LACOSAMIDE ORAL SOLUTION- lacosamide solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

LACOSAMIDE (UNII: 563KS2PQY5) (lacosamide - UNII:563KS2PQY5)

Available from:

Apotex Corp.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Lacosamide oral solution is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) oral solution. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Lacosamide oral solution is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older. None. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as lacosamide oral solution, during pregnancy. Encourage women who are taking lacosamide oral solution  during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series with lacosamide oral solution use in pregnant women are insufficient to identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Lacosamide produced developmental toxicity (increased embryofetal and perinatal mortality, growth deficit) in rats following administration during pregnancy. Developmental neurotoxicity was observed in rats following administration during a period of postnatal development corresponding to the third trimester of human pregnancy. These effects were observed at doses associated with clinically relevant plasma exposures (see Data) .   The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Animal Data Oral administration of lacosamide to pregnant rats (20, 75, or 200 mg/kg/day) and rabbits (6.25, 12.5, or 25 mg/kg/day) during the period of organogenesis did not produce any effects on the incidences of fetal structural abnormalities. However, the maximum doses evaluated were limited by maternal toxicity in both species and embryofetal death in rats. These doses were associated with maternal plasma lacosamide exposures (AUC) approximately 2 and 1 times (rat and rabbit, respectively) that in humans at the maximum recommended human dose (MRHD) of 400 mg/day.   In two studies in which lacosamide (25, 70, or 200 mg/kg/day and 50, 100, or 200 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, increased perinatal mortality and decreased body weights in the offspring were observed at the highest dose tested. The no-effect dose for pre-and postnatal developmental toxicity in rats (70 mg/kg/day) was associated with a maternal plasma lacosamide AUC similar to that in humans at the MRHD.   Oral administration of lacosamide (30, 90, or 180 mg/kg/day) to rats during the neonatal and juvenile periods of development resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide AUC less than that in humans at the MRHD.  In Vitro Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects on CNS development related to this activity cannot be ruled out. Risk Summary Data from published literature indicate that lacosamide is present in human milk. There are reports of increased sleepiness in breastfed infants exposed to lacosamide (see Clinical Considerations). There is no information on the effects of lacosamide on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lacosamide and any potential adverse effects on the breastfed infant from lacosamide or from the underlying maternal condition.  Clinical Considerations Monitor infants exposed to lacosamide through breastmilk for excess sedation. Partial-Onset Seizures Safety and effectiveness of lacosamide oral solution for the treatment of partial-onset seizures have been established in pediatric patients 4 years to less than 17 years of age. Use of lacosamide oral solution in this age group is supported by evidence from adequate and well-controlled studies of lacosamide oral solution in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 328 pediatric patients 4 years to less than 17 years of age [see Adverse Reactions (6.1),  Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2)] . Safety and effectiveness in pediatric patients below 1 month of age have not been established. Primary Generalized Tonic-Clonic Seizures Safety and effectiveness of lacosamide oral solution as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in pediatric patients with idiopathic generalized epilepsy 4 years of age and older was established in a 24-week double-blind, randomized, placebo-controlled, parallel-group, multi-center study (Study 5), which included 37 pediatric patients 4 years to less than 17 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.3)] . Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential related adverse effects on CNS development cannot be ruled out. Administration of lacosamide to rats during the neonatal and juvenile periods of postnatal development (approximately equivalent to neonatal through adolescent development in humans) resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide exposure (AUC) less than that in humans at the maximum recommended human dose of 400 mg/day. Additional pediatric use information is approved for UCB, Inc.’s VIMPAT® (lacosamide) oral solution. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information . There were insufficient numbers of elderly patients enrolled in partial-onset seizure trials (n=18) to adequately determine whether they respond differently from younger patients. No lacosamide oral solution dose adjustment based on age is necessary. In elderly patients, dose titration should be performed with caution, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic function, decreased renal function, increased cardiac conduction abnormalities, and polypharmacy [see Dosage and Administration ( 2.1, 2.4, 2.5) and Clinical Pharmacology ( 12.3)]. No dose adjustment is necessary in patients with mild to moderate renal impairment (CLCR ≥30 mL/min). In patients with severe renal impairment (CLCR <30 mL/min as estimated by the Cockcroft-Gault equation for adults; CLCR less than 30 mL/min/ 1.73m2 as estimated by the Schwartz equation for pediatric patients) and in those with end-stage renal disease, a reduction of 25% of the maximum dosage is recommended [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. In all patients with renal impairment, dose initiation and titration should be based on clinical response and tolerability. Lacosamide is effectively removed from plasma by hemodialysis. Dosage supplementation of up to 50% following hemodialysis should be considered. For adult and pediatric patients with mild to moderate hepatic impairment, a reduction of 25% of the maximum dosage is recommended. Patients with mild to moderate hepatic impairment should be observed closely for adverse reactions, and dose initiation and titration should be based on clinical response and tolerability [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]. The pharmacokinetics of lacosamide has not been evaluated in severe hepatic impairment. Lacosamide oral solution  use is not recommended in patients with severe hepatic impairment. Lacosamide oral solution contains lacosamide, a Schedule V controlled substance. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. In a human abuse potential study, single doses of 200 mg (equal to the maximum single dosage) and 800 mg lacosamide (equal to twice the recommended daily maintenance dosage)  produced euphoria-type subjective responses that differentiated statistically from placebo; at 800 mg, these euphoria-type responses were statistically indistinguishable from those produced by alprazolam, a Schedule IV drug. The duration of the euphoria-type responses following lacosamide was less than that following alprazolam. A high rate of euphoria was also reported as an adverse event in the human abuse potential study following single doses of 800 mg lacosamide (15% [5/34]) compared to placebo (0%) and in two pharmacokinetic studies following single and multiple doses of 300 to 800 mg lacosamide (ranging from 6% [2/33] to 25% [3/12]) compared to placebo (0%). However, the rate of euphoria reported as an adverse event in the lacosamide development program at therapeutic doses was less than 1%. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt termination of lacosamide in clinical trials with diabetic neuropathic pain patients produced no signs or symptoms that are associated with a withdrawal syndrome indicative of physical dependence. However, psychological dependence cannot be excluded due to the ability of lacosamide to produce euphoria-type adverse events in humans.

