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Wednesday, 28 March 2012

Nuvigil

Generic Name: Armodafinil
Class: Anorexigenic Agents and Respiratory and Cerebral Stimulants, Miscellaneous
VA Class: CN809
Chemical Name: 2-[(Diphenylmethyl)sulfinyl]acetamide
Molecular Formula: C₁₅H₁₅NO₂S
CAS Number: 112111-43-0

REMS:

FDA approved a REMS for armodafinil to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of armodafinil and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Wakefulness-promoting agent; R-enantiomer of racemic modafinil.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ¹⁰ ¹¹ ¹² ¹³ ¹⁴ ²⁶ ³⁴

Uses for Nuvigil

Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)

Symptomatic treatment (in combination with standard treatment[s] for underlying obstruction) of OSAHS to improve wakefulness in adults with excessive sleepiness.¹ ² ³ ⁴ ⁷ ⁸ ²⁴

If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, make every effort to optimize treatment with CPAP for an adequate period of time prior to initiating armodafinil.¹ If armodafinil is used adjunctively with CPAP, encourage and periodically assess CPAP compliance.¹

Careful attention to diagnosis and treatment of the sleep disorder is essential.¹ (See Diagnosis of Sleep Disorders under Cautions.)

No well-controlled clinical studies directly comparing armodafinil and modafinil in OSAHS.³⁴ Further studies needed to determine whether pharmacokinetic differences (armodafinil’s longer elimination half-life, higher plasma concentrations later in the waking day¹ ⁸ ¹⁰ ¹¹ ¹² ¹⁴ ) affect armodafinil's clinical efficacy compared with modafinil.¹²

Narcolepsy

Symptomatic treatment of narcolepsy to improve wakefulness in adults with excessive sleepiness.¹ ⁵ ⁷ ⁸ ¹⁹

Careful attention to diagnosis and treatment of the sleep disorder is essential.¹ (See Diagnosis of Sleep Disorders under Cautions.)

No well-controlled clinical studies directly comparing armodafinil and modafinil in narcolepsy.³⁴ Further studies needed to determine whether pharmacokinetic differences (armodafinil’s longer elimination half-life, higher plasma concentrations later in the waking day¹ ⁸ ¹⁰ ¹¹ ¹² ¹⁴ ) affect armodafinil's clinical efficacy compared with modafinil.¹²

Shift Work Sleep Disorder (SWSD)

Symptomatic treatment of SWSD to improve wakefulness in adults with excessive sleepiness.¹ ⁶ ⁷ ⁸

Careful attention to diagnosis and treatment of the sleep disorder is essential.¹ (See Diagnosis of Sleep Disorders under Cautions.)

No well-controlled clinical studies directly comparing armodafinil and modafinil in SWSD.³⁴ Further studies needed to determine whether pharmacokinetic differences (armodafinil’s longer elimination half-life, higher plasma concentrations later in the waking day¹ ⁸ ¹⁰ ¹¹ ¹² ¹⁴ ) affect armodafinil's clinical efficacy compared with modafinil.¹²

Nuvigil Dosage and Administration

Administration

Oral Administration

Administer orally once daily.¹ Manufacturer makes no specific recommendations regarding administration with regard to meals.¹ (See Food under Pharmacokinetics.)

In patients with narcolepsy or OSAHS, usually administer as a single dose in the morning.¹ In patients with SWSD, administer dose approximately 1 hour prior to start of work shift.¹

Dosage

Adults

OSAHS

Oral

150 or 250 mg daily.¹

Dosages up to 250 mg daily have been well tolerated, but may not provide additional clinical benefit beyond 150-mg daily dosage.¹ ²

Long-term efficacy (>12 weeks) not systematically evaluated,¹ but use for ≥12 months was associated with sustained improvement in wakefulness in patients with OSAHS in an extension study.²⁴ If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.¹

Narcolepsy

Oral

150 mg or 250 mg daily.¹

Long-term efficacy (>12 weeks) not systematically evaluated,¹ but use for ≥12 months was associated with sustained improvement in wakefulness in patients with narcolepsy in an extension study.²⁴ If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.¹

SWSD

Oral

150 mg daily.¹

Long-term efficacy (>12 weeks) not systematically evaluated,¹ but use for ≥12 months was associated with sustained improvement in wakefulness in patients with SWSD in an extension study.²⁴ If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.¹

Special Populations

Hepatic Impairment

Reduce dosage in patients with severe hepatic impairment (with or without cirrhosis).¹ (See Hepatic Impairment under Cautions.)

Renal Impairment

Current information inadequate to make specific dosage recommendations in patients with severe renal impairment.¹ (See Renal Impairment under Cautions.)

Geriatric Patients

Consider use of lower than usual recommended dosage.¹ ⁷ (See Geriatric Use under Cautions.)

Cautions for Nuvigil

Contraindications

Known hypersensitivity to armodafinil, modafinil, or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

Serious Dermatologic Reactions

Serious rash (e.g., Stevens-Johnson syndrome [SJS]) requiring hospitalization and drug discontinuance reported in adults receiving armodafinil and in adults and pediatric patients receiving modafinil.¹ ³⁰

Serious or life-threatening rash (e.g., SJS, toxic epidermal necrolysis [TEN]) and drug rash with eosinophilia and systemic symptoms (DRESS) reported rarely in adults and pediatric patients during postmarketing experience with modafinil.¹ ³⁰ Severe rash (e.g., possible SJS, multiorgan hypersensitivity reaction), sometimes associated with fever and other abnormalities (e.g., vomiting, leukopenia), also observed in pediatric clinical trials of modafinil.¹ ³⁰ A similar risk of serious rash in pediatric patients receiving armodafinil cannot be excluded.¹ Armodafinil is not approved for use in pediatric patients for any indication.¹ (See Pediatric Use under Cautions.)

