Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2021 Publisher: GlaxoSmithKline NZ Limited, Private Bag 106600, Downtown, Auckland, NEW ZEALAND, Phone: (09) 367 2900, Facsimile: (09) 367 2910
LAMICTAL is contraindicated in individuals with known hypersensitivity to lamotrigine or any other ingredient of the preparation.
A clinically significant worsening of seizure frequency instead of an improvement may be observed in patients with more than one seizure type, the observed benefit of control for one seizure type should be weighed against any observed worsening in another seizure type.
There have been reports of adverse skin reactions, which have generally occurred within the first 8 weeks after initiation of lamotrigine (LAMICTAL) treatment. The majority of rashes are mild and self limiting; however serious rashes requiring hospitalisation and discontinuation of lamotrigine have also been reported. These have included potentially life-threatening rashes such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (see section 4.8 Undesirable effects).
In adults enrolled in studies utilising the current lamotrigine dosing recommendations the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately half of these cases have been reported as SJS (1 in 1000).
In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000.
The risk of serious skin rashes in children is higher than in adults. Available data from a number of studies suggest the incidence of rashes associated with hospitalisation in children is 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:
Caution is also required when treating patients with a history of allergy or rash to other anti-epileptic medicines as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history.
All patients (adults and children) who develop a rash should be promptly evaluated and lamotrigine withdrawn immediately unless the rash is clearly not drug related. It is recommended that lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.
Rash has also been reported as part of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome. This condition is associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood, liver and kidney and aseptic meningitis (see section 4.8 Undesirable effects). The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multi-organ 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.
Postmarketing cases of aseptic meningitis have been reported in paediatric and adult patients taking LAMICTAL for various indications. Aseptic meningitis was reversible on withdrawal of the drug in most cases, but recurred in a number of cases on reexposure to lamotrigine. Re-exposure resulted in a rapid return of symptoms that were frequently more severe. Lamotrigine should not be restarted in patients who have discontinued due to aseptic meningitis associated with prior treatment of lamotrigine.
HLH has occurred in patients taking lamotrigine (see section 4.8 Undesirable effects). HLH is a syndrome of pathological immune activation, which can be life threatening,characterised by clinical signs and symptoms such as fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, high serum ferritin, hypertriglyceridaemia and abnormalities of liver function and coagulation. Symptoms occur generally within 4 weeks of treatment initiation.
Immediately evaluate patients who develop these signs and symptoms and consider a diagnosis of HLH. Lamotrigine should be discontinued unless an alternative aetiology can be established.
Symptoms of depression and/or bipolar disorder may occur in patients with epilepsy, and there is evidence that patients with epilepsy and bipolar disorder have an elevated risk for suicidality.
Twenty-five to 50% of patients with bipolar disorder attempt suicide at least once, and may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking medications for bipolar disorder, including lamotrigine.
Suicidal ideation and behaviour have been reported in patients treated with AEMs in several indications, including epilepsy and bipolar disorder. A meta-analysis of randomised placebo-controlled trials of AEMs (including lamotrigine) has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lamotrigine.
Therefore patients should be monitored for signs of suicidal ideation and behaviours. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Patients receiving lamotrigine for bipolar disorder should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Certain patients, such as those with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
An ethinylestradiol/levonorgestrel (30 micrograms/150 micrograms) combination has been demonstrated to increase the clearance of lamotrigine by approximately twofold resulting in decreased lamotrigine levels (see section 4.5 Interaction with other medicines and other forms of interaction). Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) will be needed in most cases to attain a maximal therapeutic response. In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive medication (e.g. “pill-free week”), gradual transient increases in lamotrigine levels will occur during the week of inactive medication. These increases will be greater when lamotrigine dose increases are made in the days before or during the week of inactive medication. For dosing instructions see section 4.2 Dose and method of administration – General dosing recommendations for lamotrigine in special patient populations: Women taking hormonal contraceptives. Clinicians should exercise appropriate clinical management of women starting or stopping hormonal contraceptives during lamotrigine therapy and lamotrigine dosing adjustments will be needed in most cases.
