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Special Alerts
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state “Do not use in children under four years of age.” In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include:
• Always follow dosing instructions exactly and use measuring devices provided with the medicine.
• Never give 2 medicines at the same time that contain the same active ingredient.
• Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, “Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,” MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
Medication Safety Issues
Sound-alike/look-alike issues:
Benylin® may be confused with Benadryl®, Ventolin®
Delsym® may be confused with Delfen®, Desyrel®
Pronunciation
(deks troe meth OR fan)
U.S. Brand Names
Generic Available
Yes: Excludes strip, liquid freezer pop
Pharmacologic Category
Use: Labeled Indications
Symptomatic relief of coughs caused by the common cold or inhaled irritants
Use: Unlabeled/Investigational
N-methyl-D-aspartate (NMDA) antagonist
Contraindications
Concurrent administration with or within 2 weeks of discontinuing an MAO inhibitor
Warnings/Precautions
Concurrent drug therapy issues:
• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans); especially with higher dextromethorphan doses.
Special populations:
• Debilitated patients: Use with caution in patients who are sedated, debilitated or confined to a supine position.
• Neonates: Some products may contain sodium benzoate which has been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; in vitro and animal studies have shown that benzoate, a metabolite of benzyl alcohol, displaces bilirubin from protein binding sites; avoid use of products containing sodium benzoate in neonates.
• Pediatrics: Use with caution in atopic children. Not for OTC use in children <4 years of age.
Dosage form specific issues:
• Sodium benzoate: Some products may contain sodium benzoate may cause allergic reactions in susceptible individuals.
• Tartrazine: Some products may contain tartrazine.
Other warnings/precautions:
• Abuse/misuse: Healthcare providers should be alert to problems of abuse or misuse. Abuse can cause death, brain damage, seizure, loss of consciousness, and irregular heartbeat.
• Self-medication (OTC use): When used for self medication (OTC) notify healthcare provider if symptoms do not improve within 7 days, or are accompanied by fever, rash or persistent headache. Do not use for persistent or chronic cough (as with smoking, asthma, chronic bronchitis, emphysema) or if cough is accompanied b excessive phlegm unless directed to do so by healthcare provider.
Adverse Reactions
Frequency not defined.
Central nervous system: Confusion, excitement, irritability, nervousness, serotonin syndrome
Metabolism/Transport Effects
Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
Drug Interactions
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Mechanism of Action
Decreases the sensitivity of cough receptors and interrupts cough impulse transmission by depressing the medullary cough center through sigma receptor stimulation; structurally related to codeine
Pharmacodynamics/Kinetics
Onset of action: Antitussive: 15-30 minutes
Duration: ?6 hours
Metabolism: Hepatic via demethylation via CYP2D6 to dextrorphan (active); CYP3A4 and CYP3A5 form smaller amounts of 3-hydroxy and 3-methoxy derivatives
Half-life elimination: Dextromethorphan: Extensive metabolizers: 2-4 hours; poor metabolizers: 24 hours
Time to peak: 2-3 hours
Excretion: Primarily in urine as metabolites
Dosage
Oral:
Children:
<4 years: Not for OTC use
4-6 years (syrup): 2.5-7.5 mg every 4-8 hours; extended release is 15 mg twice daily (maximum: 30 mg/24 hours)
6-12 years: 5-10 mg every 4 hours or 15 mg every 6-8 hours; extended release is 30 mg twice daily (maximum: 60 mg/24 hours)
Children >12 years and Adults: 10-20 mg every 4 hours or 30 mg every 6-8 hours; extended release: 60 mg twice daily; maximum: 120 mg/day
Test Interactions
False-positive phencyclidine (PCP), opiates, opioids and heroin urine drug screen
Dietary Considerations
Delsym® contains sodium 7 mg/5 mL.
Robitussin® Pediatric Cough contains sodium 5 mg/5 mL.
PediaCare® Children's Long-Acting Cough contains sodium 15 mg/5 mL.
Vicks® 44® Cough Relief contains sodium 10 mg/5 mL.
