Lamnet™
[Lamotrigine]
Indications
EPILEPSY: Adults (over 12 years of age): Lamotrigine is indicated for use as adjunctive or monotherapy in the treaent of epilepsy, for partial seizures and generalized seizures, including tonic-clonic seizures and the seizures associated with Lennox- Gastaut Syndrome.
BIPOLAR Disorder: Adults (18 years of age and over): Lamnet is indicated for the prevention of mood episodes in patients with bipolar disorder, predominantly by preventing depressive episodes.
Contraindication
Lamnet is contraindicated in individuals with known hypersensitivity to Lamotrigine.
Drug Interactions
There is no evidence that lamotrigine causes clinically significant induction or inhibition of hepatic oxidative drug-metabolising enzymes. Antiepileptic agents (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes enhance the metabolism of Lamotrigine .Valproate, which competes with Lamotrigine for hepatic drug-metabolising enzymes, reduces the metabolism of Lamotrigine. There have been reports of central nervous system events including dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine following the introduction of Lamotrigine. These events usually resolve when the dose of carbamazepine is reduced. Fertility: Administration of Lamotrigine did not impair fertility in animal reproductive studies. There is no experience of the effect of Lamotrigine on human fertility. Teratogenicity: Lamotrigine is a weak inhibitor of dihydrofolate reductase. There is a theoretical risk of human foetal malformations when the mother is treated with a folate inhibitor during pregnancy. However, reproductive toxicology studies with Lamotrigine in animals at doses in excess of the human therapeutic dosage showed no teratogenic effects.
Pregnancy: There are insufficient data available on the use of Lamotrigine in human pregnancy to evaluate its safety. As with most drugs, Lamotrigine should not be used in pregnancy unless, in the opinion of the physician, the potential benefits of treaent to the mother outweigh any possible risks to the developing foetus. Lactation: Preliminary data indicate that Lamotrigine passes into breast milk in concentrations usually of the order of 40-45 % of the plasma concentration. In the small number of infants known to have been breastfed, the dose of Lamotrigine received was calculated to be approximately 0.06-0.75 mg/kg/24 hours, and no adverse experiences were reported.
Effects on Ability to Drive and Use Machines: Two volunteer studies have demonstrated that the effect of Lamotrigine on fine visual motor co-ordination, eye movements, body sway and subjective sedative effects did not differ from placebo. In clinical trials with Lamotrigine adverse events of a neurological character such as dizziness and diplopia have been reported. As there is individual variation in response to all antiepileptic drug therapy patients should consult their physician on the specific issues of driving and epilepsy .
Side Effects
Adverse experiences reported during Lamotrigine monotherapy trials include headache, tiredness, rash, nausea, dizziness, drowsiness and insomnia. In double-blind, add-on clinical trials, skin rashes occurred in up to 10% of patients taking Lamotrigine and in 5% of patients taking placebo. The skin rashes led to the withdrawal of Lamotrigine treaent in 2% of patients. The rash, usually maculopapular in appearance, generally appears within 8 weeks of starting treaent and resolves on withdrawal of Lamotrigine (see Precautions and Warnings).Rarely, serious potentially life threatening skin rashes, including Stevens Johnson syndrome and toxic epidermal necrolysis (Lyell Syndrome) have been reported. Other adverse experiences reported when Lamotrigine is added-on to standard antiepileptic drug regimens have included diplopia, blurred vision, conjunctivitis, dizziness, drowsiness, headache, unsteadiness, tiredness, gastrointestinal disturbance (including vomiting), irritability/aggression, tremor, agitation, confusion and haematological abnormalities (including leucopenia and thrombocytopenia).Over dosage :Symptoms and signs Ingestion of between 1.35 and 4 g Lamotrigine has been reported in a few patients. Clinical consequences were not severe, signs and symptoms included nystagmus, ataxia, dizziness, somnolence, headache and vomiting. A patient who ingested a dose calculated to be between 4 and 5 g Lamotrigine was admitted to hospital with coma lasting 8-12 hours followed by recovery over the next 2 to 3 days. A further patient who ingested 5.6 g Lamotrigine was found unconscious. Following treaent with activated charcoal for suspected intoxication the patient recovered after sleeping for 16 hours.
Treaent: In the event of overdosage, the patient should be admitted to hospital and given appropriate supportive therapy. Gastric lavage should be performed if indicated.
