Topiramate
Topiramate Uses, Dosage, Side Effects, Food Interaction and all others data.
Topiramate is a sulfamate-substituted monosaccharide, related to fructose. Topiramate is quickly absorbed after oral use. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. Topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particularly subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages.
Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability. It is important to note that this drug may cause metabolic acidosis, mood changes, suicidal thoughts and attempts, as well as kidney stones. When topiramate is combined with valproic acid, it is known to cause hypothermia.
| Trade Name | Topiramate |
| Availability | Prescription only |
| Generic | Topiramate |
| Topiramate Other Names | Tipiramate, Tipiramato, Topiramate, Topiramato, Topiramatum |
| Related Drugs | Emgality, Trokendi XR, Reyvow, gabapentin, propranolol, clonazepam, lamotrigine, diazepam, atenolol, pregabalin |
| Weight | 15mg, 25mg, 100mg, 150mg, 200mg, 25mg, 50mg, 100mg, 200mg, 25mg, 50mg |
| Type | Oral capsule, oral capsule, extended release, oral tablet |
| Formula | C12H21NO8S |
| Weight | Average: 339.362 Monoisotopic: 339.098787343 |
| Protein binding | Topiramate is not highly bound to plasma proteins, with an estimated plasma protein binding of 9-17% according to some studies. The FDA label indicates that the protein binding of topiramate is 15-41%. |
| Groups | Approved |
| Therapeutic Class | Adjunct anti-epileptic drugs |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
This drug is used to treat epilepsy in both children and adults. In children it is also used for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delay). It is now most frequently prescribed for the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder and alcoholism.
The drug is also used to treat Post Traumatic Stress Disorder. Studies suggest that Topiramate is effective against infantile spasms.
Monotherapy in Epilepsy: Topiramate is used for initial monotherapy in patients of 10 years of age and older with partial onset or primary generalized tonic-clonic seizures.
Adjunctive Therapyin Epilepsy: Topiramate is used for adjunctive therapy for adults and pediatric patients ages 2-16 years with partial onset seizures, or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome.
Migraine: Topiramate is used for adults for the prophylaxis of migraine headache.
Topiramate is also used to associated treatment for these conditions: Alcohol Dependency, Grand mal Generalized tonic-clonic seizure, Lennox-Gastaut Syndrome (LGS), Migraine, Moods Disorders, Partial-Onset Seizures, Weight, Primary generalized tonic-clonic seizure Epilepsy, Weight Reduction
How Topiramate works
A seizure is an abnormal and unregulated electrical discharge occurring in the brain. This leads to transient interruption in brain function, manifested by reduced alertness, abnormal sensations, and focal involuntary movements or convulsions. Several types of seizures exist, with common types including tonic-clonic seizures and partial onset seizures.
The exact mechanisms by which topiramate exerts pharmacological actions on seizures and migraines are currently not fully characterized. Several properties of this drug, however, are likely to contribute to its therapeutic effects. Topiramate has been observed to exert actions on voltage-dependent sodium channels, GABA receptors, and glutamate receptors.
Topiramate stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity at both AMPA and kainate receptors. Normally, GABA-A receptors are inhibitory and glutaminergic receptors are stimulatory for neuronal activity. By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines. Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity. Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time.
Dosage
Topiramate dosage
The initial dose normally is low and increased in slow steps.The usual initial dose is 25 to 50 mg daily in 2 single doses. Recommended increments are 25 to 50 mg every 1 or 2 weeks. Common doses for maintenance treatment are 100 to 200 mg daily. The highest dose possible is 1,000 mg daily in divided doses.
Monotherapy Use: The recommended maximum dose for Topiramate monotherapy in adults and children 10 years of age and older is 400 mg/day in two divided doses.
Adjunctive Therapy Use Adults (17 Years of Age and Over): The recommended total daily dose of Topiramate is 400 mg/day in Partial Seizures or Primary Generalized Tonic-Clonic Seizures. Daily doses above 1600 mg have not been studied.
Pediatric Patients (Ages 2 to 16 Years): Partial Seizures or Primary Generalized Tonic-Clonic Seizures The recommended total daily dose of Topiramate tablets as adjunctive therapy for patients with partial seizures or primary generalized tonic-clonic seizures is approximately 5 to 9 mg/kg/day in two divided doses.Titration should begin at 25 mg (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1 or 2 week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.
Topiramate tablets can be taken without regards to meals.
Side Effects
The most common side effects include a change in taste and feelings of pins and needles in the head and extremities. Less common side effects include cognitive deficiency (particularly word-finding difficulty); difficulty in understanding, grogginess, lethargy, renal (kidney) stones, vision abnormality, weight loss, breast pain, abdominal pain, intense sweating, menstrual disorder and dry mouth.
