Differences

Last edited on April 30, 2020

This shows you the differences between two versions of the page.

--- meds:mood-stabilizers-anticonvulsants:carbamazepine [on March 21, 2020]
+++ meds:mood-stabilizers-anticonvulsants:carbamazepine [on March 6, 2021] (current)
@@ Line 1: / Line 1: @@
-====== Carbamazepine ======
+====== Carbamazepine (Tegretol) ======
+{{INLINETOC}}
 ===== Primer =====
-**Carbamazepine** is a mood stabilizer and anti epileptic used in the treatment of epilepsy and bipolar disorder. It is used in the treatment of acute mania and mixed episodes of bipolar I disorder.
+<WRAP group>
+<WRAP half column>
+**Carbamazepine** (Trade name: //Tegretol//) is a mood stabilizer and antiepileptic used in the treatment of epilepsy and bipolar disorder. It is used in the treatment of acute mania and mixed episodes of bipolar I disorder.
+</WRAP>
+<WRAP half column>
+<catlist meds:mood-stabilizers-anticonvulsants -columns:1 -noAddPageButton -sortAscending -noNSInBold>
+</WRAP>
+</WRAP>
 ===== Pharmacokinetics =====
-Is highly protein bound.
+<WRAP group>
+<WRAP half column>
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See also article: **[[meds:pharmacology:home|]]**
+</alert>
+<panel type="info" title="Pharmacokinetics of Carbamazepine" subtitle="" no-body="true" footer="">
+^ [[meds:pharmacology:home#absorption|Absorption]]             | Absorption is relatively slow, but peak plasma levels are reached within 2 hours  |
+^ [[meds:pharmacology:home#distribution|Distribution]]         | Highly protein bound (70 to 80%)                                                  |
+^ [[meds:pharmacology:home#metabolism|Metabolism]]             | Liver, primarily by CYP 3A4                                                       |
+^ [[meds:pharmacology:home#excretionelimination|Elimination]]  | 30% renally eliminated                                                            |
+^ [[meds:pharmacology:home#half-life|Half-life]]               | 35 hours                                                                          |
+</panel>
+</WRAP>
+<WRAP half column>
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See also article: **[[meds:cytochrome-p450|]]**
+</alert>
+<panel title="Carbamazepine: Cytochrome P450 Metabolism" no-body="true">
+^ Substrate of (Metabolized by)  | 3A4 (autoinduces and potent!)  |
+^ Induces                        | 3A4 (autoinduces and potent!)  |
+^ Inhibits                       |                                |
+</panel>
+</WRAP>
+</WRAP>
-===== Mechanism of Action =====
+===== Pharmacodynamics =====
+==== Mechanism of Action ====
    * Blocks α subunit of VSNaC
+   * Blocks Na+ channels
    * ?possible actions on K and Ca channels
-===== Side Effects =====
+==== Toxicity ====
-==== Common ====
+  * At toxic levels, there can be neurotoxicity
-Sedation, dizziness, fatigue, nausea, leukopenia in 7%,
+    * Dose dependent effects: diplopia, drowsiness, blurred vision, cognitive impairment
-===== Adverse Events =====
+===== Indications =====
-  * Agranulocytosis or aplastic anemia (1/10,000 to 1/125,000): monitor for fever, bruising, petechiae etc
+  * Trigeminal neuralgia
-  * GGT ↑ common; hepatotoxicity rare
+  * [[bipolar:bipolar-i|Bipolar disorder]]
+  * [[geri:dementia:1-bpsd|Behavioural and psychological symptoms of dementia]]
+===== Dosing =====
+<panel type="info" title="Dosing for Carbamazepine" no-body="true">
+^ Starting  | Start at 100 mg BID (it is usually dosed BID) |
+^ Titration | 100 mg every 2-3 days as tolerated, up to an initial target dose of at least 300 mg/day. After at least 5 days at this target dose (to allow steady state), a carbamazepine trough level should be drawn 12 hours after the last dose. |
+^ Maximum   | 1200mg |
+^ Taper     | |
+</panel>
-==== Pharmacogenetics ====
+  * The dose range for carbamazepine is between 100- (using the CR formulation), and it is usually dosed BID.
-  * Higher risk of serious cutaneous reactions in pts with Human Leukocyte Antigens (HLA)- A*3101 and HLA-B*1502
-  * Allelic frequency varies by ethnic group
-    * Consider genetic screening in at-risk population before starting Rx
-===== Dose =====
+==== Serum Levels ====
-The dose range for carbamazepine is between 100-1200mg (using the CR formulation), and it is usually dosed BID. Carbamazepine can be increased by 100 mg every 2-3 days as tolerated, up to an initial target dose of at least 300 mg/day. After at least 5 days at this target dose (to allow steady state to be achieve), a carbamazepine level should be drawn 12 hours after the last dose. If the level is:
+<panel type="info" title="Carbamazepine Levels" subtitle="" footer="Note that carbamazepine induces its own metabolism. Thus, drawing levels repeatedly for the same dose will be necessary over the first few weeks, making dose adjustments as necessary." no-body="true">
-  * <17 μmol/L, then the dose should be increased by 100 mg/day and another level should be drawn in 5 days
+^ <17 μmol/L    | Dose should be increased by 100 mg/day and another level should be drawn in 5 days  |
-  * 17-54 μmol/L, then the dose can be maintained
+^ 17-54 μmol/L  | Dose can be maintained                                                              |