Other oral contraceptive and hormone replacement therapy (HRT) treatments have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters (see section 4.2 Dose and method of administration – General Dosing Recommendations for lamotrigine in special patient populations (for dosing instructions for women taking hormonal contraceptives) and section 4.4 Special warnings and precautions for use).
An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal contraceptive (ethinylestradiol/levonorgestrel combination) are administered in combination, there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see section 4.5 Interaction with other medicines and other forms of interaction). The impact of these changes on ovarian ovulatory activity is unknown. However, the possibility of these changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations with lamotrigine cannot be excluded. Therefore, patients should be instructed to promptly report changes in their menstrual pattern, i.e. breakthrough bleeding.
Lamotrigine is an inhibitor of renal tubular secretion via OCT 2 proteins (see section 4.5 Interaction with other medicines and other forms of interaction). This may result in increased plasma levels of certain medicines that are substantially excreted via this route. Co- administration of lamotrigine with OCT 2 substrates with a narrow therapeutic index e.g. dofetilide is not recommended.
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.
LAMICTAL should not be administered to patients currently being treated with any other preparation containing lamotrigine without consulting a doctor.
A very rare association with Brugada-type ECG has been observed, although a causal relationship has not been established. Therefore, careful consideration should be given before using lamotrigine in patients with Brugada syndrome (see section 5.1 Pharmacodynamics).
In vitro testing showed that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations. Based on these in vitro findings, lamotrigine could potentially slow ventricular conduction (widen QRS) and induce proarrhythmia in patients with clinically important structural or functional heart disease. Therefore, any expected or observed benefit of lamotrigine for those patients must be carefully weighed against the potential risks for serious or fatal cardiac events. Concomitant use of other sodium channel blockers may further increase the risk of proarrhythmia (see section 5.1 Pharmacodynamics).
As with other AEMs, abrupt withdrawal of lamotrigine may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of lamotrigine should be gradually decreased over a period of 2 weeks.
There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multi-organ dysfunction and disseminated intravascular coagulation, sometimes with fatal outcome. Similar cases have occurred in association with the use of lamotrigine.
Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour in children and adolescents with major depressive disorder and other psychiatric disorders.
Uridine 5'-diphospho (UDP)-glucuronyl transferases (UGTs) have been identified as the enzymes responsible for metabolism of lamotrigine. Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGTs, may also enhance the metabolism of lamotrigine. There is no evidence that lamotrigine causes clinically significant induction or inhibition of cytochrome P450 enzymes. Lamotrigine may induce its own metabolism but the effect is modest and unlikely to have significant clinical consequences.
Those drugs that have been demonstrated to have a clinically relevant impact on lamotrigine concentration are outlined in the table below. Specific dosing guidance for these drugs is provided in section 4.2 Dose and method of administration. In addition, this table lists those drugs which have been shown to have little or no effect on the concentration of lamotrigine. Coadministration of such drugs would generally not be expected to result in any clinical impact. However, consideration should be given to patients whose epilepsy is especially sensitive to fluctuations in concentrations of lamotrigine.
Table of effects of drugs on the concentration of lamotrigine:
| Drugs that increase the concentration of lamotrigine | Drugs that decrease the concentration of lamotrigine | Drugs that have little or no effect on the concentration of lamotrigine |
|---|---|---|
| Valproate | Atazanavir/ritonavir Carbamazepine Ethinylestradiol/levonorgestrel combination Lopinavir/ritonavir Phenobarbitone Phenytoin Primidone Rifampicin | Aripiprazole Bupropion Felbamate Gabapentin Lacosaminde Levetiracetam Lithium Olanzapine Oxcarbazepine Paracetamol Perampanel Pregabalin Topiramate Zonisamide |
For dosing guidance, see section 4.2 Dose and method of administration – General Dosing Recommendations for Lamotrigine in Special Patient Populations, plus for women taking hormonal contraceptives also see section 4.4 Special warnings and precautions for use – Hormonal contraceptives.
