carbamazepine TEGRETOL
Class: AED/Mood StabilizerFDA Indications: Epilepsy, Trigeminal Neuralgia, Bipolar Disorder
Off-Label Use: Restless Leg Syndrome, Neuropathic Pain, Agitation And Aggression In Dementia
Prescribing
Forms: 100, 200mg tablet; 100, 200, 400 mg Extended-Release Capsules (Equetro®); 100 mg/5 mL po solnDose Range: 200-1600 mg/day
Starting: Usual starting dose is 200 mg BID, gradually increasing up to an average effective dose of 400 mg BID. The maximum recommended dose is 1600 mg QD (split BID).
Monitoring: Every 6 to 12 months: CBZ levels (therapeutic range 4-12 μg/mL), LFTs, CBC w/ diff & retics, serum Na+
Precautions
Contraindications: H/o bone marrow depression, known sensitivity to any of the TCAs, concomitant use of MAOIsSerious Side Effects: Stevens-Johnson syndrome/TEN (1-6:10,000, 10x higher in some Asian countries), aplastic anemia (2:1,000,000), agranulocytosis (6:1,000,000), ↑'d suicidality, DRESS
Side Effects: sedation/somnolence (32%), dizziness (44%), ataxia, hyperhidrosis, rash, pruritus, speech disturbance, xerostomia, constipation, anemia, visual changes, weakness/asthenia, hyponatremia, leukopenia, nausea (29%), vomiting (18%)
Pharmacodynamics
1° MOA: Binds to α subunit of voltage sensitive Na+ channels & possibly actions at other ion channels (Ca2+ & K+). Interference with these channels may enhance the inhibitory actions of GABA.Target: SCN5A
Pharmacokinetics
t½: 35 (28-65)° TMAX: 4-8°Substrate of: 3A4; 2C8, 1A2
Inhibits: ∅ ; Induces: 1A2, 2A6, 2B6, 2C9, 2C19, 3A4, UGTs & mEH
Active Metabolites: carbamazepine-10,11-epoxide
DDIs
- - pan-inducer of nearly all major metabolic pathways
- - induces its own metabolism — autoinduction may start within 24° of 1st dose & seems to be complete within 20-30 days
- - autoinduction of CBZ is dose dependent, so each dose ↑ will result in further autoinduction
- - combining with Li+ can ↑ neurotoxic side effects
- - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
Misc
- - t½ after a single dose varies between 28-65°, however after autoinduction is completed t½'s are in the range of 10-20°
- - HLA Genetic Testing recommened patients of East Asian descent who are at an ↑'d risk of carbamazepine-induced SJS
- - ∅ clinically significant weight gain
- - has most robust evidence, among mood-stabilizers, for use in treating non-cognitive symptoms of dementia
Special Populations
Category D—CBZ can cause fetal harm (spina bifida) when administered to a pregnant woman. Fetal plasma concentrations range between 50-80% of maternal levels. CBZ is cleared more rapidly in the 3rd trimester
RID 1.1-7.3%; some AEs reported, suggest discontinue or bottle feed
Clearance is age dependent, with higher clearance reported in younger children and lower clearances reported in older patients
Renal disease and dialysis do not alter clearance
Patients with significant liver disease may have a decreased clearance of carbamazepine
Thank you for using psychopharmacopeia.com!