No known risk factors predict the occurrence or severity of rash.¹ ³⁰ Nearly all cases occurred within 1–5 weeks following initiation of modafinil or armodafinil therapy, but cases also reported after prolonged (e.g., 3 months) treatment.¹ ³⁰

Benign rashes also occur with armodafinil; not possible to predict which rashes will become serious.¹ Therefore, discontinue drug at first sign of rash unless clearly not drug related.¹ (See Advice to Patients.) Rash may become potentially life-threatening or permanently disabling or disfiguring despite drug discontinuance.¹

Persistent Sleepiness

In patients with abnormal levels of sleepiness, level of wakefulness may improve with armodafinil therapy, but may not return to normal.¹ (See Advice to Patients.)

Frequently reassess degree of sleepiness, and, if appropriate, advise patients to avoid driving or other potentially dangerous activity.¹ Patients may not acknowledge sleepiness or drowsiness until directly questioned about these symptoms during specific activities.¹ (See Advice to Patients.)

Psychiatric Effects

Adverse psychiatric effects (e.g., mania, delusions, hallucinations, suicidal ideation, aggression), sometimes resulting in hospitalization, reported in modafinil-treated patients;¹ ⁷ ³² many, but not all, such patients had a psychiatric history.¹ ⁷ Incidence and type of psychiatric effects expected to be similar with armodafinil.¹ ⁷ ³²

In controlled clinical trials, psychiatric symptoms requiring treatment discontinuance more often for armodafinil than for placebo include anxiety, agitation, nervousness, irritability, and depression; suicidal ideation also reported.¹

Use with caution in patients with a history of psychosis, depression, or mania.¹

Some clinicians recommend careful monitoring of patients receiving armodafinil or other CNS stimulants for possible psychiatric effects.³² If psychiatric symptoms develop, consider drug discontinuance.¹ (See Advice to Patients.)

Sensitivity Reactions

Angioedema and Anaphylactoid Reactions

Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm) reported.¹

Immediately discontinue therapy if any signs or symptoms of angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue or larynx; difficulty swallowing or breathing; hoarseness) develop.¹

Multiorgan Hypersensitivity Reactions

Multiorgan hypersensitivity reactions, including at least 1 fatality, reported with modafinil.¹ Similar risk with armodafinil cannot be ruled out.¹

Reactions detected a median of 13 days (range: 4–33 days) after initiation of modafinil.¹ Clinical presentation is variable but typically included fever and rash associated with other organ system involvement (e.g., myocarditis, hepatitis, liver function test abnormalities, hematological abnormalities [e.g., eosinophilia, leukopenia, thrombocytopenia], pruritus, asthenia).¹

No risk factors known to predict occurrence or severity.¹

If a multiorgan hypersensitivity reaction is suspected, discontinue therapy.¹ Cross-sensitivity with other drugs that produce this syndrome not yet reported but is possible.¹

General Precautions

Diagnosis of Sleep Disorders

Use only in patients who have had a complete evaluation (e.g., complete history, physical examination, testing in a laboratory setting [polysomnography]) of excessive sleepiness and in whom a diagnosis of narcolepsy, OSAHS, and/or SWSD has been made in accordance with International Classification of Sleep Disorders (ICSD) or DSM diagnostic criteria.¹

Consider that >1 sleep disorder may contribute to daytime sleepiness in some patients (e.g., OSAHS and SWSD concurrently in the same patient).¹

Continuous Positive Airway Pressure (CPAP) in OSAHS

In OSAHS, armodafinil is indicated as an adjunct to standard treatment(s) for the underlying obstruction.¹ If CPAP is the treatment of choice, make a maximal effort to treat with CPAP for an adequate period of time prior to initiating armodafinil therapy.¹ If armodafinil is used adjunctively with CPAP, necessary to encourage and periodically assess CPAP compliance.¹ (See Advice to Patients.)

Cognitive/Psychomotor Impairment Effects

Although armodafinil has not been shown to cause functional impairment, altered judgment, thinking, or motor skills is possible with any drug affecting the CNS.¹ (See Advice to Patients.)

Abuse and Misuse Potential

Armodafinil is subject to control as a schedule IV (C-IV) drug.¹ ¹⁸ Abuse potential not specifically studied, but expected to be similar to that of modafinil.¹ ¹⁸

Produces psychoactive and euphoric effects and alterations in mood, perception, thinking, and feelings similar to those observed with other CNS stimulants (e.g., amphetamines, methylphenidate), but current evidence indicates risk of abuse or misuse is lower with armodafinil and modafinil than with schedule II CNS stimulants (e.g., amphetamine, methylphenidate).¹ ⁷ ⁸ ¹⁷ ¹⁸ ²⁵ (See Actions.)

Monitor patients closely during treatment for possible signs of misuse or abuse (e.g., incrementation of doses, drug-seeking behavior), particularly in those with a history of drug or stimulant abuse (e.g., amphetamine, cocaine, methylphenidate).¹ ⁷

Cardiovascular Effects

Adverse cardiovascular effects (e.g., chest pain, palpitations, dyspnea, transient ischemic T-wave changes on ECG) reported with modafinil; similar risk expected with armodafinil.¹

Not recommended in patients with history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced mitral valve prolapse syndrome (e.g., ischemic ECG changes, chest pain, arrhythmia) with CNS stimulant use.¹ If new onset of any of these symptoms of mitral valve prolapse syndrome occurs during armodafinil therapy, consider cardiac evaluation.¹

Use with caution in patients with recent history of MI or unstable angina.¹

Increased monitoring of BP may be appropriate during therapy.¹

Contraceptive Precautions

Possible reduced efficacy of hormonal contraceptives during and for 1 month after discontinuance of therapy.¹ ⁷ Alternative or concomitant contraceptive methods recommended during these periods.¹ ⁷ (See Specific Drugs under Interactions and see Advice to Patients.)

Drug Interaction with Cyclosporine

Possible reduced cyclosporine blood concentrations when given concurrently with armodafinil.¹ (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether armodafinil or its metabolites are distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Armodafinil is not approved for use in pediatric patients for any indication.¹ Safety and efficacy not established in children <17 years of age.¹

Serious rashes (e.g., erythema multiforme, Stevens-Johnson syndrome) associated with use of modafinil in pediatric patients.¹ ³⁰ (See Serious Dermatologic Reactions under Cautions.)

