CARBAMAZEPINE: Other names for the medication and med facts• Pronounced: kar-ba-MAZ-e-peen• Other names: Carbatrol, Epitol, Equetro, Novo-Carbamaz, Tegretol, Tegretol CR, Tegretol-XR, Teril• Pharmacologic class: iminostilbene derivative• Pregnancy risk category: D
CARBAMAZEPINE : Chemical structure• Carbamazepine is an iminostilbene derivative that is related chemically to the tricyclic antidepressants and is structurally similar to phenytoin.• Chemical name: 5H-Dibenz[b,f]azepine-5- carboxamide; 5-carbamoyl-5H-dibenz[b,f]azepine• Molecular formula of carbamazepine: C15H12N2O.• Molecular weight: 236.26.
CARBAMAZEPINE: Indications and Dosages• Indicated in the treatment of Generalized tonic- clonic and complex partial seizures, mixed seizure patterns (except Carbatrol)• Adults and children older than age 12: Initially, 200mg po BID (conventional or extended-release tablets), or 100mg po QID of suspension with meals• May be increased weekly by 200mg po daily in divided doses and 12 hr. intervals for extended release, 6 to 8 hr. doses for conventional tablets or suspension.
CARBAMAZEPINE: Dosage guidelinesrecommended for ages 12 to 15 years and older• Maximum dosage is 1000 mg daily in children ages 12 – 15 years of age• Ages 15 years and older, maximum dosage is 1200 mg• Usual maintenance dose is 800 to 1200 mg daily
CARBAMAZEPINE: Dosage guidelines recommended 6 to 12 years of age• Children ages 6 to 12: Initially 100 mg po BID (conventional or extended release) or 50mg suspension po QID with meals• Increased at weekly intervals up to 100mg po TID or QID in divided dosages (BID for extended release) Maximum is 1000mg daily• Usual maintenance dose is 400-800 mg daily or 20/30mg/kg in divided doses TID or QID
CARBAMAZEPINE: Dosage guidelinesrecommended for ages 6 and younger• Recommended dosages are 10 to 20 mg/kg BID or TID in divided doses (conventional tablets) or QID (suspension).• Maximum dosage is 35 mg/kg in 24 hours
CARBAMAZEPINE: Secondary usages• Acute manic and mixed episodes associated with bipolar I disorder• Trigeminal Neuralgia• Restless Leg Syndrome• Alcohol Withdrawal
CARBAMAZEPINE: Bipolar Disorder• Given for manic episodes• Usual dosage is 200mg po BID initially, then increase by 200mg daily until therapeutic response is achieved• Maximum dosage is 1600 mg daily
CARBAMAZEPINE: Trigeminal Neuralgia (except Carbatrol)• Initially 100 mg po BID tablets (conventional or extended release) or 50mg suspension QID with meals• Increased by 100mg q 12 hrs. for all tablets or 50mg for suspension until pain is relieved• Maximum dose is 1200 mg daily• Maintenance dose is usually 200mg – 400mg po BID• Carbatrol follows different guidelines
CARBAMAZEPINE: Restless Leg Syndrome and Alcohol Withdrawal• RLS: Adults 100 to 600mg po daily for up to six weeks• Alcohol Withdrawal: Adults 600 to 1200 mg on day 1 with a taper to “0” over 5 to 10 days.
CARBAMAZEPINE: Administration• Shake suspension well before administering• Contents of extended release may be sprinkled over applesauce if difficulty swallowing• Only tablets labeled “chewable” should be crushed or chewed• Never crush or split tablets/capsules or given broken or chipped tablets
CARBAMAZEPINE: Mechanism of Action• Thought to stabilize neuronal membranes and limit seizure activity by either increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses
PHARMACOKINETICS Absorption by route of exposureAbsorption of carbamazepine from thegastrointestinal tract is slow and erratic butalmost complete. Oral absorption is more rapidon a full stomach and slower from tablets thanfrom solution.
