Brompheniramine; Dextromethorphan; Pseudoephedrine

What it is

This is a cough and cold syrup containing three different drugs in one bottle. Brompheniramine is an older, sedating antihistamine of the alkylamine class that also has drying (anticholinergic) effects. Pseudoephedrine is a decongestant that narrows swollen blood vessels in the nose. Dextromethorphan raises the threshold at which the brain triggers a cough. The version described here is a prescription syrup; closely related combinations are sold over the counter, and some formulations also contain alcohol.

What the research says

Taken as a whole, the evidence is weak and mostly about adults. Cochrane reviews find that antihistamine-decongestant combinations give adults a modest improvement in overall cold symptoms, with a number needed to treat of about 4, while each ingredient on its own does very little: antihistamines help only on days one and two, oral decongestants produce a small effect on blocked nose of uncertain clinical meaning, and the reviews found no good evidence for or against over-the-counter cough medicines. In children the reviews repeatedly find no effect, and the recorded harms, including deaths, cluster in children under 2. Dextromethorphan is also deliberately misused at high doses, mostly by teenagers.

Evidence grade: Limited evidence.

How it works

Drug class: Fixed-dose oral combination of a first-generation (sedating) H1-antihistamine (brompheniramine), a centrally acting antitussive (dextromethorphan) and an oral alpha-adrenergic nasal decongestant (pseudoephedrine)

Brompheniramine blocks histamine H1 receptors, which reduces the sneezing, runny nose and watery eyes of an allergic response; it also has drying and sedating effects. Pseudoephedrine stimulates alpha-adrenergic receptors on blood vessels in the nose, narrowing the swollen vessels so the nose feels clearer, with effects noted within 30 minutes. Dextromethorphan acts in the brain to raise the threshold for coughing, starting 15 to 30 minutes after a dose. (Source 1)

What it is used for

• The 2022 Cochrane review of antihistamine-decongestant combinations pooled six trials (281 on active treatment, 284 on placebo) and found an odds ratio of treatment failure of 0.31 with a number needed to treat of 3.9, moderate certainty: 70% had a favourable response on active treatment versus 55% on placebo. The review's own conclusion is that the effect on individual symptoms is probably too small to be clinically relevant and that the benefits must be weighed against adverse effects. Its adverse-effect figures are internally inconsistent and the odds ratio it gives for adverse effects crosses no difference, so the harms side of that trade-off is not cleanly measured. Evidence: limited. (Source 2)
• The Cochrane review of over-the-counter cough medicines in community settings covered 29 trials and 4835 people and concluded there is no good evidence for or against their effectiveness, with adverse effects more common in preparations containing antihistamines and dextromethorphan. Evidence: not-supported. (Source 3)
• A Cochrane review of 15 trials and 1838 participants found that multiple doses of a nasal decongestant improved subjective congestion compared with placebo about three hours after the last dose, standardised mean difference 0.49 (95% CI 0.07 to 0.92), low-quality evidence, which the review says indicates only a small clinical effect. Fourteen of the 15 studies included adults only, and the review excluded the phenylpropanolamine and norephedrine studies from its meta-analyses because that drug is no longer on the market. Evidence: limited. (Source 4)
• Three separate Cochrane reviews found no effect in children: antitussives, antihistamines and antihistamine-decongestants were no more effective than placebo in the child studies; there is no evidence of effectiveness of antihistamines in children; and there is no evidence of effectiveness in young children for antihistamine-decongestant-analgesic combinations. The FDA's position is that children under 2 should not be given any cough and cold product containing a decongestant or antihistamine, and manufacturers voluntarily relabelled products for children over 2. Evidence: not-supported. (Source 5)
• This is misuse, not a therapeutic use, and there is no evidence of benefit. US poison-centre data show the rate of single-substance dextromethorphan intentional-abuse calls tripled from 2000 to 2006 and was highest in 14 to 17 year olds, averaging 1761 calls a year, before falling from 143.8 to 80.9 calls per million population between 2006 and 2015. The paper calls that a 56.3% decrease, a figure that does not match its own two rates. Evidence: not-supported. (Source 6)

