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Carbamazepine; Uses, Dosage, Side Effects, Drug Interactions

Carbamazepine is a tricyclic compound chemically related to tricyclic antidepressants (TCA) with anticonvulsant and analgesic properties. Carbamazepine exerts its anticonvulsant activity by reducing polysynaptic responses and blocking post-tetanic potentiation. Its analgesic activity is not understood; however, carbamazepine is commonly used to treat pain associated with trigeminal neuralgia.

An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is a little chemical resemblance between the two compounds, their three-dimensional structure is similar. It is not effective for absence seizures or myoclonic seizures. It is used in schizophrenia along with other medications and as a second line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate.

Mechanism of action of Carbamazepine

Carbamazepine inhibits sustained repetitive firing by blocking use-dependent sodium channels. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus and seizure control with a reduction of post-tetanic potentiation of synaptic transmission in the spinal cord. Carbamazepine also possesses anticholinergic, central antidiuretic, antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties.

Indications Carbamazepine

Trigeminal neuralgia.
Acute mania
Grand mal generalized tonic-clonic seizure
Mixed manic depressive episode
Restless legs syndrome
Partial onset seizure Epilepsy
Bipolar disorder
Borderline personality disorder
Epilepsy
Schizoaffective disorder
Cyclothymic disorder
Diabetic peripheral neuropathy
Dystonia
Occipital neuralgia
Peripheral neuropathy
Reflex sympathetic dystrophy syndrome
Vulvodynia

Therapeutic Indications of Carbamazepine

Analgesics, Non-Narcotic; Anticonvulsants
Carbamazepine has been shown to be effective in certain psychiatric disorders including schizoaffective illness, resistant schizophrenia, and dyscontrol syndrome, associated with limbic system dysfunction.
Carbamazepine is used for the detoxification of alcoholics. It has been found to be effective in rapidly relieving anxiety and distress of acute alcohol withdrawal and for such symptoms as seizures, hyperexcitability, and sleep disturbances.
Carbamazepine is used alone or with other agents such as clofibrate or chlorpropamide in the treatment of partial central diabetes insipidus
Carbamazepine is used alone or in combination with lithium and/or antidepressants or antipsychotics to treat patients with manic-depressive illness who are unresponsive to or cannot tolerate, lithium or neuroleptics alone.
Carbamazepine may also be used in some patients to relieve the lightning pains of tabes dorsalis; neuralgic pain associated with multiple sclerosis, acute idiopathic neuritis (Guillain-Barre syndrome), peripheral diabetic neuropathy, phantom limb, restless leg syndrome (Ekbom’s syndrome), and hemifacial spasm; post-traumatic neuropathy or neuralgia; and postherpetic neuralgia.
Carbamazepine is indicated for the relief of pain due to true trigeminal neuralgia (tic douloureux) and glossopharyngeal neuralgia.
Carbamazepine is indicated for the treatment of partial seizures with simple or complex symptomatology (psychomotor, temporal lobe); generalized tonic-clonic seizures (grand mal); mixed seizure patterns that include the above; or other partial or generalized seizures. Carbamazepine is a first-choice anticonvulsant because of its relatively low behavioral and psychological toxicity and the rarity of serious adverse effects.
Benign infantile convulsions are characterized by (1) onset at up to 2 years of age, (2) normal development, (3) mostly brief, often clustered convulsions, and (4) normal electroencephalography during the interictal stage. BIC follow a favorable course and disappear before 2-3 years of age, although convulsions for which diazepam is ineffective frequently develop.

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Contra-Indications of Carbamazepine

Syndrome of inappropriate antidiuretic hormone secretion
High cholesterol
Low amount of sodium in the blood
Hepatic porphyria
Decreased function of bone marrow
Low blood counts due to bone marrow failure
Decreased blood platelets
Deficiency of Granulocytes a type of white blood cell
Mood changes
Having thoughts of suicide
Depression
Myasthenia gravis
Increased pressure in the eye
Increased pressure in eyes
high blood pressure
Coronary artery disease
Complete heart block
abnormal heart rhythm
Chronic heart failure
Liver problems
Kidney disease with a reduction in kidney function
Cannot empty bladder
Pregnancy
Poisoning by seizure medication carbamazepine

Dosages of Carbamazepine

Strengths: 100 mg; 200 mg; 400 mg; 300 mg;100 mg/5 mL;

The amount of medicine that you take depends on the strength of the medicine.

