Drug Detail:Lamictal odt (Lamotrigine [ la-moe-tri-jeen ])
Drug Class: Triazine anticonvulsants
Usual Adult Dose for Epilepsy
Risk of rash requires adhering to specific dose escalation regimens; the effect of lamotrigine glucuronidation inducers/inhibitors on lamotrigine drug levels necessitates dosing based on concomitant therapy
ADJUNCTIVE THERAPY: Immediate-Release (IR) Formulations:
For Patients Taking VALPROATE:
- Initial dose: 25 mg orally every other day (week 1 and 2), then 25 mg orally once a day (week 3 and 4)
- Maintenance dose (week 5 and onward): Increase by 25 to 50 mg/day every 1 to 2 weeks
- Usual maintenance dose with valproate alone: 100 to 200 mg/day in 1 or 2 divided doses
- Usual maintenance dose with valproate and other drugs that induce lamotrigine glucuronidation: 100 to 400 mg/day in 1 or 2 divided doses
- Initial dose: 25 mg orally once a day (week 1 and 2), then 50 mg orally once a day (week 3 and 4)
- Maintenance dose (week 5 and onward): Increase by 50 mg/day every 1 to 2 weeks
- Usual maintenance dose: 225 to 375 mg/day in 2 divided doses
- Initial dose: 50 mg orally once a day (week 1 and 2), then 100 mg orally once a day (week 3 and 4)
- Maintenance dose (week 5 and onward): Increase by 100 mg/day every 1 to 2 weeks
- Usual maintenance dose: 300 to 500 mg/day in 2 divided doses
ADJUNCTIVE THERAPY: Extended-Release (XR) Tablets:
For Patients Taking VALPROATE:
- Initial dose: 25 mg XR orally every other day (week 1 and 2), then 25 mg XR orally once a day (week 3 and 4), then 50 mg XR orally once a day (week 5), then 100 mg XR orally once a day (week 6), then 150 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to a maintenance dose (week 8 and onward)
- Maintenance dose: 200 to 250 mg XR orally once a day
- Initial dose: 25 mg XR orally once a day (week 1 and 2), then 50 mg XR orally once a day (week 3 and 4), then 100 mg XR orally once a day (week 5), then 150 mg XR orally once a day (week 6), then 200 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to maintenance dose (week 8 and onward)
- Maintenance dose: 300 to 400 mg XR orally once a day
- Initial dose: 50 mg XR orally once a day (week 1 and 2), then 100 mg XR orally once a day (week 3 and 4), then 200 mg XR orally once a day (week 5), then 300 mg XR orally once a day (week 6), then 400 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to maintenance dose (week 8 and onward)
- Maintenance dose: 400 to 600 mg XR orally once a day
MONOTHERAPY: For patients previously receiving carbamazepine, phenytoin, phenobarbital, primidone, or valproate as single antiepileptic therapy:
Immediate-release (IR):
- Initial doses: Dose escalation as above for IR adjunctive therapy
- Maintenance dose: 500 mg IR orally in 2 divided doses per day
- CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, OR PRIMIDONE: After achieving a lamotrigine maintenance dose of 500 mg/day, begin AED withdrawal in 20% decrements/week over a 4-week period
- VALPROATE: After achieving a lamotrigine dose of 200 mg/day, decrease valproate in decrements no greater than 500 mg/day/week to 500 mg/day and maintain for 1 week, then increase lamotrigine to 300 mg orally per day while simultaneously decreasing valproate to 250 mg/day and maintain for 1 week; finally, increase lamotrigine by 100 mg/day/week to a maintenance dose of 500 mg per day (in 2 divided doses) and discontinue valproate
Extended-Release (XR):
- Initial doses: Dose escalation as above for XR adjunctive therapy
- Maintenance dose: 250 to 300 mg XR orally once a day
- CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, OR PRIMIDONE: After achieving maintenance dose of lamotrigine 500 mg XR per day, begin withdrawal of AED in 20% decrements/week over a 4-week period; two weeks after completing withdrawal of concomitant AED, decrease lamotrigine XR dose no faster than 100 mg/day/week to achieve a maintenance dose of 250 to 300 mg/day
- VALPROATE: After achieving a lamotrigine XR dose of 150 mg/day per day, decrease valproate in decrements no greater than 500 mg/day/week to 500 mg/day and maintain for 1 week, then increase lamotrigine XR to 200 mg orally per day while simultaneously decreasing valproate to 250 mg/day and maintain for 1 week; finally, increase to lamotrigine XR 250 mg or 300 mg/day and discontinue valproate
Conversion from IMMEDIATE-RELEASE (IR) to EXTENDED-RELEASE (XR)
- Patients may be converted directly from IR to XR
- Patients should be monitored closely for seizure control; some patients on concomitant enzyme-inducing AEDs may have lower plasma levels of lamotrigine on conversion and require dose adjustments
Comments:
- Initial dose and/or rate of dose escalation should not be exceeded, especially in patients with a history of allergy or rash to other antiepileptic drugs (AEDs); if drug has been discontinued for a duration exceeding 5 half-lives, initial dosing recommendations and guidelines should be followed if restarting is appropriate.