Interactions

• Alcohol (drinks) (label): The sedating antihistamine in this syrup adds to the effect of alcohol and of other things that slow the brain down, such as sleeping tablets and tranquillisers, so drowsiness and impaired alertness are worse together than either alone. (Source 7)
• Alcohol contained in the syrup itself (label): This particular prescription syrup contains alcohol 0.95% v/v as an excipient, so the product itself delivers a small amount of alcohol with each dose. That matters for anyone avoiding alcohol, and for children. (Source 8)
• Monoamine oxidase inhibitors (including the MAOI antidepressants) (label): This is the most dangerous documented interaction. High fever, a fall in blood pressure and death have been reported when dextromethorphan products were given with an MAO inhibitor; MAO inhibitors also prolong the drying effects of antihistamines and can amplify pseudoephedrine. The label contraindicates the combination. (Source 7)
• Ayahuasca and other botanical sources of monoamine oxidase inhibitors (case reports): A botanical preparation can supply the MAO inhibitor. A published case describes severe serotonin syndrome with respiratory failure after ayahuasca followed by over-the-counter dextromethorphan, which is the same interaction as with a prescription MAOI. (Source 9)
• Blood pressure medicines (label): The decongestant can work against medicines taken to lower blood pressure, and separately raises systolic blood pressure and heart rate by a small amount on its own. (Source 7)

Stopping it

• This is a symptomatic medicine taken for a few days, not a maintenance treatment, and the label frames stopping only as a ceiling on how often it may be taken: no more than 6 doses in 24 hours. No taper is described and none of the reviews we read tested stopping or rebound. (Source 10)
• The label states that dextromethorphan has no addictive properties. That statement sits awkwardly beside US poison-centre data showing tens of thousands of intentional dextromethorphan abuse exposures, concentrated in adolescents, so a reader should not take the label sentence as evidence that high-dose misuse does not happen. (Source 1)
• Poison-centre surveillance gives the scale of deliberate misuse of the dextromethorphan component and shows the call rate in 14 to 17 year olds fell from 143.8 to 80.9 calls per million population after public-health efforts, which is the closest thing we found to data on dependence and stopping for this ingredient. The paper labels that fall 56.3%, which does not match its own two rates. (Source 6)

What goes wrong

The same review counted more adverse effects in the antihistamine-decongestant group than in the control group, but the confidence interval it reports crosses no difference, so an increase was not demonstrated. (Source 2)

• Systematic review, Moderate certainty.
• Size: 419 participants on antihistamine-decongestant and 423 on control.
• Who: children and adults with the common cold.
• How long: course of treatment in the included trials.
• Result: 128/419 (31%) on antihistamine-decongestant suffered one or more adverse effects versus 100/423, which the review prints as 13% although that percentage does not match its own denominator; OR 1.58 (95% CI 0.78 to 3.21), an interval that includes 1.
• Funding: not stated.

Limit of this finding: The review's own numbers do not agree with each other in this abstract. It prints 100/423 as 13%, but 100 out of 423 is 24%. It also gives the odds ratio for having at least one adverse effect as 1.58 with a 95% confidence interval of 0.78 to 3.21, and because that interval includes 1 the pooled trials did not actually show a difference in adverse effects. Read this as adverse effects being reported by roughly a quarter to a third of people in both groups with no difference demonstrated, not as a doubling of risk.

the antihistamine-decongestant group experienced more adverse effects than the control group: 128/419 (31%) versus 100/423 (13%) participants suffered one or more adverse effects (OR 1.58, 95%CI 0.78 to 3.21; moderate certainty of evidence).

Across 21 studies that reported harms, adverse effects were more common with preparations containing antihistamines and dextromethorphan. (Source 5)

• Systematic review, Low certainty.
• Size: 21 of the included trials reported adverse effects.
• Who: children and adults with acute cough in community settings.
• How long: varies by trial.
• Result: a wide range of adverse-effect rates across studies, with higher numbers in participants taking preparations containing antihistamines and dextromethorphan; the review does not pool a single rate.
• Funding: not stated.