Toxicity
The LD50 of intraperitoneal topiramate in the rat is above 1500 mg/kg.
Overdose information
In a study of 4 healthy adult women taking topiramate, the severity of clinical effects following an overdose ranged from asymptomatic to severe, with no deaths reported. According to the FDA prescribing information for topiramate, an overdose may cause hypotension, severe metabolic acidosis, coma, abdominal pain, visual disturbances, convulsions, drowsiness, speech abnormalities, impaired mentation and coordination, stupor, agitation, dizziness, as well as depression.
In the case of a recent ingestion of topiramate, the stomach contents should be emptied through the induction of emesis or gastric lavage. Offer supportive treatment, including activated charcoal and hemodialysis.
Precaution
Concomitant administration of Topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured.
Interaction
Potential interactions between Topiramate and standard AEDs like Phenytoin, Carbamazepine and Valproic acid were observed during the concomitant treatment with these drugs for antiepileptic patients. Beside these. Concomitant use of Topiramate, a carbonic anhydrase inhibitor, with other carbonic anhydrase inhibitors, e.g., acetazolamide or dichlorphenamide, may create a physiological environment that increases the risk of renal stone formation. Digoxin, CNS depressants, oral contraceptives. Hydrochlorothiazide (HCTZ) may also interact with Topiramate.
Food Interaction
- Avoid a ketogenic diet. This type of diet increases the risk of kidney stones.
- Take with or without food. Food slightly alters absorption but not to any clinically significant extent.
Topiramate Alcohol interaction
[Moderate] GENERALLY AVOID:
Topiramate, when coadministered with other CNS depressants including alcoholic beverages, may lead to excessive somnolence and other forms of nervous system depression.
The patient should be informed to avoid alcohol or to use caution if these agents are coadministered, especially if performing hazardous tasks such as driving or operating machinery.
Topiramate Drug Interaction
Major: aripiprazole, diphenhydramineModerate: duloxetine, escitalopram, pregabalin, acetaminophen / hydrocodone, alprazolam, sertraline, cetirizineUnknown: amphetamine / dextroamphetamine, omega-3 polyunsaturated fatty acids, albuterol, montelukast, levothyroxine, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, lisdexamfetamine, bupropion
Volume of Distribution
The mean apparent volume of distribution of topiramate ranges from 0.6-0.8 L/kg when doses of 100mg to 1200mg are given. Topiramate readily crosses the blood-brain barrier.
Elimination Route
After a 400mg dose in one clinical trial, topiramate reached maximal concentrations within 1.8-4.3 hours and ranged from 1.73-28.7 ug/mL. Food did not significantly affect the extent of absorption, despite delaying time to peak concentration. In patients with normal creatinine clearance, steady state concentrations are reached within 4 days. The bioavailability of topiramate in tablet form is about 80% compared to a topiramate solution.
Half Life
The elimination half-life is reported to be in the range of 19-23 hours. If topiramate is given with enzyme-inducers, the half-life can be reduced to 12-15 hours because of increased metabolism.
Clearance
The mean oral plasma clearance of topiramate ranges from 22-36 mL/min while the renal clearance is 17-18 mL/min, according to one pharmacokinetic study. The FDA label for topiramate indicates a similar oral plasma clearance of approximately 20 to 30 mL/min in adults.
Elimination Route
Topiramate is mainly eliminated through the kidneys. About 70-80% of the eliminated dose is found unchanged in the urine.
Pregnancy & Breastfeeding use
Topiramate is pregnancy category C. So it may be given only if clearly needed and after the assessment of risk benefit ratio. It is not known whether Topiramate is excreted through breast milk. So caution should be taken if it is prescribed to a breast feeding mother.
Contraindication
Topiramate tablets are contraindicated in patients with a history of hypersensitivity to any component of this product.
Special Warning
Patients with Renal Impairment: In renally impaired subjects (creatinine clearance less than 70 ml/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.
Patients Undergoing Hemodialysis: Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause Topiramate concentration to fall below that required to maintain an anti-seizure effect.To avoid rapid drops in Topiramate plasma concentration during hemodialysis, a supplemental dose of Topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of Topiramate in the patient being dialyzed.
Acute Overdose
Overdoses of Topiramate includes convulsions, drowsiness, speech disturbance, blurred vision, diplopia, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness and depression.The clinical consequences are not severe. Topiramate overdose results in severe metabolic acidosis.
In acute Topiramate overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of ernes is. Activated charcoal has been shown to adsorb Topiramate in vitro. Hemodialysis is an effective means of removing Topiramate from the body.
