Carbamazepine

Carbamazepineis used to prevent and control seizures. This medication is known as ananticonvulsantor anti-epileptic drug. It is also used to relieve certain types of nerve pain (such as trigeminal neuralgia). This medication works by reducing the spread of seizure activity in the brain and restoring the normal balance of nerve activity.

Carbamazepine is available under the following different brand names:Tegretol,Equetro,Epitol, Tegretol XR, Carbamazepine Chewtabs, Carbamazepine CR,Carbatrol, Teril, andCarnexiv

Dosages of Carbamazepine:

Tablet, chewable (Epitol)

Adult and pediatric dosage

• 100 mg

Tablet, immediate-release (Tegretol)

Adult and pediatric dosage

• 200 mg

Tablet, extended-release (Tegretol XR)

Adult and pediatric dosage

• 100 mg
• 200 mg
• 400 mg

胶囊,延长释放(Equetro Carbatrol)

Adult and pediatric dosage

• 100 mg
• 200 mg
• 300 mg

Oral suspension (Teril)

Adult and pediatric dosage

• 100 mg/5mL

IV solution (Carnexiv)

Adult dosage only

• 10 mg/mL (200 mg/20mL single-dose vial)

Dosage Considerations – Should be Given as Follows:

Epilepsy

Indicated for the treatment of partial seizures with complex symptomatology (psychomotor,temporal lobe)，generalized tonic-clonic seizures (grand mal)，and mixed seizure patterns, which include the seizure types listed here or other partial or generalized seizures

Adult Dosage

• Maintenance dose range: 800-1,200 mg/day orally in divided doses
• Therapeutic range: 4-12 mg/L (16.9-50.8 micromoles/L)
• Maximum dose of 1,600 mg/day recommended (rarely, some patients have required 1.6-2.4 g/day)

Tablet (immediate-release)

• Initial: 200 mg orally every 12 hours
• Increase each week by 200 mg per day divided orally each 6-8 hours

Tablet/capsule (extended-release)

• Initial: 200 mg orally every 12 hours
• Increase each week by 200 mg/day orally dived every 12 hours

Oral suspension

• Initial: 10 mL (200 mg) orally every 6 hours
• Increase each week by 200 mg/day orally dived every 6-8 hours

Intravenous (IV) solution

• Indicated as replacement therapy in adults for oral carbamazepine formulations, when oral administration is temporarily not feasible
• 批准作为临时使用fo(不超过7天)r the following seizure types:
• partial seizures with complex symptomatology
• generalized tonic-clonic seizures
• mixed seizure patterns which include the above, or other partial or generalized seizures

Dose

• The total daily dose of carbamazepine intravenously is 70% of the total daily oral dose from which patients are being changed. Equally divide the total daily dose of the intravenously in four 30-minute infusions, separated by 6 hours
• Patients should be switched back to oral carbamazepine administration at their previous total daily oral dose and frequency of administration as soon as clinically appropriate
• Intravenous administration has not been studied for greater than 7 days

Limitations of use

• Not indicated for absence seizures (includingatypicalabsence); carbamazepine has been associated with increased frequency of generalized convulsions in these patients

Pediatric dosage

Children under 6 years

• 最初(口服悬挂):10-20 mg/kg/day orally every 6 hours
• Initial (tablet): 10-20 mg/kg/day orally every 8-12 hours
• Maintenance: For tablets or suspension may divide frequency into 3-4 times daily not to exceed 35 mg/kg/day

Children 6-12 years

• Initial (oral suspension): 50 mg orally every 6 hours
• Initial (tablet, immediate- or extended-release): 100 mg orally every 12 hours; may increase each week by 100 mg/day
• Maintenance: 400-800 mg/day orally every 6-8 hours (immediate-release); every 12 hours (extended-release)
• Not to exceed 1,000 mg/day

