Topiramate (brand name Topamax ) is an anticonvulsant drug (antiepileptic). By the end of 2012, topiramate is approved by the United States Food and Drug Administration (FDA) in combination with phentermine to lose weight. The drug had previously been used off-label for this purpose. Topiramate was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of Johnson & amp; Johnson Corporation. The drug was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research at McNeil Pharmaceuticals.
The commercial use of Topiramate began in 1996. Mylan Pharmaceuticals got final approval from the FDA for generic topiramate sales in the United States and its generic version was available in September 2006. The latest patent for topiramate in the US is for use. in children and ended on February 28, 2009.
Video Topiramate
Medical use
Topiramate is used to treat epilepsy in children and adults, and was initially used as an anticonvulsant. In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delays. It is also the Food and Drug Administration (FDA) approved for, and most often prescribed for, migraine prevention. It is also used to treat migraines because of their effect on blood vessels in the brain. It has been found to be increasingly effective for migraine sufferers with limited side effects.
Researching and deleting labels
Psychiatrists have used topiramate to treat bipolar disorder, although the available evidence does not support its use in every phase of bipolar disorder treatment. A more recent review, published in 2010, suggests the benefits of topiramate in the treatment of borderline personality disorder symptoms, but the authors note that this is based only on a randomized controlled trial and requires replication. Also the authors note that long-term effects have not been studied.
Topiramate has been used as a treatment for alcoholism. The 2015 VA/DoD guideline on substance use disorders lists topiramate as "strong for" in its recommendations for alcohol use disorders.
Other uses include obesity treatment and weight gain caused by antipsychotics.
The drug is also used in clinical trials to treat post traumatic stress disorder. A pilot study suggests that topiramate is effective against infantile seizures. Another study recommends topiramate as an effective treatment in the prevention of periventricular leukomalacia in premature infants after hypoxic-ischemic injury.
Recent clinical reports suggest that it may have mood stabilizer properties. Use of off-label and other topiramate investigations include treatment of essential tremor, bulimia nervosa, obsessive-compulsive disorder, idiopathic intracranial hypertension, and cluster headache. Topiramate has not been shown to work as a painkiller in diabetic neuropathy, the only neuropathic condition in which it has been adequately tested. Dispensing errors have been reported between the Topamax (topiramate) tablet and the extended-release tablet Toprol-XL (metoprolol succinate) so require extra care to ensure the correct drug has been taken. [2]
Maps Topiramate
Warnings and contraindications
People taking topiramate should be aware of the following risks:
- Avoid activities that require alertness and mental coordination until the effects of the drug are realized.
- Topiramate can damage heat settings, especially in children. Use caution with activities that lead to an increase in core temperature, such as strenuous exercise, extreme heat exposure, or dehydration.
- Topiramate may cause visual field defects.
- Topiramate may decrease the effectiveness of oral contraceptives containing estrogen.
- Taking topiramate in the first trimester of pregnancy may increase the risk of cleft lip/palate in infants.
- As for all antiepileptic drugs, it is advisable not to suddenly stop topiramate because there is a theoretical risk of a rebounding spasm.
Adverse effects
Adverse effects are based on incidence:
Very common side effects (& gt; 10% incidents) include:
Common side effects (1-10% incident) include:
Rarely, inhibition of carbonate anhydrase may be strong enough to cause clinically important metabolic acidosis.
The US Food and Drug Administration (FDA) has told prescribers that topiramate can cause acute myopia and glaucoma of secondary angle closure in a small percentage of people who regularly use topiramate. Symptoms, which usually begin in the first month of use, include blurred vision and eye pain. Termination of topiramate may stop the progression of ocular damage and may reverse the visual impairment.
Preliminary data suggest that, as with some other anti-epileptic drugs, topiramate carries an increased risk of congenital malformation. This may be very important for women who use topiramate to prevent migraine attacks. In March 2011, the FDA informed healthcare professionals and patients about the increased risk of developing cleft lip and/or cleft palate in infants born to women who were treated with Topamax (topiramate) during pregnancy and placed them in a Category Pregnancy D.
Topiramate has been associated with a statistically significant increase in suicidal cases, and "suicidal thoughts or actions" are now listed as one side effect of the drug "in very small quantities, about 1 in 500."