- Drugs that induce or inhibit lamotrigine glucuronidation alter lamotrigine drug clearance and dose adjustments are recommended; specific dose recommendations are provided for use without lamotrigine glucuronidation inhibitors/inducers; with lamotrigine glucuronidation inhibitors (valproate), and with lamotrigine glucuronidation inducers (carbamazepine, phenytoin, phenobarbital, primidone, rifampin, and lopinavir/ritonavir).
- Adjunctive maintenance doses are derived from dosing regimens in clinical trials; maintenance doses as high as 700 mg/day have been used in some patients receiving multidrug regimens with carbamazepine, phenytoin, phenobarbital, or primidone without valproate, and as high as 200 mg/day in those using valproate alone; however, these doses have not been established in clinical trials.
- The safety and effectiveness of this drug as initial monotherapy have not been established.
Uses: As adjunctive therapy for partial-onset and primary generalized tonic-clonic seizures; for use as monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as single antiepileptic therapy.
Usual Adult Dose for Bipolar Disorder
Risk of rash requires adhering to specific dose escalation regimens; the effect of lamotrigine glucuronidation inducers/inhibitors on lamotrigine drug levels necessitates dosing based on concomitant therapy
Immediate-Release Formulations Only:
Initial dose: Appropriate dose escalation is required; see below
Target dose: 200 mg/day; this dose may be higher or lower based on concomitant medications
For Patients NOT Taking CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, PRIMIDONE, OR VALPROATE:
- Initial dose: 25 mg orally once a day (week 1 and 2), then 50 mg orally once a day (week 3 and 4), then 100 mg orally once a day (week 5), then increase to maintenance dose (week 6 and onward)
- Maintenance dose: 200 mg orally once a day
For Patients Taking VALPROATE:
- Initial dose: 25 mg orally every other day (week 1 and 2), then 25 mg orally once a day (week 3 and 4), then 50 mg orally once a day (week 5), then increase to maintenance dose (week 6 and onward)
- Maintenance dose: 100 mg orally once day
For Patients Taking CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, PRIMIDONE, RIFAMPIN, or LOPINAVIR/RITONAVIR, and NOT taking VALPROATE:
- Initial dose: 50 mg orally once a day (week 1 and 2), then 100 mg orally/day in divided doses (week 3 and 4), then 200 mg orally/day in divided doses (week 5), then 300 mg orally/day in divided doses (week 6), then increase to maintenance dose (week 7 and onward)
- Maintenance dose: up to 400 mg orally/day in divided doses
Comments:
- Extended-release tablets are not indicated for use in patients with bipolar disorder.
- The goal of maintenance treatment is to delay time to occurrence of mood episodes; for patients receiving treatment for longer than 16 weeks, periodically reassess need for maintenance treatment.
- The target dose is 200 mg/day (which may be 100 mg/day for those on concomitant drugs that inhibit glucuronidation [decrease clearance] and up to 400 mg/day for those on concomitant drugs that induce glucuronidation [increase clearance]; clinical trials with doses up to 400 mg/day did not show additional benefit and therefore are not recommended.
