Zonisamide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of zonisamide.
Drugs List
Therapeutic Indications
Uses
Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Epilepsy-partial seizures with/without secondary generalisation-monotherapy
Dosage
Adults
Monotherapy for newly diagnosed adult patients
Week 1 and 2: 100mg once a day.
Week 3 and 4: 200mg once a day.
Week 5 and 6: 300mg once a day.
Maintenance dose: 300mg once a day.
If a higher dose is required: Increase by 100mg at 2 weekly intervals up to a maximum of 500mg.
Adjunctive therapy
With CYP3A4 inducing agents
Week 1: 50mg per day (in two divided doses).
Week 2: 100mg per day (in two divided doses).
Weeks 3 to 5: Increase by 100mg at weekly intervals.
Maintenance dose: 300mg to 500mg daily (once a day or two divided doses).
Without CYP3A4 inducing agents
Week 1 and 2: 50mg per day (in two divided doses).
Week 3 and 4: 100mg per day (in two divided doses).
Week 5 to 10: Increase at two-weekly intervals in increments of up to 100mg.
Maintenance dose: 300 to 500mg daily (once a day or two divided doses). Some patients may respond to lower doses.
Children
Children aged 6 years and above
Adjunctive therapy with CYP3A4 inducing agents
Week 1: 1mg/kg once a day
Weeks 2 to 8: Increase by 1mg/kg at weekly intervals.
Maintenance dose patients of weight 20 to 55kg: 6 to 8mg/kg once a day.
Maintenance dose patients weighing over 55kg: 300 to 500mg once a day.
Adjunctive therapy without CYP3A4 inducing agents
Week 1 and 2: 1mg/kg once a day.
Week 3 onwards: Increase by 1mg/kg at two weekly intervals.
Maintenance dose for patients weighing 20 to 55kg: 6 to 8mg/kg once a day.
Maintenance dose for patients weighing more than 55kg: 300 to 500mg once a day.
Some patients may respond to lower doses.
To ensure a therapeutic dose is maintained the weight of a child should be monitored and the dose reviewed as weight changes occur up to a weight of 55kg.
Withdrawal
When treatment is to be discontinued, down-titrations can be completed by dose reductions at weekly intervals according to the following schedule:
Weight 20 to 28kg: 25 to 50mg/day.
Weight 29 to 41kg: 50 to 75mg/day.
Weight greater than 42kg: 100mg/day.
Patients with Renal Impairment
There is limited information of zonisamide use in renal impairment, a slower titration rate might be required.
Week 1 and 2: 50mg per day (in two divided doses).
Week 3 and 4: 100mg per day (in two divided doses).
Week 5 to 10: Increase at two-weekly intervals in increments of up to 100mg.
Maintenance dose: 300 to 500mg daily (once a day or two divided doses).
Some patients may respond to lower doses.
Patients with Hepatic Impairment
There is limited information of zonisamide use in hepatic impairment, a slower titration rate might be required.
Week 1 and 2: 50mg per day (in two divided doses).
Week 3 and 4: 100mg per day (in two divided doses).
Week 5 to 10: Increase at two-weekly intervals in increments of up to 100mg.
Maintenance dose: 300 to 500mg daily (once a day or two divided doses).
Some patients may respond to lower doses.
Additional Dosage Information
Discontinuing treatment
Zonisamide should be withdrawn gradually to reduce the risk of seizures on withdrawal. Dose reductions of 100mg at weekly intervals have been used with concurrent adjustment of other anti-epileptic treatment. (see dosage; children for recommended withdrawal advice).
Administration
For oral administration of capsules.
For oral and gastroenteric administration of oral suspension.
Suspension should be shaken well (at least once for 30 seconds) and the dose may be administered immediately via feeding tube that must be rinsed three times immediately after administration with at least 5ml of water for each rinse. Four different sizes (CH 4.5, CH 6, CH 9 and CH 12) of PVC tubes for gastric or enteric feeding with a length of 50cm have been tested.