-  * >54 μmol/L, then the dose should be reduced by 100 mg/day and another level should be drawn in 5 days
+^ >54 μmol/L    | Dose should be reduced by 100 mg/day and another level should be drawn in 5 days    |
-Note that carbamazepine induces its own metabolism thus drawing levels repeatedly for the same dose will be necessary over the first few weeks, making dose adjustments as necessary.
+</panel>
+  * Remember that unlike [[meds:mood-stabilizers-anticonvulsants:1-lithium|lithium]] levels, the carbamazepine level correlates poorly with therapeutic and clinical effect.
+  * The purpose of drawing levels is to ensure there is no toxicity.
+==== Formulations ====
+  * Carbamazepine comes in oral formulation.
 ==== Monitoring ====
-  * Serum levels:
+  * Since carbamazepine is its own substrate for CYP 3A4 metabolism (autoinduction), you must monitor blood level weekly for the first 8 weeks of treatment.
-    * Substrate for CYP 3A4 (autoinduction): monitor blood level weekly for the first 8 weeks
+  * Serum level monitoring should also be done every 6 to 12 months to ensure that serum levels are not in the toxic range.
-  * Blood level correlates poorly with therapeutic effect
+    * Signs of high levels of carbamazepine include diplopia, poor coordination, and sedation.
-  * Signs of high blood level: diplopia, poor coordination, sedation
+  * Carbamazepine is highly protein bound, and thus albumin levels should be measured.
-===== Drug-drug Interactions =====
-Carbamazepine is a strong inducer of CYP3A4 and P-glycoprotein (P-gp). Induces CYP 1A2, 3A4, 2C9, 2B6
+===== Contraindications =====
+==== Absolute ====
+==== Relative ====
+===== Drug-Drug Interactions =====
+  * Carbamazepine is a strong inducer of CYP3A4 and P-glycoprotein (P-gp) and it induces substrates of CYP 1A2, 3A4, 2C9, 2B6.
+    * Thus it can induce ("chew up") many psychotropic medications that are typically metabolized by most CYP enzymes, leading to very low levels of those medications.
 ===== Side Effects =====
-Carbamazepine has many drug-drug interactions, more side effects in the elderly. Side effects include weight gain, neurotoxicity (dose dependent: diplopia, drowsiness, blurred vision, cognitive impairment), transaminitis, SIADH, blood dyscrasias, AV node delays, bradycardia. Hypersensitivity rashes are uncommon.
+  * Carbamazepine has many drug-drug interactions, and can cause more side effects in the elderly.
+  * Weight gain, transaminitis, SIADH, blood dyscrasias, AV node delays, bradycardia.
+  * Sedation, dizziness, fatigue, nausea, leukopenia (low white blood cell count) in up to 7%
+  * Hypersensitivity rashes and reactions are uncommon
+    * In older adults, some concerns have been raised about bone marrow suppression as well for hypersensitivity
+===== Adverse Events =====
+==== Agranulocytosis ====
+  * Agranulocytosis or aplastic anemia (1/10,000 to 1/125,000)
+    * Monitor for fever, bruising, petechiae
+==== Hepatotoxicity ====
+  * GGT increases is common but hepatotoxicity is rare
+==== Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[meds:pharmacogenetics|]]**
+</alert>
+  * Han Chinese or Asian ethnicity patients should have genotyping performed prior to starting carbamazepine to ensure that they do not have the HLA-B*1502, which confers a significant risk for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
+  * Northern European ancestry individuals may also be at increased risk if they have the HLA-A*3101 allele.[([[https://pubmed.ncbi.nlm.nih.gov/21428769/|McCormack, M., Alfirevic, A., Bourgeois, S., Farrell, J. J., Kasperavičiūtė, D., Carrington, M., ... & Pirmohamed, M. (2011). HLA-A* 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. New England Journal of Medicine, 364(12), 1134-1143.]])]
+==== Teratogen ====
+  * Carbamazepine is teratogenic and can cause neural tube defects[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279268/|Matlow, J., & Koren, G. (2012). Is carbamazepine safe to take during pregnancy?. Canadian Family Physician, 58(2), 163-164.]])]
+    * Increased risk for cleft lip/palate, and spina bifida
+===== Clinical Pearls =====
+  * It is very important to tell all patients who take carbamazepine to report to their physician any and all skin rashes and/or mouth sores that develop.
+===== Special Populations =====
+==== Geriatric ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[meds:pharmacology:geri|]]**
+</alert>
-==== Pregnancy ====
+==== Pediatric ====
-Teratogenic (neural tube defects)
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
-[[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279268/|Matlow, J., & Koren, G. (2012). Is carbamazepine safe to take during pregnancy?. Canadian Family Physician, 58(2), 163-164.]]
+See main article: **[[meds:pharmacology:pediatric|]]**
+</alert>
+==== Obstetric and Fetal ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[meds:pharmacology:obstetric-and-fetal|]]**
+</alert>
+  * As mentioned above, carbamazepine is teratogenic!
+==== Medically Ill ====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">
+See main article: **[[meds:pharmacology:psychotropic-rx-medically-ill|]]**
+</alert>
+===== Resources =====