Geriatric Use

Safety and efficacy not established in patients >65 years of age.¹

Elimination of armodafinil and its metabolites may be reduced; consider reduced dosage.¹ ⁷ (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Hepatic Impairment

Armodafinil not specifically studied in patients with hepatic impairment.¹ However, possible reduced clearance in patients with severe hepatic impairment based on pharmacokinetic studies with modafinil.¹ Reduce dosage in patients with severe hepatic impairment, with or without cirrhosis.¹ ⁷ (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Renal Impairment

Inadequate information to determine safety and efficacy in patients with severe renal impairment.¹ (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Headache, nausea, dizziness, insomnia.¹ ² ³ ⁴ ⁵ ⁷ ¹⁰ ¹² ¹³ ¹⁹

Interactions for Nuvigil

Partially metabolized by CYP3A enzymes.¹ Slightly induces CYP1A2 and possibly CYP3A, and reversibly inhibits CYP2C19 in vitro.¹ ⁷ ¹⁴ Moderately induces CYP3A4 and moderately inhibits CYP2C19, but does not appear to substantially induce CYP1A2, in vivo.¹ ⁷ ⁸ ¹⁴

Substrate of P-glycoprotein.¹

Drugs Affecting Hepatic Microsomal Enzymes

Potent inducers or inhibitors of CYP3A4/5: Potential pharmacokinetic interaction (altered plasma concentrations of armodafinil).¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4/5: Potential pharmacokinetic interaction (decreased plasma concentrations of substrate); dosage adjustment of substrate drug may be necessary.¹ ⁷ ⁸ ¹⁴

Substrates of CYP2C19: Potential pharmacokinetic interaction (increased plasma concentrations of substrate); dosage reduction and monitoring for toxicity of substrate drug may be necessary.¹ ⁷ ¹⁴

Protein-bound Drugs

Potential for interactions with highly protein-bound drugs considered unlikely.¹

Specific Drugs

Drug	Interaction	Comments
Alcohol	Concomitant use not evaluated¹	Concomitant use not recommended¹
Antifungals, azoles (itraconazole, ketoconazole)	Possible increased plasma armodafinil concentrations¹
Caffeine	Pharmacokinetics of caffeine not substantially affected during chronic armodafinil administration¹
Carbamazepine	Possible decreased plasma armodafinil concentrations¹
Clomipramine	Possible increased plasma concentrations of clomipramine and its active desmethyl metabolite¹	May need to reduce clomipramine dosage and monitor for toxicity¹
CNS-active agents	Specific drug interaction studies not conducted between armodafinil and CNS-active drugs; available drug interaction information with modafinil should also apply to armodafinil¹
Cyclosporine	Possible decreased blood concentrations and effectiveness of cyclosporine¹	Consider monitoring circulating cyclosporine concentrations; adjust cyclosporine dosage if necessary¹ ¹⁴
Dextroamphetamine	Specific drug interaction studies not conducted between armodafinil and dextroamphetamine; clinically important pharmacokinetic interaction unlikely with racemic modafinil, although modafinil absorption may be delayed by approximately 1 hour¹ ¹⁵ ²³
Diazepam	Possible increased plasma diazepam concentrations¹	May need to reduce diazepam dosage and monitor for toxicity¹
Erythromycin	Possible increased armodafinil plasma concentrations¹
Hormonal contraceptives	Potential for decreased plasma concentrations of ethinyl estradiol; possible hormonal contraceptive failure¹	Alternative or concomitant methods of contraception recommended during and for 1 month after discontinuance of armodafinil therapy ¹
Ketoconazole	Possible increased armodafinil plasma concentrations¹
MAO inhibitors	Interaction studies not performed to date¹ Acute chorea, confusion, and hyperthermia (possibly related to serotonin syndrome) reported with concurrent modafinil and tranylcypromine³⁵	Use concomitantly with caution¹
Methylphenidate	Specific drug interaction studies not conducted between armodafinil and methylphenidate; clinically important pharmacokinetic interaction unlikely with racemic modafinil, although modafinil absorption may be delayed by approximately 1 hour¹ ²² ³⁰
Midazolam	Potential for reduced systemic exposure of midazolam¹ ¹⁴	Dosage adjustment of midazolam may be necessary¹
Omeprazole	Potential for increased plasma concentrations and systemic exposure to omeprazole¹ ¹⁴	May need to reduce omeprazole dosage and monitor for toxicity¹
Phenobarbital	Possible decreased plasma armodafinil concentrations¹
Phenytoin	Possible increased plasma phenytoin concentrations¹	May need to reduce phenytoin dosage and monitor for toxicity¹
Propranolol	Possible increased plasma propranolol concentrations¹	May need to reduce propranolol dosage and monitor for toxicity¹
Rifampin	Possible decreased plasma armodafinil concentrations¹
Triazolam	Potential for reduced plasma concentrations and effectiveness of triazolam¹ ¹⁴	Dosage adjustment of triazolam may be necessary¹ ¹⁴
Warfarin	Single-dose pharmacokinetics of warfarin not substantially affected by chronic administration of modafinil¹ ¹⁶	Monitor PT and/or INR more frequently¹ ¹⁶

Nuvigil Pharmacokinetics

Absorption

Bioavailability

Readily absorbed following oral administration, with peak plasma concentrations occurring at approximately 2 hours (in the fasted state).¹ ⁷ ⁸ ¹² ¹³ Steady-state concentrations are reached within 7 days of once-daily administration.¹ ⁷ ⁸ ¹³

Absolute oral bioavailability not determined because of low aqueous solubility.¹

In healthy individuals, armodafinil produces consistently higher plasma concentrations later in the dosing period relative to modafinil on a mg-to-mg basis.¹ ⁸ ¹⁰ ¹¹ ¹² ¹⁴

Food

Food may delay time to peak plasma concentrations by approximately 2–4 hours, but does not appear to affect overall bioavailability.¹ ⁷ ⁸ ¹³

Distribution

Extent

Large volume of distribution (42 L following oral administration) suggests extensive extravascular distribution.¹ ⁸ ¹³