Vicks® DayQuil® Cough contains sodium 15 mg/15 mL.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness or depression
Mental Health: Effects on Psychiatric Treatment
Use with MAO inhibitors may cause hypertensive crisis; avoid combination
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, liquid filled, oral, as hydrobromide:
Robafen Cough: 15 mg
Robitussin® CoughGels™: 15 mg
Liquid, oral, as hydrobromide:
Creo-Terpin®: 10 mg/15 mL (120 mL) [contains ethanol 25% and tartrazine]
Scot-Tussin® Diabetes: 10 mg/5 mL (118 mL) [ethanol free, gluten free, sugar free; contains propylene glycol; cherry-strawberry flavor]
Vicks® 44® Cough Relief: 10 mg/5 mL (120 mL) [contains ethanol, propylene glycol, sodium 10 mg/5 mL, sodium benzoate]
Lozenge, oral, as hydrobromide:
Hold® DM: 5 mg (10s) [cherry or original flavor]
Trocal®: 7.5 mg (50s, 300s) [cherry flavor]
Solution, oral, as hydrochloride:
PediaCare® Children's Long-Acting Cough: 7.5 mg/5 mL (118 mL) [ethanol free; contains sodium 15 mg/5 mL, sodium benzoate; grape flavor]
Vicks® DayQuil® Cough: 15 mg/15 mL (177 mL, 295 mL) [ethanol free; contains propylene glycol, sodium 15 mg/15 mL; citrus flavor]
Strip, orally disintegrating, as hydrobromide:
Triaminic® Thin Strips™ Children's Long Acting Cough: 7.5 mg (14s, 16s) [equivalent to dextromethorphan 5.5 mg; contains ethanol; cherry flavor]
Suspension, extended release, oral:
Delsym®: Dextromethorphan polistirex [equivalent to dextromethorphan hydrobromide 30 mg/5 mL] (78 mL, 148 mL) [ethanol free; contains propylene glycol, sodium 7 mg/5 mL; grape and orange flavors]
Syrup, oral, as hydrobromide:
Creomulsion® Adult Formula: 20 mg/15 mL (120 mL) [ethanol free; contains sodium benzoate]
Creomulsion® for Children: 5 mg/5 mL (120 mL) [ethanol free; contains sodium benzoate; cherry flavor]
Father John's®: 10 mg/5 mL (118 mL, 236 mL) [ethanol free]
Robitussin® Children's Cough Long Acting: 7.5 mg/5 mL (118 mL) [ethanol free; contains propylene glycol, sodium 5 mg/5 mL, sodium benzoate, fruit punch flavor]
Robitussin® Cough Long-Acting: 15 mg/5 mL (120 mL, 240 mL) [contains ethanol, sodium benzoate]
Robitussin® Pediatric Cough: 7.5 mg/5 mL (120 mL) [ethanol free; contains propylene glycol, sodium 5 mg/5 mL, sodium benzoate; fruit punch flavor] [DSC]
Silphen DM®: 10 mg/5 mL (120 mL) [strawberry flavor]
Triaminic® Children's Cough Long Acting: 7.5 mg/5 mL (118 mL) [contains benzoic acid, propylene glycol, sodium 7 mg/5 mL]
Tablet, oral, as hydrobromide:
Nycoff: 15 mg
References
Moeller KE, Lee KC, and Kissack JC, “Urine Drug Screening: Practical Guide for Clinicians,” Mayo Clin Proc, 2008, 83(1):66-76.
Schier J, “Avoid Unfavorable Consequences: Dextromethorphan Can Bring About a False-Positive Phencyclidine Urine Drug Screen,” J Emerg Med, 2000, 18(3):379-81.
Schwartz AR, Pizon AF, and Brooks DE, “Dextromethorphan-Induced Serotonin Syndrome,” Clin Toxicol (Phila), 2008, 46(8):771-3.
Siu A and Drachtman R, “Dextromethorphan: A Review of N-methyl-D-aspartate Receptor Antagonist in the Management of Pain,” CNS Drug Rev, 2007, 13(1):96-106.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2009
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