Lamotrigine oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of lamotrigine.
Drugs List
Therapeutic Indications
Uses
Depressive episodes associated with bipolar disorder: prevention
Treatment of all forms of epilepsy
Epilepsy
Patients aged 13 years and over
Adjunctive or monotherapy treatment of partial seizures and generalised seizures, including tonic-clonic seizures.
Seizures associated with Lennox-Gastaut syndrome. Lamotrigine is given as adjunctive therapy but may be the initial antiepileptic drug to start with in Lennox-Gastaut syndrome.
Patients aged 2 to 12 years
Adjunctive treatment of partial seizures and generalised seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.
Monotherapy of typical absence seizures.
Bipolar disorder
Patients aged 18 years and over
Prevention of depressive episodes in patients with bipolar disorder who experience predominantly depressive episodes.
Unlicensed Uses
Trigeminal neuralgia
Dosage
If the required dose of lamotrigine cannot be achieved using whole tablets, the dose to be administered is that equal to the lower number of whole tablets.
The initial dose and subsequent dose escalation should not be exceeded to minimise the risk of rash.
Adults
Epilepsy
Monotherapy
Initial dose 25mg once daily for 14 days followed by 50mg once daily for 14 days. Thereafter, the dose should be increased by a maximum of 50mg to 100mg every 1 to 2 weeks until the optimal dose is achieved. The usual maintenance dose to achieve optimal response is 100mg to 200mg a day given once a day or as two divided doses. Some patients have required 500mg a day to achieve the desired response.
Add on therapy
In patients taking medicines where the pharmacokinetic interaction with lamotrigine is currently not known, the dose escalation as recommended for lamotrigine with concurrent valproate should be used, thereafter, the dose should be increased until optimal response is achieved.
Adjunctive therapy with valproate
Initially 25mg every alternate day for 14 days then 25mg daily for 14 days. Thereafter, the dose should be increased by a maximum of 25mg to 50mg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100mg to 200mg daily given once a day or as two divided doses.
Adjunctive therapy without valproate and with inducers of lamotrigine glucuronidation (Examples of enzyme inducing medicines are phenytoin, carbamazepine, phenobarbital, primidone, rifampicin and lopinavir/ritonavir)
Initial dose 50mg once daily for 14 days followed by 50mg twice daily for 14 days. Thereafter, the dose should be increased by a maximum of 100mg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 200mg to 400mg daily given in two divided doses. Some patients have required 700mg a day to achieve the desired response.
Adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation
Initial dose 25mg once daily for 14 days followed by 50mg once daily for 14 days. Thereafter, the dose should be increased by 50mg to 100mg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100mg to 200mg daily given once a day or as two divided doses.
Bipolar disorder
The target stabilisation dose will alter depending on clinical response.
Lamotrigine may be discontinued in bipolar disorder without a stepwise reduction of dose.
In patients taking medicines where the pharmacokinetic interaction with lamotrigine is currently not known, the dose escalation as recommended for lamotrigine with concurrent valproate should be used, thereafter, the dose should be increased until optimal response is achieved.
Dose escalation to the maintenance stabilisation dose
Monotherapy with lamotrigine or adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation
Initial dose 25mg once a day for 14 days, then 50mg once daily or in two divided doses for 14 days, followed by 100mg once a day or in two divided doses for 7 days. The usual target dose for optimal response is 200mg once a day or in two divided doses, but doses in the range 100mg to 400mg per day have been used.
Adjunctive therapy with valproate
Initial dose 25mg every alternate day for 14 days, then 25mg once daily for 14 days, followed by 50mg once a day or in two divided doses for 7 days. The usual target dose for optimal response is 100mg once a day or in two divided doses. Maximum dose of 200mg per day can be used depending on clinical response.
Adjunctive therapy without valproate and with inducers of lamotrigine glucuronidation
Initial dose 50mg once a day for 14 days, followed by 100mg per day in two divided doses for 14 days, then 200mg per day in two divided doses for 7 days, followed by 300mg per day in two divided doses for 7 days, increasing if necessary to a usual target dose of 400mg per day in two divided doses to achieve the optimal response.
Maintenance stabilization dose following withdrawal of concomitant medication
In patients taking medicines where the pharmacokinetic interaction with lamotrigine is currently not known, the treatment regimen recommended for lamotrigine is to initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.
Withdrawal of valproate
When valproate is withdrawn, double the stabilisation dose for lamotrigine, not exceeding an increase of more than 100mg per week as follows:
100mg per day of lamotrigine prior to withdrawal: 200mg per day for the first 7 days after withdrawal, then maintain the same dose taken in two divided doses. The dose may be increased to 400mg per day as needed from 14 days after withdrawal.
200mg per day of lamotrigine prior to withdrawal: 300mg per day for the first 7 days after withdrawal, then 400mg per day maintenance dose.
