Lacosamide

Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: (R)-2-acetamido-N-benzyl-3-methoxypropionamide
Molecular Formula: C₁₃H₁₈N₂O₃
CAS Number: 175481-36-4
Brands: Vimpat

REMS:

FDA approved a REMS for lacosamide to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Anticonvulsant; a functionalized amino acid.^{1 4 5 6 22 23 34}

Uses for Lacosamide

Seizure Disorders

Management (in combination with other anticonvulsants) of partial-onset seizures in patients ≥17 years of age with epilepsy.^{1 2 3 4 20 24 36}

IV lacosamide is used as a short-term alternative to oral therapy in patients in whom oral administration of the drug is temporarily not feasible (e.g., patients undergoing surgical procedures, those experiencing difficulty swallowing, those with acute GI disorders).^{1 20 24 36}

Neuropathic Pain

Oral lacosamide has been studied in the treatment of pain associated with diabetic peripheral neuropathy (DPN)† in several short- and long-term clinical trials; additional controlled trials needed to confirm efficacy and safety.^{14 15 16 17 18 38 43}

Lacosamide Dosage and Administration

General

• 
  

  Do not discontinue lacosamide abruptly; withdraw gradually (e.g., gradually discontinue therapy over ≥1 week and/or taper the daily dosage by 200 mg each week) to minimize the potential for increased seizure frequency in patients with seizure disorders.^{1 37}

  
  


• 
  

  Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.^{1 9 10 11 12} (See Suicidality Risk under Cautions.)

  
  

Administration

Administer orally or by IV infusion.¹ The 30- and 60-minute IV infusions are bioequivalent to the oral tablets.¹

Oral Administration

Administer twice daily without regard to food.¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.¹

Discard any unused portion of the injection.¹

Dilution

Lacosamide injection may be administered without further dilution or may be diluted with 5% dextrose, lactated Ringer's, or 0.9% sodium chloride injection.¹

Rate of Administration

Administer over 30–60 minutes.¹

Shorter IV infusion times (e.g., over 10 and 15 minutes)† have been used safely in a limited number of patients in clinical trials; further clinical experience is needed to confirm safety.^{24 36 40 41}

Dosage

Adults

Seizure Disorders

Partial Seizures

Oral or IV

Initiate treatment with either oral or IV therapy.¹ Use IV lacosamide if oral administration is temporarily not feasible.^{1 20 24 36}

Patients ≥17 years of age: Initially, 100 mg daily (given as 50 mg twice daily).¹ Based on clinical response and tolerability, may increase dosage in increments of 100 mg daily (given in 2 divided doses) at weekly intervals until the recommended maintenance dosage of 200–400 mg daily is achieved.¹

In clinical trials, an oral dosage of 600 mg daily was not more effective than 400 mg daily and was associated with a substantially higher incidence of adverse effects.¹

Conversion from Oral to IV Therapy

Initial IV dosage should be equivalent to the total daily dosage and frequency of oral lacosamide.¹ There is experience with twice-daily IV infusions for up to 5 days.^{1 24 36}

Conversion from IV to Oral Therapy

At the end of the IV treatment period, may switch to oral administration at the equivalent daily dosage and frequency of the IV administration.¹

Neuropathic Pain†

Pain Associated with Diabetic Peripheral Neuropathy†

Oral

Initial dosage of 100 mg daily (given as 50 mg twice daily) usually has been used in clinical trials, with subsequent weekly increases to reach maintenance dosages of 400–600 mg daily (given as 200–300 mg twice daily) based on individual patient response and tolerability.^{14 15 16 17 18 38}

Prescribing Limits

Adults

Seizure Disorders

Partial Seizures

Oral

Dosages of 600 mg daily were not more effective than 400 mg daily and were associated with a substantially higher incidence of adverse effects.¹

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Titrate dosage with caution; maximum dosage of 300 mg daily is recommended.¹ During dosage titration, closely monitor patients with coexisting hepatic and renal impairment.¹ (See Special Populations under Pharmacokinetics.)

Severe hepatic impairment: Use is not recommended.¹ (See Special Populations under Pharmacokinetics.)

Renal Impairment

Mild to moderate renal impairment: Dosage adjustment is not necessary.¹ (See Special Populations under Pharmacokinetics.)

Severe renal impairment (Cl_Cr ≤30 mL/minute) or end-stage renal disease: Manufacturer recommends a maximum dosage of 300 mg daily.¹ In patients undergoing hemodialysis, consider dosage supplementation of up to 50% following hemodialysis.¹ (See Special Populations under Pharmacokinetics.)

Titrate dosage with caution in patients with any degree of renal impairment.¹ During dosage titration, closely monitor patients with coexisting hepatic and renal impairment.¹

Geriatric Patients

Dosage adjustment not necessary; however, manufacturer recommends cautious dosage titration.¹ (See Special Populations under Pharmacokinetics.)

