LAMITREE 25
-
Chemical Name:
Lamotrigine -
Therapeutic Category:
Central nervous system drugs -
Pharmacologic Category:
Anticonvulsant, Miscellaneous -
Pharmaceutical Form:
Tablets -
Composition:
Lamotrigine 25mg
LAMITREE
Tablets, Chewable/Dispersibale Tablets
Lamotrigine
1.PHARMACOLOGY:
Lamotrigine is rapidly and completely absorbed from the gut. The peak plasma concentration occurs approximately 2.5 hours after oral drug administration. Following multiple administration of lamotrigine, there is modest induction of its own metabolism, but there is no evidence of induction of mono-oxygenase enzymes to an extent that would cause clinically important interactions with drugs metabolized by these enzymes.
Lamotrigine is 55% bound to plasma proteins; it is very unlikely that displacement from plasma proteins would result in toxicity. The mean elimination half-life is 29 hours and the pharmacokinetic profile is linear up to 450 mg the highest single dose tested. The half-life of Lamotrigine is greatly affected by concomitant medication with a mean value of approximately 14 hours when given with enzyme inducing drugs such as carbamazepine and phenytoin, and increasing to a mean of approximately 70 hours when co-administered with sodium valproate alone.
Clearance adjusted for bodyweight is higher in children aged 12 years and under than in adults, with the highest values in children under 5 years. The half-life of Lamotrigine is generally shorter in children than in adults with a mean value of approximately 7 hours when given with enzyme inducing drugs such as carbamazepine and phenytoin, and increasing to mean values of approximately 45 to 55 hours when co-administered with sodium valproate alone.
Metabolism: 94% of the dose of Lamotrigine is recovered in the urine over a period of 168 hours. Only 2% was recovered in the feces.
Lamotrigine is extensively metabolized in man and the major metabolite is an N-glucuronide.
2.INDICATIONS:
Lamitree is indicated in the following cases :
Adjunctive use: Lamitree is indicated as adjunctive therapy for partial seizures and generalized seizures of Lennox-Gastaut syndrome and primary generalized tonoclonic seizures in adults and pediatric patients ( ≥ 2years of age ).
Monotherapy use: Lamitree is indicated for conversion to mono therapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, Phenobarbital, primidone, or valproate. Safety and effectiveness of Lamitree has not been established 1) as initial monotherapy, 2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate, 3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.
Bipolar disorder : Lamitree is indicated for the maintenance treatment of bipolar disorder to delay the time of occurrence of mood episodes (depression, mania, mixed episodes) in patients treated for acute mood episodes with standard therapy.
3.CONTRAINDICATIONS:
Lamotrigine is contra-indicated in individuals with known hypersensitivity to Lamotrigine.
4.PRECAUTIONS :
Exceeding the recommended dose at initiation of Lamotrigine therapy may be associated with an increased incidence of rash requiring withdrawal of therapy.
It is recommended that physician closely monitor (including hepatic, renal and clotting parameters) patients who acutely develop any combination of unexplained rash, fever, flu-like syndrome, drowsiness or worsening of seizure control, especially within the first month of starting treatment with Lamotrigine.
Lamotrigine is a weak inhibitor of dihydrofolate reductase, hence there is a possibility of interference with folate metabolism during long term therapy. However, during dosing of up to 1 year, Lamotrigine did not induce significant changes in the hemoglobin concentration, erythrocyte mean cell volume, and serum or red blood cell folate concentrations.
As with other, Anti epileptic drug, abrupt withdrawal of Lamotrigine may provoke rebound seizures, this risk may be avoided by tapering the withdrawal of Lamotrigine over a period of 2 weeks.
Pregnancy and Lactation: Lamotrigine should not be used during pregnancy only if potential benefit justifies the potential risk to fetus. No information is available on the concentration of Lamotrigine or its metabolites, which may appear in human breast milk.
Carcinomatous: Lamotrigine was not carcinogenic in long-term studies in rat and mouse. Lamotrigine did not impair fertility in animal productive studies.
5.DRUG INTERACTIONS:
Antiepileptic agents which induce drug metabolizing enzymes in the liver (such as phenytoin, carbamazepine, phenobarbital and primidone) enhance the metabolism of Lamotrigine. Sodium valproate, which inhibits drug metabolizing enzymes in the liver, reduces the metabolism of Lamitree.
There is no evidence that Lamitree causes induction or inhibition of hepatic oxidative drug metabolizing enzymes.
Increases in the plasma concentrations of other antiepileptic drugs have been reported in a few patients, however controlled studies have shown no evidence that Lamotrigine affects the plasma concentration of concomitant antiepileptic drugs. Evidence from in vitro studies indicates that Lamotrigine does not displace other antiepileptic drugs from protein binding sites.
However, the patient taking oral contraceptives should be asked to report any change in the menstrual bleeding pattern.
