Topamax, a brand name for Topiramate, is also known as Topamax. It can be taken orally as an immediate-release or extended-release medicine.

Topiramate is used:

• Migraine:

  • It is used to prevent migraine headaches in patients aged 12 and over.

• Seizures

  • It can be used as a single or combination therapy to control seizures.

• Adults can use topiramate off-label

  • Weight gain induced by antipsychotics
  • Binge eating disorder
  • Cluster Headache Prevention
  • Preventing short-term unilateral neuralgiform headache attacks
  • Essential tremors

Topamax (Topiramate) Dose in Adults

Topamax dosage in the treatment of Binge-eating Disorder as an Alternative Agent (Off-label).

• Initial dose: 25 mg once daily. Gradually increase the dosage to 25-100 mg every other week. This will depend on your response and tolerance. You can take 400 mg/day.

Topamax (Topiramate), Dosage in the prevention or treatment of cluster headaches (alternative agent; adjunctive medicine):

• Initial dose: 25-50mg once daily. Gradually increase the dose in increments of 25-50mg every other week based on response. The recommended daily dose is 100-200mg/day.
• It can be combined with verapamil.

Topamax (topiramate), Dose to prevent short-lasting unilateral neuralgiform migraine attacks (alternative agent).

• Initial: 15–25 mg once every day. Depending on the response and tolerability, the dose could be increased.

Topamax (Topiramate), Dosage in Migraine Prevention

• Initial dose: Daily dose of 25 mg. Depending on how you react and how well you tolerate it, increase the dose by 25 to 50 mg every other week.

Topamax (Topiramate), Dosage in the Treatment of Seizures

• Monotherapy

  • Initial dose: 50 mg every hour, with weekly dose increases of 50 mg based on response and tolerance increasing the amount up to 200 mg each day. After that, you can go up to 400 mg per day by adding 100 mg increments each week.

• Adjunctive therapy:

  • Initial: 25-50 mg per oral daily; increasing in 25-50 mg increments weekly based on response. The maximum daily intake is 400 mg.

Dosage of Topamax (topiramate), for essential tremors (alternate drug):

• Initial: 25 mg oral O.D. or b.i.d. daily; gradually increase the dose in increments of 25-50 mg at intervals >=1week based on response.

Dosage of Topamax (topiramate): Antipsychotic-induced weight gain (alternative agent).

• Initial: 50 mg per orally per day; gradually increase to 25 to 50 mg every other week based on response and tolerance, up to a maximum of 200 mg/day.

Topamax (topiramate). Dosing conversion

• There are two types of immediate-release formulations:

  • You can convert the same daily total dose, but change the frequency of immediate-release (2x daily) or extended (once daily).

• Between ER formulations

  • Trokendi XR has not shown bioequivalence with Qudexy XR.

• Stopping therapy

  • To prevent seizure potential or withdrawal symptoms, you should gradually withdraw topiramate over several weeks to several months if you are receiving long-term treatment.

Topamax (Topiramate) Dose in Children

Notice: To avoid rebound effects, the dosage should be slowly reduced.

Topamax (Topiramate), for infantile spasms treatment:

Infantile spasm newly-diagnosed:

• Dosing per weight:

  • Children and infants 3-24 months

    • Release immediately:

      • Initial: 1 to 2 mg/kg oral per day; continue to titrate every 3-7 days in 1 to 3-mg/kg/day increments until seizures are controlled
      • Reported mean dose range: 9.1-14 mg/kg/day
      • Reported range: 4 to 27 mg/kg/day

• Refractory: Fixed dosing

  • Infants >=3 Months to Children =4 Years; Weight >=7 Kg:

    • Instant-release

      • Initial: Daily dose of 25 mg. until seizures are under control, titrate in 25 mg/day increments every two to three days.
      • Maximum daily dose 24 mg/kg/day

Topamax (Topiramate) as an adjunctive treatment for seizures:

Children and adolescents 2-16 years old

• Partial onset seizures, or Lennox–Gastaut syndrome

  • Release immediately:

  • Initial: 1 to 3 mg/kg oral daily
  • The highest dose is 25 mg/dose, given twice daily in increments of 1 or 3 mg/kg/day for a maximum of one to two weeks once a week. Titrate based on the outcome
  • In 2 doses, the maintenance dose is usually 5 to 9 mg/kg/day

  • Extended-releaseQudexyXR:

  • Initial: 25mg per oral once daily (approximately 1-to-3 mg/kg/day) taken once a night for one week. Then, increase in increments of 1-to-2 weeks at 1 to-3 mg/kg/day. Round to the closest appropriate capsule size and administered once daily.
  • Response to Titrate Dosage
  • The maintenance dose is usually 5 to 9mg/kg once daily. (range: 5-9 mg/kg/dose one time daily).