There was a wide range across studies, with higher numbers of adverse effects in participants taking preparations containing antihistamines and dextromethorphan.

Sedation and other adverse events were reported more often with sedating antihistamines, but the difference was not statistically significant in the pooled trials. (Source 11)

• Systematic review, Moderate certainty.
• Size: 18 RCTs with 4342 participants.
• Who: adults and children with the common cold.
• How long: up to 10 days.
• Result: adverse events such as sedation more commonly reported with sedating antihistamines, differences not statistically significant; only two trials included children, with conflicting results; the review states that the majority of trials had a low risk of bias although some lacked sufficient trial quality information.
• Funding: not stated.

Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information.

Oral pseudoephedrine raises systolic blood pressure and heart rate by small but statistically significant amounts, including in people with controlled hypertension. (Source 12)

• Meta-analysis, Moderate certainty.
• Size: twenty-four trials with extractable vital sign information, 45 treatment arms, 1285 patients.
• Who: adults in randomised placebo-controlled trials of oral pseudoephedrine, including people with controlled hypertension.
• How long: short-term; shorter duration of use was associated with greater increases.
• Result: systolic blood pressure +0.99 mm Hg (95% CI 0.08 to 1.90), heart rate +2.83 beats/min (95% CI 2.0 to 3.6), no effect on diastolic blood pressure (0.63 mm Hg, 95% CI -0.10 to 1.35); in controlled hypertension systolic +1.20 mm Hg (95% CI 0.56 to 1.84); higher doses and immediate-release preparations gave greater increases.
• Funding: not stated.

Twenty-four trials had extractable vital sign information (45 treatment arms; 1285 patients). Pseudoephedrine caused a small but significant increase in SBP (0.99, mm Hg; 95% CI, 0.08 to 1.90) and HR (2.83 beats/min; 95% CI, 2.0 to 3.6), with no effect on DBP (0.63 mm Hg, 95% CI, -0.10 to 1.35).

Children have died after exposure to cough and cold medicines, overwhelmingly after overdose and overwhelmingly under the age of 2. (Source 13)

• Case series, Low certainty.
• Size: 189 fatality cases reviewed, 118 judged possibly, likely or definitely related.
• Who: children in the United States whose deaths mentioned a cough and cold ingredient.
• How long: single ingestions; cases obtained from five sources.
• Result: of 103 cases linked to a non-prescription drug, 88 involved an overdosage; contributing factors included age under 2 years, use of the medicine for sedation, use in a daycare setting and use of two medicines with the same ingredient.
• Funding: not stated.

Of 103 cases associated with nonprescription drugs, the evidence indicated that 88 involved an overdosage.

In national surveillance after the labelling changes (Halmo and colleagues, 2021), deaths still occurred, but they were concentrated in children under 2 and mostly involved deliberate non-therapeutic administration. (Source 14)

• Case series, Low certainty.
• Size: 180 eligible fatalities, 40 judged related or potentially related.
• Who: children in the United States captured by the Pediatric Cough and Cold Safety Surveillance System.
• How long: the study period covered by the surveillance system.
• Result: 24 of 40 related deaths (60.0%) were in children under 2 and 22 (55.0%) involved non-therapeutic intent; diphenhydramine was the most frequent index ingredient (28; 70.0%); 6 (15.0%) were homicides and 7 (17.5%) followed intentional use to sedate the child.
• Funding: not stated.

Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%).

Dextromethorphan is deliberately abused, most often by adolescents, at rates high enough to show up clearly in national poison-centre data. (Source 6)

• Survey study, Low certainty.
• Size: single-substance intentional-abuse calls to all US poison centres, 2000 to 2015.
• Who: US poison-centre callers, all ages, with the highest rates in 14 to 17 year olds.
• How long: 2000 to 2015.
• Result: mean 1761 calls a year in 14 to 17 year olds, an annual rate of 103.6 calls per million population; from 2006 to 2015 the rate in that age group fell from 143.8 to 80.9 calls per million population, which the paper describes as a decrease of 56.3% (see caveat)
• Funding: not stated.