- If drugs that induce or inhibit glucuronidation are discontinued, gradually (over a 2-week period) adjust maintenance dose to the target dose of 200 mg/day.
- Treatment of acute manic or mixed episodes is not recommended; effectiveness of this drug in the acute treatment of mood episodes has not been established.
Use: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy.
Usual Adult Dose for Lennox-Gastaut Syndrome
Risk of rash requires adhering to specific dose escalation regimens; the effect of lamotrigine glucuronidation inducers/inhibitors on lamotrigine drug levels necessitates dosing based on concomitant therapy
Immediate-Release Formulations Only:
For Patients Taking VALPROATE:
- Initial dose: 25 mg orally once every other day (week 1 and 2), then 25 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 25 to 50 mg/day every 1 to 2 weeks
- Usual maintenance dose with valproate alone: 100 to 200 mg/day in 1 or 2 divided doses
- Usual maintenance dose with valproate and other drugs that induce glucuronidation: 100 to 400 mg/day in 1 or 2 divided doses
- Initial dose: 25 mg orally once a day (week 1 and 2), then 50 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 50 mg/day every 1 to 2 weeks
- Usual maintenance dose: 225 to 375 mg/day in 2 divided doses
- Initial dose: 50 mg orally once a day (week 1 and 2), then 100 mg orally in 2 divided doses per day (week 3 and 4)
- Maintenance dose: Increase by 100 mg/day every 1 to 2 weeks
- Usual maintenance dose: 300 to 500 mg/day in 2 divided doses
Comments:
- Extended-release tablets are not indicated for use in patients with Lennox-Gastaut syndrome.
- Initial dose and/or rate of dose escalation should not be exceeded, especially in patients with a history of allergy or rash to other antiepileptic drugs (AEDs); if drug has been discontinued for a duration exceeding 5 half-lives, initial dosing recommendations and guidelines should be followed if restarting is appropriate.
- Drugs that induce or inhibit lamotrigine glucuronidation alter lamotrigine drug clearance and dose adjustments are recommended; specific dose recommendations are provided for use without lamotrigine glucuronidation inhibitors/inducers; with lamotrigine glucuronidation inhibitors (valproate), and with lamotrigine glucuronidation inducers (carbamazepine, phenytoin, phenobarbital, primidone, rifampin, and lopinavir/ritonavir).
- Adjunctive maintenance doses are derived from dosing regimens in clinical trials; maintenance doses as high as 700 mg/day have been used in some patients receiving multidrug regimens with carbamazepine, phenytoin, phenobarbital, or primidone without valproate, and as high as 200 mg/day in those using valproate alone; however, these doses have not been established in clinical trials.
- The safety and effectiveness of this drug as initial monotherapy have not been established.
Use: For adjunctive therapy of generalized seizures of Lennox-Gastaut syndrome.
Usual Pediatric Dose for Epilepsy
Risk of rash requires adhering to specific dose escalation regimens; the effect of lamotrigine glucuronidation inducers/inhibitors on lamotrigine drug levels necessitates dosing based on concomitant therapy
ADJUNCTIVE THERAPY:
- Immediate-Release (IR): Doses should be rounded down to the nearest whole tablet - only WHOLE tablets should be used for dosing
Under 2 years: Not recommended
2 to 12 years:
For Patients Taking VALPROATE:
- Initial dose: 0.15 mg/kg/day orally in 1 or 2 divided doses (week 1 and 2), then 0.3 mg/kg/day orally in 1 or 2 divided doses (week 3 and 4), then increase by 0.3 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 1 to 5 mg/kg/day orally in 1 or 2 divided doses; Maximum dose: 200 mg/day
- Usual maintenance dose with valproate alone: 1 to 3 mg/kg/day orally in 1 or 2 divided doses
- Usual maintenance dose in patients less than 30 kg: May need to increase up to 50% based on clinical response
- Initial dose: 0.3 mg/kg/day orally in 1 or 2 divided doses (week 1 and 2), then 0.6 mg/kg/day orally in 2 divided doses (week 3 and 4), then increase by 0.6 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 4.5 to 7.5 mg/kg/day orally in 2 divided doses; Maximum dose: 300 mg/day