Withdrawal of inducers of lamotrigine glucuronidation (Examples of enzyme inducing medicines are phenytoin, carbamazepine, phenobarbital, primidone, rifampicin and lopinavir/ritonavir)
400mg per day of lamotrigine prior to withdrawal: 400mg per day for the first 7 days after withdrawal, then 300mg per day for 7 days, followed by a maintenance dose of 200mg per day (although the dose may be increased to 400mg per day as needed).
300mg per day of lamotrigine prior to withdrawal: 300mg per day for the first 7 days after withdrawal, then 225mg per day for 7 days, followed by a maintenance dose of 150mg per day (although the dose may be increased to 400mg per day as needed).
200mg per day of lamotrigine prior to withdrawal: 200mg per day for the first 7 days after withdrawal, then 150mg per day for 7 days, followed by a maintenance dose of 100mg per day (although the dose may be increased to 400mg per day as needed).
Withdrawal of medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation
Maintain the target dose achieved during dose escalation of 200mg per day in two divided doses (doses in the range 100mg to 400mg per day can be used).
Adjustment of dose following addition of other medication
In patients taking medicines where the pharmacokinetic interaction with lamotrigine is currently not known, the treatment regimen as recommended for lamotrigine with concurrent valproate, should be used.
Addition of valproate
200mg per day of lamotrigine prior to addition: 100mg per day as maintenance dose.
300mg per day of lamotrigine prior to addition: 150mg per day as maintenance dose.
400mg per day of lamotrigine prior to addition: 200mg per day as maintenance dose.
Addition of inducers of lamotrigine glucuronidation in patients not taking valproate (Examples of enzyme inducing medicines are phenytoin, carbamazepine, phenobarbital, primidone, rifampicin and lopinavir/ritonavir)
200mg per day of lamotrigine prior to addition: 200mg per day for the first 7 days after addition, then 300mg per day for 7 days, followed by a maintenance dose of 400mg per day.
150mg per day of lamotrigine prior to addition: 150mg per day for the first 7 days after addition, then 225mg per day for 7 days, followed by a maintenance dose of 300mg per day.
100mg per day of lamotrigine prior to addition: 100mg per day for the first 7 days after addition, then 150mg per day for 7 days, followed by a maintenance dose of 200mg per day.
Addition of medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation
Maintain the target dose achieved during dose escalation of 200mg per day (doses in the range 100mg to 400mg per day can be used).
Children
To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur.
If epileptic control is achieved with lamotrigine adjunct therapy, concomitant anti-epileptic drugs may be withdrawn and patients continued on lamotrigine monotherapy.
In patients taking antiepileptic drugs where the pharmacokinetic interaction with lamotrigine is currently not known, the dose escalation as recommended for lamotrigine with concurrent valproate should be used, thereafter, the dose should be increased until optimal response is achieved.
It is likely that patients aged 2 to 6 years will require a maintenance dose at the higher end of the recommended range.
Epilepsy
Over 13 years
(See Dosage; Adult)
Children 2 to 12 years
Treatment of typical absence seizures only (monotherapy)
Initial dose 300micrograms/kg bodyweight per day given once a day or two divided doses for 14 days, followed by 600micrograms/kg bodyweight per day given once a day or in two divided doses for 14 days. Thereafter, the dose should be increased by a maximum of 600micrograms/kg per day every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1mg/kg to 15mg/kg per day given once a day or in two divided doses, with a maximum of 200mg per day to achieve the desired response.
Adjunctive therapy with valproate
The initial lamotrigine dose is 150micrograms/kg bodyweight per day(*) given once a day for 14 days, followed by 300micrograms/kg/day given once a day for 14 days. Thereafter, the dose should be increased by a maximum of 300micrograms/kg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1mg/kg to 5mg/kg per day given once a day or in two divided doses to a maximum of 200mg daily.
(*) If the calculated daily dose is 1mg to 2mg, then 2mg lamotrigine may be taken on alternative days for the first 14 days. If the calculated daily dose is less than 1mg then lamotrigine should not be administered.
Adjunctive therapy without valproate and with inducers of lamotrigine glucuronidation (Examples of enzyme inducing medicines are phenytoin, carbamazepine, phenobarbital, primidone, rifampicin and lopinavir/ritonavir)
Initial is 600micrograms/kg bodyweight per day given in two divided doses for 14 days, followed by 1.2mg/kg per day for 14 days in two divided doses. Thereafter, the dose should be increased by a maximum of 1.2mg/kg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 5mg/kg to 15mg/kg per day once a day or in two divided doses, to a maximum of 400mg daily.
Adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation
The initial lamotrigine dose is 300micrograms/kg bodyweight per day given once a day or in two divided doses for 14 days, followed by 600micrograms/kg/day given once a day or in two divided doses for 14 days. Thereafter, the dose should be increased by a maximum of 600micrograms/kg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1mg/kg to 10mg/kg per day given once a day or in two divided doses, to a maximum of 200mg daily.
Patients with Hepatic Impairment
Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted according to clinical response.
Additional Dosage Information
Restarting Therapy
Prescribers should assess the need for escalation to maintenance doses when restarting patients on lamotrigine after discontinuation for any reason. The risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation. When the interval between discontinuing and restarting lamotrigine exceeds five half-lives, lamotrigine should generally be escalated to the maintenance dose as though initiating therapy.
Initiating Lamotrigine in Patients Taking Hormonal Contraceptives
Dose escalation should follow the normal guidelines (see Dosage; Adults).
Starting Hormonal Contraceptives in Patients Taking Lamotrigine
For women not taking inducers of lamotrigine glucuronidation, such as phenytoin, carbamazepine, phenobarbital, primidone or rifampicin, the maintenance dose of lamotrigine may need to be increased by up to two fold, according to clinical response. For women taking lamotrigine in addition to inducers of lamotrigine glucuronidation, adjustment of dose may not be necessary. See product literature.
Stopping Hormonal Contraceptives in Patients Taking Lamotrigine
For women not taking inducers of lamotrigine glucuronidation the maintenance dose of lamotrigine may need to be decreased by as much as 50%, according to clinical response. For women taking lamotrigine in addition to inducers of lamotrigine glucuronidation, adjustment may not be necessary. See product literature.
Contraindications
Children under 2 years
Precautions and Warnings
Females of childbearing potential
History of allergy or rash to antiepileptic drugs
Previous discontinuation due to severe rash
Suicidal ideation
Young adults
Breastfeeding
Brugada syndrome
Cardiac disorder
End stage renal disease
Galactosaemia
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Myoclonic epilepsy
Parkinson's disease
Pregnancy
Advise patient to protect skin if restarting following photosensitivity
Reduce dose in patients with moderate hepatic impairment
Reduce dose in patients with severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Consider prescribing by manufacturer to ensure seizure control maintenance
Folic acid 5mg daily required pre-conception to end of 1st trimester
Not indicated for the acute treatment of manic or depressive episodes
Some formulations contain lactose
May increase seizure frequency
Monitor body weight in children and review dose if necessary
Monitor closely patient with depression
Monitor for Antiepileptic Hypersensitivity Syndrome
Monitor for signs of bone marrow depression
Monitor for signs of suicide ideation or behaviour
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report signs of haemophagocytic lymphohistiocytosis (HLH)
Advise patient to seek immediate medical advice if rash occurs
Consider discontinuing if phototoxic reaction occurs
Discontinue if haemophagocytic lymphohistiocytosis (HLH) is suspected
May exacerbate myoclonic seizures
Gradually withdraw over 2 weeks
Advise patient to seek advice at first indications of pregnancy
Discontinue if drug-related rash or other hypersensitivity reactions occur
Maintain treatment at the lowest effective dose
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient that photosensitivity possible
Advise patient/carers to report signs of suicide ideation or behaviour
There have been reports of adverse skin reactions, generally occurring in the first 8 weeks of starting treatment. Although usually mild and self limiting, rarely life threatening skin rashes have been reported such as Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). The risk in children under 12 years is higher than in adults. Presentation of a rash and fever can be mistaken as an infection in children, consideration should be given to an adverse drug reaction if symptoms occur in the first 8 weeks of treatment. High doses of lamotrigine and exceeding the recommended dose escalation of therapy or concurrent use of valproate appears to be strongly associated with occurrence of the rash.
It is recommended that lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk. If the patient has developed SJS, TEN or DRESS with the use of lamotrigine, treatment with lamotrigine must not be restarted in this patient at any time.
Use with caution when treating patients with a history of allergy or rash to other antiepileptic drugs as frequency of non-serious rash after treatment with lamotrigine was approximately 3 times higher in these patients than in patients without any previous history.
There have been reported cases of photosensitivity with high doses (400mg or more), upon dose escalation or rapid up-titration.
Haemophagocytic lymphohistiocytosis (HLH) has been reported, generally occurring in the first 4 weeks of treatment. Immediate investigation is required in patients showing signs of HLH which include fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, high serum ferritin, hypertriglyceridaemia, abnormal liver function and abnormal coagulation. Unless an alternative aetiology can be identified, lamotrigine should be discontinued. Patients should be informed of the symptoms of HLH and advised to seek medical attention if they occur.
Patients receiving treatment for bipolar disorder should be closely monitored for worsening of depressive symptoms and suicidal behaviour. Patients, such as those with a history of suicidal behaviour, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a higher risk of suicidal behaviour, and should receive careful monitoring during treatment.