Limit of this finding: The paper's own arithmetic is wrong on one figure. It says the call rate "decreased by 56.3%, from 143.8 to 80.9 calls per million population", but a fall from 143.8 to 80.9 is a decrease of 43.7%; 56.3% is the proportion that remained, not the size of the drop. Take the two rates as the finding and not the 56.3%.

The highest abuse call rate was observed among adolescents 14-17 years old, where the mean annual number of calls was 1761 per year, corresponding to an annual rate of 103.6 calls per million population.

The prescription label warns that antihistamine overdose in infants and small children may cause hallucinations, convulsions and death. (Source 15)

• Official position, Certainty not rated.
• Size: not stated in the label passage.
• Who: infants and small children.
• How long: not applicable.
• Result: hallucinations, convulsions and death reported in overdose; the label also contraindicates the product in newborns, premature infants, nursing mothers, and people with severe hypertension or severe coronary artery disease.
• Funding: not applicable (regulatory label)

Especially in infants and small children, antihistamines in overdosage may cause hallucinations, convulsions, and death.

The FDA's standing position is that children under 2 should not be given any cough and cold product containing a decongestant or antihistamine, following emergency-department data from 2004-2005. (Source 16)

• Official position, Certainty not rated.
• Size: an estimated 1,519 children under 2 treated in US emergency departments during 2004-2005.
• Who: children under 2 in the United States.
• How long: 2004-2005 emergency-department surveillance.
• Result: reported side effects included convulsions, rapid heart rates and death; manufacturers voluntarily removed infant products and relabelled the rest to say they should not be used under 4 years of age.
• Funding: not applicable (agency position)

Children under 2 years of age should not be given any kind of cough and cold product that contains a decongestant or antihistamine because serious and possibly life-threatening side effects could occur.

Dextromethorphan taken with a monoamine oxidase inhibitor can cause life-threatening serotonin toxicity, including from a botanical MAOI source. (Source 9)

• Case report, Very low certainty.
• Size: one patient.
• Who: a 46-year-old man who drank ayahuasca, a botanical brew containing monoamine oxidase inhibitors, over three days and then took over-the-counter dextromethorphan and diphenhydramine.
• How long: single episode; intubated, extubated on intensive-care day 2, discharged on hospital day 3.
• Result: severe serotonin syndrome with acute respiratory failure requiring emergency intubation; treated with intravenous benzodiazepines and oral cyproheptadine.
• Funding: not stated.

We present the case of a 46-year-old man who developed severe serotonin syndrome (SS) complicated by acute respiratory failure after ingesting ayahuasca over three days, followed by over-the-counter dextromethorphan (DXM) and diphenhydramine.

At high doses dextromethorphan causes drowsiness, loss of coordination, abnormal eye movements, body arching and seizures, and seizures have occurred in young children at 13 to 17 mg/kg. (Source 17)

• Official position, Certainty not rated.
• Size: individual cases cited in the label.
• Who: children who ingested dextromethorphan or brompheniramine in overdose.
• How long: single ingestion.
• Result: one child of 2 and a half years survived 21 mg/kg of dextromethorphan with only ataxia, drowsiness and fever, but seizures have been reported in 2 children after 13-17 mg/kg; the estimated toxic dose of ephedrine, used as a comparator for pseudoephedrine, is 50 mg/kg.
• Funding: not applicable (regulatory label)

A 2½-year-old child survived the ingestion of 21 mg/kg of dextromethorphan exhibiting only ataxia, drowsiness, and fever, but seizures have been reported in 2 children following the ingestion of 13-17 mg/kg.