Bipolar disorder

Adults—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1600 mg per day.
Children—Use and dose must be determined by your doctor.

Epilepsy

Adults and children 12 years of age and older—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 500 to 800 mg two times a day.
Children younger than 12 years of age—Dose is based on body weight and must be determined by your doctor. However, the dose is usually not more than 1000 mg per day.

Trigeminal neuralgia

Adults—At first, 200 milligrams (mg) once a day. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 1200 mg per day.
Children—Use and dose must be determined by your doctor.
For oral dosage form (extended-release tablets)

For Epilepsy

Adults—At first, 200 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
Children younger than 6 years of age—Use and dose must be determined by your doctor.

For trigeminal neuralgia

Adults—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
Children—Use and dose must be determined by your doctor
For oral dosage form (suspension):

For epilepsy

Adults—100 milligrams (mg) or 1 teaspoon four times a day (400 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
Children 6 to 12 years of age—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken four times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.

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For trigeminal neuralgia

Adults—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
Children—Use and dose must be determined by your doctor.

For oral dosage forms (tablets or chewable tablets)

For epilepsy

Adults—At first, 200 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken two or three times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.

For trigeminal neuralgia

Adults and teenagers—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
Children—Use and dose must be determined by your doctor.

Side Effects of Carbamazepine

The most common

Common

Nausea and vomiting
Severe stomach ache
Severe diarrhea
Mouth sores
Vaginal thrush
Skin rash
A headache
Ringing or buzzing in the ears
Decreased appetite

Rare

Body aches or pain
a cough
difficulty having a bowel movement (stool)
dry mouth
ear congestion
frequent urination
a headache
lack or loss of strength
loss of appetite
loss of voice
muscle aches
nausea
sleepiness or unusual drowsiness
a sore throat
stuffy or a runny nose
sweating increased
trouble sleeping
weight loss
lack of appetite
loss of balance control
loss of interest or pleasure
muscle trembling, jerking, or stiffness

Drug Interactions of Carbamazepine

Carbamazepine may interact with following drugs, supplements & may decrease the efficacy of drugs

alpha/beta agonists (e.g., epinephrine, norepinephrine)
alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
alpha agonists (e.g., clonidine, methyldopa)
angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
angiotensin receptor blockers (ARBs; e.g., candasartan, irbesartan, losartan)
anti-psychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzepine, quetiapine,risperidone)
aripiprazole
beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
bupropion
calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
carbamazepine
celecoxib
clobazam
clopidogrel
diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
glucosamine
heparin
lorazepam
mirabegron
mirtazapine
monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, )
multivitamins with minerals
nitrates (e.g., nitroglycerin, isosorbide )
nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen, ketoprofen)
phenobarbital
quinolone antibiotics (e.g., ciprofloxacin, enoxacin, norfloxacin)
selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
serotonin/norepinephrine reuptake inhibitors (SNRIs; e.g., desvenlafaxine, duloxetine,venlafaxine)
tapentadol
tramadol
tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline, desipramine)
triptans (e.g., sumatriptan, rizatriptan)
tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib)
warfarin
valproate,
warfarin, z
zonisamide.

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Pregnancy & Lactation of Carbamazepine

FDA Pregnancy Category D

Pregnancy

Offspring of epileptic mothers with untreated epilepsy are known to be more prone to developmental disorders, including malformations. Developmental disorders and malformations, including spina bifida, and also other congenital anomalies e.g. craniofacial defects such as clept lip/palate, cardiovascular malformations, hypospadias and anomalies involving various body systems, have been reported in association with the use of Tegretol. Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening

Lactation

Carbamazepine passes into the breast milk (about 25-60% of the plasma concentrations). The benefits of breast-feeding should be weighed against the remote possibility of adverse effects occurring in the infant. Mothers taking Tegretol may breast-feed their infants, provided the infant is observed for possible adverse reactions (e.g. excessive somnolence, allergic skin reaction). There have been some reports of cholestatic hepatitis in neonates exposed to carbamazepine during antenatal and or during breast feeding. Therefore breast-fed infants of mothers treated with carbamazepine should be carefully observed for adverse hepatobiliary effects.