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medicine: tegretol
tegretol description
Go to trade names and prices
Carbamazepine (CBZ) is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, and post-traumatic stress disorder.
History
Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953. Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.
Carbamazepine was first marketed as a drug to treat trigeminal neuralgia (formerly known as tic douloureux) in 1962. It has been used as an anticonvulsant in the UK since 1965, and has been approved in the U.S. since 1974.
In 1971, Drs. Takezaki and Hanaoka first used carbamazepine to control mania in patients refractory to antipsychotics (Lithium was not available in Japan at that time). Dr. Okuma, working independently, did the same thing with success. As they were also epileptologists, they had some familiarity with the anti-aggression effects of this drug. carbamazepine would be studied for bipolar disorder throughout the 1970s.
Indications
In the United States, the FDA-approved indications for carbamazepine use are epilepsy (including partial seizures and tonic-clonic seizures), trigeminal neuralgia, and manic and mixed episodes of bipolar I disorder. Although data are still lacking, carbamazepine appears to be as effective and safe as lithium for the treatment of bipolar disorder, both in the acute and maintenance phase.
Trade names
Carbamazepine has been sold under the names Tegretol, Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Telesmin, Teril, Timonil, Trimonil, Epimaz, Carbama/Carbamaze (New Zealand), Amizepin (Poland), Hermolepsin (Sweden), and Degranol (South Africa).
Pharmacokinetics
Carbamazepine exhibits autoinduction: it induces the expression of the hepatic microsomal enzyme system CYP3A4, which metabolizes carbamazepine itself. Upon initiation of carbamazepine therapy, concentrations are predictable and follow their respective baseline clearance/half-life values that have been established for the specific patient. However, after enough carbamazepine has been presented to the liver tissue, the CYP3A4 activity increases, speeding up drug clearance and shortening the half-life. Autoinduction will continue with subsequent increases in dose but will usually reach a plateau within 5–7 days of a maintenance dose. Increases in dose at a rate of 200 mg every 1–2 weeks may be required to achieve a stable seizure threshold. Stable carbamazepine concentrations occur usually within 2–3 weeks after initiation of therapy.
Mechanism of action
The mechanism of action of carbamazepine and its derivatives is relatively well understood. Voltage-gated sodium channels are the molecular pores that allow brain cells (neurons) to generate action potentials, the electrical events that allow neurons to communicate over long distances. After the sodium channels open to start the action potential, they inactivate, essentially closing the channel. carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to subsequently open, making brain cells less excitable (less likely to fire). carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, gamma2 subunits.
Interactions
Carbamazepine has a very high potential for drug interactions; caution should be used in combining other medicines with it, including other antiepileptics and mood stabilizers. Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin (Dilantin), or primidone (Mysoline). Carbamazepine, as a CYP450 inducer, may increase clearance of many drugs, decreasing their blood levels. Drugs that are more rapidly metabolized with carbamazepine include warfarin (Coumadin), phenytoin (Dilantin), theophylline, and valproic acid (Depakote, depakote ER, Depakene, Depacon). Drugs that decrease the metabolism of carbamazepine or otherwise increase its levels include erythromycin, cimetidine (Tagamet), propoxyphene (Darvon), and calcium channel blockers. carbamazepine also increases the metabolism of the hormones in birth control pills and can reduce their effectiveness, potentially leading to unexpected pregnancies.
Valproic acid and valnoctamide both inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide into inactive metabolites. By inhibiting mEH, valproic acid and valnoctamide cause a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.
Adverse effects
Common adverse effects include drowsiness, headaches and migraines, motor coordination impairment and/or upset stomach. carbamazepine preparations typically greatly decrease a person's alcohol tolerance.
Less common side effects include cardiac arrhythmias, blurry or double vision and/or the temporary loss of blood cells or platelets and in rare cases can cause aplastic anemia. With normal use, small reductions in white cell count and serum sodium are common, however, in rare cases, the loss of platelets may become life-threatening. This occurs commonly enough that a doctor may recommend frequent blood tests during the first few months of use, followed by three to four tests per year for established patients. In the UK, testing is generally performed much less frequently for long-term carbamazepine patients—typically once per year. Additionally, carbamazepine may exacerbate preexisting cases of hypothyroidism, so yearly thyroid function tests are advisable for persons taking the drug.
There are also reports of an auditory side effect for carbamazepine use, whereby patients perceive sounds about a semitone lower than previously. Thus, middle C would be heard as the note B3 just below it, etc. The inverse effect (that is, notes sounding higher) has also been recorded. This unusual side effect is usually not noticed by most people, and quickly disappears after the person stops taking carbamazepine.
Oxcarbazepine, a derivative of carbamazepine, reportedly has fewer and less serious side effects.
Carbamazepine may cause Syndrome of inappropriate antidiuretic hormone (SIADH), since it both increases the release and potentiates the action of ADH (vasopressin).
Carbamazepine may aggravate juvenile myoclonic epilepsy, so it is important to uncover any history of jerking, especially in the morning, before starting the drug.
In addition, carbamazepine has been linked to serious adverse cognitive anomalies, including EEG slowing and cell apoptosis.
The FDA informed health care professionals that dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. In Europeans a large proportion of sensitivity is associated with HLA-B58.
See also
oxcarbazepine| Name | Information | Price* | Quantity |
| Generic Carbamazepine 200mg | 100 tablets | N/A | |
| Generic Carbamazepine Chew 100mg | 100 tablet | N/A | |
| Generic Carbamazepine Chew Tabs 200mg | 100 tablets | $14 | 100 tablets |
| Generic Carbamazepine CR 200mg | 56 tablet | $18 | 56 tablet |
| Generic Carbamazepine CR 400mg | 56 tablet | $32 | 56 tablet |
| Generic Carbamazepine Suspension 100mg/5ml | 450 ml | $56 | 450 ml |
| Tegretol 100mg | 84 tablet (carbamazepine) | $14 | 84 tablet |
| Tegretol 200mg | 100 tablets (carbamazepine) | $42 | 100 tablets |
| Tegretol 400mg | 56 tablet (carbamazepine) | $19 | 56 tablet |
| Tegretol Chew Tabs 100mg | 56 tablets (carbamazepine) | $13 | 56 tablets |
| Tegretol Chew Tabs 200mg | 56 tablets (carbamazepine) | $22 | 56 tablets |
| Tegretol Suppositories 125mg | 5 suppository (carbamazepine) | $25 | 5 suppository |
| Tegretol Suppositories 250mg | 5 suppository (carbamazepine) | $30 | 5 suppository |
| Tegretol Suspension 100mg/5ml | 300 ml (carbamazepine) | $29 | 300 ml |
| Tegretol-XR 200mg | 56 tablets (carbamazepine) | $27 | 56 tablets |
| Tegretol-XR 400mg | 56 tablets (carbamazepine) | $55 | 56 tablets |
*) Prices related to some of online drugstores. There are only approximate prices. For some of drugs is needed a prescription.
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