- Usual maintenance dose in patients less than 30 kg: May need to increase up to 50% based on clinical response
- Initial dose: 0.6 mg/kg/day orally in 2 divided doses (week 1 and 2), then 1.2 mg/kg/day orally in 2 divided doses (week 3 and 4), then increase by 1.2 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 5 to 15 mg/kg/day orally in 2 divided doses; Maximum dose: 400 mg/day
- Usual maintenance dose in patients less than 30 kg: May need to increase up to 50% based on clinical response
Over 12 years:
For Patients Taking VALPROATE:
- Initial dose: 25 mg orally every other day (week 1 and 2), then 25 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 25 to 50 mg/day every 1 to 2 weeks
- Usual maintenance dose with valproate alone: 100 to 200 mg/day in 1 or 2 divided doses
- Usual maintenance dose with valproate and other drugs that induce glucuronidation: 100 to 400 mg/day in 1 or 2 divided doses
- Initial dose: 25 mg orally once a day (week 1 and 2), then 50 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 50 mg/day every 1 to 2 weeks
- Usual maintenance dose: 225 to 375 mg/day in 2 divided doses
- Initial dose: 50 mg orally once a day (week 1 and 2), then 100 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 100 mg/day every 1 to 2 weeks
- Usual maintenance dose: 300 to 500 mg/day in 2 divided doses
ADJUNCTIVE THERAPY: Extended-Release (XR) Tablets
Under 13 years: Not Recommended
13 years or older:
For Patients Taking VALPROATE:
- Initial dose: 25 mg XR orally every other day (week 1 and 2), then 25 mg XR orally once a day (week 3 and 4), then 50 mg XR orally once a day (week 5), then 100 mg XR orally once a day (week 6), then 150 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to a maintenance dose
- Maintenance dose: 200 to 250 mg XR orally once a day
- Initial dose: 25 mg XR orally once a day (week 1 and 2), then 50 mg XR orally once a day (week 3 and 4), then 100 mg XR orally once a day (week 5), then 150 mg XR orally once a day (week 6), then 200 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to maintenance dose
- Maintenance dose: 300 to 400 mg XR orally once a day
- Initial dose: 50 mg XR orally once a day (week 1 and 2), then 100 mg XR orally once a day (week 3 and 4), then 200 mg XR orally once a day (week 5), then 300 mg XR orally once a day (week 6), then 400 mg XR once a day (week 7), then increase at doses not exceeding 100 mg XR/day/week to maintenance dose
- Maintenance dose: 400 to 600 mg XR orally once a day
MONOTHERAPY: For patients previously receiving carbamazepine, phenytoin, phenobarbital, primidone, or valproate as single antiepileptic therapy:
Under 16 years: Not Recommended
16 years or older: See Adult Dosing
Comments:
- Initial dose and/or rate of dose escalation should not be exceeded, especially in patients with a history of allergy or rash to other antiepileptic drugs (AEDs); if drug has been discontinued for a duration exceeding 5 half-lives, initial dosing recommendations and guidelines should be followed if restarting is appropriate.
- Drugs that induce or inhibit lamotrigine glucuronidation alter lamotrigine drug clearance and dose adjustments are recommended; specific dose recommendations are provided for use without lamotrigine glucuronidation inhibitors/inducers; with lamotrigine glucuronidation inhibitors (valproate), and with lamotrigine glucuronidation inducers (carbamazepine, phenytoin, phenobarbital, primidone, rifampin, and lopinavir/ritonavir).
- Adjunctive maintenance doses are derived from dosing regimens in clinical trials; maintenance doses as high as 700 mg/day have been used in some patients receiving multidrug regimens with carbamazepine, phenytoin, phenobarbital, or primidone without valproate, and as high as 200 mg/day in those using valproate alone; however, these doses have not been established in clinical trials.
- The safety and effectiveness of this drug as initial monotherapy have not been established.
Uses: As adjunctive therapy in patients 2 years or older for partial-onset and primary generalized tonic-clonic seizures; for use as monotherapy in patients 16 years or older with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as single antiepileptic therapy.