  • Extended-releaseTrokendi:

  • Initial: 25 mg once daily, administered by mouth once daily for approximately 1 to 2 weeks. Then, increase in 1- to 2-week intervals at 1 to 3, mg/kg/day increments. Each day, take 1 to 3 mg/kg/day and round to the next appropriate capsule size.
  • Maintenance: 5 to 9 mg/kg once daily

• Primary generalized tonic-clonic seizures

  • Instant-release

    • Initial: 1 to 3mg/kg per orally per day (maximum dosage: 25 mg/dose). Nightly for one week.
    • Increase the dose to 6 mg/kg/day with 2 divided doses in increments of 1 to 3 mg/kg/day.

  • Extended-releaseQudexyXR:

    • Initial: 25mg per oral once daily (approximately 1- to 3 mg/kg/day), taken once a night for one week. Then, increase in 8 weeks by increasing the dose by 1 to 3. mg/kg/day. Round to the closest capsule size and you will reach a target dose at 6 mg/kg/day.

  • Extended-releaseTrokendi:

    • Initial: 25mg once daily (approximately 1 - 3 mg/kg/day) taken once daily for one week. Then, increase in 8 weeks by increasing the dose in increments (1 to 3 mg/kg/day). Round to the closest capsule size and you will reach a daily target of 6 mg/kg.

• Adolescents >=17 Years

  • • Partial onset seizures, or Lennox–Gastaut syndrome

      • Instant-release

        • Initial: 25-50 mg daily taken orally for one week. Increase weekly by 25-50 mg/day. Take in 2 divided doses and adjust the dose according to your response.
        • Maintenance doses: 100-200 mg twice daily
        • Maximum daily intake: 1600 mg/day
        • Notification: Adult dose-response trials have not shown that higher doses than 400 mg/day increase effectiveness.

      • Extended-releaseQuedexyXR, TrokendiXR:

        • Initial: 25-50 mg once daily, once daily for one week. Increase weekly by 25-50 mg once daily. Titrate dosage to respond; longer intervals may be required between dose adjustments
        • Maintenance doses: 200-400 mg once daily
        • Maximum daily intake: 1600 mg/day

  • Primary generalized tonic-clonic seizures

    • • Release immediately:

      • Initial: 25-50 mg once daily in an oral dose for one week. Increase over 8 weeks in increments 25-50 mg/day in two divided doses. Titrate according to response
      • The normal maintenance dose is 200 mg twice daily. Use a slower initial titration rate at >2-week intervals.
      • Maximum daily intake: 1600 mg/day
      • Notice: Adult doses above 400 mg/day are not shown to be more effective in dose-response trials.

      • Extended-releaseQudexy, Trokendi and Trokendi XR

      • Initial dose: 25 mg to 50m once daily for one week. Increase weekly by 25 to 50mg/day increments once daily. Tirate according to response
      • Normal maintenance dose: 400mg once daily
      • Maximum daily intake: 1600 mg/day

Topiramate (Topamax), for seizures (Anticonvulsant monotherapy).

• Partial onset seizures, primary generalized-tonic-clonic seizures

  • Instant-release

  • Children from 2-10 years old:

    • Once daily, in the evening, 25 mg. If tolerated, the dose can be increased to 25 mg per day. The dose may be increased to 25 mg twice daily in the morning after the second week. The daily maintenance dose will then be decreased by 25 to 50 mg/day over a period of 5 to 7 weeks.
    • If additional seizure control is required and the therapy is acceptable, the dose may be increased by 25-50 mg/day at weekly intervals until the upper limit of the daily maintenance target dosing range.