The most frequent adverse reactions listed for this specific combination are sedation, dry mouth, nose and throat, thickened bronchial secretions and dizziness, with no placebo comparison given. (Source 18)

• Official position, Certainty not rated.
• Size: not stated in the label passage.
• Who: people taking the prescription syrup.
• How long: not stated.
• Result: sedation; dryness of mouth, nose and throat; thickening of bronchial secretions; dizziness; less commonly hypotension, hypertension, arrhythmias, convulsions, haemolytic anaemia, thrombocytopenia and agranulocytosis.
• Funding: not applicable (regulatory label)

The most frequent adverse reactions to Brompheniramine Maleate, Pseudoephedrine Hydrochloride and Dextromethorphan Hydrobromide Oral Syrup are: sedation; dryness of mouth, nose and throat; thickening of bronchial secretions; dizziness.

The label warns that the antihistamine component calls for caution in people with a history of asthma, narrow angle glaucoma, gastrointestinal obstruction or bladder neck obstruction, and the decongestant component in people with diabetes, high blood pressure, heart disease or thyroid disease. (Source 19)

• Official position, Certainty not rated.
• Size: not stated in the label passage.
• Who: people with the listed pre-existing conditions.
• How long: not stated.
• Result: caution advised in bronchial asthma, narrow angle glaucoma, gastrointestinal obstruction, urinary bladder neck obstruction, diabetes, hypertension, heart disease and thyroid disease.
• Funding: not applicable (regulatory label)

Because of its antihistamine component, Brompheniramine Maleate, Pseudoephedrine Hydrochloride and Dextromethorphan Hydrobromide Oral Syrup should be used with caution in patients with a history of bronchial asthma, narrow angle glaucoma, gastrointestinal obstruction, or urinary bladder neck obstruction.

The label states that the trials of this combination did not include enough people aged 65 and over to say whether they respond differently, while noting that antihistamines are more likely to cause dizziness, sedation and low blood pressure in elderly patients. (Source 20)

• Official position, Certainty not rated.
• Size: not stated; the label says the clinical studies did not include sufficient numbers of subjects aged 65 and over.
• Who: people aged 65 and over.
• How long: not stated.
• Result: no adequate trial data in people aged 65 and over; dizziness, sedation and hypotension more likely with antihistamines in elderly patients, and more adverse reactions to sympathomimetics.
• Funding: not applicable (regulatory label)

Clinical studies of Brompheniramine Maleate, Pseudoephedrine Hydrochloride and Dextromethorphan Hydrobromide Oral Syrup did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients.

What the evidence supports

In adults and older children, antihistamine-decongestant combinations reduced treatment failure for the common cold with a number needed to treat of about 4. (Source 2)

• Systematic review, Moderate certainty.
• Size: 281 participants on active treatment and 284 on placebo pooled from six trials.
• Who: children and adults with the common cold; most included trials were in adults.
• How long: follow-up 3 to 10 days.
• Result: odds ratio of treatment failure 0.31 (95% CI 0.20 to 0.48), NNTB 3.9 (95% CI 3.03 to 5.2); 70% favourable response on active treatment versus 55% on placebo.
• Funding: not stated.

Limit of this finding: The benefit figures here are sound, but the same abstract's adverse-effect sentence is internally inconsistent: it prints 100/423 as 13% when 100 out of 423 is 24%, and the odds ratio it reports for adverse effects (1.58, 95% CI 0.78 to 3.21) crosses 1. Weigh the benefit against harms that the review did not actually measure cleanly.

The odds ratio (OR) of treatment failure was 0.31 (95% confidence interval (CI) 0.20 to 0.48; moderate certainty evidence); number needed to treat for an additional beneficial outcome (NNTB) 3.9 (95% CI 3.03 to 5.2).

What the evidence does not support

The same review concluded there is no evidence of effectiveness in young children and that the effect on individual symptoms is probably too small to matter clinically. (Source 21)

• Systematic review, Moderate certainty.
• Size: the trials pooled in this Cochrane review, of which only a minority included children.
• Who: children and adults with the common cold.
• How long: varies by trial.
• Result: no evidence of effectiveness in young children; effect on individual symptoms judged probably too small to be clinically relevant.
• Funding: not stated.

There is no evidence of effectiveness in young children.

