lacosamide (Rx)

>10%

Tablets and oral solution

• Dizziness (16-53%)
• Diplopia (6-16%)
• Blurred vision (2-16%)
• Nausea (7-17%)
• Vomiting (6-16%)
• Fatigue (7-15%)
• Ataxia (11-14%)
• Nystagmus (2-10%)

IV

• Fatigue (20-63%)
• Somnolence (26-34%)
• Headache (4-16%)
• Diplopia (4-20%)
• Nausea (14-24%)
• Dry mouth (6-12%)
• Vomiting (4-12%)
• Fatigue (12-18%)
• Chest pain (3-12%)

1-10%

Tablets and oral solution

• Nystagmus (2-10%)
• Memory impairment (1-6%)
• Balance disorder (1-6%)
• Diarrhea (3-5%)
• Gait disturbance (<1-4%)
• Asthenia (1-3%)
• Vertigo (1-4%)
• Pruritus (2-3%)
• Depression (2%)

IV

• Oral paresthesia (4-8%)
• Oral hypoesthesia (5-8%)
• Diarrhea (4-8%)
• Paresthesia (4-8%)
• Gait disturbance (2-8%)
• Hyperhidrosis (2-8%)
• Tremor (4-6%)
• Abnormal coordination (3-6%)
• Pruritus (4-6%)

Frequency Not Reported

Blood and lymphatic system disorders: Neutropenia, anemia

Cardiac disorders: Palpitations Ear and labyrinth disorders: Tinnitus

Gastrointestinal disorders: Constipation, dyspepsia, dry mouth, oral hypoaesthesia

General disorders and administration site conditions: Irritability, pyrexia, feeling drunk

Injury, poisoning, and procedural complications: Fall

Musculoskeletal and connective tissue disorders: Muscle spasms

Nervous system disorders: Paresthesia, cognitive disorder, hypesthesia, dysarthria, disturbance in attention, cerebellar syndrome

Psychiatric disorders: Confusional state, mood altered, depressed mood

Postmarketing Reports

Blood and lymphatic system disorders: Agranulocytosis

Psychiatric disorders: Aggression, agitation, hallucination, insomnia, psychotic disorder

Neurologic disorders: New or worsening seizures

Skin and subcutaneous tissue disorders: Angioedema, rash, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis

Contraindications

None

Cautions

Increase the risk of suicidal thoughts or behavior; monitor for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior

Dizziness and ataxia reported; may impair ability to perform hazardous tasks

Both atrial fibrillation and atrial flutter reported in open label partial-onset seizure trials and in postmarketing experience; therapy may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease

In postmarketing setting, there have been reports of cardiac arrhythmias, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death; most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval; events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose; use with caution in patients with underlying proarrhythmic conditions (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), severe cardiac disease, including myocardial ischemia or heart failure, or structural heart disease, and cardiac sodium channelopathies (e.g., Brugada Syndrome)

Blurred vision and diplopia may occur during therapy; consider increased monitoring in patients with preexisting ocular conditions or vision-related issues

Oral solution contains aspartame, a source of phenylalanine; 200 mg dose (20 mL) contains 0.32 mg of phenylalanine

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, reported with antiepileptic drugs; some of these events have been fatal or life- threatening; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic hepatic, renal, and/or hematologic organ systems; may require gradual discontinuation and conversion to alternate therapy

Use caution in renal and hepatic impairment; dosage adjustments may be required

Withdraw gradually over 1 week; do not discontinue abruptly because of risk for increased frequency of seizures

Drug interactions overview

• Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide; dose reduction may be necessary

• Concomitant medications that prolong PR interval

  • Use with caution when administered concomitantly with medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval; obtain an ECG before beginning therapy, and after titrating to steady-state maintenance dose, in such patients; closely monitor if intravenous route used to administer medication
  • Obtain an ECG before initiating and after titrated to steady-state; additionally, monitor closely if administered IV

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs); to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/

There are no adequate data on the developmental risks associated with lacosamide use in pregnant women

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

Lactation

There are no data on the presence of lacosamide in human milk, the effects on the breastfed infant, or the effects on milk production

Studies in lactating rats have shown excretion of lacosamide and/or its metabolites in milk

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Antiepileptic effects unknown; may slowly inactivate voltage-gated Na channels

Binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein that is expressed mainly in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth

Absorption

Bioavailability: ~100%

Peak plasma time: 1-4 hr

Distribution

Protein bound: <15%

Vd: 0.6 L/kg

Metabolism

Predominantly by CYP isoenzymes 3A4 and 2C9; also 2C19

Major metabolite: O-desmethyl-lacosamide (inactive)

Elimination

Half-life: 13 hr

Primarily eliminated by renal excretion and biotransformation

Excretion: 95% urine; <5% feces

Dialyzable: Yes (hemodialysis)

IV Compatibility

0.9% NaCl, D5W, LR

IV Preparation

May be administered without dilution or diluted in compatible solutions; (see IV Compatibility)

Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit

Product with particulate matter or discoloration should not be used

Vials is for single-dose only; discard any unused portion of lacosamide injection

IV Administration

Infuse IV over 15-60 min; 30-60 min preferable, and should be used when a 15 min administration is not required

IV lacosamide may cause bradycardia or AV bock in patients with underlying cardiac disease

Monitor infusion closely patients with known cardiac conduction problems, on concomitant medications that prolong PR interval, or with severe cardiac disease (eg, myocardial ischemia, heart failure)

Oral Administration

Tablets or oral solution: Take with or without food

Swallow tablets whole with liquid; do not divide tablets

Oral solution

• Use calibrated measuring device to measure and deliver the prescribed dose accurately
• May be administered using a nasogastric tube or gastrostomy tube; discard any unused lacosamide oral solution remaining after 7 weeks of first opening the bottle

Storage

Tablet: Store at room temperature, 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F); do not freeze lacosamide oral solution

Oral solution: Store at room temperature, 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F); do not freeze lacosamide oral solution; discard any unused oral solution remaining after 7 weeks of first opening the bottle

Injection: Store at room temperature, 20-25°C (68-77°F); excursions are permitted between 15-30°C (59-86°F); do not freeze

Diluted IV solution: Store at room temperature, 20-25°C (68-77°F); for up to 4 hr