Storage Condition
Store at a cool & dry place, protected from light and moisture. Keep out of reach of the children.
Innovators Monograph
You find simplified version here Topiramate
Topiramate contains Topiramate see full prescribing information from innovator Topiramate Monograph, Topiramate MSDS, Topiramate FDA label
FAQ
What is Topiramate used for?
Topiramate is a medicine used to treat epilepsy. These are also called anti-epileptic medicines. It can also be taken to prevent migraine. This medicine is only available on prescription.
How safe is Topiramate?
Topiramate is safe for long-term use when taken as prescribed. However, several common and potentially severe side effects have been reported by a small number of patients. There are also quite a few drugs that can cause harmful interactions or become ineffective when taken in conjunction with Topiramate.
How does Topiramate work?
Topiramate works by reducing the spread of seizure activity in the brain and restoring the normal balance of nerve activity.
What are the common side effects of Topiramate?
Common side effects of Topiramate include feeling sleepy, dizziness, diarrhoea and feeling sick. These are usually mild and go away by themselves.
Is Topiramate safe during pregnancy?
If you take Topiramate during pregnancy, there is a higher risk that your baby will develop a cleft lip and cleft palate. Oral clefts happen early in pregnancy, before many women even know they are pregnant.
Is Topiramate safe during breastfeeding?
Topiramate passes into breast milk. Babies usually have very low levels of Topiramate in their systems, and side effects or harmful effects in the nursing baby are rarely reported.
Can I drink alcohol with Topiramate?
Because Topiramate can cause mental and psychological side effects, it's not recommended that you drink alcohol while taking Topiramate.
Can I drive after taking Topiramate?
Do not drive a car or operate machinery until you know how this medication affects you. if you are taking Topiramate to control seizures, you should know that you may continue to have seizures during your treatment.
When is the best time to take Topiramate?
You can take Topiramate at any time of day, but try to take your doses at the same time each day. Try to space your doses evenly through the day. For example, first thing in the morning and in the evening. Topiramate tablets can be taken with or without food.
Is Topiramate safe to take long term?
Yes, many people take Topiramate safely for many months or years.
What does Topiramate do to the brain?
Topiramate decrease abnormal excitement in the brain. Among other actions,Topiramate affects the activity of the neurotransmitter gamma-aminobutyrate.
Is Topiramate good for anxiety?
Topiramate isn't approved to treat anxiety. However, the drug may sometimes be used off-label to treat people with certain anxiety disorders, such as obsessive-compulsive disorder.
Should I take Topiramate at night or in the morning?
Topiramate is usually taken with or without food once a day in the morning. Topiramate may cause difficulty falling asleep or staying asleep if it is taken in the evening. Take phentermine and Topiramate at around the same time every day.
Can Topiramate cause a stroke?
Hypohidrosis is one of the described side effects of Topiramate, and it can contribute to the development of heart stroke in patients taking this drug.
Can Topiramate cause heart problems?
Topiramate can increase your resting heart rate.
How fast will I lose weight on Topiramate?
It can take some time to see weight loss results from taking Topiramate. Some people may not notice a difference until they've taken the drug for at least four months, while other people may start to lose weight in their first month of taking it. Weight loss results from topiramate are proven to increase over time.
How long does it take Topiramate to get out of my system?
Topiramate stays in your system between four and six days after your last dose, depending on your personal factors such as dosage and metabolism.
Is Topiramate hard on the liver?
Topiramate is thought to be rarely associated with liver injury and by and large known to cause liver toxicity in conjunction with other anticonvulsants.
Is Topiramate bad for my kidneys?
Topiramate can increase the level of acid in your blood . This can weaken your bones, cause kidney stones, or cause growth problems in children .
Does Topiramate cause chest pain?
Chest pain is a previously undocumented potential side effect of Topiramate.
Is Topiramate an anti inflammatory?
Topiramate modulates post-infarction inflammation primarily by targeting monocytes or macrophages.
Will Topiramate effect my fertility?
Topiramate for 4 weeks did not have much effect on fertility.
Can I take Topiramate long time ?
Topiramate usually takes a couple of weeks for it to work. If taking Topiramate to prevent migraines, it can take up to 3 months for it to work fully.
What happen If I stop Topiramate suddenly ?
If you suddenly stop taking Topiramate, you may have severe seizures, even if you have not had seizures in the past. Your doctor will probably decrease your dose gradually.
What happens if I overdose?
An overdose of topiramate can be fatal.
Overdose can cause drowsiness, agitation, depression, double vision, thinking problems, problems with speech or coordination, fainting, and seizure.
