Lamotrigine

Lamotrigine has a similar mechanism of action with phenytoin, it suppresses sustained rapid
firing of neurons and produces a voltage- and use-dependent blockade of Na+ channels. It
also inhibits voltage-gated Ca2+ channels, particularly the N- and P/Q-type channels. This
two features account for its efficacy in focal epilepsy and primary generalized seizures in
childhood (Katzung & Trevor, 2014).
EFFICACY
1
2
3
4

Reduces frequency of seizure

Evidence of long term remission with treatment
Clinical evidence showing the ability of the drug to achieve symptomatic
seizure relief in generalized tonic clonic seizure
Improves quality of life

POINT
S
+
+
+
+

Lamotrigine is effective in partial-onset and secondarily generalized tonic-clonic seizures,

primary generalized seizures (i.e., absence seizures, and primary generalized tonic-clonic
seizures), atypical absence seizures, tonic/atonic seizures, and Lennox-Gastaut syndrome.
In a study by Ebrahimi et al. (2012), 905 patients with epilepsy were treated, 505 patients
completing the study. Seizure was controlled in 63.5% of patients with monotherapy, a
further 21% were controlled using combined therapy with sodium valproate. Furthermore,
Lamotrigine (in the form of monotherapy or combination therapy) could control primary
generalized tonic-clonic epilepsy in higher than 88%, secondary generalized tonic-clonic
epilepsy in 71%, complex partial epilepsy in 72%, and juvenile myoclonic epilepsy in 81.5%
of the patients. Lamotrigine (monotherapy or combined therapy) was effective in 96.7% of
familial epileptic patients, and in 94% of patients with known focal lesions.
Lamotrigine was also found to be effective in providing long term remission (from treatment
to 12 months) when compared with carbamazepine, oxcarbazepine, gabapentine, and
topiramate, with no significant difference with that of carbamazepine (Marson, et al., 2007).
In a study of Viteri et al. (2010), 53 epilepsy patients underwent lamotrigine monotherapy. At
6 months follow up, patients reported better HRQoL (Health related quality of life) on both
lamotrigine (78.8 points) (p<0.05) in comparison with baseline, which is reported to be a
slight improvement. Another study by Allain et al. (2007) using Quality of Life in Epilepsy
Inventory (QOLIE)-31 questionnaire showed that among 341 patients with epilepsy, 34.6% of
patients reported improvements in energy-fatigue, medication effects, and seizure worry in
the questionnaire.
SAFETY
1
Minimal side effects
2
No adverse drug reaction
3
No drug interactions to phenytoin
4
Drug toxicity (therapeutic index) does not occur easily following the
prolonged use

POINTS
+
+

The side effects of lamotrigine includes dizziness, headache, diplopia, nausea, somnolence,
and skin rash. The rash is considered a typical hypersensitivity reaction to the drug (Katzung
& Trevor, 2014). However, most occurrences are minor, and does not require the
discontinuation of therapy.

Adverse reactions occur rarely, however, most of these consist of serious rashes which
require hospitalization. In a study of Ebrahimi et al. (2012), the major adverse events that
caused discontinuation of lamotrigine included: cutaneous reactions in 29 cases (3%);
Stevens-Johnson syndrome in 2 patients, severe headache in 9 cases (1%), exaggerated or
induced myoclonic jerk in 7 cases (0.8%), thrombocytopenia with leucopenia in 3 cases, and
dopa-responsive dystonia in 2 cases.
Lamotrigine, when given with phenytoin, may have a decreased effect due to increased
elimination through the hepatic route (Katzung & Trevor, 2014).
Lamotrigine therapeutic concentrations are generally reported in the range of 2.5 to 15.0
mcg/mL, and show signs of toxicity when the peak serum concentration is >20 mcg/mL,
some patients can tolerate peak concentrations as high as 70 mcg/mL (Johannessen and
Landmark, 2008). Data also do not indicate that lamotrigine possesses all the general
characteristics of NTI (narrow therapeutic index) drugs (Cai, et al., 2014)
NECESSITY
1
2
3

Less frequent dosing (duration) = once 2pts; twice 1pt.

No contraindications
Monotherapy

POINT
S
++
+

Evidence for monotherapy was aforementioned in the efficacy segment. For monotherapy,
dosing is initially 25 mg PO once a day for 2 weeks, followed by 50 mg/day PO for 2 weeks.
Maintenance dose 100-200 mg/day once a day or in two divided doses up to 500 mg daily.
The drug is contraindicated to those having hypersensitivity to any drug component or
formulation (MIMS, 2015).
AFFORDABILITY
1
PH P50 and below
2
PHP 51 to PHP 100
3
PHP 101 TO PHP 149
4
PHP 150 and above

POINTS
++++

Lamotrigine (Lamictal) 25 mg tablet; 50mg tablet

25 mg: 30s P660.00/pack
50 mg: 30s P1171.80/pack
1 tablet/P22.00-P39.00/day
SUMMARY: 13 PTS
Reference:
Allain, H., Schck, S., Nachit-Ouinekh, F., Plouin, P., Brunon, A.-M., Boulliat, J., . . .
El Hasnaoui, A. (2007). Improvement in quality of life after initiation of
lamotrigine therapy in patients with epilepsy in a naturalistic treatment
setting. European Journal of Epilepsy, 173184.

Cai, W., Ting, T., Polli, J., Berg, M., Privetera, M., & Jiang, W. (2014). Lamotrigine, a
Narrow Therapeutic Index Drug or Not? Neurology.
Ebrahimi, H., & Ebrahimi, F. (2012). The effect of lamotrigine on epilepsy. Iran
Journal of Neurology, 162163.
Katzung, B., & Trevor, A. (2014). Katzung Basic & Clinical Pharmacology 13 th
edition. McGraw-Hill Education.
Johannessen, S., Tomson, T. (2008) Pharmacokinetic variability of newer
antiepileptic drugs: when is monitoring needed? Clinical Pharmacokinetics,
1061-1075
Khinchi, M. S., Nielsencorrespondenceemail, K. A., Dahl, M., & Wolf, P. (2008).
Lamotrigine therapeutic thresholds. European Journal of Epilepsy, 391
395.
Marson, A., Al-Kharusi, A., Alwaidh, M., Appleton, R., Baker, G., Chadwick, D., . . .
Hughes, A. (2007). The SANAD study of effectiveness of carbamazepine,
gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of
partial epilepsy: an unblinded randomised controlled trial. The Lancet,
10001015.
Viteri, C., Codina, M., Cobaleda, S., Lahuerta, J., Barriga, J., & Morales. (2010).
Quality of life and treatment satisfaction in Spanish epilepsy patients on
monotherapy with lamotrigine or valproic acid. Seizure.