Warning and Precautions
There have been reports of adverse skin reactions, which have generally occurred within the first 8 weeks after initiation of lamotrigine treaent. The majority of rashes are mild and self limiting, however serious, potentially life threatening skin rashes including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see Adverse Reactions).The approximate incidence of serious skin rashes in adults is 1 in 1000. The risk is higher in children than in adults. Available data from a number of studies suggest the incidence in children requiring hospitalisation ranges from 1 in 300 to 1 in 100. In children, the initial presentation of a rash can be mistaken for an infection, physicians should consider the possibility of a drug reaction in children that develop symptoms of rash and fever during the first eight weeks of therapy. Additionally the overall risk of rash appears to be strongly associated with:High initial doses of Lamotrigine and exceeding the recommended dose escalation of Lamotrigine therapy (see Dosage and Administration).Concomitant use of valproate, which increases the mean half life of Lamotrigine nearly two fold (See Dosage and Administration).All patients (adults and children) who develop a rash should be promptly evaluated and Lamotrigine withdrawn immediately unless the rash is clearly not drug related. Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema and abnormalities of the blood and liver. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multiorgan failure. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and Lamotrigine discontinued if an alternative aetiology cannot be established. As with other AEDs, abrupt withdrawal of Lamotrigine may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of Lamnet should be gradually decreased over a period of 2 weeks. When concomitant antiepileptic drugs are withdrawn to achieve Lamotrigine monotherapy or other antiepileptic drugs (AEDs) are added-on to Lamotrigine monotherapy consideration should be given to the effect this may have on Lamotrigine pharmacokinetics (see Drug Interactions).Lamotrigine is a weak inhibitor of dihydrofolate reductase, hence there is a possibility of interference with folate metabolism during long-term therapy. However, during prolonged human dosing, Lamotrigine did not induce significant changes in the haemoglobin concentration, mean corpuscular volume, or serum or red blood cell folate concentrations up to 1 year or red blood cell folate concentrations for up to 5 years. In single dose studies in subjects with end stage renal failure, plasma concentrations of Lamotrigine were not significantly altered. However, accumulation of the glucuronide metabolite is to be expected; caution should therefore be exercised in treating patients with renal failure. Lamotrigine is cleared primarily by metabolism in the liver. No studies have been carried out in patients with significant impairment of hepatic function. Until such data become available Lamotrigine cannot be recommended in this condition. There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan dysfunction and disseminated intravascular coagulation, sometimes with fatal outcome. Similar cases have occurred in association with the use of Lamotrigine .
Dosage
Dosage and Administration Adults (over 12 years of age):
Dosage in Epilepsy Monotherapy: The initial Lamnet dose in monotherapy is 25mg once a day for two weeks, followed by 50 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 50 to 100 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100 to 200 mg/day given once a day or as two divided doses. Some patients have required 500 mg/day of Lamnet to achieve the desired response. Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (See Warnings and Precautions).
Dosage in Epilepsy Add-On Therapy: In patients taking valproate with/without any other AED, the initial Lamnet dose is 25mg every alternate day for two weeks, followed by 25mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 25 to 50 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100 to 200 mg/day given once a day or in two divided doses. In those patients taking concomitant AEDs or other medications (see Interactions) that induce Lamotrigine glucuronidation with/without other AEDs (except valproate). The initial Lamnet dose is 50mg once a day for two weeks, followed by 100 mg/day given in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 100mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 200 to 400 mg/day given in two divided doses. Some patients have required 700 mg/day of Lamnet to achieve the desired response. In those patients taking oxcarbazepine without any other inducers or inhibitors of Lamotrigine glucuronidation the initial Lamnet dose is 25mg once a day for two weeks, followed by 50mg once a day for two weeds. Thereafter the dose should be increased by a maximum of 50 to 100mg every one to two weeks until the optimal response achieved. The usual maintenance dose to achieve an optimal response is 100 to 200 mg/day given once a day or as two divided doses. Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Warnings and Precautions). Bipolar Disorder:
