Zanmbeel: dextromethorphan

Showing posts with label dextromethorphan. Show all posts

Monday, May 17, 2010

Acetaminophen, dextromethorphan, doxylamine, and pseudoephedrine

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.

U.S. BRAND NAMES — All-Nite Multi-Symptom Cold/Flu [OTC]; Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation

DOSING: ADULTS — Relief of cold and flu symptoms: Oral: 30 mL every 6 hours (maximum: 120 mL/24 hours)

DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Liquid:
All-Nite Multi-Symptom Cold/Flu: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (296 mL) [contains sodium 17 mg/15 mL, ethanol 10%, and propylene glycol]
Vicks® NyQuil® D Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (295 mL) [contains sodium 18 mg/15 mL, ethanol 10%, and propylene glycol]

DOSAGE FORMS: CONCISE
Liquid:
All-Nite Multi-Symptom Cold/Flu [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL
Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Administer orally; only use enclosed dosing cup or tablespoon to administer; do not use other devices.

USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, congestion, runny nose, sneezing, sore throat)

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

CONTRAINDICATIONS — Use of MAO inhibitors within 14 days, concurrent use with other products containing acetaminophen

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.

Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.

Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.

Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy

Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy

MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

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

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification

Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

DIETARY CONSIDERATIONS
All-Nite Cold contains sodium 17 mg per 15 mL.

Vicks® NyQuil® D Cold & Flu Multi-Symptom contains sodium 18 mg per 15 mL.

Acetaminophen, dextromethorphan, doxylamine, and pseudoephedrine

Acetaminophen, dextromethorphan, and phenylephrin

MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.

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.

U.S. BRAND NAMES — Alka-Seltzer Plus® Day Cold [OTC]; Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC]; Mapap® Multi-Symptom Cold [OTC]; Theraflu® Daytime Severe Cold & Cough [OTC]; Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]; Tylenol® Cold Head Congestion Daytime [OTC]; Tylenol® Cold Multi-Symptom Daytime [OTC]; Vicks® DayQuil® Cold/Flu Multi-Symptom [OTC]

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant

DOSING: ADULTS — Product labeling: Relief of cold and flu symptoms: Oral:

Alka-Seltzer Plus® Day Cold: 2 capsules or 20 mL every 4 hours (maximum: 6 doses/24 hours)

Tylenol® Cold Head Congestion Daytime: 2 caplets every 4 hours (maximum: 6 doses/24 hours)

Tylenol® Cold Multi-Symptom Daytime: 2 caplets/gelcaps or 30 mL every 4 hours (maximum: 6 doses/24 hours)

Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: 2 capsules every 4 hours (maximum: 6 doses/24 hours)

Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid: 30 mL every 4 hours (maximum: 6 doses/24 hours)

DOSING: PEDIATRIC — Product labeling: Relief of cold and flu symptoms: Oral:

Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid:
Children 6-11 years: 15 mL every 4 hours, up to 5 doses/day (maximum: 75 mL/24 hours)
Children ≥ 12 years: Refer to adult dosing.

Alka-Seltzer Plus® Day Cold, Tylenol® Cold Head Congestion Daytime, Tylenol® Cold Multi-Symptom Daytime, Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Mapap® Multi-Symptom Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Tylenol® Cold Head Congestion Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]

Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg

Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg

Gelcap:
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg

Liquid:
Alka-Seltzer Plus® Day Cold: Acetaminophen 162.5 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (180 mL) [alcohol free; contains sodium 3 mg/5 mL, propylene glycol, and sodium benzoate; berry flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (240 mL) [contains sodium 5 mg/15 mL, sodium benzoate, and propylene glycol; Citrus Burst™ flavor]
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (180 mL, 300 mL) [contains sodium 71 mg/15 mL and propylene glycol]

Powder for solution:
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine hydrochloride 10 mg/packet (6s) [contains phenylalanine 14 mg, potassium 10 mg, and sodium 20 mg/packet; berry flavor]

Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, propylene glycol, sodium 8 mg/15 mL, sodium benzoate; cherry flavor]

DOSAGE FORMS: CONCISE
Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC], Mapap® Multi-Symptom Cold [OTC], Theraflu® Daytime Severe Cold & Cough [OTC], Tylenol® Cold Head Congestion Daytime [OTC], Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg

Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg

Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg

Gelcap:
Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg

Liquid:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 162.5 mg, dextromethorphan 5 mg, and phenylephrine 2.5 mg per 5 mL
Tylenol® Cold Multi-Symptom Daytime [OTC], Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL

Powder for solution:
Theraflu® Daytime Severe Cold & Cough [OTC]: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine 10 mg/packet (6s)

Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL

GENERIC EQUIVALENT AVAILABLE — Yes: Caplet

ADMINISTRATION — Solid dosage forms should be swallowed whole; do not crush, chew or dissolve. Administer liquid capsule formulations with water.

USE — Temporary relief of common cold and flu symptoms (eg, pain, fever, cough, congestion)

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, phenylephrine, or any component of the formulation; use of MAO inhibitors within 14 days

WARNINGS / PRECAUTIONS
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.