Cautions for Lacosamide

Contraindications

• 
  

  No known contraindications in the US.¹ In the European Union, contraindicated in patients with hypersensitivity to lacosamide or any ingredient in the formulation and in patients with known second- or third-degree AV block.³⁷

  
  

Warnings/Precautions

Sensitivity Reactions

Multiorgan Hypersensitivity Reactions

One case of symptomatic hepatitis and nephritis, consistent with a delayed multiorgan hypersensitivity reaction, reported in a healthy individual 10 days after discontinuing lacosamide;¹ full recovery occurred within 1 month without specific treatment.¹ Additional cases of possible multiorgan hypersensitivity reaction include 2 cases with rash and elevated hepatic enzyme concentrations and 1 case with myocarditis and hepatitis of uncertain etiology.¹

Multiorgan hypersensitivity reactions (also known as drug reaction with eosinophilia and systemic symptoms or DRESS) also reported with other anticonvulsants; clinical presentation is variable but typically includes fever and rash associated with other organ system involvement (e.g., eosinophilia, hepatitis, nephritis, lymphadenopathy, myocarditis).¹

If a multiorgan hypersensitivity reaction is suspected, discontinue lacosamide and initiate alternative therapy.¹

Suicidality Risk

Increased risk of suicidality (suicidal ideation or behavior) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).^{1 9 10 11 12} Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.^{9 10 11} Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.^{1 9 10 11}

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.^{1 9 10 11 12} Anxiety, agitation, hostility, hypomania, and mania may be precursors to emerging suicidality.¹⁰

Balance risk of suicidality with the risk of untreated illness.^{1 10} Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.^{1 12} If suicidal thoughts or behavior emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.^{1 12} (See Advice to Patients.)

Dizziness and Ataxia

Dizziness and ataxia reported in 25 and 6%, respectively, of patients with partial-onset seizures receiving lacosamide 200–400 mg daily and 1–3 concomitant anticonvulsants compared with 8 and 2%, respectively, of placebo recipients; dizziness was the adverse effect most frequently leading to drug discontinuance (3%).¹

The onset of dizziness and ataxia was most commonly observed during dosage titration.¹ Incidence was substantially increased at dosages >400 mg daily.¹ (See Advice to Patients.)

PR-Interval Prolongation

Dose-dependent increases in PR interval observed in patients and healthy individuals receiving lacosamide.^{1 2 4 5 13 19 20 24 43} At steady state, the timing of the maximum observed mean PR interval coincided with peak plasma lacosamide concentrations.¹

Asymptomatic, first-degree AV block observed in 0.4 or 0.5% of lacosamide-treated patients with partial-onset epilepsy or diabetic neuropathy, respectively, compared with none of the placebo recipients.^{1 2 20}

When lacosamide is given with other drugs that prolong the PR interval, further PR prolongation is possible.^{1 23 37} (See Drugs that Prolong PR Interval under Interactions.)

Use lacosamide with caution in patients with known cardiac conduction abnormalities (e.g., marked first-degree AV block, second- or third-degree AV block, sick sinus syndrome without a pacemaker) or severe cardiovascular disease (e.g., myocardial ischemia, heart failure).^{1 23} The manufacturer recommends obtaining an ECG before initiating lacosamide and after titration to steady state in such patients.¹

Atrial Fibrillation and Atrial Flutter

Lacosamide may predispose patients, particularly those with diabetic neuropathy and/or cardiovascular disease, to develop atrial arrhythmias (i.e., atrial fibrillation or flutter).¹ Atrial fibrillation or flutter reported in 0.5 or 0% of patients receiving lacosamide or placebo, respectively, in diabetic neuropathy studies; no cases of atrial fibrillation or flutter reported in epilepsy studies.¹ (See Advice to Patients.)

Syncope

Syncope or loss of consciousness reported in 1.2 or 0% of patients receiving lacosamide or placebo, respectively, in short-term diabetic neuropathy trials.¹ No increase in syncope observed in short-term, controlled trials in epilepsy patients without significant systemic illness.¹

Most cases of syncope occurred with dosages >400 mg daily.¹ The cause was not determined in most cases; however, several cases were associated with orthostatic changes in BP, atrial fibrillation/flutter (and associated tachycardia), or bradycardia.¹ (See Advice to Patients.)

Discontinuance of Anticonvulsants

Abrupt withdrawal of anticonvulsants may result in increased seizure frequency in patients with seizure disorders.¹ Withdraw lacosamide gradually (e.g., over ≥1 week).¹ (See General under Dosage and Administration.)

Specific Populations

Pregnancy

Category C.¹

UCB AED Pregnancy Registry (for clinicians and patients) at 888-537-7734.¹ North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .¹

Effect on labor and delivery is unknown.¹

Lacosamide produced developmental toxicity (i.e., increased embryofetal and perinatal mortality, growth deficit) when given to pregnant animals.¹ Developmental neurotoxicity was observed in animals given lacosamide during a period of postnatal development corresponding to the third trimester of human pregnancy.¹ Effects were observed at dosages associated with clinically relevant plasma exposures.¹

Lactation

Lacosamide and/or its metabolites are distributed into milk in rats.¹ Unknown if lacosamide is distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

The manufacturer in the US states that safety and efficacy of oral and IV lacosamide have not been established in pediatric patients <17 years of age.¹ However, the drug has been used in pediatric patients ≥16 years of age in some clinical studies⁴ and is approved for such use in the European Union.^{29 37}

Lacosamide interfered with activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth, in some in vitro studies; potential adverse effects on CNS development cannot be ruled out.¹ (See Actions.)

Decreased brain weights and long-term neurobehavioral changes (e.g., altered open field performance, deficits in learning and memory) reported in rats given lacosamide during neonatal and juvenile periods of postnatal development.¹

Geriatric Use

Insufficient experience in geriatric patients to adequately assess the drug's efficacy in this population.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use is not recommended in patients with severe hepatic impairment.^{1 21} In patients with mild or moderate hepatic impairment, titrate dosage with caution.¹ During dosage titration, closely monitor patients with coexisting hepatic and renal impairment.¹ (See Hepatic Impairment under Dosage and Administration and see also Special Populations under Pharmacokinetics.)

Renal Impairment

Titrate dosage with caution.¹ During dosage titration, closely monitor patients with coexisting hepatic and renal impairment.¹ (See Renal Impairment under Dosage and Administration and see also Special Populations under Pharmacokinetics.)