Children over 12 years

• 最初(口服悬挂):10 mL (200 mg) orally every 6 hours
• Initial (tablet, immediate- or extended-release tab/cap): 200 mg orally every 12 hours
• May increase by up to 200 mg/day each week; every 12 hours (extended-release tablet); every 6-8 hours (other formulations)
• Children 12-15 years: Dose not to exceed 1,000 mg/day
• Children over 15 years: Dose not to exceed 1,200 mg/day

Dosage Modifications

Renal impairment

• Glomerularfiltration rate less than 10 mL/min: Administer 75% of dose and monitor
• Peritoneal dialysisand hemodialysis: Administer 75% of dose and monitor

Hepatic impairment

• Use caution; drug is metabolized primarily in the liver

Dosing Considerations

• Important to initiate slowly by advancing dose every 5-7 days to minimizegastrointestinalupset and allow auto-induction of liver enzymes to occur (auto-induction is complete at 3-5 weeks)
• Children under 12 years who receive over 400 mg/day may be converted to CarbatrolERat the same dose, every 12 hours orally
• Monitor: complete blood counts (CBC)，liver function tests

TrigeminalNeuralgia

Indicated for pain associated with trigeminal neuralgia; beneficial results have also been reported in glossopharyngeal neuralgia; carbamazepine is not a simpleanalgesicand should not be used for the relief of trivial aches or pains

• Maintenance dose range: 400-800 mg/day orally in divided doses; attempts to reduce or discontinue the drug should be made at least every 3 months throughout the treatment period
• Maximum dose of 1200 mg/day recommended

Tablet (immediate-release)

• Initial: 200 mg/day on day 1 divided every 12 hours
• Increase by up to 200 mg/day in increments of 100 mg every 12 hours, to dose range of 400-800 mg/day divided twice daily; not to exceed 1200 mg/day

Tablet/capsule (extended-release)

• Initial (XR tablet): 200 mg/day orally on day 1 divided every 12 hours
• Initial (XR capsules): 200 mg orally once on the first day; may increase dose by up to 200 mg/day using increments of 100 mg every 12 hours to reach an effective/tolerated dose; not to exceed 1200 mg/day
• Increase by up to 200 mg/day in increments of 100 mg every 12 hours, to dose range of 400-800 mg/day divided twice daily; not to exceed 1200 mg/day

Oral suspension

• Initial: 200 mg orally on day 1 divided every 6 hours
• Increase by up to 200 mg/day in increments of 50 mg every 6 hours, to dose range of 400-800 mg/day divided twice daily; not to exceed 1200 mg/day

BipolarMania

Equetro

• Indicated for treatment of patients with acutemanicor mixed episodes associated withbipolar I disorder
• Initial: 200 mg orally every 12 hours
• Increase by increments of 200 mg/day; not to exceed 1600 mg/day

Dosage Modifications

Renal impairment

• Glomerular filtration rate less than 10 mL/min: Administer 75% of dose and monitor
• Peritonealdialysis and hemodialysis: Administer 75% of dose and monitor

Hepatic impairment

• Use caution; drug is metabolized primarily in the liver

Restless Legs综合征(标示外)

• 100-600 mg orally at bed time for up to 5 weeks

Schizophrenia (Off-label)

• 200-1,300 mg/day for 2.5-8 weeks

Postherpatic Neuralgia

• 100-200 mg orally each day; may increase slowly to 1,200 mg/day

Common side effects of Carbamazepine include:

