Topiramate oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing topiramate.
Drugs List
Therapeutic Indications
Uses
Epilepsy (inadequately controlled) - partial seizures: adjunctive therapy
Epilepsy (inadequately controlled) - tonic-clonic seizures: adjunctive
Epilepsy (newly diagnosed) - partial seizures: monotherapy
Epilepsy (newly diagnosed) - tonic-clonic seizures: monotherapy
Migraine in adults: prophylaxis
Seizures associated with Lennox-Gastaut Syndrome: adjunctive treatment
Monotherapy in adults and children 6 years and over with:
Primary generalised tonic-clonic seizures,
Partial seizures with or without secondarily generalised seizures.
Adjunctive therapy for adults and children over 2 years of age with:
Partial seizures with or without secondarily generalised seizures,
Seizures associated with Lennox-Gastaut Syndrome,
Primary generalised tonic-clonic seizures.
Prophylaxis of migraine in adults after evaluation of alternative treatments.
Dosage
Titrations should be guided by clinical response. Use smaller increments or longer intervals if titrations are not tolerated.
Adults
Epilepsy
Monotherapy
Initial dose: 25mg at night for 1 week.
Increased thereafter by 25mg to 50mg every 1 or 2 weeks. Titration dose to be taken in two divided doses.
Maintenance dose: 100mg to 200mg daily in two divided doses, adjusted according to response. Maximum 500mg daily. Doses of 1g daily have been used in refractory epilepsy.
Patients transferring to topiramate from another antiepileptic drug should have the previous drug withdrawn gradually. A rate of one third of the dose every 2 weeks is recommended. If the previous drug is an enzyme inducer, discontinuation may increase topiramate levels. A decrease in topiramate dose may be required.
Adjunctive therapy
Initial dose: 25mg to 50mg at night for 1 week.
Increased thereafter by 25mg to 50mg every 1 to 2 weeks. Titration dose to be taken in two divided doses but some patients may achieve efficacy with a once daily dose.
Maintenance dose: 200mg to 400mg daily in two divided doses, adjusted according to response. Maximum 400mg daily.
Migraine
Initial dose: 25mg at night for 1 week.
Increased thereafter by 25mg each week.
Maintenance dose: 100mg daily in two divided doses. Some may benefit a dose of 50mg daily. Maximum dose of 200mg daily although caution is advised at higher doses due to side effects.
Children
Epilepsy
Children aged 6 to 18 years
Monotherapy
Initial dose: 0.5mg/kg to 1mg/kg at night for 1 week.
Increased thereafter by 0.5mg/kg to 1mg/kg every 1 to 2 weeks. Titration dose to be taken in two divided doses.
Maintenance dose: 100mg daily in two divided doses.
Children aged 2 to 18 years
Adjunctive therapy
Initial dose: 25mg (or 1mg/kg to 3mg/kg) at night for 1 week.
Increased thereafter by 1mg/kg to 3mg/kg every 1 to 2 weeks. Titration dose to be taken in two divided doses.
Maintenance dose: 5mg/kg to 9mg/kg daily in two, divided doses, adjusted according to response.
Doses up to 30mg/kg/day are considered to be well tolerated.
Migraine (unlicensed)
Children aged 16 to 18 years
Initial dose: 25mg at night for 1 week.
Increased thereafter by 25mg each week.
Maintenance dose: 50mg to 100mg daily in two divided doses. Maximum dose of 200mg daily although caution is advised at higher doses due to side effects.
Patients with Renal Impairment
Creatinine clearance less than 70ml/minute:
Reduce initial and maintenance dose by 50%.
Patients receiving haemodialysis
Topiramate is removed from plasma by haemodialysis. On haemodialysis days administer a supplemental dose of approximately one-half the usual daily dose. Administer in divided doses at the beginning and end of haemodialysis.
Additional Dosage Information
Discontinuing topiramate
Gradual withdrawal required. During clinical trials doses were decreased by 50mg to 100mg per week in epilepsy patients and by 25mg to 50mg per week in migraine patients. Paediatric doses were withdrawn over a 2 to 8 week period. Where abrupt withdrawal is essential, close monitoring is required.