Usual Pediatric Dose for Lennox-Gastaut Syndrome
Risk of rash requires adhering to specific dose escalation regimens; the effect of lamotrigine glucuronidation inducers/inhibitors on lamotrigine drug levels necessitates dosing based on concomitant therapy
Under 2 years: Not Recommended
Immediate-release formulations: Doses should be rounded down to the nearest whole tablet; a combination of only WHOLE tablets should be used for dosing
2 to 12 years:
For Patients Taking VALPROATE:
- Initial dose: 0.15 mg/kg/day orally in 1 or 2 divided doses (week 1 and 2), then 0.3 mg/kg/day orally in 1 or 2 divided doses (week 3 and 4), then increase by 0.3 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 1 to 5 mg/kg/day orally in 1 or 2 divided doses; Maximum dose: 200 mg/day
- Usual maintenance dose with valproate alone: 1 to 3 mg/kg/day orally in 1 or 2 divided doses
- Usual maintenance dose in patients weighing less than 30 kg: May need to increase up to 50% based on clinical response
- Initial dose: 0.3 mg/kg/day orally in 1 or 2 divided doses (week 1 and 2), then 0.6 mg/kg/day orally in 2 divided doses (week 3 and 4), then increase by 0.6 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 4.5 to 7.5 mg/kg/day orally in 2 divided doses; Maximum dose: 300 mg/day
- Usual maintenance dose in patients weighing less than 30 kg: May need to increase up to 50% based on clinical response
- Initial dose: 0.6 mg/kg/day orally in 2 divided doses (week 1 and 2), then 1.2 mg/kg/day orally in 2 divided doses (week 3 and 4), then increase by 1.2 mg/kg/day every 1 to 2 weeks until optimal response is achieved
- Usual maintenance dose: 5 to 15 mg/kg/day orally in 2 divided doses; Maximum dose: 400 mg/day
- Usual maintenance dose in patients weighing less than 30 kg: May need to increase up to 50% based on clinical response
Over 12 years:
For Patients Taking VALPROATE:
- Initial dose: 25 mg orally once every other day (week 1 and 2), then 25 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 25 to 50 mg/day every 1 to 2 weeks
- Usual maintenance dose with valproate alone: 100 to 200 mg orally in 1 or 2 divided doses per day
- Usual maintenance dose with valproate and other drugs that induce glucuronidation: 100 to 400 mg orally in 1 or 2 divided doses per day
- Initial dose: 25 mg orally once a day (week 1 and 2), then 50 mg orally once a day (week 3 and 4)
- Maintenance dose: Increase by 50 mg/day every 1 to 2 weeks
- Usual maintenance dose: 225 to 375 mg orally in 2 divided doses per day
- Initial dose: 50 mg orally once a day (week 1 and 2), then 100 mg orally in 2 divided doses per day(week 3 and 4)
- Maintenance dose: Increase by 100 mg/day every 1 to 2 weeks
- Usual maintenance dose: 300 to 500 mg orally in 2 divided doses per day
Comments:
- Extended-release tablets are not indicated for use in patients with Lennox-Gastaut syndrome.
- Initial dose and/or rate of dose escalation should not be exceeded, especially in patients with a history of allergy or rash to other antiepileptic drugs (AEDs); if drug has been discontinued for a duration exceeding 5 half-lives, initial dosing recommendations and guidelines should be followed if restarting is appropriate.
- Drugs that induce or inhibit lamotrigine glucuronidation alter lamotrigine drug clearance and dose adjustments are recommended; specific dose recommendations are provided for use without lamotrigine glucuronidation inhibitors/inducers; with lamotrigine glucuronidation inhibitors (valproate), and with lamotrigine glucuronidation inducers (carbamazepine, phenytoin, phenobarbital, primidone, rifampin, and lopinavir/ritonavir).
- Adjunctive maintenance doses are derived from dosing regimens in clinical trials; maintenance doses as high as 700 mg/day have been used in some patients receiving multidrug regimens with carbamazepine, phenytoin, phenobarbital, or primidone without valproate, and as high as 200 mg/day in those using valproate alone; however, these doses have not been established in clinical trials.
