Indicated for:

Acute Manic or Mixed Episodes associated with Bipolar I Disorder:

• The treatment of patients with acute manic or mixed episodes associated with bipolar I disorder.

Doses higher than 1600 mg per day have not been studied in mania associated with bipolar disorder.

Pain of Trigeminal Neuralgia:

• The treatment of the pain associated with trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.

Epilepsy:

• The treatment of partial seizures with complex symptomatology (e.g., 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. EQUETRO may be used alone or with other AEDs. When added to existing AEDs, add EQUETRO gradually while the dosage(s) of other AEDs are maintained or gradually decreased. Potential drug interactions should be considered when using carbamazepine with other AEDs.

EQUETRO is not indicated for the treatment of absence seizures (petit mal). Carbamazepine has been associated with increased frequency of generalized convulsions in these patients.

The safety and effectiveness of EQUETRO have not been established in pediatric patients for indications other than Epilepsy.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, have occurred with carbamazepine. Some of these events have been fatal or life-threatening.

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have occurred in patients treated with carbamazepine. The risk in patients of Asian descent is estimated to be about 10 times higher.

There is a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. Test for HLA-B*1502, prior to initiating EQUETRO in patients with an increased likelihood of carrying this allele. Avoid use of EQUETRO in patients testing positive for the allele unless the benefit clearly outweighs the risk.

Antiepileptic drugs (AEDs), including EQUETRO, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. 

Aplastic anemia and agranulocytosis occurred with EQUETRO. Obtain complete pretreatment hematological testing. Consider discontinuing EQUETRO if significant bone marrow depression develops.

Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with EQUETRO because liver damage may occur.

Hyponatremia can occur as a result of treatment with EQUETRO. In many cases, the hyponatremia appears to be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The risk of developing SIADH with EQUETRO treatment appears to be dose-related. Elderly patients and patients treated with diuretics are at greater risk of developing hyponatremia.

Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure have been reported.

AV heart block, including second and third degree block, have been reported following carbamazepine treatment.

EQUETRO has the potential to cause impairment in judgment, cognition, and motor function.

EQUETRO is contraindicated in patients with:

• Bone marrow depression
• Known hypersensitivity to any of the tricyclic compounds (e.g., amitriptyline, desipramine, imipramine, protriptyline, and nortriptyline. Hypersensitivity reactions include anaphylaxis and serious rash
• Concomitant use of delavirdine or other non-nucleoside reverse transcriptase inhibitors that are substrates for CYP3A4. EQUETRO can substantially reduce the concentrations of these drugs through induction of CYP3A4. This can lead to loss of virologic response and possible resistance to these medications
• Concomitant use of monoamine oxidase inhibitors (MAOIs). Before beginning treatment with EQUETRO, MAOIs should be discontinued for a minimum of 14 days. Concomitant use can cause serotonin syndrome

Do not discontinue EQUETRO abruptly, because of the risk of seizure and other withdrawal  signs/symptoms. Patients with seizure disorder are at increased risk of developing seizure and status epilepticus with attendant hypoxia and threat to life. 

The use of EQUETRO should be avoided in patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).

Concomitant use of nefazodone. This may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect.

Co-administration of EQUETRO with non-nucleoside reverse transcriptase inhibitors, including delavirdine, is contraindicated because it may lead to loss of virologic response and possible resistance.

Inhibitors of CYP3A4 and/or epoxide hydrolase can increase plasma levels of EQUETRO and its active metabolites, increasing plasma concentrations of EQUETRO and the risk of adverse reactions. It may be necessary to reduce the EQUETRO dose if used concomitantly with inhibitors of CYP3A4 and/or epoxide hydrolase. The following drugs are CYP3A4 inhibitors: acetazolamide, aprepitant, azole antifungals (e.g., ketoconazole, itraconazole, fluconazole, voriconazole, cimetidine, ciprofloxacin, clarithromycin, dalfopristin, danazol, dantrolene, delavirdine, diltiazem, erythromycin, fluoxetine, fluvoxamine, grapefruit juice, ibuprofen, isoniazid, loratadine, nefazodone, niacinamide, nicotinamide, olanzapine, omeprazole, oxybutynin, quinine, quinupristin, ticlopidine, troleandomycin, valproate, verapamil, zileuton.

CYP3A4 inducers can decrease serum concentrations of EQUETRO and decrease its effectiveness. It may be necessary to increase the dose of EQUETRO if used concomitantly with a CYP3A4 inducer. Such drugs include the following: Aminophylline, cisplatin, doxorubicin, felbamate, phosphenytoin, methsuximide, phenobarbital, phenytoin, primidone, rifampin and theophylline.

EQUETRO can increase the metabolism of certain oral contraceptives (through CYP3A4 induction), leading to significantly lower concentrations. This can cause contraceptive failure or breakthrough bleeding. Consider alternatives to oral contraceptives that are significantly affected by induction of CYP3A4; or consider alternatives to EQUETRO.

EQUETRO induces CYP1A2 and CYP3A4, leading to decreased concentrations of drugs metabolized by CYP3A4 or CYP1A2. It may be necessary to increase the doses of such drugs when used concomitantly with EQUETRO. Drugs metabolized by CYP3A4 or CYP1A2 include the following: acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, ethosuximide, everolimus, felbamate, glucocorticoids, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, methsuxamide, mianserin, midazolam, mirtazapine, nefazodone, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phenytoin, praziquantel, quetiapine, risperidone, sertraline, sirolimus, tadalafil, theophylline, topiramate, tiagabine, tramadol, triazolam, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), trazodone, valproate, warfarin, ziprasidone, and zonisamide.

When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled.

The use of carbamazepine with lapatinib should generally be avoided.

Use of EQUETRO with HIV protease inhibitors is not recommended.

EQUETRO can increase the concentrations of clomipramine, phenytoin, and primidone.

There is a potential for increased cyclophosphamide toxicity when co-administered with carbamazepine.

Concomitant administration of EQUETRO and lithium can increase the risk of neurotoxic adverse reactions.

Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.

The antimalarial drugs chloroquine and mefloquine can antagonize the activity of EQUETRO.

The concomitant use of EQUETRO and other CNS depressants can increase the risk of respiratory depression, profound sedation, hypotension, and syncope.

EQUETRO can cause fetal harm when administered to a pregnant woman. Apprise women of childbearing potential of this risk.

Carbamazepine and its epoxide metabolite are excreted in human milk.

GoToSource

• Use longer than 3 weeks or for prophylactic use in mania. GoToSource 

• Use in patients under the age of 18 for acute manic or mixed episodes associated with bipolar I disorder and trigeminal neuralgia pain. GoToSource

• Doses greater than 1600 mg per day for mania associated with bipolar disorder. GoToSource 

• Agitation and aggression in dementia. GoToSource

• Alcohol withdrawal syndrome. GoToSource

• Intractable hiccups. GoToSource

• Phantom-limb syndrome. GoToSource

• Post-traumatic stress disorder. GoToSource

• Intermittent explosive disorder. GoToSource 

• Borderline personality disorder. GoToSource 

• Behavioral problems with intellectual disability. GoToSource

Suicidal behavior and ideation. GoToSource

Liver injury. GoToSource

Severe and fatal skin reactions (stevens-johnson syndrome and toxic epidermal necrolysis). GoToSource

Leukopenia (decreased white blood cells), agranulocytosis (decreased granulocytes a type of white blood cell) and aplastic anemia (bone marrow does not make enough blood cells). GoToSource

Embryo-fetal toxicity. GoToSource

Hyponatremia (low sodium level). GoToSource

Sinus tachycardia, sinus and nodal bradycardia, atrioventricular block, premature ventricular contractions and ventricular tachycardia. GoToSource

Increased intraocular pressure. GoToSource

Ocular lens opacities. GoToSource

Paradoxical reaction of worsening of seizures. GoToSource

Pancreatitis and systemic lupus erythematosus-like syndrome. GoToSource

Ataxia (lack of muscle coordination) and cognitive impairment. GoToSource

Lawsuits filed for stevens-johnson syndrome and suicidal ideations and behaviors.