Common Adverse Effects

With oral lacosamide for partial-onset seizures: Dizziness,^{1 2 3 4 13 14 15 16} headache,^{1 4 13 14 15 16} diplopia,^{1 3 4 13} nausea,^{1 2 3 4 14 16} vomiting,^{1 2 3 4 13} fatigue,^{1 4 13 15 16} blurred vision,^{1 3 13} ataxia,^{1 2} somnolence,¹ tremor,^{1 3 15 16} nystagmus,^{1 2 3} memory impairment,¹ balance disorder,¹ vertigo,^{1 4} diarrhea.^{1 14}

With short-term IV lacosamide therapy for partial-onset seizures: Systemic adverse effects similar to those observed with oral therapy, local adverse effects (injection site pain or discomfort, irritation, and erythema).^{1 8 24 36}

Interactions for Lacosamide

Metabolized by CYP2C19.¹ Relative contribution of other CYP isoenzymes or non-CYP enzymes in the metabolism of lacosamide is unclear.¹

Does not substantially induce CYP isoenzymes 1A2, 2B6, 2C9, 2C19, or 3A4 in vitro.^{1 19 37}

Does not substantially inhibit CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 2E1, 3A4, or 3A5 at plasma concentrations observed in clinical studies.^{1 19 37} In vitro data suggest that lacosamide may inhibit CYP2C19 at therapeutic concentrations; however, in vivo data (with omeprazole) suggested minimal or no inhibition (see Specific Drugs under Interactions).^{1 19}

Does not inhibit and is not a substrate of the P-glycoprotein transport system.^{1 37}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential for pharmacokinetic drug interactions generally appears to be low.^{1 4 19 26 37}

In vitro data suggest that lacosamide may inhibit CYP2C19 at therapeutic concentrations; however, an in vivo study with omeprazole did not show an inhibitory effect (see Specific Drugs under Interactions).^{1 19}

Drugs Affecting or Affected by P-glycoprotein Transport

Pharmacokinetic interactions unlikely.^{1 37}

Drugs that Prolong PR Interval

Potential pharmacodynamic interaction (additive effect on PR-interval prolongation).^{1 23 37 39 42} (See PR-Interval Prolongation under Cautions and see also Specific Drugs under Interactions.)

Protein-bound Drugs

Clinically relevant pharmacokinetic interactions unlikely.^{1 16 37}

Specific Drugs

Drug	Interaction	Comments
Alcohol	No data currently available37 41
β-adrenergic blocking agents	Potential additive effect on PR-interval prolongation1 13 23
Calcium-channel blocking agents	Potential additive effect on PR-interval prolongation1 23
Carbamazepine	No change in pharmacokinetics of either drug in healthy individuals1 In patients with partial-onset seizures, no change in steady-state plasma concentrations of carbamazepine and its epoxide metabolite1 Small (15–20%) reductions in plasma lacosamide concentrations observed during concurrent administration of carbamazepine, phenobarbital, or phenytoin in population pharmacokinetic studies in patients with partial-onset seizures1 19 20 37 Potential additive effect on PR-interval prolongation; however, subgroup analysis did not reveal an increased magnitude of PR prolongation during concurrent administration1 23 37
Clonazepam	No change in steady-state plasma clonazepam concentrations1 22
Digoxin	Lacosamide did not alter digoxin pharmacokinetics in healthy individuals1 22 37 Potential additive effect on PR-interval prolongation1 23 42
Gabapentin	No change in steady-state gabapentin concentrations1 22
Lamotrigine	No change in steady-state lamotrigine concentrations1 22 Potential additive effect on PR-interval prolongation; however, subgroup analysis did not reveal an increased magnitude of PR prolongation during concurrent administration1 23 37
Levetiracetam	No change in steady-state levetiracetam concentrations1 22
Metformin	No clinically important changes in metformin concentrations1 22 Metformin did not alter lacosamide pharmacokinetics1
Omeprazole	Lacosamide did not alter pharmacokinetics of single-dose omeprazole in healthy individuals1 Omeprazole reduced plasma concentrations of lacosamide's inactive O-desmethyl metabolite by about 60%1
Oral contraceptives	Ethinyl estradiol/levonorgestrel: No substantial change in pharmacodynamics and pharmacokinetics of the oral contraceptive; small (20%) increase in peak plasma ethinyl estradiol concentrations1 22 37
Oxcarbazepine	No change in steady-state concentrations of oxcarbazepine's active monohydroxy metabolite (MHD)1 22
Phenobarbital	No change in steady-state plasma phenobarbital concentrations1 22 Small (15–20%) reductions in plasma lacosamide concentrations observed during concurrent administration of carbamazepine, phenobarbital, or phenytoin in population pharmacokinetic studies in patients with partial-onset seizures1 19 20 37
Phenytoin	No change in steady-state plasma phenytoin concentrations1 Small (15–20%) reductions in plasma lacosamide concentrations observed during concurrent administration of carbamazepine, phenobarbital, or phenytoin in population pharmacokinetic studies in patients with partial-onset seizures1 19 20 37
Pregabalin	Potential additive effect on PR-interval prolongation1 37 39
Topiramate	No change in steady-state plasma topiramate concentrations1
Valproic Acid	No change in pharmacokinetics of either drug in healthy individuals1 In patients with partial-onset seizures, no change in steady-state plasma concentrations of valproic acid1
Zonisamide	No change in steady-state plasma zonisamide concentrations1

Lacosamide Pharmacokinetics

Absorption

Pharmacokinetics of oral and IV lacosamide are generally dose-proportional over a range of 100–800 mg.^{1 19}