- The safety and effectiveness of this drug as initial monotherapy have not been established.
Use: For adjunctive therapy of generalized seizures of Lennox-Gastaut syndrome.
Renal Dose Adjustments
Use caution
- Significant renal impairment: Consider reduced maintenance doses as these may be effective
Liver Dose Adjustments
Mild hepatic impairment: No adjustment recommended
Moderate and severe hepatic impairment without ascites: Decrease initial escalation and maintenance doses by approximately 25%; adjust doses based on clinical response
Severe hepatic impairment with ascites: Decrease initial escalation and maintenance doses by approximately 50%; adjust doses based on clinical response
Dose Adjustments
Therapeutic Drug Monitoring:
- The value of monitoring plasma concentrations in patients with epilepsy or bipolar disorder has not been established; dosing should be based on therapeutic response.
Concomitant use with Known Glucuronidation Inhibitors/Inducers:
- Specific dose recommendations are provided in the dosing section for concomitant use with known inhibitors (i.e, valproate) and known inducers (i.e., carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir)
- Upon discontinuation of known inhibitors/inducers, changes in lamotrigine clearance and half-life will necessitate lamotrigine dose adjustments.
Concomitant Use with Estrogen-Containing Oral Contraceptives:
Initial lamotrigine dose escalation: No adjustment recommended; follow dose-escalation guidelines based on concomitant AED or other concomitant medications
Maintenance lamotrigine dose:
- For women currently on estrogen-containing oral contraceptives and NOT taking glucuronidation inducer: Lamotrigine maintenance dose may need to be increased up to 2-fold the recommended target dose
- For women on a stable lamotrigine maintenance dose and starting an estrogen-containing oral contraceptive while NOT taking a lamotrigine glucuronidation inducer: Increase lamotrigine (50 to 100 mg/day weekly) when the oral contraceptive is started; maintenance dose may need to be increased up to 2-fold higher than recommended target dose
- For women maintained on lamotrigine and a lamotrigine glucuronidation inducer: Changes to lamotrigine maintenance dose should not be necessary
- NOTE: Pill-free weeks (inactive hormonal pills) may result in transient increases in lamotrigine plasma levels; consider this when adjusting doses; dose adjustments occurring only during the pill-free week are not recommended.
STOPPING Estrogen-Containing Oral Contraceptives in Women on Lamotrigine:
- For women not taking lamotrigine glucuronidation inducers: Maintenance dose of lamotrigine will most likely need to be decreased by as much as 50% (e.g., decrease by 25% per week over a 2-week period)
- For women taking a lamotrigine glucuronidation inducer: No adjustment should be needed
Concomitant Use of Atazanavir/Ritonavir:
Initial lamotrigine dose escalation: No adjustment recommended; follow dose-escalation guidelines based on concomitant AED or other concomitant medications
Maintenance lamotrigine dose: For patients not taking glucuronidation inducers, may need to increase or decrease lamotrigine dose if atazanavir/ritonavir is added or discontinued, respectively.
Restarting Therapy:
- Restarting this drug in patients who have stopped due to rash is not recommended unless the potential benefits clearly outweigh the risks; if restarting after stopping for more than 5 half-lives, the initial dosing recommendations should be followed (note: half-life of this drug is affected by concomitant medications).
Discontinuation Strategy:
- Step-wise dose reduction over at least 2-weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal
Precautions
US BOXED WARNINGS: SERIOUS SKIN RASHES
- This drug can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome is approximately 0.3% to 0.8% in pediatric patients (aged 2 to 17 years) and 0.08% to 0.3% in adults. One-rash related death was reported in a prospectively followed cohort of 1983 pediatric patients (aged 2 to 16 years) with epilepsy taking this drug as adjunctive therapy. In worldwide postmarketing experience, rare case of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.
- Other than age, there are no factors identified that are known to predict the risk of occurrence or the severity of rash caused by this drug. There are suggestions, yet to be proven, that the risk of rash may also be increased by coadministration of this drug with valproate (includes valproic acid and divalproex sodium); exceeding the recommended initial dose; or exceeding the recommended dose escalation. However, cases have occurred in the absence of these factors.