Valproate, which inhibits the glucuronidation of lamotrigine, reduces the metabolism of lamotrigine and increases the mean half-life of lamotrigine nearly two-fold.
Certain AEMs (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce cytochrome P450 enzymes also induce UGTs and, therefore, enhance 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. A similar effect was seen during a study of lamotrigine IR and oxcarbazepine in healthy adult volunteers, but dose reduction was not investigated.
In a study in healthy adult volunteers using doses of 200 mg lamotrigine and 1200 mg oxcarbazepine, oxcarbazepine did not alter the metabolism of lamotrigine and lamotrigine did not alter the metabolism of oxcarbazepine.
In a study of healthy volunteers, co-administration of felbamate (1200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine. Based on a retrospective analysis of plasma levels in patients who received lamotrigine both with and without gabapentin, gabapentin does not appear to change the apparent clearance of lamotrigine.
Potential medicine interactions between levetiracetam and lamotrigine were assessed by evaluating serum concentrations of both agents during placebocontrolled clinical trials. These data indicate that lamotrigine does not influence the pharmacokinetics of levetiracetam and that levetiracetam does not influence the pharmacokinetics of lamotrigine.
Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin (200 mg 3 times daily) administration. There are no pharmacokinetic interactions between lamotrigine and pregabalin.
Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.
In a study of patients with epilepsy, co-administration of zonisamide (200 to 400 mg/day) with lamotrigine (150 to 500 mg/day) for 35 days had no significant effect on the pharmacokinetics of lamotrigine.
Plasma concentrations of lamotrigine were not affected by concomitant lacosamide (200, 400 or 400 mg/day) in placebo-controlled clinical trials in patients with partialonset seizures.
In a pooled analysis of data from three placebo-controlled clinical trials investigating adjunctive perampanel in patients with partial-onset and primary generalised tonicclonic seizures, the highest perampanel dose evaluated (12 mg/day) increased lamotrigine clearance by less than 10%.
Although changes in the plasma concentrations of other anti-epileptic medicines have been reported, controlled studies have shown no evidence that lamotrigine affects the plasma concentrations of concomitant anti-epileptic medicines. Evidence from in vitro studies indicates that lamotrigine does not displace other anti-epileptic medicines from protein binding sites.
The pharmacokinetics of lithium after 2g of anhydrous lithium gluconate given twice daily for six days to 20 healthy subjects were not altered by co-administration of 100 mg/day lamotrigine.
Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.
In a study in healthy adult volunteers, 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20%, respectively. Lamotrigine at 200 mg did not affect the pharmacokinetics of olanzapine.
Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers. Following the co-administration of risperidone 2 mg with lamotrigine, 12 out of the 14 volunteers reported somnolence compared to 1 out of 20 when risperidone was given alone, and none when lamotrigine was administered alone.
In a study of 18 adult patients with bipolar I disorder, receiving an established regimen of lamotrigine (>/=100 mg/day), doses of aripiprazole were increased from 10 mg/day to a target of 30 mg/day over a 7 day period and continued once daily for a further 7 days. An average reduction of approximately 10% in Cmax and AUC of lamotrigine was observed.
In vitro inhibition experiments indicated that the formation of lamotrigine’s primary metabolite, the 2-N-glucuronide, was minimally affected by co-incubation with amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol, or lorazepam. Bufuralol metabolism data from human liver microsome suggested that lamotrigine does not reduce the clearance of medicines eliminated predominantly by CYP2D6. Results of in vitro experiments also suggest that clearance of lamotrigine is unlikely to be affected by clozapine, phenelzine, risperidone, sertraline or trazodone.
