Pharm

Carbamazepine

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Carbamazepine, Tegretol, Carbamazepine Poisoning

  • Indication
  1. Simple Partial Seizures
  2. Complex Partial Seizures
  3. Generalized Tonic Clonic Seizures
  4. Trigeminal Neuralgia
  5. Bipolar Disorder
    1. Frequently reserved for use as a second agent
  6. Resistant Schizophrenia
  7. Restless Leg Syndrome
  8. Psychosis in Dementia
  9. Post-Traumatic Stress Disorder
  • Contraindications
  1. MAO inhibitor use within last 14 days
  2. Bone Marrow suppression
  3. Pregnancy
  4. Tricyclic compound sensitivity
  5. Asian patients who are positive for HLA-B1502
    1. Risk of Steven's Johnson: 5% if HLA-B1502 positive
    2. Also associated with Toxic Epidermal Necrolysis
    3. FDA has issued a black box warning
    4. Man (2007) Epilepsia 48(5):1015-8 [PubMed]
  • Adverse Effects
  • Dose related
  1. Gradual tolerance to side effects (slowly titrate)
  2. Common
    1. Headache
    2. Lethargy, Fatigue or Somnolence
    3. Nausea and Vomiting
  3. Toxicity, Poisoning or Overdose
    1. Hypotension
    2. Neurologic
      1. Tremor or Myoclonus
      2. Nystagmus
      3. Dizziness
      4. Ataxia or altered coordination
      5. Diplopia
      6. Seizures
    3. Anticholingeric Poisoning
      1. Mydriasis
      2. Skin Flushing
      3. Dry Skin and mucous membranes
      4. Tachycardia
      5. QRS Prolongation
  • Adverse Effects
  • Other
  1. Morbilliform rash
  2. Gingival Hyperplasia
  3. Blood dyscrasias
    1. Agranulocytosis
    2. Aplastic Anemia
    3. Leukopenia
  4. Cardiac conduction abnormality (increases A-V delay)
  5. Hyponatremia
    1. Occurs in up to 40% of patients
    2. Elderly are at higher risk of SIADH
  6. Liver failure
  7. Osteoporosis
  8. Serum Sickness
  9. Stevens-Johnson Syndrome
  10. Toxic Epidermal Necrolysis
  • Mechanism
  1. Binds Sodium channels that are in an inactive state
  2. Inhibits Neuron depolarization and glutamate release
  • Pharmacokinetics
  1. Delayed effects after ingestion, peaking at up to 12 hours after ingestion (96 hours for extended release formulations)
  2. Elimination half-life: 18 hours
    1. Zero order kinetics in Overdose (linear, constant elimination rate regardless of concentration)
  • Drug Interactions (Numerous)
  1. Substrate of Cytochrome P450 2C8/9
  2. Substrate of Cytochrome P450 3A4
  3. Induces Cytochrome P450 1A2
  4. Induces Cytochrome P450 2B6
  5. Induces Cytochrome P450 2C8/9
  6. Induces Cytochrome P450 2C19
  7. Induces Cytochrome P450 3A4
  1. Titrate dose to serum concentration and effect
  2. Target serum concentration: 4-12 mcg/ml
    1. Observe closely for concentration 8 mcg/ml or higher
  3. Toxic serum concentration: >15 mcg/ml
  • Dose
  • Adults
  1. Seizure Disorder
    1. Initial: 200 mg orally twice daily
    2. Increase by 200 mg/day increments weekly
      1. Typically up to 800-1200 mg/day (max: 2400 mg/day) in divided dosing
    3. Target concentration: 4 to 12 mcg/ml
  2. Trigeminal Neuralgia
    1. Initial: 100 mg orally twice daily
    2. Increase by 100 mg/day increments weekly
    3. Target: 400-800 mg/day divided twice daily
  3. Bipolar Disorder
    1. Initial: 200 mg twice daily
    2. Increase by 200 mg as often as daily in acute mania as tolerated
      1. Slower titration results in fewer side effects
    3. Target: 200-1600 mg per day
    4. Target serum level: 4 to 12 mcg/ml
  • Dose
  • Elderly
  1. Initial: 100 mg orally twice daily
  2. Increase by 100 mg/day increments weekly
  3. Target: 400-1000 mg/day divided three to four times daily
  1. See Adverse Effects above (dose dependent)
  2. Lab Testing and Diagnostics
    1. See Unknown Ingestion (includes Serum Glucose, other Toxicology Screening)
    2. Serial Serum Carbamazepine levels
    3. Electrocardiogram (EKG)
  3. Supportive Care
    1. Oral Activated Charcoal in an alert patient if presentation within 1-2 hours of ingestion
    2. Whole Bowel Irrigation (and repeat Activated Charcoal) if sustained release Carbamazepine ingestion
    3. Hypotension management
      1. Intravenous Fluids
      2. Vasopressors
    4. QRS Widening
      1. Sodium Bicarbonate IV ampules until QRS narrows
    5. Seizures
      1. See Status Epilepticus
      2. Benzodiazepines
      3. Propofol
    6. Hemodialysis Indications
      1. Refractory Seizures
      2. Cardiac Instability
  4. Disposition
    1. May discharge home if asymptomatic at 4 to 6 hours after ingestion and decreasing Serum Carbamazepine levels
  • Monitoring
  1. Routine labs
    1. Obtain monthly for first 2 months, then every 3 to 12 months
    2. Complete Blood Count with Platelet Count
    3. Liver Function Tests
  2. HLA-B1502
    1. Indicated before starting in asian patients
    2. See contraindications above
  3. Serum Carbamazepine level
    1. Initial: Every 1-2 weeks
    2. Later: Every 3-6 months
    3. Also check before and after dose changes
  4. Other tests previously monitored with Carbamazepine use
    1. Serum Iron
    2. Urinalysis
    3. Serum Sodium
    4. Blood Urea Nitrogen
    5. Thyroid Stimulating Hormone
  • References
  1. Tomaszewski (2022) Crit Dec Emerg Med 36(9): 32