Side effects
Side effects such as rash, fever, and fatigue are very serious, as they may indicate incipient SJS, TEN, DRESS syndrome, or aseptic meningitis.[47]
Lamotrigine prescribing information has a black box warning about life-threatening skin reactions, including Stevens–Johnson syndrome (SJS), DRESS syndrome, and toxic epidermal necrolysis (TEN). The manufacturer states that nearly all cases appear in the first two to eight weeks of therapy. Patients should seek medical attention for any unexpected skin rash, as its presence is an indication of a possible serious or even deadly side effect of the drug.
Not all rashes that occur while taking lamotrigine progress to SJS or TEN. Between 5 and 10% of patients will develop a rash, but only one in a thousand patients will develop a serious rash. Rash and other skin reactions are more common in children, so this medication is often reserved for adults.
For patients whose lamotrigine has been stopped after the development of a rash, rechallenge with lamotrigine is also a viable option. Usually, rechallenge is done by reinstating lamotrigine at a smaller dose (5mg/day). However, it does not apply to very serious cases.[48] The incidence of these eruptions increases in patients who are currently on, or recently discontinued, a valproate-type anticonvulsant drug, as these medications interact in such a way that the clearance of both is decreased and the effective dose of lamotrigine is increased.
Due to the possibility of serious skin rashes, lamotrigine has a 5-week graduated dosing schedule for starting the medication.[49][50]
In 2018, the FDA required a new warning for the risk of hemophagocytic lymphohistiocytosis. This serious reaction can occur between days to weeks after starting the treatment.[51]
Other side effects include alopecia (hair loss), loss of balance or coordination, double vision, crossed eyes, pupil constriction, blurred vision, dizziness and lack of coordination, drowsiness, insomnia, anxiety, vivid dreams or nightmares, dry mouth, mouth ulcers, memory problems, mood changes, itchiness, runny nose, cough, nausea, indigestion, abdominal pain, weight loss, missed or painful menstrual periods, and vaginitis. The side-effects profile varies for different patient populations.[47] Overall adverse effects in treatment are similar between men, women, geriatric, pediatric, and racial groups.
Lamotrigine has been associated with a decrease in white blood cell count (leukopenia).[52] Lamotrigine does not prolong QT/QTc in Thorough QT (TQT) studies in healthy subjects.[53]
In people taking antipsychotics, cases of lamotrigine-precipitated neuroleptic malignant syndrome have been reported.[54][55]
Women
Women are more likely than men to have side effects.
Some evidence shows interactions between lamotrigine and female hormones, which can be of particular concern for women on estrogen-containing hormonal contraceptives. Ethinylestradiol, an ingredient of such contraceptives, has been shown to decrease serum levels of lamotrigine.[56] Women starting an estrogen-containing oral contraceptive may need to increase the dosage of lamotrigine to maintain its level of efficacy. Likewise, women may experience an increase in lamotrigine side effects upon discontinuation of birth control pills. This may include the "pill-free" week where lamotrigine serum levels have been shown to increase twofold.
Many studies have found no association between lamotrigine exposure in utero and birth defects, while those that have found an association have found only slight associations with minor malformations such as cleft palates.[57] Review studies have found that overall rates of congenital malformations in infants exposed to lamotrigine in utero are relatively low (1–4%), which is similar to the rate of malformations in the general population.[58]
