Topiramate
 | |
 | |
| Systematic (IUPAC) name | |
|---|---|
| 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate | |
| Clinical data | |
| Trade names | Topamax, Trokendi XR |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a697012 |
| Licence data | US FDA:link |
| |
| Oral | |
| Pharmacokinetic data | |
| Bioavailability | 80% |
| Protein binding | 13-17%; 15-41% |
| Metabolism | Hepatic (20-30%) |
| Half-life | 19-25 hours |
| Excretion | Urine (70-80%) |
| Identifiers | |
97240-79-4  | |
| N03AX11 | |
| PubChem | CID 5284627 |
| DrugBank |
DB00273  |
| ChemSpider |
4447672 |
| UNII |
0H73WJJ391 |
| KEGG |
D00537 |
| ChEMBL |
CHEMBL220492 |
| Chemical data | |
| Formula | C12H21NO8S |
| 339.363 g/mol | |
|
SMILES
| |
| |
| (what is this?) (verify) | |
Topiramate (brand name Topamax) is an 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 Pharmaceutical.[1][2][3] Topiramate was first approved in the US in 1996.[4] Generic versions are available in Canada and these were approved by the FDA in September 2006. Mylan Pharmaceuticals was recently granted final approval for generic topiramate 25, 100, and 200 mg tablets and sprinkle capsules by the FDA for sale in the United States. 50 mg tablets were granted tentative approval.[5] The last patent for topiramate in the U.S. was for pediatric use; this patent expired on February 28, 2009.[6]
Medical uses
Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant. In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is also Food and Drug Administration (FDA) approved for, and most frequently prescribed for, the prevention of migraines. Psychiatrists have used topiramate to treat bipolar disorder, although the available evidence does not support its use in any phase of bipolar disorder treatment.[7][8][9] A more recent review, published in 2010, suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder, however the authors note that this was based only on one randomized controlled trial and requires replication. Also the Authors noted that the long-term effects have not been studied.[10]
This drug has been used successfully as a treatment for alcoholism,[11] methamphetamine addiction, cocaine addiction,[12][13] obesity[14][15] and antipsychotic-induced weight gain.[16][17] This drug is also widely used to treat migraines due to the effect it has on the blood vessels in the brain. It is used as a preventative for atypical migraine sufferers. It widens the blood vessels in the brain which become restricted by increased serotonin levels. It has been found to be increasingly effective for migraine sufferers with limited side effects.[18][19]
The drug is also used in clinical trials to treat post traumatic stress disorder.[20] A pilot study suggested that topiramate is effective against infantile spasms.[21] Another study recommends topiramate as an effective treatment in the prevention of periventricular leukomalacia in preterm infants after an hypoxic-ischemic injury.[22]
Recent clinical reports indicate that it may have mood stabilizing properties.[23] Other off-label and investigational uses of topiramate include the treatment of essential tremor, bulimia nervosa,[24] obsessive-compulsive disorder, smoking cessation,[25] idiopathic intracranial hypertension[26] and cluster headache[27] Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition in which it has been adequately tested.[28] Dispensing errors have been reported between TOPAMAX (topiramate) tablets and TOPROL-XL (metoprolol succinate) extended-release tablets.