Product summary:

Lacosamide  oral solution, USP 10 mg/mL is a clear, colorless to yellow or yellow-brown, strawberry-flavored liquid. It is supplied in HDPE bottles as follows: 200 mL bottles NDC 60505-0405-4 465 mL bottles NDC 60505-0405-6 Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature].   Do not freeze lacosamide oral solution. Discard any unused lacosamide oral solution, USP  remaining after six (6) months of first opening the bottle.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Apotex Corp.
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MEDICATION GUIDE
Lacosamide (la koe' sa mide) Oral Solution, USP CV
Read this Medication Guide before you start taking lacosamide oral
solution and each time you get a
refill. There may be new information. This Medication Guide describes
important safety information
about lacosamide oral solution. This information does not take the
place of talking to your healthcare
provider about your medical condition or treatment.
What is the most important information I should know about lacosamide
oral solution?
Do not stop taking lacosamide oral solution without first talking to
your healthcare provider.
Stopping lacosamide oral solution suddenly can cause serious problems.
Stopping seizure medicine
suddenly in a patient who has epilepsy can cause seizures that will
not stop (status epilepticus).
Lacosamide oral solution can cause serious side effects, including:
1.
Like other antiepileptic drugs, lacosamide oral solution may cause
suicidal thoughts or actions in a
very small number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these
symptoms, especially if they are new,
worse, or worry you:
•
thoughts about suicide or dying
•
attempt to commit suicide
•
new or worse depression
•
new or worse anxiety
•
feeling agitated or restless
•
panic attacks
•
trouble sleeping (insomnia)
•
new or worse irritability
•
acting aggressive, being angry, or violent
•
acting on dangerous impulses
•
an extreme increase in activity and talking (mania)
•
other unusual changes in behavior or mood
How can I watch for early symptoms of suicidal thoughts and actions?
•
Pay attention to any changes, especially sudden changes, in mood,
behaviors, thoughts, or
feelings.
•
Keep all follow-up visits with your healthcare provider as scheduled.
•
Call your healthcare provider between visits as needed, especially if
you are worried about
symptoms.
•
Suicidal thoughts or actions can be caused by things other than
medicines. If you have
suicidal thoughts or actions,

Summary of Product characteristics

LACOSAMIDE ORAL SOLUTION- LACOSAMIDE SOLUTION
APOTEX CORP.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LACOSAMIDE ORAL
SOLUTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
LACOSAMIDE ORAL
SOLUTION.
LACOSAMIDE ORAL SOLUTION, CV
INITIAL U.S. APPROVAL: 2008
RECENT MAJOR CHANGES
Dosage and Administration (2.1, 2.2) 4/2023
INDICATIONS AND USAGE
Lacosamide oral solution is indicated for:
Treatment of partial-onset seizures in patients 4 years of age and
older (1.1)
Adjunctive therapy in the treatment of primary generalized
tonic-clonic seizures in patients 4 years of
age and older (1.2)
DOSAGE AND ADMINISTRATION
_Adults (17 years and older):_
Initial dosage for monotherapy for the treatment of partial-onset
seizures is 100 mg twice daily (2.1)
Initial dosage for adjunctive therapy for the treatment of
partial-onset seizures or primary
generalized tonic-clonic seizures is 50 mg twice daily (2.1)
Maximum recommended dosage for monotherapy and adjunctive therapy is
200 mg twice daily (2.1)
_Pediatric Patients_ 4 years to less than 17 years: The recommended
dosage is based on body weight
and is administered orally twice daily (2.1)
Increase dosage based on clinical response and tolerability, no more
frequently than once per week
(2.1)
Dose adjustment is recommended for severe renal impairment (2.4, 12.3)
Dose adjustment is recommended for mild or moderate hepatic
impairment; use in patients with
severe hepatic impairment is not recommended (2.5, 12.3)
DOSAGE FORMS AND STRENGTHS
10 mg/mL oral solution (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Monitor patients for suicidal behavior and ideation (5.1)
Lacosamide oral solution may cause dizziness and ataxia (5.2)
Cardiac Rhythm and Conduction Abnormalities: Obtaining ECG before
beginning and after titration to
steady-state maintenance is recommended in patients with underlying
proarrhythmic conditions or on
concomitant medications that affect cardiac conduction; closely
monito