Contraindications
Children under 2 years
Breastfeeding
Porphyria
Pregnancy
Precautions and Warnings
Family history of nephrolithiasis
Females of childbearing potential
Predisposition to acidosis
Predisposition to nephrolithiasis
Restricted sodium intake
Suicidal ideation
Depression
Galactosaemia
Glucose-galactose malabsorption syndrome
Haemodialysis
Hereditary fructose intolerance
History of depression
History of eye disorder
History of nephrolithiasis
Hypercalciuria
Lactose intolerance
Moderate hepatic impairment
Renal impairment - creatinine clearance below 70ml/min
Ensure adequate hydration in history of nephrolithiasis
Reduce dose in patients with renal impairment
Sodium content of oral solution may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider prescribing by manufacturer to ensure seizure control maintenance
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Oral solution contains glycerol
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain benzoic acid
Some formulations contain lactose
Some formulations contain sucrose
Exclude pregnancy prior to initiation of treatment
May cause an increase in seizure frequency or onset of new seizure types
Monitor ammonia levels if hyperammonaemia suspected
Monitor for development of acidosis
Monitor patient for signs and symptoms of depression
Monitor patient for weight loss
Refer immediately if raised intra-ocular pressure suspected to specialist
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report new visual problems and symptoms
Advise patients/carers to seek medical advice if suicidal intent develops
Consider dose reduction or withdrawal if metabolic acidosis occurs
Paediatric patients: Increased risk of heatstroke and dehydration
Avoid abrupt withdrawal
Discontinue if patient develops decreased visual acuity +/or ocular pain
Not licensed for all indications in all age groups
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Effect of hormonal contraceptive may be reduced
Female: Ensure adequate contraception during treatment
Advise patient/carer how to prevent heatstroke and dehydration
Acute myopia with secondary angle-closure glaucoma has been reported often presenting within 1 month of starting treatment. Discontinue topiramate and refer to a specialist if symptoms of decreased visual acuity and or ocular pain occur. Visual field defects have also been reported, independent of elevated intraocular pressure. Consider discontinuing topiramate if any visual field defects occur.
Cognitive impairment has been reported. Whilst this is multifactoral, some adults have required dose reduction or discontinuation of topiramate. Studies on cognitive outcomes in children are insufficient and at present, the effect in children is unclear.
Hyperammonaemia (with or without encephalopathy) has been reported in patients receiving topiramate. If patients develop unexplained lethargy or changes in mental state, consider measuring ammonia levels. The risk appears to be dose related. Frequency is also increased when treatment is combined with valproic acid.
At initiation, all female patients of child bearing potential should be fully informed of the risks related to the use of topiramate during pregnancy (see Pregnancy). Adequate contraception is required throughout treatment. Topiramate may reduce the effect of hormonal contraception, as such the use of non-hormonal contraception should be considered. Breakthrough bleeding has been reported in patients using combined oral contraceptives. Patients using oestrogen containing contraceptives are advised to report changes to bleeding patterns although it should be noted that decreased contraceptive efficacy can occur in the absence of break through bleeding.
Oligohydrosis (decreased sweating) has been reported leading in some cases to hyperthermia. Adequate hydration is essential, particularly during exercise or exposure to warm temperatures and can reduce the risk of nephrolithiosis. Particular caution is required in children.
Hyperchloraemic, non-anion gap, metabolic acidosis has been reported, often during early treatment but can occur at any time. Bicarbonate decreases are usually mild to moderate but can be worsened by additional risk factors such as renal disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic diet and concomitant medicines. Chronic metabolic acidosis increases the risk of renal stone formation, may lead to osteopenia and can reduce growth rate in children. Investigate following symptoms of metabolic acidosis and consider reducing or discontinuing treatment.
Pregnancy and Lactation
Pregnancy
Topiramate is contraindicated during pregnancy.
The use of topiramate during pregnancy has been associated with a 3-fold higher prevalence of major congenital malformations, particularly when used during the first trimester. In addition to teratogenic effects, topiramate has also been associated with a higher prevalence of low birth weight and being small for gestational age. Some studies have reported an increased risk of autism spectrum disorders, intellectual disability, and neurodevelopmental disorders.
Where discontinuation of the medication is deemed appropriate, treatment must be withdrawn gradually. Sudden discontinuation may lead to breakthrough seizures which can have serious consequences for both the patient and the unborn child. Monotherapy is preferred when possible due to concomitant use of additional antiepileptic drugs being associated with an increase risk of congenital malformations.
In patients using topiramate for epilepsy, patients should be fully informed of the potential risks of uncontrolled epilepsy during pregnancy (to both the mother and unborn child) in addition to the potential risks of the medicinal product to the foetus. A preconceptual visit is recommended in order to reassess the treatment, and to consider alternative therapeutic options. If used during the first trimester, patients should undergo careful prenatal monitoring.