Adverse effects
Adverse effects by incidence:[29][30][31][32]
Very common (>10% incidence) adverse effects include:
- Dizziness
- Weight loss
- Paraesthesia - e.g., pins and needles
- Somnolence
- Nausea
- Diarrhea
- Fatigue
- Nasopharyngitis - common cold
- Depression
Common (1-10% incidence) adverse effects include:
- Weight gain
- Anaemia
- Disturbance in attention
- Memory impairment
- Amnesia
- Cognitive disorder
- Mental impairment
- Psychomotor skills impaired
- Convulsion
- Coordination abnormal
- Tremor
- Lethargy
- Hypoaesthesia
- Nystagmus
- Dysgeusia
- Balance disorder
- Dysarthria
- Intention tremor
- Sedation
- Vision blurred
- Diplopia
- Visual disturbance
- Vertigo
- Tinnitus
- Ear pain
- Dyspnoea
- Epistaxis
- Nasal congestion
- Rhinorrhoea
- Vomiting
- Constipation
- Abdominal pain upper
- Dyspepsia
- Abdominal pain
- Dry mouth
- Stomach discomfort
- Paraesthesia oral
- Gastritis
- Abdominal discomfort
- Nephrolithiasis
- Pollakisuria
- Dysuria
- Alopecia (hair loss)
- Rash
- Pruritus
- Arthralgia
- Muscle spasms
- Myalgia
- Muscle twitching
- Muscular weakness
- Musculoskeletal chest pain
- Anorexia
- Decreased appetite
- Pyrexia
- Asthenia
- Irritability
- Gait disturbance
- Feeling abnormal
- Malaise
- Hypersensitivity
- Bradyphrenia
- Insomnia
- Expressive language disorder
- Anxiety
- Confusional state
- Disorientation
- Aggression
- Mood altered
- Agitation
- Mood swings
- Anger
- Abnormal behaviour
Uncommon (0.1-1% incidence) adverse effects include:
- Crystal urine present
- Tandem gait test abnormal
- White blood cell count decreased
- Bradycardia
- Sinus bradycardia
- Palpitations
- Leucopenia
- Thrombocytopenia
- Lymphadenopathy
- Eosinophilia
- Depressed level of consciousness
- Grand mal convulsion
- Visual field defect
- Complex partial seizures
- Speech disorder
- Psychomotor hyperactivity
- Syncope, sensory disturbance
- Drooling
- Hypersomnia
- Aphasia
- Repetitive speech
- Hypokinesia
- Dyskinesia
- Dizziness postural
- Poor quality sleep
- Burning sensation
- Sensory loss
- Parosmia
- Cerebellar syndrome
- Dysaesthesia
- Hypogeusia
- Stupor
- Clumsiness
- Aura
- Ageusia
- Dysgraphia
- Dysphasia
- Neuropathy peripheral
- Presyncope
- Dystonia
- Formication (the sensation of insects crawling under the skin)
- Visual acuity reduced
- Scotoma
- Myopia
- Abnormal sensation in eye
- Dry eye
- Photophobia
- Blepharospasm
- Lacrimation increased
- Photopsia
- Mydriasis
- Presbyopia
- Deafness
- Deafness unilateral
- Deafness neurosensory
- Ear discomfort
- Hearing impaired
- Dyspnoea exertional
- Paranasal sinus hypersecretion
- Dysphonia
- Pancreatitis
- Flatulence
- Gastrooesophageal reflux disease
- Abdominal pain lower
- Hypoaesthesia oral
- Gingival bleeding
- Abdominal distension
- Epigastric discomfort
- Abdominal tenderness
- Salivary hypersecretion
- Oral pain
- Breath odour
- Glossodynia
- Calculus urinary
- Urinary incontinence
- Haematuria (blood in urine)
- Incontinence
- Micturition urgency
- Renal colic
- Renal pain
- Anhidrosis
- Hypoaesthesia facial
- Urticaria
- Erythema
- Pruritus generalized
- Rash macular
- Skin discolouration
- Allergic dermatitis
- Swelling face
- Joint swelling
- Musculoskeletal stiffness
- Flank pain
- Muscle fatigue
- Metabolic acidosis
- Hypokalaemia
- Increased appetite
- Polydipsia
- Hypotension
- Orthostatic hypotension flushing
- Hot flush
- Hyperthermia
- Thirst
- Influenza like illness
- Sluggishness
- Peripheral coldness
- Feeling drunk
- Feeling jittery
- Learning disability
- Erectile dysfunction
- Sexual dysfunction
- Suicidal ideation
- Suicide attempt
- Hallucination
- Psychotic disorder
- Apathy
- Lack of spontaneous speech
- Sleep disorder
- Affect lability
- Libido decreased
- Restlessness
- Crying
- Dysphemia
- Euphoric mood
- Paranoia
- Perseveration
- Panic attack
- Tearfulness
- Reading disorder
- Initial insomnia
- Flat affect
- Thinking abnormal
- Loss of libido
- Listless
- Middle insomnia
- Distractibility
- Early morning awakening
- Panic reaction
