Acetaminophen, chlorpheniramine, 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 one case, the infant received both a prescription product containing pseudoephedrine and an over-the-counter (OTC) product, also containing pseudoephedrine. Alternatives to nasal decongestants in this age group may be softening nasal secretions with saline drops or a cool-mist humidifier and/or the removal of nasal secretions with the use of rubber suction bulb.
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 — Actifed® Cold and Sinus [OTC]; Alka-Seltzer® Plus Cold Liqui-Gels® [OTC]; Comtrex® Flu Therapy Day/Night [OTC]; Comtrex® Flu Therapy Nighttime [OTC]; Drinex [OTC]; Kolephrin® [OTC]; Sinutab® Sinus Allergy Maximum Strength [OTC]; Tylenol® Allergy Complete [OTC] [DSC]; Tylenol® Children's Plus Cold Nighttime [OTC]
PHARMACOLOGIC CATEGORY Analgesic, MiscellaneousAntihistamine
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-6 hours as needed; do not exceed 4 g/day
Rhinitis (Antihistamine): Oral: Based on chlorpheniramine maleate component: 4 mg every 4-6 hours (maximum: 24 mg/24 hours)
Nasal congestion (Decongestant): Oral: Based on pseudoephedrine component: 60 mg every 4 hours (maximum: 360 mg/24 hours)
Product labeling:
Alka-Seltzer Plus® Cold Medicine Liqui-Gels®: Oral: 2 softgels every 4 hours with water (maximum: 4 doses/24 hours)
Sinutab® Sinus Allergy Maximum Strength: Oral: 2 tablets/caplets 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 in 24 hours.
Antihistamine: Oral: Based on chlorpheniramine maleate component: 2-6 years: 1 mg every 4-6 hours (maximum: 6 mg/24 hours) 6-12 years: 2 mg every 4-6 hours (maximum: 12 mg/24 hours) Children >12 years: Refer to adult dosing.
Decongestant: Oral: Based on pseudoephedrine component: 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:
Alka-Seltzer Plus® Cold Medicine Liqui-Gels®: Oral: Children 6-12 years: 1 softgel every 4 hours with water (maximum: 4 doses/24 hours) Children >12 years: Refer to adult dosing.
Sinutab® Sinus Allergy 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: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg Actifed® Cold and Sinus, Sinutab® Sinus Allergy Maximum Strength, Tylenol® Allergy Complete [DSC]: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg Kolephrin®: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Capsule, softgel: Alka-Seltzer® Plus Cold Liqui-Gels®: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg [contains potassium 25 mg]
Combination package: (Comtrex® Flu Therapy Day/Night): Caplet [Daytime]: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg Caplet [Nighttime]: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Liquid: Comtrex® Flu Therapy Nighttime: Acetaminophen 100 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg per 30 mL (240 mL) [contains alcohol; cherry flavor] Tylenol® Children's Plus Cold Nighttime: Acetaminophen 160 mg, chlorpheniramine maleate 1 mg, and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL) [contains sodium benzoate; grape flavor]
Tablet: Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Actifed® Cold and Sinus [OTC], Sinutab® Sinus Allergy Maximum Strength [OTC]: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Kolephrin® [OTC]: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Capsule, softgel: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Alka-Seltzer® Plus Cold Liqui-Gels® [OTC]: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Combination package: Acetaminophen 500 mg and pseudoephedrine 30 mg and acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Comtrex® Flu Therapy Day/Night [OTC]: Caplet [Daytime]: Acetaminophen 500 mg and pseudoephedrine 30 mg Caplet [Nighttime]: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Liquid: Acetaminophen 100 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg per 30 mL; acetaminophen 160 mg, chlorpheniramine 1 mg, and pseudoephedrine 15 mg per 5 mL Comtrex® Flu Therapy Nighttime [OTC]: Acetaminophen 100 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg per 30 mL Tylenol® Children's Plus Cold Nighttime [OTC]: Acetaminophen 160 mg, chlorpheniramine 1 mg, and pseudoephedrine 15 mg per 5 mL
Tablet: Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Temporary relief of sinus symptoms
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Chlorpheniramine: Substrate of CYP2D6 (minor), 3A4 (major); 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.
PREGNANCY RISK FACTOR — B (show table)
DIETARY CONSIDERATIONS Children's Tylenol® Plus Cold contains phenylalanine 6 mg/tablet.
Thera-Flu® Cold and Sore Throat Night Time contains phenylalanine 11 mg/packet.
CANADIAN BRAND NAMES — Sinutab® Sinus & Allergy; Tylenol® Allergy Sinus
INTERNATIONAL BRAND NAMES — Sinutab Sinus & Allergy (CA); Tylenol Allergy Sinus (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.