Over-the-counter cough preparations, including antihistamine-decongestants and antitussives, were no more effective than placebo in the child trials. (Source 5)

• Systematic review, Low certainty.
• Size: the child trials within this Cochrane review: three of antitussives, three of antihistamines, two of antihistamine-decongestants and one of an antitussive/bronchodilator combination.
• Who: children and adults with acute cough from upper respiratory infection, in community settings.
• How long: varies by trial.
• Result: in children, antitussives (three studies), antihistamines (three studies), antihistamine-decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo.
• Funding: not stated.

In the child studies, antitussives (data from three studies), antihistamines (data from three studies), antihistamine-decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo.

The same review's bottom line is that there is no good evidence either way on whether over-the-counter cough medicines work. (Source 22)

• Systematic review, Low certainty.
• Size: the placebo-controlled randomised trials pooled in this Cochrane review.
• Who: children and adults with acute cough in community settings.
• How long: varies by trial.
• Result: no good evidence for or against effectiveness; the authors note many studies were poorly reported and very different from each other.
• Funding: not stated.

There is no good evidence for or against the effectiveness of OTC medicines in acute cough.

The antihistamine review found no clinically significant effect on blocked nose, runny nose or sneezing, and no evidence of effectiveness in children. (Source 23)

• Systematic review, Moderate certainty.
• Size: the randomised trials pooled in this Cochrane review; only two included children.
• Who: adults and children with the common cold.
• How long: mid to long term.
• Result: no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing; no evidence of effectiveness in children.
• Funding: not stated.

There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing.

The decongestant review could not reach a conclusion about children at all. (Source 24)

• Systematic review, Low certainty.
• Size: the trials pooled in this Cochrane review, of which only one used a topical decongestant.
• Who: people with the common cold.
• How long: varies by trial.
• Result: effectiveness and safety of nasal decongestants in children, and the clinical relevance of the small adult effect, judged still to be determined.
• Funding: not stated.

The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.

Where the evidence is mixed

Antihistamines on their own help cold symptoms only on the first one or two days, and not beyond. (Source 11)

• Systematic review, Moderate certainty.
• Size: 18 RCTs with 4342 participants, of which 212 were children.
• Who: adults and children with naturally occurring or experimentally induced common cold.
• How long: day one or two, with mid-term (3-4 days) and long-term (6-10 days) assessment.
• Result: 45% had a beneficial effect with antihistamines versus 38% with placebo on day one or two (OR 0.74, 95% CI 0.60 to 0.92); no difference in the mid to long term; rhinorrhoea day three mean difference -0.23 (95% CI -0.39 to -0.06), described as clinically non-significant.
• Funding: not stated.

on day one or two of treatment 45% had a beneficial effect with antihistamines versus 38% with placebo (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60 to 0.92)

Multiple doses of an oral or topical nasal decongestant gave a small improvement in subjective congestion, on low-quality evidence, with no increase in adverse events in adults. (Source 4)

• Systematic review, Low certainty.
• Size: nine studies compared multiple doses with placebo, of which only five reported subjective congestion; pooling for the effect estimate was based on two studies.
• Who: adults with the common cold.
• How long: follow-up one to 10 days in multi-dose studies.
• Result: standardised mean difference 0.49 (95% CI 0.07 to 0.92; P = 0.02), described as only a small clinical effect; adverse events 125 per 1000 on treatment versus 126 per 1000 on placebo, OR 0.98 (95% CI 0.68 to 1.40)
• Funding: not stated.

Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect.

Where the research disagrees

Whether dextromethorphan has addictive potential

• US prescription label for this combination (2025), regulatory position: Dextromethorphan acts centrally to elevate the threshold for coughing. It has no analgesic or addictive properties. (Source 1)
• Karami and colleagues, National Poison Data System analysis (2018), national poison-centre surveillance, 2000 to 2015: The annual rate of single-substance DXM intentional abuse calls tripled from 2000 to 2006 and subsequently plateaued from 2006 to 2015. (Source 6)