- Elevated mood
Rare (0.01-0.1% incidence) adverse effects include:
- Blood bicarbonate decreased
- Neutropaenia
- Apraxia
- Circadian rhythm sleep disorder
- Hyperaesthesia
- Hyposmia
- Anosmia
- Essential tremor
- Akinesia
- Unresponsive to stimuli
- Blindness unilateral
- Blindness transient
- Glaucoma
- Accommodation disorder
- Altered visual depth perception
- Scintillating scotoma
- Eyelid oedema
- Night blindness
- Amblyopia
- Calculus ureteric
- Renal tubular acidosis
- Stevens-Johnson syndrome
- Erythema multiforme
- Skin odour abnormal
- Periorbital oedema
- Urticaria localised
- Limb discomfort
- Acidosis hyperchloraemic
- Raynaud's phenomenon
- Face oedema
- Calcinosis
- Mania
- Anorgasmia
- Panic disorder
- Disturbance in sexual arousal
- Feeling of despair
- Orgasm abnormal
- Hypomania
- Orgasmic sensation decreased
Unknown incidence adverse effects include:
- Angle closure glaucoma
- Maculopathy
- Eye movement disorder
- Toxic epidermal necrolysis
- Allergic oedema
- Conjunctival oedema
Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.[33]
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.[34] 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.[35] This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011 the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D.[36]
Topiramate has been associated with a statistically significant increase in suicidality,[37] and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."[38][39]
Interactions
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.[40] Neither intrauterine devices (IUDs) nor Depo-Provera are affected by topiramate.[40]
- 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'.[41]
- Oligohidrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.
Overdose
Overdose is rare. In most cases, acute exposure produced only minimal to moderate effects. Fatalities have occurred, but were the result of polydrug exposure.
Symptoms of overdose may include but are not limited to:
- Agitation
- Depression
- Speech problems
- Blurred vision, double vision
- Troubled thinking
- Loss of coordination
- Inability to respond to things around you
- Loss of consciousness
- Confusion and coma
- Fainting
- Upset stomach and stomach pain
- Loss of appetite and vomiting
- Shortness of breath; fast, shallow breathing
- Pounding or irregular heartbeat
- Muscle weakness
- Bone pain
- Seizures
A specific antidote is not available. Treatment is entirely supportive.
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.[42][43][44]
Warnings
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,[38] 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.[45]
- Topiramate may decrease effectiveness of estrogen-containing oral contraceptives.
- Taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in infant.[36]
- 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.
- Avoid evening primrose (seizure threshold decreased) [46]
Pharmacology
Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an anticonvulsant.
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.[47] These include (1) voltage-gated sodium channels; (2) high-voltage-activated calcium channels; (3) GABA-A receptors; (4) AMPA/kainate receptors; and (5) carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by a direct action.[48] 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.[49]
While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is the only anticonvulsant that does not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.[50]
References
- ↑ Maryanoff, BE; Nortey, SO; Gardocki, JF; Shank, RP; Dodgson, SP (1987). "Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds". Journal of Medical Chemistry 30 (5): 880–7. doi:10.1021/jm00388a023. PMID 3572976.
- ↑ Maryanoff, BE; Costanzo, MJ; Nortey, SO; Greco, MN; Shank, RP; Schupsky, JJ; Ortegon, MP; Vaught, JL (1998). "Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives". Journal of Medical Chemistry 41 (8): 1315–43. doi:10.1021/jm970790w. PMID 9548821.