In a study of 16 female volunteers, 30 micrograms ethinylestradiol/150 micrograms levonorgestrel in a combined oral contraceptive pill caused an approximately two-fold increase in lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively. Serum lamotrigine concentrations gradually increased during the course of the week of inactive medication (e.g. “pill-free” week), with pre-dose concentrations at the end of the week of inactive medication being, on average, approximately two-fold higher than during co-therapy (see section 4.2 Dose and method of administration – General Dosing Recommendations for lamotrigine in special patient populations (for dosing instructions for women taking hormonal contraceptives) and section 4.4 Special warnings and precautions for use – Hormonal contraceptives).
In a study of 16 female volunteers, a steady state dose of 300 mg lamotrigine had no effect on the pharmacokinetics of the ethinylestradiol component of a combined oral contraceptive pill. A modest increase in oral clearance of the levonorgestrel component was observed, resulting in an average 19% and 12% reduction in levonorgestrel AUC and Cmax, respectively. Measurement of serum FSH, LH and estradiol during the study indicated some loss of suppression of ovarian hormonal activity in some women, although measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of the 16 subjects. The impact of the modest increase in levonorgestrel clearance, and the changes in serum FSH and LH, on ovarian ovulatory activity is unknown (see section 4.4 Special warnings and precautions for use). The effects of doses of lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparations have not been conducted.
In a study in 10 male volunteers, rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the treatment regimen recommended for lamotrigine and concurrent glucuronidation inducers should be used (see section 4.2 Dose and method of administration).
In a study in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentrations of lamotrigine, probably by induction of glucuronidation. In patients receiving concomitant therapy with lopinavir/ritonavir, the treatment regimen recommended for lamotrigine and concurrent glucuronidation inducers should be used (see section 4.2 Dose and method of administration).
In a study in healthy adult volunteers, atazanavir/ritonavir (300 mg/100 mg) reduced the plasma AUC and Cmax of lamotrigine (single 100 mg dose) by an average of 32% and 6%, respectively (see section 4.2 Dose and method of administration – General Dosing Recommendations for Lamotrigine in Special Patient Populations).
In a study in healthy adult volunteers, paracetamol 1g (four times daily) reduced the plasma AUC and Cmin of lamotrigine by an average of 20% and 25%, respectively.
Data from in vitro assessment of the effect of lamotrigine at OCT 2 demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of OCT 2 at potentially clinically relevant concentrations. These data demonstrate that lamotrigine is an inhibitor of OCT 2, with an IC50 value of 53.8 µM (see section 4.4 Special warnings and precautions for use).
Lamotrigine has been reported to interfere with the assay used in some rapid urine drug screens, which can result in false positive readings, particularly for phencyclidine (PCP). A more specific alternative chemical method should be used to confirm a positive result.
Lamotrigine should not be used in pregnancy unless, in the opinion of the physician, the potential benefits of treatment to the mother outweigh any possible risks to the developing foetus.
Postmarketing data from several prospective pregnancy registries have documented outcomes in over 8,700 women exposed to lamotrigine monotherapy during the first trimester of pregnancy. Overall, these data do not suggest a substantial increase in the risk for major congenital malformations. Although data from a limited number of registries have reported an increase in the risk of isolated oral cleft malformations, a completed case control study did not demonstrate an increased risk of oral clefts compared to other major congenital malformations following exposure to lamotrigine (see section 5.3 Preclinical safety data).
The data on use of lamotrigine in polytherapy combinations are insufficient to assess whether the risk of malformation associated with other agents is affected by concomitant lamotrigine use.
Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy. Appropriate clinical management of pregnant women during lamotrigine therapy should be ensured.
Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in total lamotrigine levels in infants of up to approximately 50% of the mother’s. Therefore, in some breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur.
The potential benefits of breast feeding should be weighed against the potential risk of adverse effects occurring in the infant.
Administration of lamotrigine did not impair fertility in animal reproductive studies.
There is no experience of the effect of lamotrigine on human fertility.
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. Therefore, patients should see how lamotrigine therapy affects them before driving or operating machinery.
As there is individual variation in response to all anti-epileptic medicine therapy patients should consult their physician on the specific issues of driving and epilepsy.
