Brands, Medical Use, Clinical Data
Drug Category
- Analgesics
- Antimanic Agents
- Anticonvulsants
Dosage Forms
- Suspension
- Tablet
- Tablet (extended-release)
Brands / Synonyms
Apo-Carbamazepine; Atretol; Biston; Calepsin; Carbamazepen; Carbamazepine; Carbamezepine; Carbatrol; Carbazepine; Carbelan; Epitol; Equetro; Finlepsin; Karbamazepin; Lexin; Neurotol; Novo-Carbamaz; Nu-Carbamazepine; Sirtal; Stazepin; Stazepine; Taro-Carbamazepine; Taro-Carbamazepine Cr; Tegretal; Tegretol; Tegretol Chewtabs; Tegretol Cr; Tegretol-XR; Telesmin; Teril; Timonil
Indications
For the treatment of epilepsy and pain associated with true trigeminal neuralgia.
Pharmacology
Carbamazepine, an anticonvulsant structurally similar to tricyclic antidepressants, is used to treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal neuralgia, and psychiatric disorders including manic-depressive illness and aggression due to dementia.
Mechanism of Action
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 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.
Absorption
Not Available
Toxicity
Mild ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations. Severe intoxications may produce coma, seizures, respiratory depression, and hypotension
Biotrnasformation / Drug Metabolism
Hepatic
Contraindications
Carbamazepine should not be used in patients with a history of previous bone marrow depression, hypersensitivity
to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine,
protriptyline and nortriptyline. Likewise, on theoretical grounds its use with monoamine oxidase inhibitors is not
recommended. Before administration of carbamazepine, MAO inhibitors should be discontinued for a minimum of 14 days,
or longer if the clinical situation permits.
Drug Interactions
Clinically meaningful drug interactions have occurred with concomitant medications and include, but are not
limited to the following:
Agents Highly Bound to Plasma Protein
Carbamazepine is not highly bound to plasma proteins; therefore, administration of EQUETROTM to a
patient taking another drug that is highly protein bound should not cause increased free concentrations of the other
drug.
Agents that Inhibit Cytochrome P450 Isoenzymes and/or Epoxide Hydrolase
Carbamazepine is metabolized mainly by cytochrome P450 (CYP) 3A4 to the active carbamazepine 10,11-epoxide, which
is further metabolized to the trans-diol by epoxide hydrolase. Therefore, the potential exists for interaction
between carbamazepine and any agent that inhibits CYP3A4 and/or epoxide hydrolase. Agents that are CYP3A4 inhibitors
that have been found, or are expected, to increase plasma levels of EQUETROTM are the following:
Acetazolamide, azole antifungals, cimetidine, clarithromycin(1), dalfopristin, danazol,
delavirdine, diltiazem, erythromycin(1), fluoxetine, fluvoxamine, grapefruit juice, isoniazid,
itraconazole, ketoconazole, loratadine, nefazodone, niacinamide, nicotinamide, protease inhibitors, propoxyphene,
quinine, quinupristin, troleandomycin, valproate(1), verapamil, zileuton.
Thus, if a patient has been titrated to a stable dosage of EQUETROTM, and then begins a course of
treatment with one of these CYP3A4 or epoxide hydrolase inhibitors, it is reasonable to expect that a dose reduction
for EQUETROTM may be necessary.
Agents that Induce Cytochrome P450 Isoenzymes
Carbamazepine is metabolized by CYP3A4. Therefore, the potential exists for interaction between carbamazepine and
any agent that induces CYP3A4. Agents that are CYP inducers that have been found, or are expected, to decrease plasma
levels of EQUETROTM are the following:
Cisplatin, doxorubicin HCL, felbamate, rifampin, phenobarbital, Phenytoin(2), primidone,
methsuximide, and theophylline
Thus, if a patient has been titrated to a stable dosage on EQUETROTM, and then begins a course of
treatment with one of these CYP3A4 inducers, it is reasonable to expect that a dose increase for EQUETROTM
may be necessary.
Agents with Decreased Levels in the Presence of Carbamazepine due to Induction of Cytochrome P450
Enzymes
Carbamazepine is known to induce CYP1A2 and CYP3A4. Therefore, the potential exists for interaction between
carbamazepine and any agent metabolized by one (or more) of these enzymes. Agents that have been found, or are
expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are
the following:
Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam,
clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate,
felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam,
mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4),
praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam,
valproate, warfarin(5) , ziprasidone, and zonisamide.
Thus, if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a
course of treatment with EQUETROTM, it is reasonable to expect that a dose increase for the concomitant
agent may be necessary.
Agents with Increased Levels in the Presence of Carbamazepine:
EQUETROTM increases the plasma levels of the following agents:
Clomipramine HCl, Phenytoin(6), and primidone
Thus, if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a
course of the treatment with EQUETROTM, it is reasonable to expect that a dose decrease for the
concomitant agent may be necessary.
Pharmacological/Pharmacodynamic Interactions with Carbamazepine
Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side effects.
Given the anticonvulsant properties of carbamazepine, EQUETROTM may reduce the thyroid function as has
been reported with other anticonvulsants. Additionally, anti-malarial drugs, such as chloroquine and mefloquine, may
antagonize the activity of carbamazepine.
Thus if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a
course of treatment with EQUETROTM, it is reasonable to expect that a dose adjustment may be
necessary.
Because of its primary CNS effect, caution should be used when EQUETROTM is taken with other centrally
acting drugs and alcohol.
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