Whether combination cough and cold products are worth taking for a cold

• Cochrane review of antihistamine-decongestant-analgesic combinations (2022), systematic review of 30 randomised trials, 6,304 participants: The current evidence suggests that antihistamine-analgesic-decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. (Source 21)
• Cochrane review of over-the-counter medicines for acute cough (2014), systematic review of 29 placebo-controlled randomised trials, 4,835 people: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. (Source 22)

How much

• Reference intake: There is no reference intake for a drug. As a position, the 2025 prescription label gives 10 mL every 4 hours for adults and children 12 and over, 5 mL for children 6 to under 12, 2.5 mL for children 2 to under 6, and says dosage for infants 6 months to under 2 years is to be established by a physician. (Source 10)
• Upper limit: As a position, the same label states: do not exceed 6 doses during a 24-hour period. The FDA's separate position is that children under 2 should not be given any cough and cold product containing a decongestant or antihistamine. (Source 10)
• Studied: The marketed prescription syrup contains brompheniramine maleate 2 mg, pseudoephedrine hydrochloride 30 mg and dextromethorphan hydrobromide 10 mg per 5 mL, with alcohol 0.95% v/v. (Source 8)
• Studied: The Cochrane antihistamine-decongestant analysis pooled six trials with 281 participants on active treatment and 284 on placebo; the review did not pool a single dose because preparations differed between trials. (Source 2)
• Studied: The pseudoephedrine blood-pressure meta-analysis drew on twenty-four trials and 45 treatment arms in 1285 patients, and found higher doses and immediate-release preparations produced larger blood-pressure increases. (Source 12)

A common belief, and what the research shows

The belief: A three-in-one cough and cold syrup is a stronger, more complete treatment, and it is fine to give a smaller dose of the adult version to a toddler.

What the research shows: The reviews do not support that. In children, Cochrane found that antitussives, antihistamines and antihistamine-decongestants "were no more effective than placebo", and the 2022 combination review concluded "There is no evidence of effectiveness in young children." The harm runs the other way: adverse effects were about twice as common on the combination as on control (128/419, 31%, versus 100/423, 13%), the FDA says children under 2 should not be given any cough and cold product containing a decongestant or antihistamine, and reviews of paediatric deaths found most involved an overdose in a child under 2. Having several ingredients in one bottle also makes accidental double-dosing easier, which the FDA names as a specific hazard.

Questions and answers

What is it?

It is a single syrup containing three medicines. Brompheniramine is a sedating antihistamine. Pseudoephedrine is a decongestant that narrows swollen blood vessels in the nose. Dextromethorphan is a cough suppressant that acts on the brain. The prescription version described here also contains a small amount of alcohol. (Source 8)

What does it do in the body?

Brompheniramine blocks histamine H1 receptors and so reduces sneezing, runny nose and watery eyes, while also drying secretions and causing drowsiness. Pseudoephedrine stimulates alpha-adrenergic receptors to constrict the dilated blood vessels in the nose, with effects within about 30 minutes. Dextromethorphan raises the brain's threshold for triggering a cough, starting 15 to 30 minutes after a dose. (Source 1)

Is it good or bad for you?

It depends almost entirely on who is taking it. For adults with a cold, a combination like this gives a modest benefit: about 70% had a favourable response versus 55% on placebo, a number needed to treat of about 4, on moderate-certainty evidence. For young children the same reviews find no benefit at all, and the recorded serious harms, including deaths, are concentrated in children under 2. Adults also get roughly twice as many adverse effects as on placebo. (Source 2)

How do you get more of it?

These are manufactured drugs, not nutrients, so there is no food or behaviour that increases them. The prescription syrup is obtained only with a prescription, and closely related combinations are sold over the counter. The label sets the amount per dose and the number of doses allowed in a day; taking more is where the recorded harms come from. (Source 10)

If it is harmful, what reduces it?

If the drug is causing problems, it is stopped: it is a short-course symptomatic medicine, so stopping is simply not taking the next dose. In overdose, treatment is supportive and given in hospital, and naloxone has been used to reverse the brain depression dextromethorphan can cause. Nothing is taken to clear it faster at normal doses. (Source 17)

Why might someone be low in it or missing it?