Adults (18 year of age and above): Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Warnings and Precautions). Lamnet is recommended for use in Bipolar patients at risk for future depressive episodes. The following transition regimen should be followed to prevent recurrence of depressive episodes. The transition regimen involves escalating the dose of Lamnet to a maintenance stabilization dose over six weeks after which other psychotropic and / or anti-epileptic drugs can be withdrawn, if clinically indicated. Adjunctive therapy should be considered for the prevention of manic episodes, as efficacy with Lamnet in mania has not been conclusively established. Adjunct therapy with inhibitors of lamotrigine glucuronidation e.g. Valproate. In patients taking glucuronidation inhibiting concomitant drugs such as valproate the initial Lamnet dose is 25mg every alternate day for two weeks, followed by 25 mg once a day for two weeks. The dose should be increased to 50mg once a day (or in two divided doses) in week 5. The usual target dose to achieve optimal response is 100mg/day given once a day or in two divided doses. However, the dose can be increased to a maximum daily dose of 200mg, depending on clinical response. b) Adjunct therapy with inducers of Lamotrigine glucuronidation in patients NOT taking inhibitors such as Valproate. This dosage regimen should be used with phenytoin, carbamazepine, phenobarbitone, primidone and other drugs known to induce lamotrigine glucuronidation (see interactions). In those patients currently taking drugs that induce lamotrigine glucuronidation and NOT taking valproate, the initial Lamnet dose is 50mg once a day for two weeks, followed by 100mg/day given in two divided doses for two weeks. The dose should be increased to 200 mg/day given as two divided doses in week 5. The dose may be increased in week 6 to 300 mg/day however, the usual target dose to achieve optimal response is 400 mg/day given in two divided doses which may be given from week 7. c) Monotherapy with Lamnet OR Adjunctive therapy in patients taking lithium, bupropion, olanzapine, oxcarbazepine, or other agents known not to significantly induce or inhibit lamotrigine glucuronidation. The initial Lamnet dose in patients who are taking lithium, bupropion, olanzapine, oxcarbazepine AND are not taking inducers or inhibitors of Lamotrigine glucuronidation or are taking Lamnet in monotherapy. is 25mg once a day for two weeks, followed by 50mg once a day (or in two divided doses) for two weeks. The dose should be increased to 100 mg/day in week 5. The usual target dose to achieve optimal response is 200 mg/day given once a day or as two divided doses. However. a range of 100 to 400mg was used in clinical trials. Once the target daily maintenance stabilisation dose has been achieved, other psychotropic medications may be withdrawn as laid out in the dosage schedule below .Following withdrawal of adjunct therapy with inhibitors of Lamotrigine glucuronidation e.g. valproate. The dose of Lamnet should be increased to double the original target stabilisation dose and maintained at this, once valproate has been terminated.
(b) Following withdrawal of adjunct therapy with inducers of lamotrigine glucuronidation depending on original maintenance dose. This regimen should be used with phenytoin, carbamazepine, phenobarbitone, primidone or other drugs known to induce Lamnet glucuronidation (see Interactions). The dose of Lamnet should be gradually reduced over three weeks as the glucuronidation inducer is withdrawn.
(c) Following withdrawal of adjunct therapy with other psychotropic or anti-epileptic drugs with no significant pharmacokinetic interaction with LAMNET e.g. lithium, bupropion, olanzapine, oxcarbazepine. The target dose achieved in the dose escalation programme should be maintained throughout withdrawal of the other medication. Adjusent of Lamnet daily dosing in patients with BIPOLAR DISORDER following addition of other medicatios. There is no clinical experience in adjusting the Lamnet daily dose following the addition of other medications. However, based on drug interaction studies, the following Recommendations can be made Discontinuation of Lamotrigine in Patients with Bipolar Disorder: In clinical trials, there was no increase in the incidence, severity or type of adverse experiences following abrupt termination of Lamotrigine versus placebo. Therefore, patients may terminate without a step-wise reduction of dose.
Children (less than 18 years of age): Safety and efficacy of Lamotrigine in bipolar disorder has not been evaluated in this age group. Therefore, a dosage recommendation cannot be made. The Elderly; There is limited information on the use of Lamotrigine in elderly patients. To date, there is no evidence to suggest that the response of this age group differs from that in the young. However, elderly patients should be treated cautiously.
Presentations Available
Tablets
White, rounded tablets, engraved SEARLE' on one side each containing 25 mg Lamotrigine . Lamnet
Tablets 50 mg: Pink, rounded -scored tablets, engraved 'SEARLE' on one side, each containing 50 mg Lamotrigine.
Lamnet Tablets 100 mg: Pink, rounded - scored tablets, engraved 'SEARLE' on one side, each containing 100 mg Lamotrigine.
Storage: Protect from moisture, freezing, excessive heat and sun-light. Lamnet 25 mg, 50mg and 100mg each packs are available in packs of 30's.
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