    • Daily maintenance targets:

    • 11kgs or less:

      • 150-250 mg/day in two divided doses

    • 12-22 kg

      • 200-300 mg/day in 2 equal doses

    • 23 to 31 Kilograms

      • 200-350 mg/day in 2 equal doses

    • 32-38 kg

      • 250-350 mg/day in two divided doses

    • >38 kg

      • 250-400 mg/day in 2 equal doses

  • Children >=10 Years and Adolescents

    • 25 mg twice daily, once in the morning and again at night.
    • The dose may then be increased by 100 mg/day increments to achieve 200 mg twice a day. Weekly intervals are increased by 50 mg/day increments to 100 mg twice a day (week four dose).

  • Extended-releaseQudexy, Trokendi, XR:

    • Adolescents and children >=10 years

      • 50 mg daily, for a week.
      • You can increase the weekly dose by 50 mg/day increments to 200 mg once daily (week four-dose); after that, you may increase the weekly dose by 100 mg/day increments to 400 mg once daily.

Topamax Dose for Migraine Prophylaxis:

• Children aged 6-12 years, weight >=20 kg

  • Instant-release

    • 15 mg per mouth, once daily, for the first week. After a week, increase to 15 mg twice daily. Then, for seven days, increase to 25 mg twice daily.
  • The maximum daily intake is 200 mg/day

• Adolescents and children >=12 years

  • 25 mg/day taken orally once daily at night, for a period of 1 week. Then, increase in weekly increments of 25 mg/day as tolerated.

Topiramate pregnancy risk category: D

• Topiramate may cause harm to the foetus by crossing into other areas.
• Females should take topiramate to achieve effective contraception
• Metabolic acidosis can lead to fetal death and other adverse effects during pregnancy.
• Congenital malformations are more common in .

Breastfeeding

• Breastmilk contains topiramate.
• If the infant's dose of medication is less than 10%, breastfeeding is allowed. It should not exceed 25%.
• It can cause diarrhea and somnolence in infants who are breastfed.
• According the manufacturer of this product, it is important that you weigh the risks and benefits associated with breastfeeding therapy.

Topamax Dose Adjustment in Renal Disease:

• Creatinine clearance >=70mL/minute/1.73m 2

  • No dosage adjustments are included in the manufacturer's labeling

• Creatinine clearance 70mL/minute/1.73m 2

  • 50% dose reduction is required.

• Hemodialysis

  • 50 to 100mg twice daily. After dialysis, give a supplement of 50 to 100mg to the patient.

Topamax Dose Adjustment in Liver Disease:

• The manufacturer's labeling does not include any dosage adjustments.
• However, in severe hepatic impairment, topiramate clearance might be decreased.

Common Side Effects of Topamax (Topiramate):

• Central Nervous System:

  • Paresthesia
  • Fatigue
  • Drowsiness
  • Dizziness
  • Memory Impairment

• Endocrine & Metabolic:

  • Decreased Serum Bicarbonate
  • Hyperammonemia
  • Weight Loss

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Dysgeusia
  • Nausea
  • Diarrhea

• Respiratory:

  • Upper Respiratory Tract Infection

• Miscellaneous:

  • Fever

Less Common Side Effects Of Topamax (Topiramate):

• Cardiovascular:

  • Flushing
  • Chest Pain

• Central Nervous System:

  • Disturbance In Attention
  • Lack Of Concentration
  • Depression
  • Insomnia
  • Mood Disorder
  • Hypoesthesia
  • Anxiety
  • Cognitive Dysfunction
  • Psychomotor Impairment
  • Headache
  • Nervousness
  • Ataxia
  • Behavioral Problems
  • Confusion
  • Hypertonia
  • Vertigo
  • Agitation
  • Exacerbation Of Depression
  • Speech Disturbance

• Dermatologic:

  • Alopecia
  • Pruritus
  • Skin Rash
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Menstrual Disease
  • Intermenstrual Bleeding
  • Increased Gamma-Glutamyl Transferase
  • Increased Thirst

• Gastrointestinal:

  • Dyspepsia
  • Constipation
  • Gastroenteritis
  • Gastritis
  • Xerostomia
  • Gastroesophageal Reflux Disease
  • Ageusia