Special populations: Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics. Pediatrics: Use with caution in children; do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.

Dosage form specific issues: Phenylalanine: Some products may contain phenylalanine. Sodium: Some products may contain sodium; use with caution in sodium restricted patients.

Other warnings/precautions: OTC labeling: Patients with hypertension, hyperthyroidism, diabetes mellitus, glaucoma, cardiovascular disease, or prostatic hyperplasia should consult a physician prior to use. Patients with chronic cough (associated with COPD or smoking) and/or productive cough (eg, copious amounts of phlegm) should be evaluated by a healthcare provider prior to use. Products containing acetaminophen are not recommended in patients consuming ≥ 3 alcoholic beverages/day; consult a physician. If pain, nasal congestion, or cough increases in severity or persists >7 days in adults (or >5 days in children) during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. Do not use in children <2 years of age.

METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)

Dextromethorphan: Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)

DRUG INTERACTIONS
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification

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

Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy

MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. 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

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

DIETARY CONSIDERATIONS
Alka-Seltzer Plus® Day Cold liquid contains sodium 3 mg per 5 mL.

Theraflu® Daytime Severe Cold & Cough (powder for solution) contains phenylalanine 14 mg and sodium 20 mg per packet.

Theraflu® Warming Relief Daytime Severe Cold & Cough syrup contains sodium 8 mg per 15 mL.

Tylenol® Cold Multi-Symptom Daytime liquid contains sodium 5 mg per 15 mL.

Vicks® DayQuil® Cold/Flu Multi-Symptom Relief liquid contains sodium 71 mg per 15 mL.

INTERNATIONAL BRAND NAMES — Tusedex (PH)

Acetaminophen, dextromethorphan, and phenylephrin

Acetaminophen, dextromethorphan, and doxylamine

MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.

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.

U.S. BRAND NAMES — All-Nite [OTC]; Tylenol® Cough & Sore Throat Nighttime [OTC]; Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation

DOSING: ADULTS — Relief of cold and flu symptoms: Oral: Two capsules/caplets or 30 mL every 6 hours (maximum: 8 capsules or 240 mL/24 hours)

DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg [contains vitamin C]

Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg

Liquid:
All-Nite: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (177 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; Cool Burst™ flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; honey lemon flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; original flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 19 mg/15 mL, ethanol, and propylene glycol; cherry flavor]

DOSAGE FORMS: CONCISE
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg dextromethorphan 15 mg, and doxylamine 6.25 mg

Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg

Liquid:
All-Nite [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Tylenol® Cough & Sore Throat Nighttime [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Liquid: Only use enclosed dosing cup or tablespoon to administer; do not use other devices.

USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, runny nose, sneezing, sore throat)

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen; pediatric sedation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.

Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician. Do not use in children <4 years of age.

Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.

Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy

Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. 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

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

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

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

DIETARY CONSIDERATIONS
All-Nite contains sodium 18 mg per 15 mL.

Tylenol® Cough & Sore Throat Nighttime contains sodium 11 mg per 15 mL.

Vicks® NyQuil® Cold & Flu Multi-Symptom liquid contains sodium 18 mg per 15 mL (original flavor) or 19 mg per 15 mL (cherry flavor).

Acetaminophen, dextromethorphan, and doxylamine

MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.

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.

U.S. BRAND NAMES — All-Nite [OTC]; Tylenol® Cough & Sore Throat Nighttime [OTC]; Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation

DOSING: ADULTS — Relief of cold and flu symptoms: Oral: Two capsules/caplets or 30 mL every 6 hours (maximum: 8 capsules or 240 mL/24 hours)

DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg [contains vitamin C]

Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg

Liquid:
All-Nite: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (177 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; Cool Burst™ flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; honey lemon flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; original flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 19 mg/15 mL, ethanol, and propylene glycol; cherry flavor]

DOSAGE FORMS: CONCISE
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg dextromethorphan 15 mg, and doxylamine 6.25 mg

Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg

Liquid:
All-Nite [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Tylenol® Cough & Sore Throat Nighttime [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Liquid: Only use enclosed dosing cup or tablespoon to administer; do not use other devices.

USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, runny nose, sneezing, sore throat)

ADVERSE REACTIONS SIGNIFICANT — See individual agents.

CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen; pediatric sedation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.

Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician. Do not use in children <4 years of age.

Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.

Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.

DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy

Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. 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

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

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

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

DIETARY CONSIDERATIONS
All-Nite contains sodium 18 mg per 15 mL.

Tylenol® Cough & Sore Throat Nighttime contains sodium 11 mg per 15 mL.

Vicks® NyQuil® Cold & Flu Multi-Symptom liquid contains sodium 18 mg per 15 mL (original flavor) or 19 mg per 15 mL (cherry flavor).

