Tegretol: profile and news

Schuckit Addresses State-of-the-Art Addiction Treatments  May 14, 2006
Carbamaze-pine (Tegretol), valproic acid (Depakene) or gabapentin (Neurontin) are no better, they cost more and they are more dangerous than the benzodiazepines ... - Psychiatric Times,

Neuropathic Pain: An Update on Effective Management Strategies  May 5, 2006
These are carbamazepine (Tegretol [Novartis]) for trigeminal neuralgia, gabapentin (Neurontin [Parke-Davis]) and transdermal lidocaine (LidoDerm [Endo]) for ... - Medscape (subscription)

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 EQUETRO^TM 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 EQUETRO^TM 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 EQUETRO^TM, 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 EQUETRO^TM 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 EQUETRO^TM 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 EQUETRO^TM, and then begins a course of treatment with one of these CYP3A4 inducers, it is reasonable to expect that a dose increase for EQUETRO^TM 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 EQUETRO^TM 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 EQUETRO^TM, 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:

EQUETRO^TM 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 EQUETRO^TM, 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, EQUETRO^TM 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 EQUETRO^TM, it is reasonable to expect that a dose adjustment may be necessary.

Because of its primary CNS effect, caution should be used when EQUETRO^TM is taken with other centrally acting drugs and alcohol.