Overdose
Acute and acute symptoms of chronic exposure to topiramate range from asymptomatic to epileptic status, including in patients without a history of seizures. In children, an overdose can also cause hallucinations. Topiramate has been considered a major substance that causes a fatal overdose in cases complicated by polydrug exposure. The most common signs of overdose are enlarged pupils, somnolent, dizziness, psychomotor agitation, and abnormal and uncoordinated body movements.
Overdose symptoms may include but are not limited to:
Special antidote not available. Treatment is fully supportive.
Interactions
Topiramate has many drug-drug interactions. Some of the most common are listed below:
- Because topiramate inhibits carbonic anhydrase, used with other anhydrase carbonate inhibitors (eg acetazolamide) increases the risk of kidney stones.
- The enzyme induser (eg carbamazepine) may increase topiramate elimination, possibly requiring a topiramate dose escalation.
- Topiramate may increase phenytoin plasma levels.
- Topiramate itself is a weak inhibitor of CYP2C19 and induces CYP3A4; decreased levels of estrogen and digoxin plasma have been noted during topiramate therapy. This can reduce the effectiveness of oral contraceptives (birth control pills); the use of alternative birth control methods is recommended. Both intrauterine devices (IUDs) and Depo-Provera are affected by topiramate. Alcohol can cause increased sedation or drowsiness, and increase the risk of seizures.
- As noted in the 06/29/2005 label posted on the Drug @ FDA 14, "conditions or therapies affecting acidosis may be in addition to the effects of reducing bicarbonate from Topiramate.
- Oligohidrosis and hyperthermia are reported in post-marketing reports on topiramate; antimuscarinic drugs (such as trospium) can exacerbate this disorder.
Pharmacology
Chemically, topiramate is a sulfamic-modified diacetonide fructose - a rather unusual chemical structure for pharmaceuticals.
Topiramate is quickly absorbed after oral use. Most drugs (70%) excreted in urine remain unchanged. The remainder are extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitute more than 5% of the given dose.
Several cellular targets have been proposed to be relevant to therapeutic topiramate activity. These include (1) a voltage-gated sodium channel; (2) high voltage active calcium channels; (3) GABA-A receptor; (4) AMPA/fabricate receptors; and (5) isoenzyme carbonate anhydrase. There is evidence that topiramate can alter its target activity by modifying their phosphorylation state rather than by direct action. Effects on the sodium channel can be of particular relevance to seizure protection. Although topiramate does not inhibit the active high-voltage calcium channel, its relevance to clinical activity is uncertain. Effects on specific GABA-A isoform receptors may also contribute to drug antiseizure activity. Topiramate selectively inhibits cytosolic (type II) and related membranes (type IV) form of carbonate anhydrase. Actions on isoenzyme carbonate anhydrase may contribute to the side effects of the drug, including its tendency to cause metabolic acidosis and calcium phosphate kidney stones.
Topiramate inhibits maxillary shock and pentylenetetrazol-induced seizures as well as general and general secondary tonic-clonal seizures in firewood models, findings that predict the wide spectrum of clinical activities. Its action on the pores of mitochondrial permeability transition has been proposed as a mechanism.
While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of very few anticonvulsants [see: levetiracetam, carbamazepine, lamotrigine] which does not induce apoptosis in young animals at the dose required to produce anticonvulsant effects..
Detection in body fluids
Blood, serum, or plasma topiramate concentrations can be measured using immunoassay or chromatographic methods to monitor therapy, confirm the diagnosis of poisoning in hospitalized patients, or to assist in investigation of medicolegal death. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10-150 mg/L in overdose victims.
References
External links
- Topamax (topiramate): Treatment for Migraine Prevention
- Topamax: Treatment for Epilepsy
- Currently listed clinical trials related to topiramate
- FDA topiramate security
- MSN articles
- MedlinePlus: Topiramate
- FAQ: Topiramate (Topamax), Mood Disorder, and PTSD
- RxList.com: Topiramate
- Focus on Topiramate - a new anti-epilepsy, Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1
- Topiramate is bound to proteins in GDP
Source of the article : Wikipedia
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