CARBAMAZEPINE

brands

Class

• Neuroscience-based Nomenclature: glutamate, voltage-gated sodium and calcium channel blocker (Glu-CB)
• Anticonvulsant, antineuralgic for chronic pain, voltage-sensitive sodium channel antagonist

CARBAMAZEPINE commonly prescribed for

(Bold for FDA approved)

How CARBAMAZEPINE works

• Acts as a use-dependent blocker of voltagesensitive sodium channels

• Interacts with the open-channel conformation of voltage-sensitive sodium channels

• Interacts at a specific site of the alpha pore-forming subunit of voltage-sensitive sodium channels

• Inhibits release of glutamate

How long until CARBAMAZEPINE works

• For acute mania, effects should occur within a few weeks

• May take several weeks to months to optimize an effect on mood stabilization

• Should reduce seizures by 2 weeks

Notable Side Effects

• Sedation, dizziness, confusion, unsteadiness, headache

• Nausea, vomiting, diarrhea

• Blurred vision

• Benign leukopenia (transient; in up to 10%)

• Rash

Life Threatening Side Effects

• Rare aplastic anemia, agranulocytosis (unusual bleeding or bruising, mouth sores, infections, fever, sore throat)

• Rare severe dermatologic reactions (purpura, Stevens–Johnson syndrome)

• Rare anaphylaxis and angioedema

• Rare cardiac problems

• Rare induction of psychosis or mania

• SIADH (syndrome of inappropriate antidiuretic hormone secretion) with hyponatremia

• Increased frequency of generalized convulsions (in patients with atypical absence seizures)

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

not usual

sedation

problematic

What to do about CARBAMAZEPINE side effects

• Wait

• Wait

• Wait

• Take with food or split dose to avoid gastrointestinal effects

• Extended-release carbamazepine can be sprinkled on soft food

• Take at night to reduce daytime sedation

• Switch to another agent or to extendedrelease carbamazepine

usual dosage range

• 400–1200 mg/day

• Under age 6: 10–20 mg/kg per day

Dosage Forms

• Tablet 100 mg, 200 mg

• Tablet 100 mg chewable, 200 mg chewable

• Extended-release tablet 100 mg, 200 mg, 400 mg

• Extended-release capsule 100 mg, 200 mg, 300 mg

• Oral suspension 100 mg/5 mL (450 mL)

long term use

• May lower sex drive

• Monitoring of liver, kidney, thyroid functions, blood counts, and sodium may be required

habit forming

• No

Renal Impairment

• Carbamazepine is renally secreted, so the dose may need to be lowered

Hepatic Impairment

• Drug should be used with caution

• Rare cases of hepatic failure have occurred

Cardiac Impairment

• Drug should be used with caution

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Approved use for epilepsy; therapeutic range of total carbamazepine in plasma is considered the same for children and adults

• Ages 6–12: initial dose 100 mg twice daily (tablets) or 0.5 teaspoon (50 mg) 4 times a day (suspension); each week increase by up to 100 mg/day in divided doses (2 doses for extended-release formulation, 3–4 doses for all other formulations); maximum dose generally 1000 mg/day; maintenance dose generally 400–800 mg/day

• Ages 5 and younger: initial 10–20 mg/ kg per day in divided doses (2–3 doses for tablet formulations, 4 doses for suspension); increase weekly as needed; maximum dose generally 35 mg/kg/day

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Use during first trimester may raise risk of neural tube defects (e.g., spina bifida) or other congenital anomalies

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• If drug is continued, perform tests to detect birth defects

• If drug is continued, start on folate 1 mg/ day early in pregnancy to reduce risk of neural tube defects

• Antiepileptic Drug Pregnancy Registry: 1-888-233-2334, www.aedpregnancyregistry.org

• Use of anticonvulsants in combination may cause a higher prevalence of teratogenic effects than anticonvulsant monotherapy

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

• For bipolar patients, carbamazepine should generally be discontinued before anticipated pregnancies

• Recurrent bipolar illness during pregnancy can be quite disruptive

• For bipolar patients, given the risk of relapse in the postpartum period, some form of mood stabilizer treatment may need to be restarted immediately after delivery if patient is unmedicated during pregnancy

• Atypical antipsychotics may be preferable to lithium or anticonvulsants such as carbamazepine if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects, including hematological effects

• If infant shows signs of irritability or sedation, drug may need to be discontinued

• Some cases of neonatal seizures, respiratory depression, vomiting, and diarrhea have been reported in infants whose mothers received carbamazepine during pregnancy

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer than carbamazepine during the postpartum period when breast feeding