6.SIDE EFFECTS:
- There have been reports of headache, nausea, dizziness, diplopia, and ataxia in patients taking Carbamazepine following the introduction of Lamotrigine. These usually resolve when the dose of either drug is reduced.
- Severe skin rash may occur and lead to withdrawal of Lamotrigine treatment. The rash is usually maculopapular in appearance, generally appears within 4 weeks of starting treatment and resolves on withdrawal of Lamotrigine. Severe skin reactions including angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. All patients who develop a rash should be promptly evaluated and consideration should be given to the withdrawal of Lamotrigine.
- Various reactions including fever, malaise, flu-like symptoms, drowsiness and rarely hepatic dysfunction, lymphadenopathy, leucopenia and thrombocytopenia have been reported in conjunction with skin rash.
- Other adverse reactions reported when Lamotrigine is added on standard antiepileptic drug regiments have been included diplopia, blurred vision, dizziness, drowsiness, headache, ataxia, tiredness, gastrointestinal disturbance, irritability, aggression, tremor, agitation and confusion.
7.DOSAGE & ADMINISTRATION:
As adjunctive therapy in epileptic patients :
Lamitree added to an antiepileptic regimen containing valproate in patients from 2 to 12 years of age :
Table 1:
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Weeks 1 and 2: 0.15 mg/kg/day in 1 or 2 divided doses
Weeks 3 and 4: 0.3 mg/kg/day in 1 or 2 divided doses
Weight based dosing can be achieved by using the following guide :
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| Greater than | Less than | Weeks 1 and 2 | Weeks 3 and 4 |
| 6.7 kg | 14 kg | 2 mg every day | 2 mg every day |
| 14.1 kg | 27 kg | 2 mg every day | 4 mg every day |
| 27.1 kg | 34 kg | 4 mg every day | 8 mg every day |
| 34.1 kg | 40 kg | 5 mg every day | 10 mg every day |
|
Usual maintenance dose (week 5 and thereafter): 1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses), 1-3 mg/Kg/day with valproate alone. The dose should be increased every 1-2 weeks as follows: Calculate 0.3 mg/Kg/day, round this amount down to the nearest whole tablet and add this amount to previously administered daily dose.
Maintenance doses in patients weighing less than 30 kg: may need to be increased by as much as 50 % based on clinical response.
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Lamitree added for patients taking carbamazepine, phenytoin, phenobarbital, and primidone (without valproate) in patients of 2 to 12 years of age:
Table 2:
Weeks 1 and 2: 0.6 mg/kg/day in 2 divided doses
Weeks 3 and 4: 1.2 mg/kg/day in 2 divided doses
Usual maintenance dose (week 5 and thereafter): 5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided doses). The dose should be increased every 1-2 weeks as follows: Calculate 1.2 mg/Kg/day, round this amount down to the nearest whole tablet and add this amount to previously administered daily dose.
Maintenance doses in patients weighing less than 30 kg: may need to be increased by as much as 50 % based on clinical response.
Lamitree for patients from 2-12 years of age taking AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate :
Table 3 :
Weeks 1 and 2: 0.3 mg/kg/day in 1 or 2 divided doses .
Weeks 3 and 4: 0.6 mg/kg/day in 2 divided doses.
Usual maintenance dose (week 5 and thereafter): 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses). The dose should be increased every 1 to 2 weeks as follows: Calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet and add this amount to the previously administered daily dose.
Maintenance doses in patients weighing less than 30 kg: may need to be increased by as much as 50 % based on clinical response.
Lamitree added to an antiepileptic drug regimen containing valproate in patients over 12 years of age:
Table 4:
Weeks 1 and 2: 25 mg every other day
Weeks 3 and 4: 25 mg every day
Usual maintenance dose (weeks 5 and thereafter): 100 to 400 mg/day (in 1 or 2 divided doses), 100-200 mg/day with valproate alone. To achieve the usual maintenance dose, doses may increase by 25 mg to 50 mg/day every 1 to 2 weeks.
Lamitree added for patients taking carbamazepine, phenytoin, phenobarbital, and primidone (without valproate) in patients over 12 years of age:
Table 5:
Weeks 1 and 2: 50 mg/day
Weeks 3 and 4: 100 mg/day (in 2 divided doses)
Usual maintenance dose (week 5 and thereafter): 300 to 500 mg /day (in 2 divided doses). To achieve maintenance, doses may be increased by 100 mg/day every 1 to 2 weeks.
Lamitree for patients over 12 years of age taking AEDs other than carbamazepine, phenytoin, phenobarbital, primidone or valproate:
Table 6:
Weeks 1 and 2: 25 mg every day
Weeks 3 and 4: 50 mg/day
Usual Maintenance dose (Weeks 5 and thereafter): 225 to 375 mg/day (in 2 divided doses). To achieve maintenance, doses may be increased by 50 mg/day every 1 to 2 weeks.
