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Topiramate (brand name Topamax ) is a broad-spectrum anticonvulsant (antiepilepsy) drug. In late 2012, topiramate was approved by the United States Food and Drug Administration (FDA) in combination with phentermine for weight loss. 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 the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals.
The commercial usage of Topiramate began in 1996.
1 Medical uses
2 Warnings and contraindications
3 Adverse effects
6.1 Detection in body fluids
8 External links
Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant.
A 2018 review found topiramate of no use in chronic low back pain.
The available evidence does not support its use in any phase of bipolar disorder treatment.
Topiramate has been used as a treatment for alcoholism.
Other uses include treatment of obesity
Warnings and contraindications
People taking topiramate should be aware of the following risks:
Avoid activities requiring mental alertness and coordination until drug effects are realized.
Topiramate may impair heat regulation, especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration.
Topiramate may cause visual field defects.
Topiramate may decrease effectiveness of oestrogen-containing oral contraceptives.
Taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in infant.
As is the case for all antiepileptic drugs, it is advisable not to suddenly discontinue topiramate as there is a theoretical risk of rebound seizures.
Adverse effects by incidence:
Very common (>10% incidence) adverse effects include:
Paraesthesia – e.g., pins and needles
Common (1-10% incidence) adverse effects include:
Disturbance in attention
Psychomotor skills impaired
Hypoaesthesia (reduced sense of touch)
Diplopia (double vision)
Abdominal pain upper
Alopecia (hair loss)
Musculoskeletal chest pain
Bradyphrenia (slowness of thought)
Expressive language disorder
Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.
The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage and may reverse the visual impairment.
Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.
Topiramate has been associated with a statistically significant increase in suicidality,
Symptoms of acute and acute on chronic exposure to topiramate range from asymptomatic to status epilepticus, including in patients with no seizure history.
Symptoms of overdose may include but are not limited to:
Blurred vision, double vision
Loss of coordination
Inability to respond to things around you
Loss of consciousness
Confusion and coma
Upset stomach and stomach pain
Loss of appetite and vomiting
Shortness of breath; fast, shallow breathing
Pounding or irregular heartbeat
A specific antidote is not available. Treatment is entirely supportive.
Topiramate has many drug-drug interactions. Some of the most common are listed below:
As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide ) increases the risk of kidney stones.
Enzyme inducers (e.g. carbamazepine ) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.
Topiramate may increase the plasma-levels of phenytoin.
Topiramate itself is a weak inhibitor of CYP2C19 and induces CYP3A4 ; a decrease in plasma levels of estrogens and digoxin has been noted during topiramate therapy. This can reduce the effectiveness of oral contraceptives (birth control pills); use of alternative birth control methods is recommended.
Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
As listed in the 06/29/2005 label posted at the Drugs@FDA website page 14,’conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of Topiramate’.
Oligohidrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.
Chemically, topiramate is a sulfamate modified fructose di acetonide – a rather unusual chemical structure for a pharmaceutical.
Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.
Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate. The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, the relevance to clinical activity is uncertain. Effects on specific GABA-A receptor isoforms could also contribute to the antiseizure activity of the drug. Topiramate selectively inhibits cytosolic (type II) and membrane associated (type IV) forms of carbonic anhydrase. The action on carbonic anhydrase isoenzymes may contribute to the drug’s side-effects, including its propensity to cause metabolic acidosis and calcium phosphate kidney stones.
Topiramate inhibits maximal electroshock and pentylenetetrazol -induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores 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 the very few anticonvulsants
Detection in body fluids
Blood, serum, or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, or to assist in a medicolegal death investigation. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10–150 mg/L in overdose victims.
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