Contraindications
Children under 6 years
Breastfeeding
Severe hepatic impairment
Precautions and Warnings
Children weighing less than 20kg
Elderly
Family history of nephrolithiasis
Females of childbearing potential
Hypersensitivity to soya or soya derivative
Predisposition to acidosis
Predisposition to nephrolithiasis
Underweight patients
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of eye disorder
History of nephrolithiasis
Hypercalciuria
Hypersensitivity to arachis oil (peanuts)
Mild hepatic impairment
Pregnancy
Renal impairment
Ensure adequate hydration in history of nephrolithiasis
Advise ability to drive/operate machinery may be affected by side effects
Consider prescribing by manufacturer to ensure seizure control maintenance
Oral solution contains sucrose and hydroxybenzoates
Some formulations contain fructose
Some formulations contain glucose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Some products contain arachis (peanut) oil, soya or soya derivative
Investigate patients experiencing flank pain for nephrolithiasis
Maintain hydration and urinary output
Monitor ammonia levels if hyperammonaemia suspected
Monitor creatine kinase levels in patients reporting myalgia
Monitor for development of acidosis
Monitor for signs of suicide ideation or behaviour
Monitor patient's weight
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum lipase in patients at risk of pancreatitis
Monitor serum sodium bicarbonate
Refer immediately if raised intra-ocular pressure suspected to specialist
Refer women considering pregnancy for specialist advice and monitoring
Consider discontinuation if dehydration, oligohydrosis or high temp. occur
Consider discontinuation if pancreatitis occurs
Consider dose reduction or withdrawal if metabolic acidosis occurs
Discontinue or interrupt therapy if nephrolithiasis occurs
May cause heat prostration when used in high environmental temperatures
Paediatric patients: Increased risk of heatstroke and dehydration
Avoid abrupt withdrawal
Consider discontinuation if serum creatinine continues to rise
Consider discontinuation if symptoms of severe rhabdomyolysis occur
Consider discontinuing if patient develops an unexplained rash
Discontinue if liver function tests become abnormal
Discontinue if renal failure develops
Discontinue if substantial undesirable weight loss occurs
Discontinue if symptoms of acute angle closure glaucoma occur
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Advise patient/carer how to prevent heatstroke and dehydration
Advise patient/carers to report signs of suicide ideation or behaviour
Studies have shown cognition may be impaired in children and adolescents using zonisamide.
Zonisamide contains a sulfonamide group, which has been associated with serious immune based reactions. Serious immune based adverse reactions that are associated with medicinal products containing a sulfonamide group include rash, allergic reaction and major haematological disturbances, including aplastic anaemia, which very rarely can be fatal. The relationship between dose and/or duration of treatment is unknown.
The risk of metabolic acidosis appears to be more frequent and severe in younger patients. Metabolic acidosis occurs generally early in treatment although cases can occur at any time during treatment. Appropriate monitoring of serum bicarbonate levels should be carried out in patients taking zonisamide who have underlying conditions which might increase the risk of acidosis, in patients who are at an increased risk of adverse consequences of metabolic acidosis and in patients with symptoms suggestive of metabolic acidosis. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide as osteopenia may develop. If patients continue with treatment in the face of persistent acidosis, alkali treatment should be considered.
Metabolic acidosis can potentially lead to hyperammonaemia which has been reported with or without encephalopathy during zonisamide treatment. The risk of developing hyperammonaemia may be increased in patients taking other medications that cause hyperammonaemia or who have an underlying urea cycle disorder or reduced hepatic mitochondrial activity. If patients develop unexplained lethargy or changes in mental status, it is recommended to consider hyperammonaemic encephalopathy and to measure ammonia levels.
Consider dietary supplements or increased food intake in patients losing weight, children and those failing to gain weight in accordance with growth charts, otherwise zonisamide should be discontinued. Zonisamide is not recommended in children who are underweight or have a decreased appetite.
It is recommended to assess markers of muscle damage, including serum creatine phosphokinase and aldolase levels, in patients taking zonisamide, in whom severe muscle pain and/or weakness develop either in the presence or absence of a fever. If elevated, in the absence of another obvious cause such as trauma or grand mal seizures, it is recommended that zonisamide discontinuation be considered and appropriate treatment initiated.
Pregnancy and Lactation
Pregnancy
Use zonisamide with caution during pregnancy.
The manufacturer does not recommend the use of zonisamide during pregnancy unless clearly necessary and only if the potential benefit is considered to justify the risk to the foetus. If zonisamide is prescribed during pregnancy, patients should be fully informed of the potential harm to the foetus and use of minimal effective dose is advised along with careful monitoring.
At the time of writing, there is limited data on the use of zonisamide in pregnant women. Data suggests there is an increased proportion of babies born at low birth weight (LBW), pre-term or small for gestational age. Animal studies have shown reproductive toxicity. The risk to humans is unknown.
Lactation
Zonisamide is contraindicated during breastfeeding.