• Genitourinary:

  • Urinary Tract Infection
  • Premature Ejaculation
  • Decreased Libido
  • Urinary Frequency
  • Vaginal Hemorrhage
  • Cystitis
  • Urinary Incontinence
  • Dysuria

• Hematologic & Oncologic:

  • Hemorrhage
  • Anemia
  • Neoplasm

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Viral Infection
  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Asthenia
  • Muscle Spasm
  • Lower Extremity Pain

• Ophthalmic:

  • Conjunctivitis
  • Blurred Vision
  • Visual Disturbance

• Otic:

  • Otitis Media

• Renal:

  • Nephrolithiasis

• Respiratory:

  • Sinusitis
  • Cough
  • Rhinitis
  • Pharyngitis
  • Bronchitis
  • Epistaxis
  • Dyspnea

• Miscellaneous:

  • Accidental Injury
  • Language Problems

Uncommon side effects of Topamax:

• Cardiovascular:

  • Hypotension
  • Orthostatic Hypotension
  • Syncope

• Central Nervous System:

  • Suicidal Ideation
  • Suicidal Tendencies

• Endocrine & Metabolic:

  • Hyperchloremia
  • Increased Serum Total Protein
  • Increased Uric Acid

• Gastrointestinal:

  • Gingival Hemorrhage
  • Hematuria

• Hematologic & Oncologic:

  • Abnormal Serum Phosphorus Level
  • Decreased Neutrophils
  • Decreased White Blood Cell Count
  • Eosinophilia
  • Quantitative Disorders Of Platelets

• Hepatic:

  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Myalgia

• Ophthalmic:

  • Myopia
  • Scotoma
  • Visual Field Defect

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine

Contraindications to Topamax, Topiramate

• Extended-release

  • Recent alcohol intake (i.e. within 6 hours prior and 6 hours following administration) (Trokendi extended release only)
  • Metabolic acidosis with concurrent Metformin (Qudexy extended Delivery only).

• Instant-release

  • There are no warnings stated on the packaging from the manufacturer.

• Canadian labeling

  • Hypersensitivity of topiramate to any component of the formula/container
  • Pregnancy

Warnings & Precautions

• CNS results

  • Use can cause cognitive dysfunction such as poor concentration, confusion and slowing down of the motor system.
  • It is crucial to exercise caution when operating machinery or driving.
  • It can also cause paraesthesia, dizziness, and ataxia.

• Encephalopathy / Hyperammonemia

  • Encephalopathy and hyperammonemia are possible causes of hyperammonemia. 
  • Inborn metabolic errors and reduced hepatic mitochondrial activity increase the risk of developing encephalopathy.

• Metabolic acidosis

  • This condition could be caused by decreased carbonic anhydrase activity and increased renal loss.
  • Risk factors include diabetes, kidney failure, ketogenic eating and status epilepticus.
  • Patients suffering from severe or persistent metabolic acidosis need to have their dosage reduced or stopped

• Hyperthermia/Oligohidrosis:

  • Exercise at high temperatures or strenuous activity is a dangerous way to increase your risk of hyperthermia and oligohidrosis.

• Ophthalmic effects

  • Children and adults should be treated for acute myopia.

• Calculus renal

  • Topiramate can have weak carbonic anhydrase inhibitory actions and increase your chance of developing kidney stones.
  • Ketogenic diets increase the risk while adequate water intake reduces it.

• Suicidal thoughts

  • Suicidal thoughts can result.

• Eating disorders

  • Topiramate has been associated with bulimia, anorexia and nervosa.
  • Compulsive exercising and over-exercising should be addressed.

Topiramate: Drug Interaction

Monitoring parameters:

• Electrolytes in serum
• Ammonia levels
• Hydration status
• Seizure frequency
• Renal function tests
• Glaucoma symptoms/intraocular pressure
• Suicidal thoughts/behavioral and behavioral changes
• Weight and eating habits

How do you administer Topamax (Topiramate).

• It is best to take the medication orally without crushing or chewing.
• You can also open QudexyXR or Sprinkle capsules to sprinkle their entire contents onto a small amount of soft food. 
• These capsules can be opened immediately and eaten whole, without needing to be chewed.
• Do not keep it. Stop drinking alcohol with Trokendi XR tablets within 6 hours after administration and 6 hours thereafter.