The adverse reactions identified from epilepsy or bipolar disorder clinical trial data have been divided into indication specific sections. Additional adverse reactions identified through post-marketing surveillance for both indications are included in the post-marketing section. All three sections should be consulted when considering the overall safety profile of lamotrigine.
The following convention has been utilised for the classification of undesirable effects: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000).
The following adverse reactions were identified during epilepsy clinical trials and should be considered alongside those seen in the bipolar disorder clinical trials and post-marketing sections for an overall safety profile of lamotrigine.
Very common: Skin rash
Rare: Stevens-Johnson syndrome
Very rare: Toxic epidermal necrolysis
In double-blind, add-on clinical trials in adults, 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 treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within 8 weeks of starting treatment and resolves on withdrawal of lamotrigine (see section 4.4 Special warnings and precautions for use).
Rarely, serious potentially life-threatening skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome) have been reported. Although the majority recover on drug withdrawal, some patients experience irreversible scarring and there have been rare cases of associated death (See section 4.4 Special warnings and precautions for use).
The overall risk of rash, appears to be strongly associated with:
Rash has also been reported as part of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome. This condition is associated with a variable pattern of systemic symptoms (see section 4.4 Special warnings and precautions for use and Immune system disorders**).
Very rare: Haematological abnormalities (including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis), lymphadenopathy
Haematological abnormalities and lymphadenopathy may or may not be associated with DRESS/Hypersensitivity Syndrome (see section 4.4 Special warnings and precautions for use and Immune system disorders**).
Very rare: DRESS/Hypersensitivity syndrome** including such symptoms as fever, lymphadenopathy, facial oedema, abnormalities of the blood, liver and kidney.
** Rash has also been reported as part of this syndrome which shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multi-organ 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.
Common: Aggression, irritability
Very rare: Tics, hallucinations, confusion
Anti-epileptic medicines have been associated with an increased risk of suicidal behaviour, suicidal ideation and emergence or worsening of existing depression.
Very common: Headache
Common: Somnolence, insomnia, dizziness tremor
Rare: Ataxia
Very rare: Nystagmus
Uncommon: Diplopia, blurred vision
Very common: Nausea, vomiting, diarrhoea
Very rare: Increased liver function tests, hepatic dysfunction, hepatic failure
Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.
Very rare: Lupus-like reactions
Common: Tiredness
The following adverse reactions were identified during bipolar disorder clinical trials and should be considered alongside those seen in the epilepsy clinical trials and post-marketing sections for an overall safety profile of lamotrigine.
Very Common: Skin rash
Rare: Stevens-Johnson syndrome
When all bipolar disorder studies (controlled and uncontrolled) conducted with lamotrigine are considered, skin rashes occurred in 12% of patients on lamotrigine. Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 8% of patients taking lamotrigine and in 6% of patients taking placebo.
Very Common: Headache
Common: Agitation, somnolence, dizziness
Common: Arthralgia
Common: Pain, back pain
This section includes adverse reactions identified through post-marketing surveillance for both indications. These adverse reactions should be considered alongside those seen in the epilepsy and bipolar disorder clinical trials sections for an overall safety profile of lamotrigine.
Very rare: Haemophagocytic lymphohistiocytosis (see section 4.4 Special Warnings and precautions for use)
Very rare: Hypogammaglobulinaemia
Rare: Alopecia
Very rare: Nightmares
Very common: Somnolence, ataxia, headache, dizziness.
Common: Nystagmus, tremor, insomnia.
Rare: Aseptic meningitis (see section 4.4 Special warnings and precautions for use),Agitation, unsteadiness, movement disorders, worsening of Parkinson’s disease, extrapyramidal effects, choreoathetosis, increase in seizure frequency.
There have been reports that lamotrigine may worsen parkinsonian symptoms in patients with pre-existing Parkinson’s disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.
Rare: Conjunctivitis.
Very Rare: Tubulointerstitial nephritis*
* may occur in association with uveitis
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via: https://nzphvc.otago.ac.nz/reporting.
None reported.
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