Bioavailability

Oral bioavailability is approximately 100%.¹ Peak plasma lacosamide concentrations attained within 0.5–4 hours after oral administration.^{1 8 22} Peak plasma concentrations of inactive O-desmethyl metabolite attained within 0.5–12 hours after oral administration.¹

Lacosamide 30- and 60-minute IV infusions are bioequivalent to the oral tablet.¹ Peak plasma concentrations reached at end of infusion.¹

Food

Food does not affect rate or extent of absorption.¹

Distribution

Extent

Lacosamide and/or metabolites distribute into milk in rats; unknown if distributed into human milk.¹

Plasma Protein Binding

<15%.¹

Elimination

Metabolism

Metabolized by CYP2C19; effect of other CYP isoenzymes or non-CYP enzymes in the metabolism of lacosamide is unclear.¹

Elimination Route

Eliminated primarily by renal excretion and biotransformation.^{1 19} Following oral and IV administration of a 100-mg radiolabeled dose, approximately 95% of the dose was recovered in urine and <0.5% was recovered in feces; the principal compounds excreted were unchanged lacosamide (approximately 40%), O-desmethyl-lacosamide (approximately 30%; inactive metabolite), and a structurally unknown polar fraction (approximately 20%; possibly serine derivatives).^{1 37}

Half-life

Lacosamide: Approximately 12–13 hours.^{1 19 22}

O-desmethyl metabolite: 15–23 hours.¹

Special Populations

In individuals with mild or moderate renal impairment, AUC is increased by approximately 25%.^{1 41} In individuals with severe renal impairment, AUC is increased by approximately 60%.^{1 41} However, peak plasma concentrations were unaffected.^{1 41} A 4-hour hemodialysis session reduces the AUC by approximately 50%.¹

Individuals with moderate hepatic impairment (Child-Pugh class B) had higher plasma concentrations of lacosamide (approximately 50–60% higher AUCs) compared with healthy individuals.¹ Pharmacokinetics not specifically evaluated in individuals with severe hepatic impairment.¹

In geriatric individuals, AUCs and peak plasma concentrations (normalized for dosage and body weight) were approximately 20% higher compared with younger individuals, possibly related to differences in total body water and age-associated reductions in renal clearance.¹

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).¹

Parenteral

Injection for IV Infusion

20–25°C (may be exposed to 15–30°C).¹

Discard any unused portion of the injection.¹

When stored in glass or PVC bags at 15–30°C, injection that has been diluted with 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection is stable for ≥24 hours.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible1
Dextrose 5% in water
Ringer's injection, lactated
Sodium chloride 0.9%

Actions

• 
  

  Exact mechanism(s) of anticonvulsant and antinociceptive action is unknown.^{1 2 4 5 7 8 14 15 16 19 21 22 25 26 27 41}

  
  


• 
  

  In vitro electrophysiologic studies have shown that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, which results in stablilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing.^{1 2 4 5 7 8 16 19 22 25 27}

  
  


• 
  

  In some preclinical tests, lacosamide was found to bind to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein that is mainly expressed in the nervous system and involved in neuronal differentiation, polarization, gene expression, and control of axonal outgrowth.^{1 7 8 13 16 25 27 28 30} It was suggested that this binding may contribute to the anticonvulsant and antinociceptive activity of the drug.^{1 7 8 13 16 25 27 28 30} However, binding was not confirmed in subsequent tests.⁴¹

  
  


• 
  

  Does not exhibit binding affinity for GABA, N-methyl-D-aspartic acid (NMDA), adenosine, muscarinic, serotonin, histamine, dopamine, or other receptors.^{14 20 26} Does not affect reuptake or metabolism of norepinephrine, dopamine, serotonin, or GABA.^{6 7 20 26} Does not affect voltage-activated calcium channels (L-, –, P/Q-, or T-type) or voltage-activated potassium channels and does not modulate delayed-rectifier or A-type potassium currents.^{6 20 22 26}

  
  

Advice to Patients

• 
  

  Importance of providing copy of written patient information (medication guide) each time lacosamide is dispensed; importance of patient reading this information prior to taking the drug.¹

  
  


• 
  

  Risk of suicidality (anticonvulsants, including lacosamide, may increase risk of suicidal thoughts or actions in about 1 in 500 people).^{1 10 12} Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).^{1 10}

  
  


• 
  

  Importance of taking lacosamide only as prescribed.¹

  
  


• 
  

  Risk of dizziness, drowsiness, blurred vision, or problems with coordination and balance.^{1 6 35} Importance of advising patients not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects.^{1 35 37}

  
  


• 
  

  Risk of dizziness, lightheadedness, fainting, or irregular heart beat, particularly in patients with underlying cardiovascular disease or cardiac conduction abnormalities and in those taking drugs that affect the heart.^{1 35} These symptoms are more likely to occur when rising quickly from a recumbent position.³⁵ Importance of advising patients to lie down with their legs raised until they feel better if such symptoms develop and to contact their clinician promptly.^{1 35} Importance of patients also being aware of possible symptoms of cardiac rhythm and conduction abnormalities (e.g., atrial fibrillation and flutter), including palpitations, rapid heart beat, and shortness of breath; importance of patients contacting their clinician should any of these symptoms occur.¹

  
  


• 
  

  Risk of serious hypersensitivity reactions affecting multiple organs (e.g., liver, kidney); lacosamide should be discontinued if serious hypersensitivity reactions are suspected.¹ Importance of informing patients to contact their clinician promptly if symptoms suggestive of liver damage occur (e.g., fatigue, jaundice, dark urine).¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 35} Importance of clinicians informing women about the existence of and encouraging enrollment in pregnancy registries (see Pregnancy under Cautions).¹

  
  


• 
  

  Importance of informing patients not to stop taking lacosamide without first talking to their clinician since stopping the drug suddenly can cause serious problems, including seizures.^{1 35}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illness (e.g., heart disease, kidney disease, liver disease, depression, bipolar disorder) or family history of suicidality or bipolar disorder.^{1 35}

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule V (C-V) drug.

Lacosamide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	50 mg	Vimpat (C-V)	UCB
		100 mg	Vimpat (C-V)	UCB
		150 mg	Vimpat (C-V)	UCB
		200 mg	Vimpat (C-V)	UCB
Parenteral	Injection, for IV infusion	10 mg/mL	Vimpat (C-V; available in single-use glass vials)	UCB

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Vimpat 100MG Tablets (SCHWARZ PHARMA): 60/$415.97 or 180/$1,185.98

Vimpat 150MG Tablets (SCHWARZ PHARMA): 60/$439.99 or 180/$1,260.02

Vimpat 200MG Tablets (SCHWARZ PHARMA): 60/$439.97 or 180/$1,259.96

Vimpat 50MG Tablets (SCHWARZ PHARMA): 60/$265.98 or 180/$749.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. UCB, Inc. Vimpat (lacosamide) tablets and injection for intravenous use prescribing information. Smyrna, GA; 2009 Jan.

2. Ben-Menachem E, Biton V, Jatuzis D et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007; 48:1308-17. [PubMed 17635557]

3. Chung S, Sperling M, Biton V et al. Lacosamide: efficacy and safety as oral adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007; 48 (Suppl. 7):57. Abstr. No. 065.

4. Halász P, Kälviäinen R, Mazurkiewicz-Beldzinska M et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009; 50:443-53. [PubMed 19183227]

5. Doty P, Rudd GD, Stoehr T et al. Lacosamide. Neurotherapeutics. 2007; 4:145-8. [PubMed 17199030]

6. Beydoun A, D'Souza J, Hebert D et al. Lacosamide: pharmacology, mechanisms of action and pooled efficacy and safety data in partial-onset seizures. Expert Rev Neurother. 2009; 9:33-42. [PubMed 19102666]

7. Beyreuther BK, Freitag J, Heers C et al. Lacosamide: a review of preclinical properties. CNS Drug Rev. 2007; 13:21-42. [PubMed 17461888]

8. Ben-Menachem E. Lacosamide: an investigational drug for adjunctive treatment of partial-onset seizures. Drugs Today (Barc). 2008; 44:35-40. [PubMed 18301802]

9. Food and Drug Administration. FDA Alert: Suicidality and antiepileptic drugs. Rockville, MD; 2008 Jan 31. From the FDA website.

Lunesta

Generic Name: Eszopiclone
Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
Chemical Name: (5S - 6 - (5 - chloro - 2 - pyridinyl) - 6,7 - dihydro - 7 - oxo - 5H - pyrrolol[3,4 - b]pyrazin - 5 - yl - ester - 4 - methyl - 1 - piperazinecarboxylic acid
Molecular Formula: C₁₇H₁₇ClN₆O₃
CAS Number: 138729-47-2

Introduction

Sedative and hypnotic; pyrrolopyrazine derivative; structurally unrelated to benzodiazepines.^{1 1 2 3 5 10 11}

Uses for Lunesta

Insomnia

Management of transient and chronic insomnia.^{1 2 3 11}

Decreases sleep latency and prolongs total sleep time in patients with chronic or transient insomnia;^{1 2 3} reportedly effective with repeated (i.e., nightly) use for periods up to 6 months in duration.^{1 2 3}

Sleep architecture (i.e., the percentage of time spent in each sleep stage) generally is preserved at usual dosages.⁵

Evidence is lacking to suggest that sleep improvement is maintained following discontinuance;¹³ some clinicians suggest that use of hypnotic agents in the management of chronic insomnia should be reserved for patients nonresponsive to psychotherapy/behavioral therapies (e.g., relaxation techniques, sleep hygiene education, sleep curtailment, stimulus control therapy).^{6 7 8}

Lunesta Dosage and Administration

Administration

Oral Administration

Administer only immediately before retiring (when ready to sleep) or after retiring when experiencing difficulty falling asleep.¹

Swallow tablets intact; do not chew, crush, or divide.¹

Avoid administration with or immediately after a heavy, high-fat meal; may decrease rate of absorption and effect on sleep latency.¹

Use only when able to get ≥8 hours of sleep before it is necessary to be active again.¹

Dosage

Individualize dosage;¹ use smallest effective dosage to minimize adverse effects.¹

If used concomitantly with a potent CYP3A4 inhibitor, adjustment of eszopiclone dosage is recommended.¹ (See Interactions.)

Adults

Insomnia

Oral

Adults <65 years of age: Initially, 2 mg.¹ May consider an initial dosage of 3 mg or an increase in dosage to 3 mg if clinically indicated; 3-mg dosage is more effective than 2-mg dosage for sleep maintenance.¹

Special Populations

Hepatic Impairment

In patients with severe hepatic impairment, 1 mg initially;¹ doses >2 mg not recommended.¹

No dosage adjustment required in patients with mild to moderate hepatic impairment.¹

Renal Impairment

No dosage adjustment required.¹

Geriatric Patients

In adults ≥65 years of age experiencing difficulty falling asleep, 1 mg initially.¹ May increase dosage to 2 mg if clinically indicated.¹

In adults ≥65 years of age experiencing difficulty staying asleep, 2 mg.¹

Do not exceed 2 mg daily in adults ≥65 years of age.¹

Debilitated Patients

Do not exceed 1 mg.^{1 13}

Cautions for Lunesta

Contraindications

• 
  

  None known.¹

  
  

Warnings/Precautions

Warnings

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.¹

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.¹

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g., decreased inhibition, uncharacteristic extroversion and aggressiveness, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur unpredictably.¹ Immediately evaluate any new behavioral sign or symptom.¹

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), making phone calls, or preparing and eating food while asleep.¹⁴

Withdrawal Effects

Rapid dosage reduction or abrupt discontinuance of sedatives or hypnotics has resulted in signs and symptoms of withdrawal.^{1 3}

Rebound insomnia of 1 day’s duration reported in clinical trials of eszopiclone.¹

Abuse Potential

Abuse potential of high doses (2–4 times recommended hypnotic dose) in individuals with a history of benzodiazepine abuse appeared to be similar to that of benzodiazepines (e.g., diazepam 20 mg).¹

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.¹

CNS Effects

Rapid onset of CNS effects (short-term memory impairment, hallucinations, impaired coordination, dizziness, lightheadedness); administer only immediately before going to bed or after unsuccessfully attempting to sleep.¹

Performance of activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) may be impaired the day after ingestion.¹

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.¹ (See Specific Drugs under Interactions.)

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur as early as with the first dose of drug.¹⁴

General Precautions

Concomitant Disease

Limited experience in patients with concomitant systemic disease.¹ Use with caution in patients with diseases affecting metabolism and/or hemodynamic response.¹

Respiratory depression was not reported in clinical studies to date in healthy individuals receiving doses 2.5-fold higher than the recommended dose;¹ however, caution is advised in patients with impaired respiratory function.¹

Debilitated Patients

Potential increased sensitivity to sedatives and hypnotics or impaired motor or cognitive performance after repeated exposure.¹ Reduce dosage and monitor closely.¹ (See Debilitated Patients under Dosage and Administration.)

Suicide

Use with caution in depressed patients.¹ Potential for suicidal tendencies; overdosage more frequent in such patients.¹ Prescribe and dispense drug in the smallest feasible quantity.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether distributed into human milk;¹ however, racemic zopiclone is distributed into milk.⁴ Use not recommended.^{1 13}

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

Pharmacokinetic changes in geriatric patients compared with younger adults.¹ (See Absorption and also Elimination, under Pharmacokinetics.)

Possibility exists of greater sensitivity to pharmacologic and adverse effects of sedatives and hypnotics in patients ≥65 years of age;¹ reduce initial and maximum dosages.¹ (See Geriatric Patients under Dosage and Administration.)¹

The adverse effect profile of the 2-mg dosage in geriatric patients (median age: 71 years) was similar to that observed in clinical trials of the drug in younger adults.¹

Hepatic Impairment

Use with caution.¹ Systemic exposure increased twofold in patients with severe hepatic impairment compared with healthy individuals.¹ Reduce dosage for severe hepatic impairment.¹ (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Headache,^{1 3} dry mouth,^{1 3} dizziness,^{1 3} somnolence,¹ nervousness,¹ dyspepsia,¹ nausea,^{1 3} infection,¹ unpleasant taste.^{1 3}

Interactions for Lunesta

Metabolized principally by CYP3A4 and CYP2E1.¹

Does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.¹

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased plasma eszopiclone concentrations).¹ In patients receiving a potent CYP3A4 inhibitor, initial eszopiclone dosage should not exceed 1 mg; dosage may be increased to 2 mg if clinically indicated.¹

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased plasma eszopiclone concentrations).¹

Protein-bound Drugs

Pharmacokinetic interaction unlikely; not highly bound to plasma proteins.¹

Specific Drugs

Drug	Interaction	Comments
Antifungals, azoles (itraconazole, ketoconazole)	Increased plasma eszopiclone concentrations; 2.2-fold increase in eszopiclone exposure reported following concomitant use of eszopiclone 3 mg and ketoconazole 400 mg1	Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1
CNS depressants (e.g., psychotropic drugs, anticonvulsants, antihistamines, alcohol)	Possible additive CNS-depressant effects1	Do not use with alcohol; consider dosage reduction if eszopiclone is used concomitantly with other CNS depressants1
Digoxin	Pharmacokinetic or pharmacodynamic interactions unlikely1
HIV protease inhibitors (nelfinavir, ritonavir)	Increased plasma eszopiclone concentrations1	Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1
Lorazepam	No clinically important pharmacokinetic or pharmacodynamic interactions observed following single-dose administration of eszopiclone 3 mg with lorazepam 2 mg1 13
Macrolide antibiotics (clarithromycin, troleandomycin)	Increased plasma eszopiclone concentrations1	Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1
Nefazodone	Increased plasma eszopiclone concentrations1	Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1
Olanzapine	Decreased psychomotor performance noted following single-dose administration of eszopiclone 3 mg with olanzapine 10 mg;1 pharmacokinetic interaction unlikely1
Paroxetine	Pharmacokinetic or pharmacodynamic interactions unlikely; concomitant use (eszopiclone 3 mg and paroxetine 20 mg daily for 7 days) did not alter relevant parameters1
Rifampin	Decreased plasma eszopiclone concentrations1
Warfarin	Pharmacokinetic or pharmacodynamic (PT) interactions unlikely1 13

Lunesta Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration, with peak plasma concentration attained in about 1 hour.^{1 2 3 4}

Food

High-fat meal decreases peak plasma concentration by 21% and prolongs the time to peak plasma concentration by about 1 hour;¹ effect on sleep onset may be decreased.¹

Special Populations

In geriatric patients, AUC is increased by 41% compared with younger adults.¹

In patients with severe hepatic impairment, systemic exposure is 2 times higher than in healthy individuals.¹

Distribution

Plasma Protein Binding

Approximately 52–59%.¹

Elimination

Metabolism

Extensively metabolized via oxidation and demethylation, principally by CYP3A4 and CYP2E1 to 2 major metabolites; (S)-N-desmethyl zopiclone is considerably less active than the parent drug, and (S)-zopiclone-N-oxide is inactive.^{1 2}

Elimination Route

Racemic zopiclone excreted principally in urine (75%), mainly as metabolites.¹ Similar excretion profile expected for eszopiclone, the S-isomer of racemic zopiclone;¹ <10% of eszopiclone dose excreted unchanged in urine.¹

Half-life

Approximately 6 hours.¹

Special Populations

In geriatric patients, half-life is approximately 9 hours.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

ActionsActions

• 
  

  Interacts with the CNS GABA_A-receptor complex at binding domains located close to or allosterically coupled to benzodiazepine receptors.^{1 2 10 11}

  
  


• 
  

  Pharmacologically similar to zaleplon and zolpidem.^{1 2 10 11}

  
  


• 
  

  Structurally unrelated to benzodiazepines and other sedative and hypnotic agents that are commercially available in the US, including barbiturates, imidazopyridines (e.g., zolpidem), and pyrazolopyrimidines (e.g., zaleplon).^{1 2 3 5 10}

  
  


• 
  

  S-enantiomer of zopiclone (a hypnotic agent not commercially available in the US).¹

  
  


• 
  

  Binding affinity (in vitro) for benzodiazepine receptors is about 50 times that of the R-enantiomer of racemic zopiclone.^{2 10}

  
  

Advice to Patients

• 
  

  Provide patient with a copy of manufacturer’s patient information.¹

  
  


• 
  

  Importance of administering immediately before retiring or after attempting to fall asleep.¹

  
  


• 
  

  Importance of taking only when able to get a full night’s sleep (i.e., ≥8 hours) before being active again.¹

  
  


• 
  

  Importance of taking only as prescribed (e.g., not with or immediately after a high-fat meal); do not increase dosage or duration of therapy unless otherwise instructed by a clinician.¹

  
  


• 
  

  Potential for drug to cause somnolence, dizziness, and/or coordination difficulties; importance of exercising caution when operating machinery or performing hazardous tasks.¹

  
  


• 
  

  Advise of the possibility of adverse effects such as unpleasant taste, headache, and cold-like symptoms.¹

  
  


• 
  

  Importance of reporting to clinicians any unusual and/or disturbing thoughts or behavior, memory impairment, or dependence/withdrawal symptoms after multiple dosing.¹

  
  


• 
  

  Advise of possible rebound insomnia for 1 or 2 nights after discontinuance.¹

  
  


• 
  

  Importance of avoiding alcohol-containing beverages or products.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as concomitant or past illnesses (e.g., depression, substance abuse).¹

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.¹

Eszopiclone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	1 mg	Lunesta (C-IV)	Sepracor
		2 mg	Lunesta (C-IV)	Sepracor
		3 mg	Lunesta (C-IV)	Sepracor

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lunesta 1MG Tablets (SUNOVION PHARMACEUTICALS): 30/$217.99 or 90/$621.99

Lunesta 2MG Tablets (SUNOVION PHARMACEUTICALS): 30/$220 or 90/$645.95

Lunesta 3MG Tablets (SUNOVION PHARMACEUTICALS): 30/$220 or 90/$630

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sepracor Inc. Lunesta (eszopiclone) tablets prescribing information. Marlborough, MA; 2005 Feb.

2. Mack A, Salazar JO. Eszopiclone: a novel cyclopyrrolone with potential benefit in both transient and chronic insomnia. Formulary. 2003; 38:582-93.

3. Krystal AD, Walsh JK, Laska E et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003; 26:793-9. [IDIS 527792] [PubMed 14655910]

4. Fernandez C, Martin C, Gimenez F et al. Clinical pharmacokinetics of zopiclone. Clin Pharmacokinet. 1995; 29:431-41. [PubMed 8787948]

5. Rosenberg R, Caron J, Roth T et al. An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med. 2005; 6:15-22. [IDIS 528997] [PubMed 15680290]

6. Schenck CH, Mahowald MW, Sack RL. Assessment and management of insomnia. JAMA. 2003; 289:2475-9. [IDIS 499774] [PubMed 12759306]

7. Jacobs GD, Pace-Schott EF, Stickgold R et al. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med. 2004; 164:1888-96. [IDIS 524535] [PubMed 15451764]

8. Morin CM, Colecchi C, Stone J et al. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999; 281:991-9. [IDIS 421436] [PubMed 10086433]

9. Walsh JK. Pharmacologic management of insomnia. J Clin Psychiatry. 2004; 65(suppl 16):41-5. [IDIS 526373] [PubMed 15575804]

10. Georgiev V. (S)-Zopiclone Sepracor. Curr Opin Investig Drugs. 2001; 2:271-3. [PubMed 11816843]

11. Anon. Eszopiclone (Lunesta), a new hypnotic. Med Lett Drugs Ther. 2005; 47:17-9. [PubMed 15767972]

12. Zammit GK, McNabb LJ, Caron J et al. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004; 20:1979-91. [IDIS 528996] [PubMed 15701215]

13. Sepracor, Marlborough, MA: Personal communication.

14. Food and Drug Administration. Lunesta (eszopiclone) tablets. [March 14, 2007: Sepracor] MedWatch drug labeling changes. Rockville, MD; April 2007. From FDA websites and

More Lunesta resources

• Lunesta Side Effects (in more detail)
• Lunesta Use in Pregnancy & Breastfeeding
• Drug Images
• Lunesta Drug Interactions
• Lunesta Support Group
• 78 Reviews for Lunesta - Add your own review/rating

• Lunesta Prescribing Information (FDA)


• Lunesta Consumer Overview


• Lunesta Advanced Consumer (Micromedex) - Includes Dosage Information


• Lunesta MedFacts Consumer Leaflet (Wolters Kluwer)


• Eszopiclone Professional Patient Advice (Wolters Kluwer)

Compare Lunesta with other medications

• Insomnia

Limbrel

Generic Name: flavocoxid (Oral route)

flay-voe-COX-id

Commonly used brand name(s)

In the U.S.

• Limbrel

Available Dosage Forms:

• Capsule

Therapeutic Class: Nutriceutical

Uses For Limbrel

Flavocoxid is used to treat moderate to severe symptoms of osteoarthritis. This medicine is used in patients 18 years of age or older. Flavocoxid will not cure the disease, but will help with the symptoms as long as you continue to take it.

Before Using Limbrel

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on flavocoxid have been done only in adult patients, and there is no specific information comparing the use flavocoxid in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of flavocoxid in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems than it does in younger adults.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Stomach ulcers—May be worsened by flavocoxid

Proper Use of Limbrel

You should take flavocoxid one hour before or after the consumption of food

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules)
  
  • For rheumatoid arthritis:
    
    • Adults—250 milligrams (mg) every 12 hours.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Limbrel Side Effects

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Blurred vision


• dizziness


• dull ache or feeling of pressure or heaviness in legs


• fluid accumulation in the knee


• headache


• itching skin near damaged veins


• nervousness


• pounding in the ears


• red, scaling, or cursed skin


• slow or fast heartbeat


• swollen feet and ankles

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Limbrel resources

• Limbrel Side Effects (in more detail)
• Limbrel Use in Pregnancy & Breastfeeding
• Drug Images
• Limbrel Drug Interactions
• Limbrel Support Group
• 3 Reviews for Limbrel - Add your own review/rating

• Limbrel Concise Consumer Information (Cerner Multum)


• Limbrel MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Limbrel with other medications

• Osteoarthritis

Leader Acid Reducer Maximum Strength

Generic Name: famotidine

Dosage Form: tablet
Cardinal Health Acid Reducer Tablets Drug Facts

Active ingredient (in each tablet)

Famotidine 20 mg

Purpose

Acid reducer

Uses

• relieves heartburn associated with acid indigestion and sour stomach


• prevents heartburn associated with acid indigestion and sour stomach brought on by eating or drinking certain food and beverages

Warnings

Allergy alert: Do not use if you are allergic to famotidine or other acid reducers

Do not use

• if you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor.


• if you have kidney disease, except under the advice and supervision of a doctor


• with other acid reducers

Ask a doctor before use if you have

• had heartburn over 3 months. This may be a sign of a more serious condition.


• heartburn with lightheadedness, sweating, or dizziness


• chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness


• frequent chest pain


• frequent wheezing, particularly with heartburn


• unexplained weight loss


• nausea or vomiting


• stomach pain

Stop use and ask a doctor if

• your heartburn continues or worsens


• you need to take this product for more than 14 days

If pregnant or breast-feeding,

ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away.

Directions

• adults and children 12 years and over:


• to relieve symptoms, swallow 1 tablet with a glass of water. Do not chew.


• to prevent symptoms, swallow 1 tablet with a glass of water at any time from 10 to 60 minutes before eating food or drinking beverages that cause heartburn


• do not use more than 2 tablets in 24 hours


• children under 12 years: ask a doctor

Other information

• read the directions and warnings before use


• keep the carton. It contains important information.


• store at 20°-25°C (68°-77°F)


• protect from moisture and light

Inactive ingredients

carnauba wax, colloidal silicon dioxide, croscarmellose sodium, lactose (monohydrate), magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide

Questions or comments?

1-800-719-9260

Principal Display Panel

Compare to Maximum Strength Pepcid® AC active ingredient

Maximum Strength

Famotidine Tablets, 20 mg

Acid Reducer

Just One Tablet Prevents & Relieves Heartburn Due to Acid Indigestion

Actual Size

Acid Reducer Tablets Carton

LEADER ACID REDUCER  MAXIMUM STRENGTH famotidine  tablet

Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 37205-861 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength FAMOTIDINE (FAMOTIDINE) FAMOTIDINE 20 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color WHITE Score no score Shape CAPSULE Size 8mm Flavor Imprint Code L194 Contains

Packaging # NDC Package Description Multilevel Packaging 1 37205-861-63 5 BLISTER PACK In 1 CARTON contains a BLISTER PACK 1 5 TABLET In 1 BLISTER PACK This package is contained within the CARTON (37205-861-63)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA077351	11/02/2006

Labeler - Cardinal Health (097537435)

Revised: 07/2009Cardinal Health

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• Leader Acid Reducer Maximum Strength Side Effects (in more detail)
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• Leader Acid Reducer Maximum Strength Support Group
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Compare Leader Acid Reducer Maximum Strength with other medications

• Allergic Urticaria
• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• GERD
• Indigestion
• Pathological Hypersecretory Conditions
• Peptic Ulcer
• Stomach Ulcer
• Upper GI Hemorrhage
• Urticaria
• Zollinger-Ellison Syndrome