Conversion from adjunctive therapy with carbamazepine, phenytoin, phenobarbital, primidone or valproate as the single AED to monotherapy with Lamitree in patients ≥ 16 years of age with epilepsy:
The conversion regimen involves 2 steps, in the first, Lamitree is titrated to the targeted dose while maintaining the dose of AED at a fixed level, in the second, the AED is gradually withdrawn over a period of 4 weeks.
The recommended maintenance dose of Lamitree as monotherapy is 500 mg/day given in 2 divided doses to avoid risk of rash, the recommended initial dose and subsequent dose escalation should not be exceeded.
Conversion from Adjunctive therapy with carbamazepine, phenytoin, phenobarbital, or primidone to monotherapy with Lamitree:
Lamitree should be added to an AED to achieve a dose of 500 mg/day according to tables 4 and 5 listed above. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled clinical trial. In that trial the concomitant AED was withdrawn by 20% each week over a 4-week period.
Conversion from adjunctive therapy with valproate to monotherapy with Lamitree:
The conversion regimen involves the following 4 steps:
Step 1: Lamitree: Achieve a dose of 200 mg/day according to the guidelines in tables 4 and 5 (if not already 200 mg/day).
Valproate: Maintain previous stable dose.
Step 2: Lamitree: Maintain at 200 mg/day.
Valproate: Decrease to 500 mg/day by decrements no greater than 500 mg/day per week and then maintain the dose of 500 mg/day for 1 week.
Step 3: Lamitree: Increase to 300 mg/day and maintain for 1 week.
Valproate: Simultaneously decrease to 250 mg/day and maintain for 1 week.
Step 4: Lamitree: Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day.
Valproate: Discontinue.
Usual maintenance dose for epilepsy:
In patients receiving multi-drug regimens including AEDs without valproate, maintenance doses in patients of adjunctive Lamitree is as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive Lamitree as high as 200 mg/day have been used.
Discontinuation strategy for Lamitree in patients with epilepsy:
For patients receiving Lamitree in combination with other AEDs, a re-evaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse experiences is observed.
If a decision is made to discontinue therapy with Lamitree, a reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal.
Discontinuing an AED should prolong the half-life of Lamitree; discontinuing valproate should shorten the half-life of Lamitree.
Regimen for Lamitree for patients with bipolar disorders:
Table 7:
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|
Patients not taking carbamazepine, phenytoin, phenobarbital, primidone or rifampin and not taking valproate | Patients taking valproate | Patients taking carbamazepine, phenytoin, phenobarbital, primidone or rifampin and not taking Valproate |
| Weeks 1 & 2 | 25 mg daily | 25 mg every other day | 50 mg daily |
| Weeks 3 & 4 | 50 mg daily | 25 mg daily | 100 mg daily in divided doses |
| Weeks 5 | 100 mg daily | 50 mg daily | 200 mg daily in divided doses |
| Weeks 6 | 200 mg daily | 100 mg daily | 300 mg daily in divided doses |
| Weeks 7 | 200 mg daily | 100 mg daily | Up to 400 mg daily in divided doses |
Adjustments to Lamitree dosing for patients with bipolar disorder following discontinuation of psychotropic medications:
Table 8:
| Discontinuation of psychotropic drugs excluding valproate, carbamazepine, or other enzyme inducing drugs | After discontinuation of valproate | After discontinuation of carbamazepine or, phenytoin, phenobarbital, primidone or rifampin | |
| Current Lamitree dose 100 mg/day | Current Lamitree dose 400 mg/day | ||
| Weeks 1 | Maintain current Lamitree dose | 150 | 400 |
| Weeks 2 | Maintain current Lamitree dose | 200 | 300 |
| Weeks 3 onward | Maintain current Lamitree dose | 200 | 200 |
Administration:
Lamitree dispersible may be chewed. swallowed or dispersed in a small volume of water at least enough to cover the whole tablet(1 teaspoon) and after one minute of dispersing the tablet stir the solution and swallow the whole solution.
Lamitree the whole tablet should be swallowed.
8.PACKAGING AND COMPOSITION:
- LAMITREE 25 – Tablets: A pack of 10 tablets. Each tablet contains Lamotrigine 25 mg.
- LAMITREE 100 – Tablets: A pack of 10 tablets. Each tablet contains Lamotrigine 100 mg.
- LAMITREE 150 – Tablets: A pack of 10 tablets. Each tablet contains Lamotrigine 150 mg.
- LAMITREE 200 – Tablets: A pack of 10 tablets. Each tablet contains Lamotrigine 200 mg.
- LAMITREE 5 – Chewable/Dispersible Tablets: A pack of 20 tablets. Each tablet contains Lamotrigine 5 mg.
9.STORAGE CONDITIONS:
Store LAMITREE – Tablets or Chewable Tablets at temperature between (15-30)°C in a dry place. Protect from light.
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