• lack of muscle coordination
• dizziness
• drowsiness
• nausea
• vomiting
• dry mouth
• Hemopoieticsystem: deficiency of all blood cells (aplastic anemia),血不足(agranulocytosis)，deficiency ofred blood cells, white cells and platelets in the blood (pancytopenia)，bone marrowdepression, low count of platelets in your blood (thrombocytopenia), reduction of white cells in your blood (leukopenia)，elevated white cells (leukocytosis)，increase of eosinophils in the blood (eosinophilia)，anemia, acute intermittent abnormal metabolization ofhemoglobin(porphyria), variegate porphyria (autosomal dominant)，porphyria cutanea tarda(莫st common, may result in skin conditions)
• Skin: Toxicepidermalnecrolysis (TEN) andStevens-Johnson syndrome(SJS)，sensation to scratch itchy and red rashes, hives, sensitivity to light reactions, alterations in skinpigmentation, scaly and flaky rash, hyper sensitivity (erythema multiforme) and red tender lumps on the front of the legs, rash, aggravation of disseminated lupus erythematosus, hair loss, abnormal sweating, generalized skin rash beginning 5 days after the medication was started, and shredding of the nails
• Cardiovascular system: Congestive heart failure, swelling (edema), aggravation ofhigh blood pressure(hypertension)，low blood pressure (hypotension)，fainting, and collapse, aggravation ofcoronary artery disease, irregular heart beat (arrhythmias) and房室block of the heart, problems withcirculation(thrombophlebitis)，blood clot, and enlargement of lymph nodes
• Liver: Abnormalities in liver function tests, reduction or stoppage ofbileflow and increased bilirubin in the blood due to liver disease (hepatocellular jaundice), inflammation of the liver (hepatitis); very rare cases ofliver failure
• Pancreatic:Pancreatitis
• Respiratory System: Pulmonary hypersensitivity characterized by fever, difficulty breathing, inflammation of the walls of thealveoliin thelungs或肺炎
• GenitourinarySystem: Urinary frequency, acute urinary retention, production of small amounts of urine with elevated blood pressure, elevation of liver and kidney values together with serum creatinine levels, kidney (renal) failure, andimpotence(rare reports of impaired male fertility and/or abnormalspermatogenesis)
• Laboratory:albuminin the urine, sugar in the urine, elevated kidney and liver function, decreased plasma calcium, andmicroscopicdeposits in the urine, decreased values ofthyroidfunction tests
• Nervous system: Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, intermittent double vision,involuntaryeye movements, repetitive eye movements, speech disturbances, abnormal involuntary movements, numbness and pain in hands or feet with abnormal skin sensations, depression with agitation, talkativeness,ringing in the ears(tinnitus)，sensitivity to certain sounds, and isolated cases ofneurolepticmalignantsyndrome (fever, altered mental status, muscle rigidity, autonomic nerve dysfunction, dizziness, fainting, low blood pressure when standing up and an inability to alter heart rate with exercise)
• Digestive system: Nausea, vomiting,gastricdistress and abdominal pain, diarrhea, constipation, loss of appetite, and dryness of the mouth andpharynx, including inflammation of the tongue, and inflammation of themucousmembranes of the mouth, and liver damage
• Eyes: Scattered punctatecorticallensopacities, increased眼内前ssureas well as pink eye (conjunctivitis)
• Musculoskeletal system: Aching joints and muscles, and leg cramps
• Metabolism: Fever and chills; Syndrome of Inappropriate Antidiuretic Hormone (SIADH); cases of frankwater intoxication, with decreased serum sodium (hyponatremia) and confusion; decreased levels of plasma calcium leading toosteoporosis
• Other: Multi-organ hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases, signs or symptoms may include fever, skin rashes, inflammation of blood vessel(s), disease of the lymph nodes, disorders mimickinglymphoma, joint pain, reduction of white blood cells (leukopenia), increase of white blood cells (eosinophilia), swelling of the liver andspleen, and abnormal liver function tests

Rare side effects of Carbamazepine include:

• heart attack (myocardial infarction)
• Stevens-Johnson syndrome
• cataracts
• syndrome of inappropriateantidiuretic hormonesecretion (SIADH)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Carbamazepine has severe interactions with at least 40 different drugs.

Carbamazepine has serious interactions with at least 164 different drugs.

Carbamazepine has moderate interactions with at least 277 different drugs.