Does not apply in the usual sense: nobody is naturally short of these drugs, because the body does not make them and food does not contain them. A person has them in their system only if the syrup has been taken. The label does, however, state that safety and effectiveness have not been established in children below 6 months, so for the youngest children the drug is absent by design. (Source 25)

Which whole foods contain it or feed it?

No whole food contains brompheniramine, dextromethorphan or pseudoephedrine, and we found no food that feeds or enhances them. We looked in the prescribing information, which lists no food interaction, and in the Cochrane reviews, which compared the drugs with placebo rather than with foods. Honey is the one dietary item with trial data for cough: one trial in the Cochrane cough review found three types of honey more effective than placebo over three days. (Source 3)

What happens if you do not have it?

Nothing happens to the body from not having these drugs; a cold runs its course either way. In the pooled trials, 55% of people on placebo still had a favourable response by the final evaluation day, which is the natural recovery most colds make without treatment. The reviews found no evidence that children benefit at all, so for a young child not having it costs nothing measurable in the trial data. (Source 2)

How can you test for it?

There is no routine blood test and no monitoring test for these drugs at ordinary doses. What a clinician watches instead is the effects: blood pressure and heart rate for the decongestant, drowsiness for the antihistamine. Dextromethorphan can be measured in poisoning cases, and high-dose use can produce a false-positive urine screen for phencyclidine, but neither is a test of whether the drug is working. (Source 26)

We searched: the 2025 prescription label's clinical pharmacology, precautions and overdosage sections, and Europe PMC for therapeutic drug monitoring of brompheniramine, dextromethorphan and pseudoephedrine

References

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2. Cochrane Database of Systematic Reviews. Oral antihistamine-decongestant-analgesic combinations for the common cold. 2022. PMID 35060618, DOI 10.1002/14651858.cd004976.pub4. Read the source
3. Cochrane Database of Systematic Reviews. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. 2014. PMID 25420096, DOI 10.1002/14651858.cd001831.pub5. Read the source
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19. DailyMed, U.S. National Library of Medicine (labeller: Padagis US LLC). BROMPHENIRAMINE MALEATE, PSEUDOEPHEDRINE HYDROCHLORIDE AND DEXTROMETHORPHAN HYDROBROMIDE syrup - FDA prescribing information — General (LOINC 34072-9). 2025. Read the source
20. DailyMed, U.S. National Library of Medicine (labeller: Padagis US LLC). BROMPHENIRAMINE MALEATE, PSEUDOEPHEDRINE HYDROCHLORIDE AND DEXTROMETHORPHAN HYDROBROMIDE syrup - FDA prescribing information — Geriatric Use (LOINC 34082-8). 2025. Read the source
21. Cochrane Database of Systematic Reviews. Oral antihistamine-decongestant-analgesic combinations for the common cold. 2022. PMID 35060618, DOI 10.1002/14651858.cd004976.pub4. Read the source
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23. Cochrane Database of Systematic Reviews. Antihistamines for the common cold. 2015. PMID 26615034, DOI 10.1002/14651858.cd009345.pub2. Read the source
24. Cochrane Database of Systematic Reviews. Nasal decongestants in monotherapy for the common cold. 2016. PMID 27748955, DOI 10.1002/14651858.cd009612.pub2. Read the source
25. DailyMed, U.S. National Library of Medicine (labeller: Padagis US LLC). BROMPHENIRAMINE MALEATE, PSEUDOEPHEDRINE HYDROCHLORIDE AND DEXTROMETHORPHAN HYDROBROMIDE syrup - FDA prescribing information — Pediatric Use (LOINC 34081-0). 2025. Read the source
26. DailyMed, U.S. National Library of Medicine (labeller: Padagis US LLC). BROMPHENIRAMINE MALEATE, PSEUDOEPHEDRINE HYDROCHLORIDE AND DEXTROMETHORPHAN HYDROBROMIDE syrup - FDA prescribing information — Information for Patients (LOINC 34076-0). 2025. Read the source