acetaminophen/doxylamine/dextromethorphan/phenylephrine (Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid, Alka-Seltzer Plus Night Severe Cold, Cough and Flu, Alka-Seltzer Plus Night Sinus Congestion, Allergy and Cough)

Dosing and uses of Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid (acetaminophen/doxylamine/dextromethorphan/phenylephrine)

• Adult
• Pediatric

 

Adult dosage forms and strengths

acetaminophen/doxylamine/dextromethorphan/phenylephrine

capsule

• 325mg/6.25mg/10mg/5mg

 

Congestion, Rhinorrhea, Cough, Sore Throat, Headache, Fever, Minor Aches & Pains

2 caps PO q4hr PRN; not to exceed 12 caps/day

 

Pediatric dosage forms and strengths

acetaminophen/doxylamine/dextromethorphan/phenylephrine

capsule

• 325mg/6.25mg/10mg/5mg

 

Congestion, Rhinorrhea, Cough, Sore Throat, Headache, Fever, Minor Aches & Pains

<12 Years

• Ask a pediatrician

≥12 Years

• 2 caps PO q4hr PRN; not to exceed 12 caps/day

 

Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid (acetaminophen/doxylamine/dextromethorphan/phenylephrine) adverse (side) effects

Frequency not defined

Hypertension

Reflex tachycardia

Severe peripheral and visceral vasoconstriction

Dizziness

Drowsiness

Excitability

Headache

Restlessness

Tremor

Dermatologic rash

GI disturbances

Anemia blood dyscrasias (neutropenia, pancytopenia, leukopenia)

Bilirubin & alkaline phosphatase may increase

Dry mouth, throat, and nose

Thickening of mucus in nose or throat

 

Warnings

Contraindications

Hypersensitivity

Asthma

Narrow-angle glaucoma

Symptomatic prostate hypertrophy

Bladder-neck obstruction

Stenosing peptic ulcer

G-6-PD deficiency

Severe hepatic impairment

 

Cautions

Acetaminophen hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness

Acetaminophen contained in many OTC products & combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose

Do not take dextromethorphan for persistent or chronic cough associated with smoking, asthma, or emphysema, or if it is accompanied by excessive phlegm unless directed by a healthcare provider

Dextromethorphan may slow respiration rate

Doxylamine may exacerbate angle closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

 

Pregnancy and lactation

Pregnancy category: C

Lactation: excreted in breast milk, use caution

Pregnant or breastfeeding patients should seek advice of health professional before using OTC drugs

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid (acetaminophen/doxylamine/dextromethorphan/phenylephrine)

Mechanism of action

Acetaminophen: blocks pain impulse generation peripherally & may inhibit the generation of prostaglandin in the CNS; reduces fever by inhibiting the hypothalamic heat-regulating center

Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

Dextromethorphan: cough suppressant that acts centrally on the cough center in the medulla

Doxylamine competitively blocks histamine from binding to H1 receptors; significant antimuscarinic activity and penetrates CNS, which causes pronounced tendency to induce sedation

Phenylephrine is a vasoconstrictor and a decongestant that relieves symptoms resulting from irritation of upper respiratory tract tissue; shrinks swollen mucous membranes, reduces nasal congestion and tissue hyperemia

 

Pharmacokinetics

Acetaminophen

• Peak plasma time: 10-60 min (PO immediate release); 60-120 min (PO extended release); 6 hr (PO 500 mg tablet); 8 hr (PO 650 mg extended release tablet)
• Vd: 1 L/kg
• Protein binding: 10-25%
• Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic acid)
• Half-life: 1.25-3hr
• Excretion: Urine

Dextromethorphan

• Onset: 15-30 min
• Duration: 3-6 hr
• Metabolism: Hepatic P450 enzyme CYP2D6
• Excretion: Urine
• Half-life: 2-4 hr (extensive metabolizers); 24 hr (poor metabolizers)
• Peak plasma time: 2-3 hr

Phenylephrine

• Half-life: 2-3 hr
• Onset: 10-15 min
• Duration: 15 min
• Bioavailability: < 38%
• Excretion: Urine (80-90%)
• Peak plasma time: 0.75-2 hr
• Vd: 26-61 L
• Vdss: 340 L

Doxylamine

• Peak plasma time: 2-3 hr
• Half-life: 10-12 hr
• Excretion: Urine
• Metabolism: Liver (CYP450)