Lamitrin^®

Lamitrin® is a preparation of Lamotrigine. The precise mechanisms by which Lamotrigine exerts its anticonvulsant action are unknown. Lamotrigine involves an effect on sodium channels. Lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). The mechanisms by which Lamotrigine exerts its therapeutic action in bipolar disorder have not been established.

No Data

Lamitrin® is indicated for:
i) Epilepsy-adjunctive therapy in patients aged 2 years and older.

Partial-onset seizures

Primary generalized tonic-clonic seizures (PGTC)

Generalized seizures of Lennox-Gastaut syndrome

ii) Epilepsy-monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone or valproate as the single antiepileptic drug
iii) Bipolar disorder
Lamitrin ® ER is indicated for:
i) Adjunctive therapy for primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years and older
ii) Conversion to monotherapy in patients aged 13 years and older with partial-onset seizures
who are receiving treatment with a single antiepileptic drug

Route of administration:
Lamitrin ® and Lamitrin ER ® tablets are taken in oral route. Lamitrin® chewable/dispersible tablets should be placed onto the tongue and moved around in the mouth. Lamitrin® ER tablets must be swallowed whole and must not be chewed, crushed or divided. Lamitrin ® tablets Epilepsy-Adjunctive therapy

Table-1: Escalation regimen for Lamitrin® in patients older than 12 years with epilepsy
	In patients taking Valpoate	In patients not taking carbamazepine, phenytoin, phenobarbital, primidone or valproate	In patients taking carbamazepine, phenytoin, phenobarbital or primidone and not taking valproate
Weeks 1 and 2	25 mg every other day	25 mg everyday	50 mg/day
Weeks 3 and 4	25 mg everyday	50 mg/day	100 mg/day (in 2 divided doses)
Week 5 onward to maintenance	Should be increased by 25 to 50 mg/day every 1 to 2 weeks	Should be increased by 50 mg/day every 1 to 2 weeks	Should be increased by 100 mg/day every 1 to 2 weeks
Usual maintenance dose	100 to 200 mg/day with valproate alone. 100 to 400 mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses)	225 to 375 mg/day (in 2 divided doses)	300 to 500 mg/day (in 2 divided doses)

Table-2: Escalation regimen for Lamitrin@ in paiients aged 2 to 12 years with epilepsy
	In patients taking valproate	In patients not taking carbamazepine, phenytoin, phenobarbital, primidone or valproate	In patients taking carbamazepine, phenytoin, phenobarbital or primidone and not taking valproate
Weeks 1 and 2	0.15 mg/kg/day in 1 or 2 divided doses (see Table-3 for weight-based dosing guide)	0.3 mg/kg/day in 1 or 2 divided doses	0.6 mg/kg/day in 2 divided doses
Weeks 3 and 4	0.3 mg/kg/day in 1 or 2 divided doses (see Table-3 for weight-based dosing guide)	0.6 mg/kg/day in 2 divided doses	1.2 mg/kg/day in 2 divided doses
Week 5 onward to maintenance	The dose should be increased every 1 to 2 weeks as follows: 0.3 mg/kg/day should be calculated and this should be added to the previously administered daily dose	The dose should be increased every 1 to 2 weeks as follows: 0.6 mg/kg/day should be calculated and this should be added to the previously administered daily dose	The dose should be increased every 1 to 2 weeks as follows: 1.2 mg/kg/day should be calculated and this should be added to the previously administered daily dose
Usual maintenance dose	100 to 200 mg/day with valproate alone. 100 to 400 mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses)	225 to 375 mg/day (in 2 divided doses)	300 to 500 mg/day (in 2 divided doses)
Usual maintenance dose	1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses). 1 to 3 mg/kg/day with valproate alone	4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses)	5 to 15 mg(kg/day (maximum 400 mg/day in, 2 divided doses)
Maintenance dose in patients < 30 kg	May need to be increased by as much as 50%, based on clinical response	May need to be increasey by as much as 50%, pased clinical response	May need to be increased by as much as 50%, based on clinical response

Table-3: The initial weight-based dosing guide for patients aged 2 to 12 years taking
If the patient's weight		Give this daily dose, using the most appropriate combination of Lamitrin 2 mg and 5 mg tablets
Greater than or equal	And less than or equal	Weeks 1 and 2	Weeks 3 and 4
6.7 kg	14 kg	2 mg every other day	2 mg everyday
14.1 kg	27 kg	2 mg everyday	4 mg everyday
27.1 kg	34 kg	4 mg everyday	8 mg everyday
34.1 kg	40 kg	5 mg everyday	10 mg everyday