Topiramate is contraindicated for migraine prophylaxis, in pregnancy and in women of childbearing potential where a highly effective form of contraception is not used.
Lactation
Topiramate is contraindicated in breastfeeding.
Limited observations suggest topiramate is extensively excreted in human breast milk. Observed effects include diarrhoea, drowsiness, irritability and inadequate weight gain.
The manufacturers advise to either suspend breastfeeding or discontinue topiramate, with consideration to importance of topiramate treatment to the mother.
Side Effects
Abdominal distension
Abnormal vision
Aggression
Agitation
Alopecia
Amnesia
Anaemia
Anxiety
Apathy
Asthenia
Behavioural disturbances
Bradycardia
Bradyphrenia
Changes in blood chemistry
Cognitive impairment
Concentration difficulties
Confusion
Convulsions
Crystalluria
Decreased appetite
Depression
Discomfort in limb
Disturbances in sweating
Disturbances of sensation
Dizziness
Dysgeusia
Dyspnoea
Eosinophilia
Erythema multiforme
Extrapyramidal effects
Facial oedema
Fatigue
Feeling abnormal
Feeling drunk
Flushing
Gait abnormality
Gastro-intestinal symptoms
Gingival bleeding
Glaucoma
Haematuria
Hallucinations
Hearing disturbances
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hypoaesthesia
Hypotension
Impaired co-ordination
Impaired consciousness
Impaired memory
Influenza-like symptoms
Insomnia
Joint swelling
Lacrimation
Leucopenia
Lymphadenopathy
Memory disturbances
Metabolic acidosis
Mood changes
Movement disturbances
Nasal congestion
Nasopharyngitis
Nephrolithiasis
Neutropenia
Nystagmus
Pain
Palpitations
Pancreatitis
Paraesthesia
Parosmia
Periorbital oedema
Peripheral neuropathy
Photophobia
Pollakiuria
Polydipsia
Postural hypotension
Pruritus
Psychomotor impairment
Psychotic disorder
Raynaud's syndrome
Renal colic
Rhinorrhoea
Rise in body temperature
Salivation changes
Sedation
Seizures
Sexual disturbances
Skin discolouration
Skin odour changes
Sleep disturbances
Somnolence
Speech disturbances
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Urinary urgency
Vertigo
Visual disturbances
Weight changes
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Topamax 25 mg Tablets. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 50mg Tablets. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 100mg Tablets. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 200mg Tablets. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 15mg Sprinkle Capsules. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 25mg Sprinkle Capsules. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topamax 50mg Sprinkle Capsules. Janssen-Cilag Ltd. Revised December 2017.
Summary of Product Characteristics: Topiramate 25mg film-coated tablets. Teva UK Ltd. Revised February 2015.
Summary of Product Characteristics: Topiramate 50mg film-coated tablets. Teva UK Ltd. Revised February 2015.
Summary of Product Characteristics: Topiramate 100mg film-coated tablets. Teva UK Ltd. Revised February 2015.
Summary of Product Characteristics: Topiramate 200mg film-coated tablets. Teva UK Ltd. Revised February 2015.
Summary of Product Characteristics: Topiramate 25mg film-coated tablets. Generics UK Ltd. Revised February 2011.
Summary of Product Characteristics: Topiramate 50mg film-coated tablets. Generics UK Ltd. Revised February 2011.
Summary of Product Characteristics: Topiramate 100mg film-coated tablets. Generics UK Ltd. Revised February 2011.
Summary of Product Characteristics: Topiramate 200mg film-coated tablets. Generics UK Ltd. Revised February 2011.
Summary of Product Characteristics: Topiramate 15mg capsules, hard (Arrow). Actavis UK Ltd. Revised January 2018.
Summary of Product Characteristics: Topiramate 25mg capsules, hard (Arrow). Actavis UK Ltd. Revised January 2018.
Summary of Product Characteristics: Topiramate 50mg capsules, hard (Arrow). Actavis UK Ltd. Revised January 2018.
Summary of Product Characteristics: Topiramate Rosemont 10mg/ml Oral Suspension. Rosemont Pharmaceuticals Ltd. Revised December 2018.
Summary of Product Characteristics: Topiramate Rosemont 20mg/ml Oral Suspension. Rosemont Pharmaceuticals Ltd. Revised December 2018.
MHRA Drug Safety Update July 2022
Available at: https://www.mhra.gov.uk
Last accessed: 19 October 2022
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 October 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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