CARBAMAZEPINE IN PAEDIATRICS

By : Vijit Agrawal, B.Pharm

Pharm.D 5th Year

JSS College of Pharmacy,

Mysore - 570015

Doses Indicated in Epilepsy DOSE

AGE

DOSE FOR PAEDIATRICS

INITIAL DOSE MAXIMUM DOSE

< 6 Yrs 10-20 mg/kg/day PO q6hr Not to exceed 35 mg/kg/day

6-12 Yrs 50 mg PO q6hr Not to exceed 1000 mg/day

> 12 Yrs 200 mg PO q6hr Not to exceed 1000 mg/day

12-15 Yrs 200 mg PO q6hr Not to exceed 1200 mg/day

Drug should be taken with food.

Monitoring

• CBC• Blood chemistry• Kidney and liver function tests• Eye exams• Carbamazepine blood levels [ (4-12 mg/L) or

(16.9-50.8 micromoles/L) ]

Serious Interactions

• Tenofovir (Decreased level of Tenofovir)• Linezolid (Increase toxicity)• Selegiline (Increase toxicity)

ADRs

>10%

• Ataxia (15%) (lack of voluntary muscle movements)

• Dizziness (44%)• Drowsiness (32%)• Nausea (29%)• Vomiting (18%)

ADRs Cont…

1-10 %

• Dry Mouth (10%)

Rare• MI• Stevens-Johnson syndrome (HLA-B*1502)• TEN (HLA-B*1502) • Hepatic failure• Syndrome of inappropriate antidiuretic hormone secretion

(SIADH)

BLACK BOX WARNING

Contraindications

• Documented hypersensitivity• History of bone marrow suppression• Administration of MAO inhibitors within last 14 days• Coadministration with nefazodone (Decresed Level)• Coadministration with NNRTIs (Reduce NNRTI

serum concentration)• Jaundice, hepatitis• Pregnancy (especially first trimester: risk of fetal

carbamazepine syndrome)

Pregnancy & Lactation

• Pregnancy category : D• Lactation: Enters breast milk; not

recommended

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

Mechanism of Action

• Stabilizes inactivated state of sodium channels, thereby making neurons less excitable

Pharmacology

Absorption• Bioavailability: 85% (oral suspension) Distribution• Protein bound: 75-90%• Vd: 1.5 L/kg (neonates); 1.9 L/kg (children); 0.59-2 L/kg (adults) Metabolism• Via hepatic CYP3A4• Enzymes induced: CYP1A2, CYP2C9, CYP3A4 Elimination• Half-life: 25-65 hr (initial dosing); decreases to 10-20 hr after

autoinduction• Excretion: Urine (72%)

Pharmacogenomics

• It is estimated that 1 in 20 patients with HLA-B*1502 will have a severe dermatologic

reaction (eg, TEN, SJS) when taking carbamazepine.