Sunday, January 20, 2008

Acetaminophen, dextromethorphan, and pseudoephedrine

SPECIAL ALERTS Infant Deaths Associated with Cough and Cold Medications - January 2007
The Centers for Disease Control and Prevention (CDC) has released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group. The CDC notes that during 2004 and 2005, ~ 1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications.
During this time period, 3 infants <6 months of age died. All 3 had postmortem blood levels of pseudoephedrine, ranging from 4743-7100 ng/mL (therapeutic levels for children 2-12 years: 180-500 ng/mL). In addition, 2 of the 3 infants also had detectable levels of dextromethorphan. Although dextromethorphan has been shown to be effective to reduce cough in adults, the same efficacy has not been documented in young children. The American Academy of Pediatrics and the American College of Chest Physicians do not recommend the use of dextromethorphan for over-the-counter (OTC) use in young children.
Safety and efficacy for the use of cough and cold products in children <2 years of age is limited. The Food and Drug Administration (FDA) notes that there are no approved OTC uses for these products in children <2 years of age. Clinicians are reminded to ask caregivers about the use of OTC products in order to avoid exposure to multiple medications containing the same ingredient. Caregivers are reminded that OTC cough and cold products should not be used in children <2 years of age except under specific direction by their healthcare provider.
For additional information, refer to the following CDC website: 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.
U.S. BRAND NAMES — Comtrex® Non-Drowsy Cold and Cough Relief [OTC] [DSC]; Infants' Tylenol® Cold Plus Cough Concentrated Drops [OTC] [DSC]; Sudafed® Severe Cold [OTC]; Triaminic® Cough and Sore Throat Formula [OTC] [DSC]; Tylenol® Cold Day Non-Drowsy [OTC]; Tylenol® Flu Non-Drowsy Maximum Strength [OTC]; Vicks® DayQuil® Multi-Symptom Cold and Flu [OTC] [DSC]
PHARMACOLOGIC CATEGORY AntihistamineAntitussive
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-7 hours as needed; do not exceed 4 g/day
Cough suppressant (Antitussive): Oral: Based on dextromethorphan component: 10-20 mg every 4-8 hours or 30 mg every 8 hours; do not exceed 120 mg/24 hours
Nasal congestion (Decongestant): Oral: Based on pseudoephedrine component: 60 mg every 4 hours (maximum: 360 mg/24 hours)
Product labeling:
Sudafed® Severe Cold, Tylenol® Flu Non-Drowsy Maximum Strength: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
Tylenol® Cold Non-Drowsy: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
DOSING: PEDIATRIC Analgesic: Oral: Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses/24 hours.
Cough suppressant: Oral: Based on dextromethorphan component: Children 6-12 years: 15 mg every 6-8 hours; do not exceed 60 mg/24 hours Children >12 years: Refer to adult dosing.
Decongestant: Oral: Based on pseudoephedrine component: Children: 2-6 years: 15 mg every 4 hours (maximum: 90 mg/24 hours) 6-12 years: 30 mg every 4 hours (maximum: 180 mg/24 hours) Children >12 years: Refer to adult dosing.
Product labeling:
Infants' Tylenol® Cold Plus Cough Concentrated Drops: Oral: Children 2-3 years (24-55 lb): 2 dropperfuls every 4-6 hours (maximum: 4 doses/24 hours)
Sudafed® Severe Cold, Thera-Flu® Non-Drowsy Maximum Strength (gelcap), Tylenol® Flu Non-Drowsy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
Tylenol® Cold Non-Drowsy: Oral: Children 6-11 years: 1 dose every 6 hours (maximum: 4 doses/24 hours) Children 12 years: Refer to adult dosing.
Thera-Flu® Non-Drowsy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: Comtrex® Non-Drowsy Cold and Cough Relief: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzoic acid] [DSC] Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Capsule, liquid: Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 250 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg [DSC]
Gelcap: Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzyl alcohol] [DSC] Tylenol® Flu Non-Drowsy Maximum Strength: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Liquid: Triaminic® Cough and Sore Throat Formula: Acetaminophen 160 mg, dextromethorphan hydrobromide 7.5 mg, and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL, 240 mL) [contains benzoic acid; grape flavor] [DSC] Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg per 15 mL (175 mL) [DSC]
Suspension, oral [drops]: Infants' Tylenol® Cold Plus Cough Concentrated Drops: Acetaminophen 160 mg, dextromethorphan hydrobromide 5 mg, and pseudoephedrine hydrochloride 15 mg per 1.6 mL (15 mL) [1.6 mL = 2 dropperfuls] [cherry flavor] [DSC]
DOSAGE FORMS: CONCISE Caplet: Sudafed® Severe Cold [OTC], Tylenol® Cold Day Non-Drowsy [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
Gelcap: Tylenol® Flu Non-Drowsy Maximum Strength [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of mild-to-moderate pain and fever; symptomatic relief of cough and congestion
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, pseudoephedrine, or any component of the formulation
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Dextromethorphan: Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
CANADIAN BRAND NAMES — Contac® Complete; Contac® Cough, Cold and Flu Day & Night™; Sudafed® Cold & Cough Extra Strength; Tylenol® Cold Daytime
INTERNATIONAL BRAND NAMES — Contac Complete (CA); Contac Cough, Cold and Flu Day & Night® (CA); Sudafed Cold & Cough Extra Strength (CA); Tylenol Cold Daytime (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.

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