- ↑ B. E. Maryanoff and J. F. Gardocki, "Anticonvulsant sulfamate derivatives", U.S. Patent number 4,513,006 (1985)
- ↑ "Topamax (Topiramate) Tablet, Coated Topamax (Topiramate) Capsule, Coated Pellets [Janssen Pharmaceuticals, Inc.]". Dailymed.nlm.nih.gov. Retrieved 2013-07-11.
- ↑ "First-Time Generic Approvals: Seasonale, Imodium Advanced, and Topamax". Medscape.com. 2006-09-22. Retrieved 2013-07-11.
- ↑ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". Accessdata.fda.gov. Retrieved 17 October 2014.
- ↑ Arnone, D (2005). "Review of the use of Topiramate for treatment of psychiatric disorders". Annals of general psychiatry 4 (1): 5. doi:10.1186/1744-859X-4-5. PMC 1088011. PMID 15845141.
- ↑ Vasudev, K; Macritchie, K; Geddes, J; Watson, S; Young, A (25 January 2006). "Topiramate for acute affective episodes in bipolar disorder." (PDF). The Cochrane Database of Systematic Reviews (1): CD003384. doi:10.1002/14651858.CD003384.pub2. PMID 16437453.
- ↑ Cipriani, A; Barbui, C; Salanti, G; Rendell, J; Brown, R; Stockton, S; Purgato, M; Spineli, LM; Goodwin, GM; Geddes, JR (8 October 2011). "Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis.". Lancet 378 (9799): 1306–15. doi:10.1016/s0140-6736(11)60873-8. PMID 21851976.
- ↑ Leib, Klaus; Völlm, Birgit; Rücker, Gerta; Timmer, Antje; Stoffers, Jutta M (2010). "Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials". British Journal of Psychiatry 196 (1): 4–12. doi:10.1192/bjp.bp.108.062984. PMID 20044651.
- ↑ Johnson, BA; Ait-Daoud, N (2010). "Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients." (PDF). Current Pharmaceutical Design 16 (19): 2103–12. doi:10.2174/138161210791516404. PMC 3063512. PMID 20482511.
- ↑ Kampman, KM; Pettinati, HM; Lynch, KG; Spratt, K; Wierzbicki, MR; O’Brien, CP (November 2013). "A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence". Drug and Alcohol Dependence 133 (1): 94–99. doi:10.1016/j.drugalcdep.2013.05.026. PMID 23810644.
- ↑ Shinn, AK; Greenfield, SF (May 2010). "Topiramate in the treatment of substance-related disorders: a critical review of the literature." (PDF). The Journal of Clinical Psychiatry 71 (5): 634–48. doi:10.4088/JCP.08r04062gry. PMC 3736141. PMID 20361908.
- ↑ Verrotti, A; Scaparrotta, A; Agostinelli, S; Di Pillo, S; Chiarelli, F; Grosso, S (August 2011). "Topiramate-induced weight loss: a review.". Epilepsy Research 95 (3): 189–99. doi:10.1016/j.eplepsyres.2011.05.014. PMID 21684121.
- ↑ Kramer, CK; Leitão, CB; Pinto, LC; Canani, LH; Azevedo, MJ; Gross, JL (May 2011). "Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials.". Obesity Reviews 12 (5): e338–47. doi:10.1111/j.1467-789X.2010.00846.x. PMID 21438989.
- ↑ Hahn, MK; Cohn, T; Teo, C; Remington, G (January 2013). "Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters.". Clinical schizophrenia & related psychoses 6 (4): 186–96. doi:10.3371/CSRP.HACO.01062013. PMID 23302448.
- ↑ Mahmood, S; Booker, I; Huang, J; Coleman, CI (February 2013). "Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents.". Journal of Clinical Psychopharmacology 33 (1): 90–4. doi:10.1097/JCP.0b013e31827cb2b7. PMID 23277264.