Carbamazepine has minor interactions with at least 76 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

• This medication contains carbamazepine. Do not take Tegretol, Equetro, Epitol, Tegretol XR, Carbamazepine Chewtabs, Carbamazepine CR, Carbatrol, Teril, or Carnexiv if you are allergic to carbamazepine or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Documented hypersensitivity
• History of bone marrow suppression
• Administration of monoamine oxidase (MAO) inhibitors within last 14 days
• Coadministration with nefazodone; carbamazepine decreases plasma levels of nefazodone and its active metabolite
• Coadministration with non-nucleosidereverse transcriptaseinhibitors (NNRTIs) (delavirdine, efavirenz, etravirine, nevirapine, rilpivirine); carbamazepine induces CYP3A4 and may substantially reduce NNRTI serum concentration.
• Jaundice, hepatitis
• Pregnancy (especially first trimester: risk of fetal carbamazepine syndrome)

Effects of Drug Abuse

• No information provided

Short-Term Effects

• See "What Are Side Effects Associated with Using Carbamazepine?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Carbamazepine?"

注意事项

• Monitor for notable changes in behavior that might indicate suicidal thoughts or depression and notify healthcare provider immediately if behavioral changes observed
• Discontinue if significant bone marrow depression occurs
• Withdraw gradually
• Increased risk of agranulocytosis and aplastic anemia
• May causeECGabnormalities; use caution in patients with conduction abnormalities; AVheart block, including second and third degree block, reported following carbamazepine treatment; effect occurred generally, but not solely, in patients with underlying EKG abnormalities or risk factors for conduction disturbances
• May exacerbate absence seizures; in the event of allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary
• Bipolar mania: Efficacy inconsistent; American Psychological Association (APA) recommends use after failure of or if there is resistance tolithiumand valproate
• May causepsychosis, confusion, and/or agitation; elderly patients are at greater risk
• May render oral contraceptives ineffective
• Higher risk of potentially fatal skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been found in patients of Asian ancestry (genetic testingrecommended); increased risk of developing hypersensitivity reactions with presence of HLAA*3101 orHLA-B*1502, inheritedallelicvariants of the HLA-A and HLA-B gene (seePharmacogenomicsin thePharmacologysection)
• Hyponatremia may occur and appears to be a result of SIADH; may be dose-related and elderly individuals are at greater risk
• Associated with hypotension,bradycardia, AV block, and signs and symptoms of HF
• Fataldermatologicreactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), reported
• Not a simple analgesic; do not use to relieve minor aches and pains
• Tegretol suspension containssorbitol; not for administration to patients with rare hereditary problems offructoseintolerance AV heart block, including second and third degree block, reported following carbamazepine treatment; effect occurred generally, but not solely, in patients with underlying EKG abnormalities or risk factors for conduction disturbances
• Mildanticholinergicactivity; use caution in patients with sensitivity to anticholinergic effects
• Liver (Hepatic) effects
• Hepatic effects reported ranging from slight elevations in liver enzymes to rare cases of hepatic failure
• In some cases, hepatic effects may progress despite discontinuation
• Rare instances of vanishing bileductsyndrome reported; consists of a variable clinical course ranging from fulminant to indolent, involving the destruction and disappearance of theintrahepaticbile ducts
• Some cases associated other immunoallergenic syndromes (multiorgan hypersensitivity [DRESS syndrome], serious dermatologic reactions)
• As an example there has been a report of vanishing bile duct syndrome associated with Stevens-Johnson syndrome, and in another case an association with fever and eosinophilia
• Baseline and periodic evaluations of liver function, particularly in patients with history of liver disease, must be performed during treatment with this drug since liver damage may occur; drug should be discontinued immediately in cases of aggravated liver dysfunction or active liver disease

Pregnancy and Lactation

• Use carbamazepine during pregnancy only in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk.
• Carbamazepine enters breast milk; use is not recommended (the American Associates ofPediatricsstates carbamazepine is compatible with nursing; however, adverse reactions in breastfeeding infant are possible; take into account the importance of the drug to the mother before deciding to discontinue breastfeeding or the drug)