Epilepsy-Conversion from adjunctive therapy to monotherapy The recommended maintenance dose of Lamitrin® as monotherapy is 500 mg/day given in 2 divided doses. Conversion from adjunctive therapy with carbamazepine, primidone to monotherapy with Lamitrin® : After achieving a dose of 500 mg/day of Lamitrin® using the guidelines in Table-1, the concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week period Conversion from adjunctive therapy with valproate to monotherapy with Lamitrin®

Table-4: Conversion from adjunctive therapy with valproate to monotherapy with Lamitrin in patients aged 16 years and older with epilepsy
If the patient's weight		Give this daily dose, using the most appropriate combination of Lamitrin 2 mg and 5 mg tablets
	Lamitrin®	valproate
Step 1	A dose of 200 mg/day should be achieved Established stable dose should be according to guidelines in Table-1	Established stable dose should be maintained.
Step 2	Should be maintained at 200 mg/day.	Dose should be decreased by decrements not greater than 500 mg/day/week to 500 mg/day and then maintained for 1 week.
Step 3	Should be increased to 300 mg/day and maintained for 1 week.	Should be simultaneously decreased to 250 mg/day and maintained for 1 week.
Step 4	Should be increased by 100 mg/day every week to achieve maintenance dose of 500 mg/day.	Should be discontinued.

Conversion from adjunctive therapy with antiepileptic drugs other than carbamazepine, phenytoin, phenobarbital, primidone or valproate to monotherapy with Lamitrin® No specific dosing guidelines can be provided for conversion monotherapy with Lamitrin® with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone or valproate.
Bipolar disorder

Table-5: Escalation regimen for Lamitrin® in adults with bipolar disorder
	In patients taking valproate	In patients not taking carbamazepine, phenytoin, phenobarbital, primidone or valproate	In patients taking carbamazepine, phenytoin, phenobarbital or primidone and not taking valproate
Weeks 1 and 2	25 mg every other day	25 mg daily	50 mg daily
Weeks 3 and 4	25 mg daily	50 mg daily	100 mg daily, in divided doses
Weeks 5	50 mg daily	100 mg daily	200 mg daily, in divided doses
Weeks 6	100 mg daily	200 mg daily	300 mg daily, in divided doses
Weeks 7	100 mg daily	200 mg daily	upto 400 mg daily, in divided doses

Lamitrin ® ER tablets
Conversion from immediate-release Lamitrin ® tablets to Lamitrin ® ER Patients may be converted directly from immediate-release Lamitrin ® to Lamitrin ER ® extended-release tablets. The initial dose of Lamitrin ® ER should match the total daily dose of immediate-release Lamitrin ® . Following conversion to Lamitrin ® ER, all patients should be closely monitored for seizure control. Depending on the therapeutic response after conversion, the total daily dose may need to be adjusted.

Pregnancy:
If therapy with lamotrigine is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.
Lactation:
Lamotrigine is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for lamotrigine and any potential adverse effects on the breastfed infant from lamotrigine or from the underlying maternal condition. Use in children and adolescents
Lamotrigine immediate-release tablets are indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of Lennox-Gastaut syndrome and PGTC seizures. Safety and efficacy of lamotrigine immediate-release tablets for the maintenance treatment of bipolar disorder for pediatric patients are not established. Safety and effectiveness of lamotrigine extended-release tablets for any use in patients younger than 13 years have not been established.

No Data

Life-threatening serious rash and/or rash-related death may occur. Lamotrigine should be discontinued at the first sign of rash. The diagnosis of hemophagocytic lymphohistiocytosis should be considered and patients should immediately be evaluated if they develop signs or symptoms of systemic inflammation. On that case, lamotrigine should be discontinued. Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms, may be fatal or life threatening. Early signs may include rash, fever and lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic failure, blood dyscrasias or acute multiorgan failure. On that case, lamotrigine should be discontinued. Lamotrigine could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Blood dyscrasias (e.g.. neutropenia, thrombocytopenia and pancytopenia) may occur. Patients should be monitored for signs of anemia, unexpected infection, bleeding, suicidal thoughts or behaviors and signs of meningitis.

Most common side effects are dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, rash, vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, tremor, insomnia, back pain, fatigue and xerostomia.

Lamotrigine is contraindicated in patients with known hypersensitivity to lamotrigine or any other components of this product.

Drug interaction with medication: Valproate increases lamotrigine concentrations more than 2-fold, Carbamazepine, phenytoin, phenobarbital, primidone and rifampin decrease lamotrigine concentrations. Estrogen containing oral contraceptives decrease lamotrigine concentration. Protease inhibitors e.g., lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure. Co-administration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended.
Drug interaction with food and others:
Not applicable.