The manufacturer recommends that a decision must be made whether to discontinue breastfeeding or to discontinue zonisamide therapy. Due to the long retention time of zonisamide in the body, breastfeeding must not be resumed until one month after zonisamide therapy is completed.
Zonisamide is excreted in breast milk at a concentration which is similar to that in maternal plasma. LactMed (2020), suggests alternative drugs are used, but if use of zonisamide is unavoidable the infant should be monitored for drowsiness. adequate weight gain and developmental milestones, particularly in younger or exclusively breastfed infants.
Counselling
Advise patient to not take the suspension with carbonated beverages.
Advise patient to mix the suspension with yoghurt in case the taste is required to be masked.
Advise patient not to take St. John's wort concurrently.
Specialist advice should be given to women who are of childbearing potential regarding the possible of zonisamide on the foetus.
Advise patient to report signs of suicide ideation or behaviour.
Children taking zonisamide; should stay cool and avoid heavy exercise especially in hot weather and drink plenty of water. The child needs urgent medical attention if the skin feels very hot with little or no sweating, or if the child becomes confused or has muscle cramps, or the childs heartbeat or breathing become rapid. Take the child to a cool shaded place, keep the childs skin cool with water and give the child cool water to drink.
Parents/carers should read the advice in the Packaging Leaflet on preventing heat stroke.
Advise patient that ability to drive or operate machinery may be affected by side effects.
Side Effects
Abdominal pain
Acute myopia
Aggression
Agitation
Agranulocytosis
Alanine aminotransferase increased
Allergic reaction
Alopecia
Altered liver function tests
Amnesia
Anger
Anhidrosis
Anorexia
Anxiety
Aplastic anaemia
Aspartate aminotransferase increased
Ataxia
Attention disturbances
Blood disorders
Blood urea increased
Blurred vision
Bradyphrenia
Calculus formation
Cholecystitis
Cholelithiasis
Coma
Confusion
Constipation
Convulsions
Creatine phosphokinase increased
Decrease in blood bicarbonate
Decreased appetite
Decreased sweating
Depression
Diarrhoea
Diplopia
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyspepsia
Dyspnoea
Ecchymosis
Erythema multiforme
Eye pain
Fatigue
Glaucoma (acute closed angle)-age and shallow anterior chamber predisposes
Grand mal seizure
Hallucinations
Heat stroke
Hydronephrosis
Hyperammonaemia
Hypersensitivity reactions
Hypokalaemia
Impaired memory
Influenza-like syndrome
Insomnia
Irritability
Lability of affect
Leucocytosis
Leucopenia
Lymphadenopathy
Metabolic acidosis
Myasthenia
Nausea
Nephrolithiasis
Neuroleptic malignant syndrome
Nystagmus
Ocular hyperaemia
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral oedema
Pneumonia
Pneumonia aspiration
Pruritus
Psychotic symptoms
Pyrexia
Rash
Reduced visual acuity
Renal failure
Renal tubular acidosis
Respiratory disorders
Rhabdomyolysis
Serum creatinine increased
Severe hepatocellular damage
Somnolence
Speech disturbances
Status epilepticus
Stevens-Johnson syndrome
Sudden unexplained death
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Urinary tract infections
Urine abnormality
Vomiting
Weight loss
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: January 2021
Reference Sources
Summary of Product Characteristics: Desizon 20mg/ml oral suspension. Desitin Pharma Ltd. Revised February 2021.
Summary of Product Characteristics: Zonegran 25, 50, 100mg Hard Capsules. Eisai Ltd. Revised March 2021.
Summary of Product Characteristics: Zonisamide 25mg Hard Capsules. Accord Ltd. Revised March 2019.
Summary of Product Characteristics: Zonisamide 50mg Hard Capsules. Accord Ltd. Revised March 2019.
Summary of Product Characteristics: Zonisamide 100mg Hard Capsules. Accord Ltd. Revised March 2019.
Summary of Product Characteristics: Zonisamide 25mg Hard Capsules. Dr. Reddy's Laboratories Ltd. Revised February 2018.
Summary of Product Characteristics: Zonisamide 50mg Hard Capsules. Dr. Reddy's Laboratories Ltd. Revised February 2018.
Summary of Product Characteristics: Zonisamide 100mg Hard Capsules. Dr. Reddy's Laboratories Ltd. Revised February 2018.
MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: March 12, 2013
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 January 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Zonisamide Last revised: 21 September 2020
Last accessed: 18 January 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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