Not known whether armodafinil or its metabolites are distributed into milk.¹

Plasma Protein Binding

Armodafinil: Data not available.¹

Modafinil: approximately 60% (mainly albumin).¹

Elimination

Metabolism

Metabolized to inactive metabolites via hydrolytic deamidation, S-oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation.¹ Partially metabolized by CYP3A isoenzymes.¹

Elimination Route

Metabolic fate of armodafinil not specifically studied; however, modafinil is excreted in urine (80%) and in feces (1%), mainly as metabolites.¹

Half-life

Approximately 15 hours.¹ ¹² ¹³

Special Populations

In patients with severe hepatic impairment and cirrhosis (Child-Pugh class B, B+, C, or C+), clearance of modafinil is decreased and steady-state concentrations are increased.¹

In patients with severe chronic renal impairment (Cl_cr ≤20 mL/minute), pharmacokinetics of modafinil are not substantially altered, but exposure to modafinil acid (an inactive metabolite) is increased ninefold compared with healthy individuals.¹

In geriatric patients, clearance of armodafinil and its metabolites may be reduced.¹

Stability

Storage

Oral

Tablets

20–25°C.¹

Actions

Armodafinil, a nonamphetamine wakefulness-promoting agent, is the longer-lasting R-enantiomer of racemic modafinil (a 50:50 mixture of the of the R- and S-enantiomers); exhibits pharmacologic properties similar to those of modafinil.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ¹⁰ ¹¹ ¹² ¹³ ²⁶ ³⁴

Armodafinil and modafinil differ primarily in their pharmacokinetic profiles.¹ ⁸ ¹⁰ ¹¹ ¹² ¹⁴ Compared with modafinil, armodafinil produces consistently higher plasma drug concentrations later in the day; however, further study is needed to determine whether this difference results in improved clinical response.¹ ⁴ ⁵ ⁷ ¹⁰ ¹¹ ¹² ¹⁴

Promotes vigilance and wakefulness.¹ Exact mechanism of action unknown, but may involve activation of certain areas of the brain that control wakefulness.¹ ⁷ ⁸ ²¹

Does not appear to act as a direct- or indirect-acting dopamine-receptor or α₁-adrenergic agonist, but has been shown in in vitro studies to bind to the dopamine transporter and inhibit dopamine reuptake.¹ ⁷ Modafinil blocked dopamine transporters and increased dopamine concentrations in the human brain (including the nucleus accumbens) in one study; drugs with such activity generally have abuse potential.²⁷ Stimulant effects of modafinil can be attenuated by the α₁-adrenergic receptor antagonist, prazosin.¹ ⁷

At pharmacologically relevant concentrations, does not bind to or inhibit certain receptors and enzymes (e.g., serotonin, dopamine, adenosine, galanin, melatonin, melanocortin, orexin-1, orphanin, pituitary adenylate cyclase-activating polypeptide [PACAP], benzodiazepines); transporters for GABA, serotonin, norepinephrine, or choline; or phosphodiesterase VI, catechol-O-methyl transferase (COMT), GABA transaminase, or tyrosine hydroxylase, which may regulate sleep and wakefulness.¹ ⁷

Does not inhibit activity of type B MAO (MAO-B) or phosphodiesterases II-IV.¹

Reinforcing properties in animals; produces psychoactive (e.g., alterations in mood and thinking), euphoric, and subjective effects typical of classic CNS stimulants (e.g., amphetamines, methylphenidate) in humans.¹ ⁷ ¹⁸

Advice to Patients

Importance of reading patient information leaflet provided by the manufacturer prior to initiating therapy.¹

Importance of advising clinician of existing or contemplated therapy, including prescription and OTC drugs and/or herbal supplements, as well as any concomitant illnesses.¹ Advise patient that it is prudent to avoid alcohol since combined use has not been studied.¹

Potential increased risk of pregnancy in women taking hormonal contraceptives (including oral contraceptives, injectable or implantable contraceptives, transdermal systems, vaginal rings, and intrauterine devices) during and for 1 month after discontinuing armodafinil therapy; discuss use of alternative or concomitant methods of contraception during these periods.¹ (See Contraceptive Precautions under Cautions.) Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

Risk of serious rash or serious allergic reaction.¹ Advise patient to immediately discontinue armodafinil and notify their clinician if they develop a rash or other manifestations of an allergic reaction (e.g., hives, mouth sores, blisters, peeling skin, difficulty swallowing or breathing, related allergic phenomenon).¹

Risk of mental (psychiatric) symptoms.¹ Importance of discontinuing armodafinil and informing clinician if depression, anxiety, hallucinations, mania, suicidal thoughts, aggression, or other psychiatric symptoms associated with psychosis or mania occur.¹

Risk of heart problems.¹ Importance of discontinuing armodafinil and informing clinician if heart problems, including chest pain, occur.¹

Advise that armodafinil may affect judgment, thinking, or motor skills.¹ Use caution when operating machinery or driving a motor vehicle until effects of the drug are known.¹

Advise patient that armodafinil may improve, but not eliminate, the abnormal tendency to fall asleep.¹ Therefore, stress importance of not altering previous behavior with regard to potentially dangerous activities (e.g., driving, operating machinery) or other activities requiring appropriate levels of wakefulness until and unless armodafinil produces sufficient wakefulness that permits such activities.¹ Advise that armodafinil therapy is not a replacement for sleep.¹

Importance of continuing previously prescribed therapy (e.g., patients with OSAHS should continue using their CPAP machine while sleeping).¹

Importance of advising 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 ¹⁸

Armodafinil
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	50 mg	Nuvigil (C-IV)	Cephalon
		150 mg	Nuvigil (C-IV)	Cephalon
		250 mg	Nuvigil (C-IV)	Cephalon

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.

Nuvigil 150MG Tablets (CEPHALON): 30/$350.98 or 90/$1,033.93

Nuvigil 250MG Tablets (CEPHALON): 30/$352.00 or 90/$1,039.02

Nuvigil 50MG Tablets (CEPHALON): 30/$122.99 or 90/$340.97

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.