Mechanism of Topamax (Topiramate),:

• It increases gamma aminobutyric (GABA) activity and blocks neuronal voltage dependent sodium channels. 
• It inhibits carbonic anhydrase and antagonizes AMPA/kainate glucose.

Notice:

• The capsule and the tablet are bioequivalents to immediate-release formulations. Extended-release capsules (Trokendi XR) are twice daily administered and are bioequivalent to immediate-release formulations.

Absorption:

• Fast and efficient. The immediate-release formulation is unaffected by food. A single TrokendiXR dose taken with high-fat meals reduced the T by around 8 hours and increased Cmax by 37% Repeated administrations of TrokendiXR reduce this effect significantly. After a single QudexyXR dosage, the Tmax was delayed 4 hours.

Protein binding:

• 15% to 41% (inversely proportional plasma concentrations).

Metabolism:

• The hepatic metabolism is restricted to hydrolysis, hydrogenation and glucuronidation. 
• Patients receiving enzyme inducers (e.g.Carmazepine,Phenytoin. There is evidence of renal tubular absorption.

Bioavailability:

• 80% (immediate-release)

Eliminating half-life:

Release immediately:

If you are receiving any concomitant enzyme inducers or valproic acids.

• Hypothermia in neonates (full-term).: 43 hours
• Infants and children 9 months to 4 years10.4 hours (range: 8.5-8.3 hours).
• Children aged 4-7 yearsAverage range: 7.7 to 8.8 hours
• Children aged 8-11 yearsAverage range: 11.3 to 11 hours
• Children and adolescents 12-17 years oldAverage range: 12.3 to 12.8 Hours

Concomitant use of enzyme inducers (eg carbamazepine or phenytoin):

• Hypothermia in neonates (full-term).: 26.5 Hours
• Infants and children 9 months to 4 years6.5 hours (range 3.75-10.2 hours).
• Children and adolescents 4-17 years old7.5 hours

Receiving Valproic acid:

• Infants and children 9 months to 4 Years:9.2 hours (range 7.23 to 12.4 hours).
• Adults: 19-23 hours (mean: 21hrs)
• Adults with severe renal impairment: 59 +- 11 Hours

Extended-release

• QudexyXR:56 hours
• Trokendi:31 hours

Time until peak serum concentrations are reached:

Release immediately:

• Hypothermia in neonates (full-term), 3.8 hours
• Infants and children 9 months to 4 years: 3.7 Hours (range: 1.5-10.2 Hours).
• Children aged 4-17 years: Average range: 1 to 2 hours
• Adults: 2 Hours; range: 1.4-4.3 hours

Extended-release

• QudexyXR: 20 Hours
• TrokendiXR: 24 Hours

Excretion: Occurs in the urine (70% for unchanged drug); could undergo renal tubular absorption.

Topiramate Brand Names (International):

• Qudexy XR
• Topamax
• Topamax Sprinkle
• Trokendi XR
• Abbott-Topiramate
• ACCEL-Topiramate
• AG-Topiramate
• APO-Topiramate
• AuroTopiramate
• DOM-Topiramate
• GLN-Topiramate
• JAMP-Topiramate
• Mar-Topiramate
• MINTTopiramate
• MYLAN-Topiramate
• PHL-Topiramate
• PMS-Topiramate
• PRO-Topiramate
• RANTopiramate
• SANDOZ Topiramate
• TEVA-Topiramate
• Topamax
• Topamax Sprinkle
• Acomicil
• Conviban
• Epilramate
• Epimate
• Epiramat
• Epitomax
• Epitop
• Etopira
• Fagodol
• Gabatopa
• Ipramax
• Moramax
• Piramed
• Pradox
• Seziril
• Tamate
• Tiramate
• Topagan
• Topamac
• Topamax
• Topamax Sprinkle
• Topictal
• Topilepsin
• Topimax
• Topina
• Topinmate
• Topirol
• Topiromax
• Topiron
• Topirva
• Topitrim
• Topmate
• Topnotch
• Topomac
• Topvex
• Toramat
• Toramate

Topiramate Brand Names in Pakistan: