"The U.S. Food and Drug Administration today approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat seizures associated with epilepsy.
Epilepsy is a brain disorder caused by abnormal or excessive activity in the brain"...
If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive patient with epilepsy may lead to seizures or even status epilepticus with its life-threatening hazards.
The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimize the possibility of such reactions, therapy should be initiated at the lowest dosage recommended.
The following additional adverse reactions were previously reported with carbamazepine:
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) (see BOXED WARNING), pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, and diaphoresis. In certain cases, discontinuation of therapy may be necessary. Isolated cases of hirsutism have been reported, but a causal relationship is not clear.
Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism, and adenopathy or lymphadenopathy. Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been associated with other tricyclic compounds.
Urinaryfrequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence. Albuminuria, glycosuria, elevated BUN, and microscopic deposits in the urine have also been reported.
Testicular atrophy occurred in rats receiving carbamazepine orally from 4-52 weeks at dosage levels of 50-400 mg/kg/day. Additionally, rats receiving carbamazepine in the diet for 2 years at dosage levels of 25, 75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and aspermatogenesis. In dogs, it produced a brownish discoloration, presumably a metabolite, in the urinary bladder at dosage levels of 50 mg/kg/day and higher. Relevance of these findings to humans is unknown.
Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, and hyperacusis.
There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established.
Isolated cases of neuroleptic malignant syndrome have been reported with concomitant use of psychotropic drugs.
Scattered punctate cortical lens opacities, as well as conjunctivitis, have been reported. Although a direct causal relationship has not been established, many phenothiazines and related drugs have been shown to cause eye changes.
Aching joints and muscles, and leg cramps.
Fever and chills, inappropriate antidiuretic hormone (ADH) secretion syndrome has been reported. Cases of frank water intoxication, with decreased serum sodium (hyponatremia) and confusion have been reported in association with carbamazepine use (see PRECAUTIONS, Laboratory Tests). Decreased levels of plasma calcium have been reported.
Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants.
A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine.
Drug Abuse And Dependence
No evidence of abuse potential has been associated with carbamazepine, nor is there evidence of psychological or physical dependence in humans.
Read the Carbatrol (carbamazepine extended-release) Side Effects Center for a complete guide to possible side effects
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 Carbatrol® (carbamazepine extended-release) to a patient taking another drug that is highly protein bound should not cause increased free concentrations of the other drug.
Agents that Inhibits 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 Carbatrol® (carbamazepine extended-release) 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.
(1)also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide
Thus, if a patient has been titrated to a stable dosage of Carbatrol® (carbamazepine extended-release) , 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 Carbatrol® (carbamazepine extended-release) 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 Carbatrol® (carbamazepine extended-release) are the following:
Cisplatin, doxorubicin HCL, felbamate, rifampin, phenobarbital, phenytoin(2), primidone, methsuximide, and theophylline
(2) Phenytoin plasma levels have also been reported to increase and decrease in the presence of carbamazepine, see below.
Thus, if a patient has been titrated to a stable dosage on Carbatrol® (carbamazepine extended-release) , and then begins a course of treatment with one of these CYP3A4 inducers, it is reasonable to expect that a dose increase for Carbatrol® (carbamazepine extended-release) 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 Carbatrol® (carbamazepine extended-release) 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, trazodone(5), valproate, warfarin(6), nefazodone, ziprasidone, and zonisamide.
(3)Break through bleeding has been reported among patients receiving concomitant oral contraceptives and their reliability may be adversely affected.
(4)Phenytoin has also been reported to increase in the presence of carbamazepine. Careful monitoring of phenytoin plasma levels following co-medication with carbamazepine is advised.
(5)Following co-administration of carbamazepine 400mg/day with trazodone 100mg to 300mg daily, carbamazepine reduced trough plasma concentrations of trazodone (as well as metachlorophenylpiperazine [mCPP]) by 76 and 60% respectively, compared to precarbamazepine values.
(6)Warfarin's anticoagulant effect can be reduced in the presence of carbamazepine.
Coadministration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Coadministration of carbamazepine with nefazodone is contraindicated (see CONTRAINDICATIONS).
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 Carbatrol® (carbamazepine extended-release) , 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
Carbatrol® (carbamazepine extended-release) increases the plasma levels of the following agents:
Clomipramine HCl, phenytoin(7), and primidone
(7)Phenytoin has also been reported to decrease in the presence of carbamazepine. Careful monitoring of phenytoin plasma levels following co-medication with carbamazepine is advised.
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 Carbatrol® (carbamazepine extended-release) , it is reasonable to expect that a dose decrease for the concomitant agent may be necessary.
Pharmacological/Pharmacodynamic Interactions with Carbamazepine
Given the anticonvulsant properties of carbamazepine, Carbatrol® (carbamazepine extended-release) 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 Carbatrol® (carbamazepine extended-release) , it is reasonable to expect that a dose adjustment may be necessary.
Because of its primary CNS effect, caution should be used when Carbatrol (carbamazepine extended-release) ® is taken with other centrally acting drugs and alcohol.
Read the Carbatrol Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/18/2011
This monograph has been modified to include the generic and brand name in many instances.
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