References

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22. Wong YN, King SP, Laughton WB et al. Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998; 38:276-82. [PubMed 9549666]

23. Wong YN, Wang L, Hartman L et al. Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998; 38:971-8. [PubMed 9807980]

24. Schwartz JR, Khan A, McCall V et al. A 12-month or more open-label study of the efficacy and tolerability of armodafinil. Sleep. 2009; 32 (Suppl.):A50-1. Abstr. No. 0148.

25. Drug Enforcement Administration, US Department of Justice, Office of Diversion Control. Lists of: scheduling actions, controlled substances, regulated chemicals. 2010 Sep. Accessed online on 2010 Sep 24.

26. Anon. Armodafinil (Nuvigil) for wakefulness. Med Lett Drugs Ther. 2010; 52:61-2. [PubMed 20697340]

27. Volkow ND, Fowler JS, Logan J et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA. 2009; 301:1148-54. [PubMed 19293415]

28. Roth T, Schwartz JRL, Hirshkowitz M et al. Evaluation of the safety of modafinil for treatment of

Monday, 26 March 2012

Original Andrews Salts

1. Name Of The Medicinal Product

Original Andrews Salts

2. Qualitative And Quantitative Composition

Effervescent Powder containing magnesium sulphate 17.4% w/w, Sodium Hydrogen Carbonate Ph Eur 22.6% w/w and Citric Acid (anhydrous) Ph Eur 19.5% w/w.

3. Pharmaceutical Form

Effervescent powder for oral use.

4. Clinical Particulars

4.1 Therapeutic Indications

The product is recommended as a laxative and as an antacid for the relief of upset stomach, indigestion and biliousness.

4.2 Posology And Method Of Administration

Adults (including the elderly): As an antacid, measure one level spoonful (5 ml spoonful) and take in a glass of water repeated as necessary, up to a maximum of four times a day.

As a laxative, measure two level spoonfuls (two 5 ml spoonfuls) and take in a glass of water before breakfast or at bedtime.

Children over 3 years: Half the adult dose.

Not suitable for children under 3 years of age.

4.3 Contraindications

None.

4.4 Special Warnings And Precautions For Use

Because of the sodium content, frequent use by patients on a low sodium diet should be avoided. This includes patients with hypertension and cardiac or renal dysfunction. Because of the sucrose content, diabetics should use with caution. If a laxative is required every day, if there is persistent abdominal pain, or if symptoms persist consult your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Magnesium sulphate, in common with other magnesium salts, may interfere with the absorption of tetracycline and alkalinisation of the urine may modify excretion of drugs for which the excretion is pH sensitive.

4.6 Pregnancy And Lactation

For Magnesium sulphate no clinical data on exposed pregnancies are available.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Caution should be exercised when recommending to pregnant women.

4.7 Effects On Ability To Drive And Use Machines

No effect on mental alertness.

4.8 Undesirable Effects

Diarrhoea may occur with extensive usage. Frequent or prolonged use in patients with severe renal dysfunction may lead to hypermagnesaemia and hypocalcaemia.

4.9 Overdose

Diarrhoea may occur with excessive usage. Hypermagnesaemia and hypocalcaemia may also occur in the presence of impaired renal function. Treatment is symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Sodium hydrogen carbonate exerts an immediate antacid effect in the stomach by neutralising acid secretion with the liberation of carbon dioxide.

Citric acid and sodium hydrogen carbonate in solution have a buffering capacity which alleviates discomfort caused by acidity in the stomach.

Magnesium sulphate is not readily absorbed from the intestine and acts as a saline purgative. Magnesium ions in the gut have also been shown to cause secretion of cholecystokinin which favours intraluminal accumulation of water and electrolytes.

5.2 Pharmacokinetic Properties

The product has a local gastrointestinal action and so detailed pharmacokinetic data are not available. It has been shown that less than 10% of ionic magnesium is absorbed when the product was given to healthy subjects. The magnesium that is absorbed is excreted by the kidney.

After absorption, the hydrogen carbonate is retained by the kidney to meet any deficit of hydrogen carbonate in the plasma.

Citric acid is absorbed by the gastrointestinal tract and is oxidised in the body to carbon dioxide and water.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which is additional to that already included in other sections of the SmPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sucrose Ph Eur.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Five years (tin and laminate sachets).

Three years (plastic containers).

6.4 Special Precautions For Storage

Store below 25°C and away from strong odours.

6.5 Nature And Contents Of Container

Tin with tamper evident paper seal and pressfit lid containing 110 g, 113 g, 200 g or 227 g.

4 or 8 laminate sachets containing 5 g packed into cardboard cartons.

White oval plastic containers sealed with aluminium foil and fitted with a blue plastic overcap with hinged lid containing 150 g or 250 g.

6.6 Special Precautions For Disposal And Other Handling

Use within 3 months of opening (plastic container only).

7. Marketing Authorisation Holder

SmithKline Beecham (SWG) Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

Trading as: GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS, U.K..

8. Marketing Authorisation Number(S)

PL 00071/5000R

9. Date Of First Authorisation/Renewal Of The Authorisation

30 January 1990

10. Date Of Revision Of The Text

October 2006

Saturday, 24 March 2012

Phenchlor Tannate Pediatric

Generic Name: chlorpheniramine and phenylephrine (KLOR fen IR a meen and FEN il EFF rin)

Brand Names: Actifed Cold & Allergy, Allan Tannate Pediatric, Allerest PE, AlleRx, BP Allergy JR, C Phen, Cardec, Ceron, Chlor-Mes Jr, ChlorTan D, Cold & Allergy Relief, CP Dec, Dallergy Drops, Dallergy-JR, Dec-Chlorphen, Ed A-Hist, Ed ChlorPed D, Histadec, Nasohist Pediatric, NoHist, Ny-Tannic, PD-Hist D, PD-Hist D Drops, PediaTan D, Phenchlor Tannate Pediatric, R-Tanna, Relera, Rinate Pediatric, Rondec, Rondex, Rynatan, Rynatan Pediatric, Sildec-PE, Sinus & Allergy Maximum Strength, Sinus & Allergy PE, Sonahist, Sudafed PE Sinus & Allergy, Tanahist-D, Triaminic Cold & Allergy

What is Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of chlorpheniramine and phenylephrine is used to treat symptoms of the common cold or seasonal allergies, including sneezing, runny or stuffy nose, and itchy, watery eyes.

Chlorpheniramine and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

There are many brands and forms of this medication available and not all brands are listed on this leaflet.

Do not use chlorpheniramine and phenylephrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. You should not use this medication if you are allergic to chlorpheniramine or phenylephrine, or if you have severe high blood pressure or coronary artery disease, narrow-angle glaucoma, a stomach ulcer, or if you are unable to urinate.

Do not use this medication during an asthma attack.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine and phenylephrine. Older adults may be more likely to have side effects from this medicine. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

What should I discuss with my healthcare provider before taking Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

severe or uncontrolled high blood pressure;

severe coronary artery disease;

narrow angle glaucoma;

a stomach ulcer;

if you are unable to urinate; or

if you are having an asthma attack.

Ask a doctor or pharmacist if it is safe for you to take this medication if you have:

kidney disease;

liver disease;

diabetes;

glaucoma;

circulation problems;

heart disease or high blood pressure;

overactive thyroid;

a seizure disorder such as epilepsy;

asthma, emphysema or chronic bronchitis; or

urination problems or an enlarged prostate.

It is not known whether chlorpheniramine and phenylephrine is harmful to an unborn baby. Do not take this medication with a doctor's advice if you are pregnant. It is not known whether chlorpheniramine and phenylephrine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Older adults may be more likely to have side effects from this medicine.

Artificially sweetened liquid cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

The chewable tablet must be chewed before swallowing.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

This medication can cause unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

If you need surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold medicine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

What should I avoid while taking Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine and phenylephrine. Ask a doctor or pharmacist before using any other cold, allergy, or sleep medicine. Chlorpheniramine and phenylephrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine or decongestant.

Avoid taking this medication if you also take diet pills, caffeine pills, or other stimulants (such as ADHD medications). Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

fast or pounding heartbeats;

confusion, hallucinations, unusual thoughts or behavior;

severe dizziness, anxiety, restless feeling, nervousness;

urinating less than usual or not at all;

easy bruising or bleeding, unusual weakness; or

seizure (black-out or convulsions).

Less serious side effects may include:

blurred vision;

dry nose or mouth;

nausea, stomach pain, constipation, loss of appetite;

dizziness, drowsiness;

problems with memory or concentration;

ringing in your ears; or

feeling restless or excited (especially in children).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1 800 FDA 1088.

What other drugs will affect Phenchlor Tannate Pediatric (chlorpheniramine and phenylephrine)?

Before using this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as other cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine.

Tell your doctor about all other medications you use, especially:

mecamylamine (Inversine);

methyldopa (Aldomet);

reserpine;

a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;

a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Solfoton); or

an antidepressant such as amitriptyline (Elavil, Vanatrip), doxepin (Sinequan), nortriptyline (Pamelor), and others.

This list is not complete and other drugs may interact with chlorpheniramine and phenylephrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Phenchlor Tannate Pediatric resources

Phenchlor Tannate Pediatric Side Effects (in more detail)
Phenchlor Tannate Pediatric Use in Pregnancy & Breastfeeding
Phenchlor Tannate Pediatric Drug Interactions
0 Reviews for Phenchlor Tannate Pediatric - Add your own review/rating

AlleRx Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

Cardec Drops MedFacts Consumer Leaflet (Wolters Kluwer)

Dallergy-JR Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Ny-Tannic MedFacts Consumer Leaflet (Wolters Kluwer)

Relera Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Rondec MedFacts Consumer Leaflet (Wolters Kluwer)

Rynatan Prescribing Information (FDA)

Sonahist Prescribing Information (FDA)

Compare Phenchlor Tannate Pediatric with other medications

Cold Symptoms
Hay Fever

Where can I get more information?

Your pharmacist can provide more information about chlorpheniramine and phenylephrine.

See also: Phenchlor Tannate Pediatric side effects (in more detail)

Saturday, 17 March 2012

Sumatriptan Tablets

Pronunciation: SOO-ma-TRIP-tan
Generic Name: Sumatriptan
Brand Name: Imitrex

Sumatriptan is used for:

The treatment of migraine headaches with or without aura (eg, flashing lights, wavy lines, dark spots). It may also be used for other conditions as determined by your doctor.

Sumatriptan is a serotonin 5-HT ₁ receptor agonist ("triptan"). It works by narrowing blood vessels in the brain, which helps to relieve migraines.

Do NOT use Sumatriptan if:

you are allergic to any ingredient in Sumatriptan

you have a history of ischemic heart disease (eg, angina, heart attack), coronary artery disease (CAD), other moderate to severe heart problems, brain blood vessel disease (eg, stroke, transient ischemic attack), or other blood vessel disease (eg, Raynaud syndrome, ischemic bowel disease)

you have uncontrolled high blood pressure or severe liver problems

you have certain types of migraines (eg, hemiplegic, basilar)

you are taking or have taken a monamine oxidase inhibitor (MAOI) (eg, phenelzine) within the past 14 days

you have used certain other migraine medicines within the past 24 hours (eg, an ergot derivative [eg, dihydroergotamine, methysergide], another serotonin 5-HT ₁ receptor agonist [eg, eletriptan, rizatriptan])

you are taking sibutramine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Sumatriptan:

Some medical conditions may interact with Sumatriptan. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have history of liver or kidney problems, seizures (eg epilepsy), heart problems, or other types of headaches (eg, cluster headaches)

if you have shortness of breath, chest pain, or a history of high blood pressure, heart attack, stroke, high cholesterol, diabetes, or smoking

if you are a woman who is past menopause

if you are a man who is more than 40 years old

if you are very overweight

if a family member has had heart disease or a stroke

Some MEDICINES MAY INTERACT with Sumatriptan. Tell your health care provider if you are taking any other medicines, especially any of the following:

Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), serotonin norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine), orsibutramine because the risk of a serious side effect called serotonin syndrome may be increased. Symptoms of serotonin syndrome may include mental or mood changes, hallucinations, fast heartbeat, fever, loss of coordination, muscle spasms, increased sweating, nausea, vomiting, or diarrhea

MAOIs (eg, phenelzine) because they may increase the risk of Sumatriptan's side effects

Ergot derivatives (eg, dihydroergotamine, methysergide) or other serotonin 5-HT ₁ receptor agonists (eg, eletriptan, rizatriptan) because the risk of their side effects may be increased by Sumatriptan

This may not be a complete list of all interactions that may occur. Ask your health care provider if Sumatriptan may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Sumatriptan:

Use Sumatriptan as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Sumatriptan. Talk to your pharmacist if you have questions about this information.

Take Sumatriptan by mouth with or without food.

Swallow Sumatriptan whole. Do not break, crush, or chew before swallowing.

It is best to take a dose of Sumatriptan as soon as you notice symptoms of a migraine attack.

If your migraine symptoms go away and then come back, or if you have a partial response to the first dose, you may take a second dose as directed by your doctor. Wait at least 2 hours between doses.

If your symptoms do not improve after the first dose, do not take a second dose for the same attack. Contact your doctor.

Do not take more than the amount prescribed by your doctor in a 24-hour period or treat more than 4 headaches within 30 days without checking with your doctor.

If you miss a dose of Sumatriptan and you still have a headache, follow your doctor's dosing instructions. Contact your doctor immediately if you are unsure of what to do if you miss a dose. Do not take Sumatriptan more often than prescribed. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Sumatriptan.

Important safety information:

Sumatriptan may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Sumatriptan with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Overuse of Sumatriptan can cause your headache to become worse. Do NOT take more than the recommended dose or use more often than prescribed without checking with your doctor.

Rarely, serious heart problems (eg, heart attack, irregular heartbeat) have been reported within a few hours of using Sumatriptan. Contact your doctor at once if fast or irregular heartbeat; chest, jaw, or neck pain or numbness; numbness of an arm or leg; severe stomach pain, dizziness, or vomiting; fainting; or vision changes occur. Discuss any questions or concerns with your doctor.

Serotonin syndrome is a possibly fatal syndrome that can be caused by Sumatriptan. Your risk may be greater if you take Sumatriptan with certain other medicines (eg, SSRIs, SNRIs). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.

Sumatriptan should not be used to prevent or reduce the number of migraine headaches you have. If you have a headache that is different than your usual migraine headaches, check with your doctor before using Sumatriptan.

Lab tests, including heart function tests, may be performed while you use Sumatriptan. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Sumatriptan should not be used in the ELDERLY; the risk of serious side effects (eg, heart problems, high blood pressure) may be increased.

Sumatriptan should not be used in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: It is not known if Sumatriptan can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Sumatriptan while you are pregnant. Sumatriptan is found in breast milk. If you are or will be breast-feeding while you use Sumatriptan, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Sumatriptan:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Burning; dizziness; drowsiness; feeling of heaviness or pressure; muscle aches; numbness or tingling of the skin; sick feeling; tingling; tiredness; warm/hot sensation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody diarrhea; chest pain; confusion; fainting; fast or irregular heartbeat; fever; hallucination; hearing problems; numbness or tingling of an arm or leg; one-sided weakness; pain, tightness, or pressure in the jaw, neck, or chest; seizures; severe headache, dizziness, or vomiting; severe or prolonged flushing; severe stomach pain; shortness of breath; speech changes; very cold or blue fingers or toes; vision changes or loss of vision; wheezing.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Sumatriptan side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blue skin or lips; chest pain; dilated pupils; loss of coordination; paralysis; redness of the fingers or toes; seizures; slow or difficult breathing; tremor.

Proper storage of Sumatriptan:

Store Sumatriptan between 36 and 86 degrees F (2 and 30 degrees C). Store away from heat, moisture, and light. Do not freeze. Do not store at temperatures above 86 degrees F (30 degrees C). Do not store in the bathroom. Keep Sumatriptan in the case provided. Throw away expired medicine as directed by your doctor (the expiration date is printed on the treatment pack). Keep Sumatriptan out of the reach of children and away from pets.

General information:

If you have any questions about Sumatriptan, please talk with your doctor, pharmacist, or other health care provider.

Sumatriptan is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is summary only. It does not contain all information about Sumatriptan. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Sumatriptan resources

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

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Tuesday, 13 March 2012

Exocin

1. Name Of The Medicinal Product

EXOCIN^® 3 mg/ml Eye Drops, Solution.

2. Qualitative And Quantitative Composition

One millilitre contains 3 mg ofloxacin.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Eye drops, solution.

Clear, pale to light yellow-green solution, practically free from visible particles.

4. Clinical Particulars

4.1 Therapeutic Indications

EXOCIN^® is indicated for the topical treatment of external ocular infections (such as conjunctivitis and keratoconjunctivitis) in adults and children caused by ofloxacin - sensitive organisms. Safety and efficacy in the treatment of ophthalmia neonatorum has not been established.

4.2 Posology And Method Of Administration

Topical ocular instillation.

For all ages: one to two drops in the affected eye(s) every two to four hours for the first two days and then four times daily. The length of treatment should not exceed ten days.

4.3 Contraindications

EXOCIN^® is contra-indicated in individuals who have shown hypersensitivity to ofloxacin or any of its excipients.

4.4 Special Warnings And Precautions For Use

EXOCIN^® is not for injection.

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.

If an allergic reaction to EXOCIN^® occurs, discontinue the drug. Use EXOCIN^® with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents.

When using EXOCIN^® the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms.

If worsening infection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.

Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established.

Cardiac disorders

Caution should be taken when using fluoroquinolones, including EXOCIN^® in patients with known risk factors for prolongation of the QT interval such as, for example:

- congenital long QT syndrome

- concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)

- uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)

- elderly

- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

(See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).

Use EXOCIN^® with caution in patients who have exhibited sensitivities to other quinolone antibacterial agents.

Data are very limited to establish efficacy and safety of EXOCIN^® eye drops 0.3% in the treatment of conjunctivitis in neonates.

The use of EXOCIN^® in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use in elderly: No comparative data are available with topical dosing in elderly versus other age groups.

Clinical and non-clinical publications have reported the occurrence of corneal perforation in patients with pre-existing corneal epithelial defect or corneal ulcer, when treated with topical fluoroquinolone antibiotics. However, significant confounding factors were involved in many of these reports, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g. severe dry eye), systemic inflammatory diseases (e.g. rheumatoid arthritis), and concomitant use of ocular steroids or non-steroidal anti-inflammatory drugs. Nevertheless, it is necessary to advise caution regarding the risk of corneal perforation when using product to treat patients with corneal epithelial defects or corneal ulcers.

Corneal precipitates have been reported during treatment with topical ophthalmic ofloxacin. However, a causal relationship has not been established.

Long-term, high-dose use of other fluoroquinolones in experimental animals has caused lenticular opacities. However, this effect has not been reported in human patients, nor has it been noted following topical ophthalmic treatment with ofloxacin for up to six months in animal studies including studies in monkeys.

EXOCIN^® contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.

Use of contact lenses is not recommended in patients receiving treatment for an eye infection.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No interaction studies have been performed.

It has been shown that the systemic administration of some quinolones inhibits the metabolic clearance of caffeine and theophylline. Drug interaction studies conducted with systemic ofloxacin have demonstrated that metabolic clearance of caffeine and theophylline are not significantly affected by ofloxacin.

Although there have been reports of an increased prevalence of CNS toxicity with systemic dosing of fluoroquinolones when used concomitantly with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.

EXOCIN^®, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).

4.6 Pregnancy And Lactation

Use in pregnancy: There have been no adequate and well-controlled studies performed in pregnant women. Since systemic quinolones have been shown to cause arthropathy in immature animals, it is recommended that EXOCIN^® not be used in pregnant women.

Use during lactation: Because ofloxacin and other quinolones taken systemically are excreted in breast milk, and there is potential for harm to nursing infants, a decision should be made whether to temporarily discontinue nursing or not to administer the drug, taking into account the importance of the drug to the mother.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed.

Transient blurring of vision may occur on instillation of eye drops. Do not drive or operate hazardous machinery unless vision is clear.

4.8 Undesirable Effects

General

Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, side-effects reported with systemic use could possibly occur.

Frequency categories: Very common (

Immune System Disorders:

Not known: Hypersensitivity (including Eye allergy)

Nervous System Disorders

Not known: Dizziness

Eye Disorders

Common: Eye irritation; Ocular discomfort

Not known: Keratitis; Conjunctivitis; Vision blurred; Photophobia; Eye oedema; Foreign body sensation in eyes; Lacrimation increased; Dry eye; Eye pain; Eye pruritus; Eyelids pruritus; Ocular hyperaemia

Cardiac disorders

Not known : ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9).

Gastrointestinal Disorders

Not known: Nausea

Skin and Subcutaneous Tissue Disorders

Not Known: Periorbital oedema

General Disorders and Administration Site Conditions

Not known: Facial oedema

4.9 Overdose

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, quinolones

ATC code: S 01 AX 11.

ofloxacin is a synthetic fluorinated 4-quinolone antibacterial agent with activity against a broad spectrum of Gram negative and to a lesser degree Gram positive organisms.

ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically in ophthalmic infections. Clinical trial evidence of the efficacy of EXOCIN^® against S. pneumoniae was based on a limited number of isolates.

Gram-negative bacteria: Acinetobacter calcoaceticus var. anitratum, and A. calcoaceticus var. iwoffi; Enterobacter Sp. including E. cloacae; Haemophilis Sp, including H. influenza and H. aegyptius; Klebsiella Sp., including K. Pneumoniae; Moraxella Sp., Morganella morganii; Proteus Sp., including P. Mirabilis; Pseudomonas Sp.; including P. Aeruginosa, P. cepacia, and P. fluoroscens; and Serratia Sp., including S. marcescens.

Gram-positive bacteria: Bacillus Sp.; Corynebacterium Sp.; Micrococcus Sp.; Staphylococcus Sp., including S. aureus and S. epidermidis; Streptococcus Sp., including S. Pneumoniae (see above), S. viridans and Beta-haemolytic.

The primary mechanisms of action is through inhibition of bacterial DNA gyrase, the enzyme responsible for maintaining the structure of DNA.

ofloxacin is not subject to degradation by beta-lactamase enzymes nor is it modified by enzymes such as aminoglycoside adenylases or phosphorylases, or chloramphenicol acetyltransferase.

5.2 Pharmacokinetic Properties

After ophthalmic instillation, ofloxacin is well maintained in the tear-film.

In a healthy volunteer study, mean tear film concentrations of ofloxacin measured four hours after topical dosing (9.2 µg/g) were higher than the 2µg/ml minimum concentration of ofloxacin necessary to inhibit 90% of most ocular bacterial strains (MIC90) in-vitro.

Maximum serum ofloxacin concentrations after ten days of topical dosing were about 1000 times lower than those reported after standard oral doses of ofloxacin, and no systemic side-effects attributable to topical ofloxacin were observed.

5.3 Preclinical Safety Data

There are no toxicological safety issues with this product in man as the level of systemic absorption from topical ocular administration of ofloxacin is minimal.

Animal studies in the dog have found cases of arthropathy in weight bearing joints of juvenile animals after high oral doses of certain quinolones. However, these findings have not been seen in clinical studies and their relevance to man is unknown.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzalkonium chloride (EP) 0.005% w/v

Sodium chloride (EP) 0.9% w/v

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Purified water (EP)

6.2 Incompatibilities

None known.

6.3 Shelf Life

2 years unopened.

Discard 28 days after first opening.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

A bottle and an applicator tip of low density polyethylene (LDPE) and medium or high impact polystyrene cap.

The bottle contains 5 ml or 10 ml of suspension.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

There is no special requirement for disposal.

Any unused product or waste material should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

Allergan Ltd

Marlow International

The Parkway

Marlow

Bucks SL7 1YL

United Kingdom

8. Marketing Authorisation Number(S)

PL 00426/0070

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 26^th October 1992

Date of last renewal: 8^th November 2004

10. Date Of Revision Of The Text

17^th May 2011