- Nearly all cases of life-threatening rashes caused by this drug have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.
- Although benign rashes are also caused by this drug, it is not possible to predict reliably which rashes will prove to be serious or life-threatening. Accordingly, this drug should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring.
CONTRAINDICATIONS:
- Demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the active substance or any of the ingredients
Safety and effectiveness of extended-release (XR) have not been established in pediatric patients less than 13 years of age.
Safety and effectiveness of the immediate-release formulations have not been established in pediatric patients less than 2 years of age.
Consult WARNINGS section for additional precautions.
Dialysis
Hemodialysis: No specific guidelines provided; in a small study (n=6), about 20% of drug was removed by hemodialysis during a 4 hour session
Peritoneal dialysis: Data not available
Other Comments
Administration advice:
- May take with or without food
- Dose with whole tablets; if the calculated dose cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet
Tablets (Immediate-release and Extended-release):
- Swallow whole; do not chew, crush, or divide
- If a patient has difficulty swallowing whole tablets, another formulation may be more appropriate
Orally Disintegrating Tablets (ODT):
- Place tablet on tongue and move around mouth; tablet will rapidly disintegrate and should then be swallowed with or without water
Chewable Dispersible Tablets:
- May be swallowed whole, chewed, or mixed in water, or mixed in fruit juice mixed with water
- If tablets are chewed, follow with a small amount of water or fruit juice mixed with water to help with swallowing
- If tablets are dispersed, add tablets to small amount of water (enough to cover medicine); wait at least 1 minute or until tablets are completely broken up, mix the solution and swallow entire amount right away
MISSED DOSE: If a dose is missed, take as soon as remembered, if it is almost time for next dose, skip the missed dose and take the next dose at the scheduled time; do not take 2 doses at the same time
General:
- Dosing is based on concomitant medications; to avoid increased risk of rash, initial dose and subsequent dose escalations should not be exceeded.
- It is believed that the risk of severe, life-threatening rash may be increased by coadministration with valproate, exceeding the recommended initial dose, and/or exceeding the recommended dose escalation; however, cases have occurred in the absence of these factors.
- Restarting this drug in patients who have stopped due to rash is not recommended unless the potential benefits clearly outweigh the risks; if restarting after stopping for more than 5 half-lives, the initial dosing recommendations should be followed (note: half-life of this drug is affected by concomitant medications).
Monitoring:
- Monitor for rash
- Monitor for signs or symptoms of hypersensitivity such as fever, lymphadenopathy
- Monitor for blood dyscrasias, e.g., signs of anemia, unexpected infection, or bleeding
- Monitor for emergence of worsening depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior
- Monitor for meningitis
Patient advice:
- Patients should be instructed to read the US FDA-approved medication guide.
- Patients should understand that the development of rash or other signs of hypersensitivity such as a fever or lymphadenopathy, may signal a serious adverse event and should be immediately reported to their healthcare provider.
- Patients, families, and caregivers should understand that this drug may increase the risk of suicidal thoughts and behavior and they should be instructed to report any unusual change in mood or behavior, worsening of depression, or suicidal thoughts or behaviors to their healthcare provider immediately.
- Patients should be instructed not to stop therapy without speaking with their healthcare provider; additionally, they should not start or stop any other medications without consulting with their healthcare provider due to the high risk of drug interactions.
- Patients should be instructed to visually inspect their tablets with each new prescription; if there are changes, they should consult with their pharmacist.
- Women of childbearing potential should speak with their healthcare provider about any changes in contraceptive use, specifically estrogen-containing oral contraceptives; they should speak to their healthcare provider if they become or intend to become pregnant, and if they intend or are breastfeeding.
- Patients should be instructed not to drive a car or perform hazardous tasks until they gain sufficient experience with this drug to understand how it affects their mental and/or motor performance.
Frequently asked questions
- What should I do if I develop a rash while taking lamotrigine?
- Is it better to take lamotrigine at night?
- If you are taking lamotrigine how long does it take to get out of your system?
