Rashes lamotrigine

Lamotrigine Modulate sodium channels Loading dose Not recommended due to increased risk of rash Maintenance dose 1 50-800 mg/day in 2-3 divided doses. Doses should be initiated and titrated according to the manufacturer s recommendations to reduce the risk of rash Half-life Not established Monotherapy 24 hours Concurrent enzyme inducers 12-15 hours Concurrent enzyme inhibitors 55-60 hours Apparent volume of distribution 1.1 L/kg Protein binding 55% Primary elimination route Hepatic Ataxia, drowsiness, headache, insomnia, sedation Rash... 

Lamotrigine is not approved for the acute treatment of depression, and the dose must be started low and slowly titrated up to decrease adverse effects if used for maintenance therapy of bipolar I disorder. A drug interaction and a severe dermatologic rash may occur when lamotrigine is combined with valproate (i.e., lamotrigine doses must be halved from standard dosing titration). 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Lamotrigine Diplopia Dizziness Unsteadiness Headache Rash Not established... 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

A concern with the administration of lamotrigine is that it has the potential to induce the Stevens-Johnson syndrome (exfoliative dermatitis). The incidence of a serious rash in clinical trials appears to be about 0.08% with monotherapy and 0.13% with combination therapy. The rash usually resolves when lamotrigine is stopped, but all patients starting lamotrigine should be cautioned to be vigilant for the development of a rash, especially during the first 6 months of treatment. 

Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with lamotrigine use. The incidence of these rashes, which include Stevens-Johnson syndrome, is approximately 1 % in pediatric patients (younger than 16 years of age) and 0.3% in adults. 

In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08% in adult patients receiving lamotrigine as initial monotherapy and 0.13% in adult patients receiving lamotrigine as adjunctive therapy. 

Other than age, no factors have been identified that are known to predict the risk of occurrence or the severity of rash associated with lamotrigine. It is suggested, yet to be proven, that the risk of rash may also be increased by 1) coadministration of lamotrigine with valproic acid (VPA), 2) exceeding the recommended initial dose of lamotrigine, or 3) exceeding the recommended dose escalation for lamotrigine. However, cases have been reported in the absence of these factors. 

Nearly all cases of life-threatening rashes associated with lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have been reported after prolonged treatment (eg, 6 months). Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash. 

Serious rashes associated with hospitalization and discontinuation of lamotrigine have been reported. It is recommended that lamotrigine not be restarted in patients who discontinued use due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine, assess the need to restart with the initial dosing recommendations (See Administration and Dosage). 

Severe skin rashes appear to be the major concern with lamotrigine use. The incidence of rash is greater in children than in adults. Other adverse effects are similar to those of drugs with the same mechanism of action, such as cerebellovestibular changes leading to dizziness, diplopia, ataxia, and blurred vision. Disseminated intravascular coagulation has been reported. 

It is very important to choose medications with the least possibility of making an ill pediatric patient suffer additional morbidity from side effects to medication directed at mood or behavior. For these reasons, mood stabilizers such as lamotrigine (which carries with it the risk of a severely toxic rash) should be seen only as third- or fourth-line agents. 

Valproate may increase concentrations of phenobarbital, etho-suximide, and the active 10,11-epoxide metabolite of carba-mazepine, increasing the risk of toxicity. Valproate may also raise lamotrigine levels, increasing the risk of rash. 

Lamotrigine is well tolerated and is not associated with hepatotox-icity, weight gain, or significant sedation. Common early side effects include headache, dizziness, gastrointestinal distress, and blurred or double vision. The most serious potential side effect is rash (described in the following subsection). 

A maculopapular rash develops in 5%-10% of patients taking lamotrigine, usually in the first 8 weeks of treatment. Serious rashes requiring hospitalization and discontinuation of treatment may occur. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.08% (0.8 per 1,000). Stevens-Johnson syndrome is potentially fatal. Patients must be advised of this risk and of the necessity to call the office at once if they develop a rash. Development of a rash with concomitant systemic symptoms is a particularly ominous sign, and the patient should be evaluated immediately. 

These early trials indicate a possible bimodal therapeutic effect with lamotrigine for both the manic and depressed phases. Low starting doses and slow titration are required, however, due to the increased risk of rash (approximately 10%), of which 1% may be more severe and possibly life-threatening ( 233), limiting this agent s use for acute episodes. 

Wong 1C, Mawer GE, Sander JW. Factors influencing the incidence of lamotrigine-related skin rash. Ann Pharmacother 1999 33 1037-1042. 

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