CARBAMAZEPINE:Pharmacodyamics/Pharmacotherapeutics• Pharmacodyamics: Very similar to Phenytoin in the fact that the anticonvulsant action of the drug can occur because of its ability to inhibit the spread of seizure activity or neuromuscular transmission in general• Pharmacotherapeutics: Drug of choice in adults as well as children for the treatment f generalized tonic-clonic seizures as well as simple and complex partial seizures
CARBAMAZEPINE: Peak and Half-life time• Onset time for all routes is unknown• Peak time for PO, conventional tablets is 1.5 – 12 hrs. with duration unknown• Peak time for PO, extended release is 4 – 8 hrs.• Half-life is 25 to 65 hours with a single dose, 8 to 29 hours with long-term use
CARBAMAZEPINE: Drug to Drug Interactions• Atracurium, Cisatracturium, Pancuronium, Rocuronium, Vecuronium: May decrease the effects of nondepolarizating muscle relaxant, causing it to be less-effective• Cimetidine, Danazol, Diltiazem, Fluoxetine, Fluvoxamine, Isoniazid, Macrolides, Propoxyphene, Valproic Acid, Verapamil: May increase Carbamazepine levels, use together cautiously• Doxycycline, felbate, Haloperidol, Hormonal contraceptives, Phenytoin, Theophylline, Tiagabine, Topiramate, Valproate, Warfarin: May decrease levels of these drugs, watch for decreased effect closely
CARBAMAZEPINE: Specific Drug to Drug interactions• Lamotrigine: May decrease level and increase Carbamazepine level. Monitor closely for clinical effects and toxicity.• Lithium: May increase CNS toxicity of Lithium. Avoid using together• MAO Inhibitors: May increase depressant and anti-cholinergic effects. Avoid using together.• Nefazodone: May increase Carbamazepine levels and toxicity while reducing Nefazodone levels and therapeutic benefit. Use together is contraindicated
CARBAMAZEPINE: Effects on Lab Testing PATIENTS MUST HAVE TESTING DONE ROUTINELY TO MONITOR THE FOLLOWING:• May increase BUN level• May decrease hemoglobin and hematocrit• May increase Liver function tests• Increase eosinophil and white blood cell count• Decrease thyroid function test• Decrease granulocyte and platelet counts• May cause false pregnancy test results
CARBAMAZEPINE: ResearchIn cats, carbamazepine depresses thalamicpotential and bulbar and polysynapticreflexes. Its capacity to increase discharges ofnoradrenergic neurones may contribute to itsanti-epileptic actions (Rall & Schleifer, 1985).
CARBAMAZEPINE: Contraindications and general cautions Contraindicated• Hypersensitivity to this drug or tricyclic antidepressants• History of bone marrow suppression• MAO inhibitor use within 14 days Use with caution• Mixed seizure disorder diagnosis (may experience increase in seizures)• Hepatic dysfunction
CARBAMAZEPINE: Considerations• Asian patients at greater risk for serious skin reactions. Screen for HLA-B*1502 allele before beginning treatment• Watch for worsening of seizures, especially in patients with mixed seizure disorders, including atypical absence seizures• Watch for worsening of depression, anxiety, suicidal thoughts or behavior.
CARBAMAZEPINE: Black box warning Aplastic anemia and Agranulocytosishave been reported in association withCarbamazepine therapy. Must obtaincomplete pretreatment hematologic testing asa baseline. If during treatment, patientexhibits low or decreased WBC or platelet counts, i.e. any evidence ofsuppressed bone marrow,CONSIDER DISCONTINUING THERAPY
CARBAMAZEPINE: Patient assessment• Assess seizure disorder or trigeminal neuralgia prior to initiation of medication and routinely during course of treatment• Obtain baseline urinalysis, blood urea nitrogen level, liver function, CBC, platelet and reticulocyte counts, iron levels and reassess routinely.• Monitor drug level and drug effects closely, therapeutic level ranges from 4 to 12 mcg/ml. Toxic level is >15 mcg/ml.• Monitor the patient’s response to the prescribed drug and serum levels as indicated.• Monitor the patient for adverse reactions• Assess the patients compliance with therapy at each follow- up visit
CARBAMAZEPINE: Patient teaching• Take with food to decrease GI distress• Shake suspension prior to administration• Never crush or chew extended release form or take broken or chipped tablets• Tegretol-XR may appear in stool since it is not absorbed• Keep medication in original container, tightly sealed, away from moisture to ensure full effectiveness• Notify MD immediately if fever, sore throat, mouth ulcers, excess bruising or bleeding occurs.• Avoid taking while completing activities that require alertness (drowsiness is side effect)• Regular eye exams are recommended to ensure eye health
CARBAMAZEPINE: Pharmacy Handout Per “Medicine Shoppe”, Crossville, TN• Medication name• Instruction on how to use handout• Common brand names• Warning: May cause fatal skin reaction in certain ethic groups. Testing for HLA-B 1502 indicated for Asian descent.• No research listed
MY PRESCRIPTION County ClinicName: S. SOSICK Date: August 3,ind: Partial Complex SeizuresRx Carbamazepine tabletsSig 200mg. po BID X 30 days# 60 (sixty)Refills 0 1 2 3 4 5 (indicating zero refills)
REFERENCES• International Program on Chemical Safety, Chemical Safety Information from Intergovernmental Organizations, “CARBAMAZEPINE” August 3, 2012 retrieved from http://www.inchem.org/documents/pims/pharm/pim100.ht m#PartTitle:1.%20%20NAME• Medicine Shoppe, (2012, July) “Carbamazepine, Patient Information”• Nursing 2010 Drug Handbook (2010) Wolters Kluwer, Lippincott Williams & Wilkins• Nursing Pharmacology Made Incredibly Easy, 2nd Ed. (2009) ) Wolters Kluwer, Lippincott Williams & Wilkins