mg per hari

Profilaksis migrain

▶ OLEH MULUT

▶ Dewasa: Awalnya 25 mg sekali sehari selama 1 minggu, dosisnya

diambil di malam hari, kemudian meningkat dalam langkah masing-masing 25 mg

minggu; Dosis biasa 50-100 mg setiap hari dalam 2 dosis terbagi;

maksimal 200 mg per hari

l PERHATIAN Hindari porfiria akut p. 930. resiko dari

asidosis metabolik risiko nefrolithiasis - pastikan

hidrasi yang adekuat (terutama dalam aktivitas berat atau

lingkungan yang hangat)

l INTERAKSI → Lampiran 1 (topiramate).

l SIDE-EFFECTS

▶ Nyeri perut umum atau sangat umum. agresi

agitasi alopesia. anemia kecemasan perubahan selera

arthralgia gangguan kognitif . kebingungan . sembelit

. depresi. diare . pusing kantuk mulut kering

. dispepsia. dyspnoea. epistaksis gastritis terganggu

perhatian . gangguan koordinasi lekas marah. malaise

perubahan mood gangguan gerakan kejang otot.

kelemahan otot. mialgia mual nephrolithiasis

nystagmus paraestesi pruritus ruam kejang. tidur

gangguan . gangguan bicara rasa gangguan tinnitus

getaran. gangguan kencing. gangguan penglihatan. muntah

▶ Abdominal jarang distensi. indera penciuman yang berubah

blefarospasme kelainan darah bradikardia mata kering

perut kembung pembilasan perdarahan gingiva glossodynia

haematuria. halitosis gangguan pendengaran hipokalemia

hipotensi meningkatnya lakrimasi seperti influenza

gejala. leucopenia. asidosis metabolik mydriasis

neutropenia palpitasi pankreatitis serangan panik .

neuropati perifer. fotofobia postural

hipotensi psikosis mengurangi keringat air liur.

disfungsi seksual perubahan warna kulit. Pemikiran bunuh diri .

haus trombositopenia kalkulus urin

▶ Kelinci Abnormal bau kulit. kalsinosis gagal hati.

hepatitis. edema periorbital Sindrom Raynaud.

Sindrom Stevens-Johnson kebutaan unilateral

▶ Glaukoma Angle-closure yang sangat jarang terjadi

▶ Frekuensi tidak diketahui Encephalopathy. hiperonaemia

. maculopathy nekrolisis epidermal toksik

EFEK SAMPING, INFORMASI LEBIH LANJUT

▶ Miopia akut dengan sudut pandang sekunder

Glaukoma Topiramate telah dikaitkan dengan akut

miopia dengan glaukoma sudut sekunder penutupan, biasanya

terjadi dalam waktu 1 bulan mulai pengobatan. Choroidal

efusi menghasilkan perpindahan anterior lensa

dan iris juga telah dilaporkan. Jika dibesarkan intra okular

tekanan terjadi:

. mencari saran oftalmologis spesialis;

. gunakan tindakan yang tepat untuk mengurangi intra okular

tekanan;

. hentikan topiramate secepat mungkin

KEHAMILAN Meningkatkan risiko celah langit-langit jika dikonsumsi di

trimester pertama kehamilan.

Dosis harus dipantau dengan hati-hati selama

kehamilan dan setelah lahir, dan penyesuaian padaa

dasar klinis.

Dianjurkan agar pertumbuhan janin seharusnya

dipantau.

PABRIK PAYUDARA Produsen menyarankan agar tidak hadir

susu.

PERBAIKAN HEPATIK Gunakan dengan hati-hati dalam ukuran sedang

Kerusakan parah-clearancemay bisa dikurangi.

l RENAL IMPAIRMENT
▶ Pada orang dewasa Setengah dosis awal dan perawatan biasa jika eGFR

kurang dari 70 mL / menit / 1.73m