Interacting drugs- summary

              + Lamotrigine-
            
              Carbamazepine +  Lamotrigine    or lamotrigine + Cabamazepine
               lamotrigine concentration decreased by about 70%
               carbamazepime epoxide levels may be increased
              
              Phenobarbital / Primidone   
               lamotrigine concentration is decreased by about 40%
                                     
             Phenytoin 
              lamotrigine concentration is decreased by 45% to 54%

               Valoproic acid +   or    Lamotrigine +  Valproic acid
               lamotrigine concentration increased twofold and
                 valproic acid concentration is decreased by 25%
           

Most common- experiences associated with use of lamotrigine in combination with other antiepileptic drugs were- Dizziness, diplopia, ataxia, blurred vision, nausea, vomiting, and saomnlence, headache, and rash.

Body as a whole- Headache, accidental injury, flu syndrome, fever, abdominal pain, infection, neck pain, seizure exacerabation, chills

Cardiovascular- Hot flushes, palpitations

GI - Nausea, vomiting, diarrhea, dyspepsia, constipation, tooth disorder, dry mouth

Musculoskeltal- Arthtalgia, joint disorder, myasthenia

CNS- Dizziness, artaxia, somnolencce, incordination, insomnia, depression

Dermatolgic- Dry skin, ezema, erythema, hirsutism, maculopapular rash, sweating, urticaria, angioedema, fungal dermitisis, hepes zoster, leukoderma, petechial rash, pustular rash, seborrhea, skin discoloration, Stevens- Johnson synrome, vesiculobullous rash.

Special senses- Abnormality of accomodation, conjuntivitis, oscillopsia, photophobia, taste perversion, deafness, dry eyes, lacrimation disorder.

GU- Female lactation, hematuria, polyuria, urinary frequency/incontinence, urinary tract infection, vaginal moniliasis, abnornal ejaculation, acute kidney failure, breast pain, breast abscess, cystisis

Hypersens to the drug

Special precautions:

Serious rash leading to hospitilisation. Sudden unexplained deaths in epilepsy. Abrupt withdrawal. Renal/hepatic impairment.

Pregnancy, lactation. Monitoring- the value of monitoring plasma concentrations of lamotrigine has not been established

Special risk patients- caution is adviced when using lamotrigine in patients with diseases or conditions that could affect metabolism or elimination of the drug, such as renal or hepatic functin impairment or cardiac function impairment. Melanin -containing tissues- because lamotrigine binds to melanin it could accumulate i

n melanin rich tissues over time.Be aware of the possibility of long-term ophthlmic changes Photosentisization- may occur. Wear protective clothing

Warnings-

Dermatologic- priorto initiation oif treatment, instruct patients that rash may occur,that it may herald a serious medical event and that should it occur, it must be reported promptly to their physician.

Serious rash leading to hospitalization- rash resulting hospitalization occurred in 0.3% of the 3400 subjects who participated in clinical trials. No fatalities occurred among these individuals., but rash has been associated with fatal oucome in reports from non-domestic post marketing experience.

Sudden unexplained death in epilepsy- (SUDEP)- during premarketing development 20 sudden and unexplained deaths were recoreded among a cohort of 4700 patients with epilepsy Withdrawal seizures- as a rule AEDs should not be abruptly discontinued because of the possibility of increasing seizure frequency.

Unless safety concerns require a more rapid withdrawal, taper the dose of lamotrigine over a period of at least 2 weeks.

Satus epilepticus- valid estimates of the incidence of treatment energent status epilepticus among lamotrigine-treated patients are difficult to obtain.

Organ failure- a case of fulminant hepatic failure has been reported.

Renal/hepatic impairment- because there is no expereience with the use of lamotrigine in patients with impaired liver function, the use in such patients may be associated with risks.

Elderly- in a single dose study (150mg) the pharmacokinetics of lamotrigine in 12 elderly voulnteers between the ages of 65 to 76 years ( mean creatinine clearance, 61 ml/min,range 33 to 108) were similar to those of young healthy volunteers in other studies.

Pregnancy- use during pregnancy only if the potential benefit justifies te potential risk to the fetus.

Lactation- becuase the efects on the infants exposed to lamotrigine are not known, breast feeding while taking lamotrigine is not recommended.

Children- safety and efficacy for use inchildren < 16 years of age have not been established.

Epilepsy

Dosage: Adults- more than 16 years of age- recommended add on therapy- initial dose in patients not taking sodium valproate is 50mg once a day for 2 weeks, followed by 100mg/day given in 2 divided doses for 2 weeks.

Usual maintenance dose is 300 to 500mg/day given in 2 divided doses. Patients taking valproic acid- initial dose is 25mg every other day for 2 weeks followed by 25mg once a day for 2 weeks.

Overdosage-

Symptoms The highest known overdioses were in two women who each ingested doses > 4000mg. The plasma concentration of lamotrignine in one woman was 52 mcg/ml 4 hours after ingestion ( avalue 10 times greater than that seen in clinical trials). She became comatose and remained comatose for 8 to 12 hours. No ECG abnormalities were detected.

The other patient had dizziness,headache, and somnolence. Both women recoverd without sequelae.

Treatment

1. There are no specific antidotes for lamotrigine.

2. General supportive care is indicated including frequent monitoring of vital signs and close observation of the patient.

3. If indicated, induce emesis or perform gastric lavage.

4. Observe usual precautions to protect airway.

5. Keep in mind that lamotrignine is rapidly absorbed. 7. It is uncertain whether hemodialysis is an effective means of removing lamatrigine from the blood. 

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

1. Advise patients to notify their physician immediately if they develop a skin rash or if they actuely develop any worsening seizure control while taking lamotrigine

2. Lamotrigine may cause dizziness, somnolence and other symptoms and signs of CNS depression. Patients should observe caution while driving or performing tasks requiring alertness, coordination or physical dexterity.

3. Photosensitisation may occur. Caution patients to take protective measures against exposure to sunlight or ultraviolet light.

ANTICONVULSANTS INCLUDES - BARBITURATES - OXAZOLIDINEDIONES- MISCELLANEOUS- Phenobarbitone Paramethadione Lamotrigine Trimethadione Primidone HYDANTOINS- Valproic acid Phenytoin BENZODIAPINES- Cabamazepine Mephenytoin Clonazepam Phenacemide Ethotoin Clorazepate Felbamate Diazepam Gabapentin SUCCINIMIDES- Ethosuximide Methsuximide Phensuximide REFER PHENYTOIN SODIUM - 

Pharmacology:

Lamotrigine is an antiepileptic drug of pheyltriazine class. Thre precise mechanism of action is not known

Pharmacokinetics:

Lamotrigine is rapidly and completely absorbed after oral administration with negligable first pass metabolism. The bioavailability is not affected by food. Peak plasma conc occur anywhere from 1.4 to 4.8 hrs following drug administration.

Not affected

Pregnancy:

Use during pregnancy only if the potential benefits outweigh the risks

Lactation:

Breast feeding while taking lamotrigine is not recommended.

Children:

Safety and efficacy for use inchildren < 16 years of age have not been established.