- ↑ Linde, M; Mulleners, WM; Chronicle, EP; McCrory, DC (24 June 2013). "Topiramate for the prophylaxis of episodic migraine in adults." (PDF). The Cochrane Database of Systematic Reviews 6: CD010610. doi:10.1002/14651858.CD010610. PMID 23797676.
- ↑ Ferrari, A; Tiraferri, I; Neri, L; Sternieri, E (September 2011). "Clinical pharmacology of topiramate in migraine prevention.". Expert Opinion on Drug Metabolism & Toxicology 7 (9): 1169–81. doi:10.1517/17425255.2011.602067. PMID 21756204.
- ↑ Andrus, MR; Gilbert, E (November 2010). "Treatment of civilian and combat-related posttraumatic stress disorder with topiramate.". The Annals of Pharmacotherapy 44 (11): 1810–6. doi:10.1345/aph.1P163. PMID 20923947.
- ↑ Glauser, TA; Clark, PO; Strawsburg, R (1998). "A pilot study of topiramate in the treatment of infantile spasms". Epilepsia 39 (12): 1324–8. doi:10.1111/j.1528-1157.1998.tb01331.x. PMID 9860068.
- ↑ Follett, PL; Deng, W; Dai, W; Talos, DM; Massillon, LJ; Rosenberg, PA; Volpe, JJ; Jensen, FE (2004). "Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate". Journal of Neuroscience 24 (18): 4412–20. doi:10.1523/JNEUROSCI.0477-04.2004. PMID 15128855.
- ↑ Letmaier, M; Schreinzer, D; Wolf, R; Kasper, S (2001). "Topiramate as a mood stabilizer". International clinical psychopharmacology 16 (5): 295–8. doi:10.1097/00004850-200109000-00008. PMID 11552774.
- ↑ Hoopes, SP; Reimherr, FW; Hedges, DW; Rosenthal, NR; Kamin, M; Karim, R; Capece, JA; Karvois, D (2003). "Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures". The Journal of clinical psychiatry 64 (11): 1335–41. doi:10.4088/JCP.v64n1109. PMID 14658948.
- ↑ Khazaal, Y; Cornuz, J; Bilancioni, R; Zullino, DF (2006). "Topiramate for smoking cessation". Psychiatry and clinical neurosciences 60 (3): 384–8. doi:10.1111/j.1440-1819.2006.01518.x. PMID 16732758.
- ↑ Celebisoy, N; Gökçay, F; Sirin, H; Akyürekli, O (2007). "Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study". Acta neurologica Scandinavica 116 (5): 322–7. doi:10.1111/j.1600-0404.2007.00905.x. PMID 17922725.
- ↑ Láinez, MJ; Pascual, J; Pascual, AM; Santonja, JM; Ponz, A; Salvador, A (2003). "Topiramate in the prophylactic treatment of cluster headache". Headache 43 (7): 784–9. doi:10.1046/j.1526-4610.2003.03137.x. PMID 12890134.
- ↑ Wiffen, PJ; Derry S; Lunn MPT; Moore R. (August 2013). "Topiramate for neuropathic pain and fibromyalgia in adults". Cochrane Database of Systematic Reviews (8). doi:10.1002/14651858.CD008314.pub3. Retrieved 6 September 2013.
- ↑ "TOPAMAX® Tablets and Sprinkle Capsules PRODUCT INFORMATION" (PDF). TGA eBusiness Services. JANSSEN-CILAG Pty Ltd. 30 May 2013. Retrieved 18 November 2013.
- ↑ "topiramate (Rx) - Topamax, Trokendi XR". Medscape Reference. WebMD. Retrieved 18 November 2013.
- ↑ "Topiramate 100 mg film-coated Tablets". electronic Medicines Compendium. Sandoz Limited. 6 March 2013. Retrieved 18 November 2013.
- ↑ "TOPIRAMATE ( topiramate ) tablet TOPIRAMATE ( topiramate ) tablet [Torrent Pharmaceuticals Limited]". DailyMed. Torrent Pharmaceuticals Limited. August 2011. Retrieved 18 November 2013.