During clinical experience with lamotrigine, rarely, there have been deaths following rapidly progressive illnesses with status epilepticus, rhabdomyolysis, multiorgan dysfunction and disseminated intravascular coagulation. The contribution of lamotrigine to these events remains to be established.
In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive treatment (for example 'pill-free week'), gradual transient increases in lamotrigine levels will occur during that week with the possibility of adverse effects. Therefore, consideration should be given to using contraception without a pill-free week as first-line therapy.
Consultation with a cardiologist should be arranged before initiation of lamotrigine in patients with clinically important structural or functional heart diseases (Brugada syndrome, other cardiac channelopathies, heart failure, ischemic heart disease, heart block, ventricular arrhythmias) if the use of lamotrigine is clinically justified.
Pregnancy and Lactation
Pregnancy
Use lamotrigine with caution in pregnancy.
The manufacturer advises caution if lamotrigine is used during pregnancy.
Women of child bearing potential wherever possible should be prescribed monotherapy. The incidence of congenital abnormalities is less in the offspring of monotherapy patients.
There is an increased risk of teratogenicity during pregnancy, particularly if the woman is being treated with a combination of epileptic drugs. If treatment with lamotrigine is required during pregnancy, the lowest possible therapeutic dose is recommended.
Patients should be counselled regarding the possibility of increased risk of malformations and given the opportunity of antenatal screening.
Folic acid deficiency is known to occur during pregnancy. Antiepileptic medication is known to aggravate this deficiency. Folic acid supplementation is therefore recommended.
Epidemiological studies involving lamotrigine monotherapy cannot exclude an increased risk of congenital malformations. One registry has reported an increased incidence of facial clefts. Animal studies have shown development toxicity.
Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. It is recommended that lamotrigine serum levels are monitored before, during and after pregnancy.
Dose adjustment may be necessary during pregnancy and post-partum.
Lactation
Use lamotrigine with caution in breastfeeding.
The manufacturer advises caution if lamotrigine is used when breastfeeding.
Breastfed infants whose mothers are taking lamotrigine have relatively high plasma lamotrigine levels, averaging 30% of maternal serum levels, infant plasma levels up to 50% of maternal levels have been reported.
Mild thrombocytosis has been reported in some infants and withdrawal symptoms can occur if breastfeeding is abruptly discontinued. Lamotrigine can cause rare, but potentially fatal skin reactions, although none has been reported in breastfed infants.
The potential benefits of breastfeeding should be weighed against the potential risk of adverse affects occurring in the infant. Exposed infants should be monitored for adverse effects including poor weight gain, sedation and rash.
Counselling
Subdivision of dispersible/chewable tablets
Administration of partial quantities of the chewable/dispersible tablets is not advisable.
Side Effects
Aggression
Agitation
Agranulocytosis
Alopecia
Altered liver function tests
Anaemia
Aplastic anaemia
Arthralgia
Aseptic meningitis
Ataxia
Back pain
Blurred vision
Brugada ECG pattern
Choreo-athetoid movements
Confusion
Conjunctivitis
Decrease in bone mineral density
Diarrhoea
Diplopia
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Extrapyramidal effects
Facial oedema
Fever
Fractures
Gastro-intestinal symptoms
Haematological disorders
Haemophagocytic syndrome
Hallucinations
Headache
Hepatic failure
Hepatic impairment
Hypersensitivity syndrome
Hypogammaglobulinaemia
Insomnia
Intravascular coagulation (disseminated)
Irritability
Leucopenia
Lupus erythematosus-like syndrome
Lymphadenopathy
Movement disturbances
Multiorgan failure
Nausea
Nephritis
Neutropenia
Nightmares
Nystagmus
Osteopenia
Osteoporosis
Pain
Pancytopenia
Photosensitivity
Rash
Seizure frequency increased
Somnolence
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Tics
Tiredness
Toxic epidermal necrolysis
Tremor
Unsteady gait
Uveitis
Vomiting
Worsening of Parkinson's disease
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 2022
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.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Lamictal Tablets. GlaxoSmithKline UK. Revised February 2022.
Summary of Product Characteristics: Lamictal Dispersible. GlaxoSmithKline UK. Revised February 2022.
Summary of Product Characteristics: Lamotrigine tablets. Accord Healthcare Ltd. Revised October 2021.
Summary of Product Characteristics: Lamotrigine dispersible tablets. Accord-UK Ltd. Revised February 2022.
Summary of Product Characteristics: Lamotrigine tablets. Teva UK Limited. Revised February 2021.
MHRA Drug Safety Update January 2021
Available at: https://www.mhra.gov.uk
Last accessed: 12 May 2021
NICE Evidence Services
Available at: www.nice.org.uk
Last accessed: 18 March 2022
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Lamotrigine. Last revised: 20 February, 2022
Last accessed: 18 March, 2022
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