- ↑ Mirza, Nasir; Marson, Anthony G.; Pirmohamed, Munir (2009). "Effect of topiramate on acid-base balance: extent, mechanism and effects". British Journal of Clinical Pharmacology 68 (5): 655–61. doi:10.1111/j.1365-2125.2009.03521.x. PMC 2791971. PMID 19916989.
- ↑ "IMPORTANT DRUG WARNING" (PDF). Fda.gov. Retrieved 17 October 2014.
- ↑ Hunt, S; Russell, A; Smithson, WH; Parsons, L; Robertson, I; Waddell, R; Irwin, B; Morrison, PJ; Morrow, J (2008). "Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register". Neurology 71 (4): 272–6. doi:10.1212/01.wnl.0000318293.28278.33. PMID 18645165.
- ↑ 36.0 36.1 Report a Serious Problem (2011-01-06). "FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate)". Fda.gov. Retrieved 2013-07-11.
- ↑ "Suicidality and Antiepileptic Drugs" (PDF). Retrieved 2013-07-11.
- ↑ 38.0 38.1 "Possible Side Effects - TOPAMAX® (topiramate)". Topamax.xom. Retrieved 17 October 2014.
- ↑
- ↑ 40.0 40.1 Sweetman, Sean C., ed. (2009). "Sex hormones and their modulators". Martindale: The complete drug reference (36th ed.). London: Pharmaceutical Press. p. 2068. ISBN 978-0-85369-840-1.
- ↑ FDA.gov
- ↑ Goswami D, Kumar A, Khuroo AH, et al. Bioanalytical LC-MS/MS method validation for plasma determination of topiramate in healthy Indian volunteers. Biomed. Chromatogr. 23: 1227-1241, 2009.
- ↑ Brandt C; Elsner H; Füratsch N et al. (2010). "Topiramate overdose: a case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticus". Epilepsia 51 (6): 1090–1093. doi:10.1111/j.1528-1167.2009.02395.x. PMID 19889015.
- ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1567-1569.
- ↑ "Topamax (topiramate) tablets and sprinkle capsules". Fda.gov. Retrieved 17 October 2014.
- ↑ Lexi-Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2011; February 18, 2011.
- ↑ Porter RJ, Dhir A, Macdonald RL, Rogawski MA (2012). "Mechanisms of action of antiseizure drugs". Handb Clin Neurol 108. pp. 663–681. doi:10.1016/B978-0-444-52899-5.00021-6.
- ↑ Meldrum BS, Rogawski MA (2007). "Molecular targets for antiepileptic drug development". Neurotherapeutics 4 (1): 18–61. doi:10.1016/j.nurt.2006.11.010. PMC 1852436. PMID 17199015.
- ↑ Kudin, AP; Debska-Vielhaber, G; Vielhaber, S; Elger, CE; Kunz, WS (2004). "The mechanism of neuroprotection by topiramate in an animal model of epilepsy". Epilepsia 45 (12): 1478–87. doi:10.1111/j.0013-9580.2004.13504.x. PMID 15571505.
- ↑ Czuczwar, K; Czuczwar, M; Cieszczyk, J; Gawlik, P; Luszczki, JJ; Borowicz, KK; Czuczwar, SJ (2004). "Neuroprotective activity of antiepileptic drugs". Przeglad lekarski 61 (11): 1268–71. PMID 15727029.
External links
 |
Wikimedia Commons has media related to Topiramate. |
- Topamax (topiramate): Treatment for Migraine Prevention
- Topamax: Treatment for Epilepsy
- Currently listed clinical trials related to topiramate
- FDA topiramate safety
- MSN article
- MedlinePlus: Topiramate
- FAQ: Topiramate (Topamax), Mood Disorders and PTSD
- RxList.com: Topiramate
- Focus on Topiramate - a new anti-epileptic, Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1
- Topiramate bound to proteins in the PDB
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||