Your activity: 2 p.v.

Chlorpheniramine: Drug information

Chlorpheniramine: Drug information
(For additional information see "Chlorpheniramine: Patient drug information" and see "Chlorpheniramine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Aller-Chlor [OTC];
  • Allergy Relief [OTC];
  • Allergy [OTC];
  • Allergy-Time [OTC] [DSC];
  • Chlor-Trimeton Allergy [OTC];
  • Chlor-Trimeton [OTC];
  • Chlorphen SR [OTC] [DSC];
  • Ed Chlorped Jr [OTC];
  • Ed ChlorPed [OTC] [DSC];
  • Pharbechlor [OTC]
Pharmacologic Category
  • Alkylamine Derivative;
  • Histamine H1 Antagonist;
  • Histamine H1 Antagonist, First Generation
Dosing: Adult
Upper respiratory tract conditions

Upper respiratory tract conditions:

Note: Second-generation H1-antihistamines are generally preferred due to less sedating and anticholinergic effects. Avoid use in patients with high-risk occupations (eg, pilots, bus drivers) or who may be more prone to anticholinergic effects (eg, older adults); however, may be preferred during pregnancy if bedtime sedating effect is desired (AAAAI/ACAAI [Bernstein 2014]; Asero 2021; BSACI [Scadding 2017]; deShazo 2021; EAACI [Zuberbier 2018]; Khan 2021; Murase 2014).

Immediate release: Oral: 4 mg every 4 to 6 hours; do not exceed 24 mg/24 hours.

Extended release: Oral: 12 mg every 12 hours; do not exceed 24 mg/24 hours.

Motion sickness

Motion sickness (off-label use): Immediate release: Oral: 4 to 12 mg administered 3 hours prior to initiating stimulus for motion sickness (Buckey 2004). Note: Avoid use if it is unsafe for patient to be sedated.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, chlorpheniramine is metabolized via the liver; therefore, a dose adjustment may be necessary.

Dosing: Pediatric

(For additional information see "Chlorpheniramine: Pediatric drug information")

Note: Safety and efficacy for the use of cough and cold products in infants and young children is limited; the AAP warns against the use of these products for respiratory illnesses in infants and young children; the FDA does not recommend OTC use in infants and children <2 years of age due to the risk of serious and life-threatening adverse effects (including death) and recommends to use with caution in pediatric patients ≥2 years of age (AAP 2018; FDA 2017).

Allergic symptoms

Allergic symptoms: Oral:

Immediate release:

Oral liquid (2 mg/5 mL):

Children 2 to <6 years: Limited data available: 1 mg every 4 to 6 hours; maximum daily dose: 6 mg/day (Fitzsimons 2015)

Children 6 to <12 years: 2 mg every 4 to 6 hours; maximum daily dose: 12 mg/day.

Children ≥12 years and Adolescents: 4 mg every 4 to 6 hours; maximum daily dose: 24 mg/day.

Tablets:

Children 6 to <12 years: 2 mg every 4 to 6 hours; maximum daily dose: 12 mg/day.

Children ≥12 years and Adolescents: 4 mg every 4 to 6 hours; maximum daily dose: 24 mg/day.

Extended-release tablet: Children ≥12 years and Adolescents: 12 mg every 12 hours; maximum dose: 24 mg in 24 hours.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, chlorpheniramine is metabolized via the liver; therefore, a dose adjustment may be necessary.

Dosing: Older Adult

Avoid use (Beers Criteria [AGS 2019]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Oral, as maleate:

Ed ChlorPed: 2 mg/mL (60 mL [DSC]) [contains fd&c red #40 (allura red ac dye), propylene glycol, saccharin sodium, sodium benzoate]

Syrup, Oral, as maleate:

Chlor-Trimeton: 2 mg/5 mL (120 mL) [contains alcohol, usp]

Ed Chlorped Jr: 2 mg/5 mL (118 mL [DSC]) [alcohol free, sugar free; contains fd&c red #40 (allura red ac dye), methylparaben, propylene glycol, propylparaben]

Ed Chlorped Jr: 2 mg/5 mL (473 mL) [alcohol free, sugar free; contains fd&c red #40 (allura red ac dye), methylparaben, propylene glycol, propylparaben; cherry flavor]

Tablet, Oral, as maleate:

Aller-Chlor: 4 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]

Aller-Chlor: 4 mg [scored; contains quinoline (d&c yellow #10) aluminum lake]

Allergy: 4 mg [scored; contains corn starch, quinoline (d&c yellow #10) aluminum lake]

Allergy Relief: 4 mg [contains corn starch, quinoline (d&c yellow #10) aluminum lake]

Allergy Relief: 4 mg [scored; contains corn starch, quinoline (d&c yellow #10) aluminum lake]

Allergy Relief: 4 mg [DSC] [scored; contains quinoline (d&c yellow #10) aluminum lake]

Allergy-Time: 4 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]

Chlor-Trimeton: 4 mg [scored]

Pharbechlor: 4 mg

Generic: 4 mg

Tablet Extended Release, Oral, as maleate:

Chlor-Trimeton Allergy: 12 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]

Chlor-Trimeton Allergy: 12 mg [contains fd&c yellow #6 (sunset yellow), fd&c yellow #6(sunset yellow)alumin lake]

Chlorphen SR: 12 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6 (sunset yellow), quinoline (d&c yellow #10) aluminum lake, sodium benzoate]

Generic: 12 mg

Generic Equivalent Available: US

May be product dependent

Administration: Adult

Oral:

May be administered with food or water. Timed release oral forms are to be swallowed whole, not crushed or chewed. Administer liquid formulations with an accurate measuring device; do not use a household teaspoon (overdosage may occur). If used for motion sickness, administer 3 hours before stimulus.

Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.

Administration: Pediatric

Oral: Administer liquid formulations with an accurate measuring device; do not use a household teaspoon (overdosage may occur). Extended-release oral forms are to be swallowed whole, not crushed or chewed.

Use: Labeled Indications

Upper respiratory tract conditions: Temporary relief of symptoms (runny nose; sneezing; itching of the eyes, nose, or throat) associated with the hay fever (allergic rhinitis) and other upper respiratory tract conditions.

Use: Off-Label: Adult

Motion sickness

Medication Safety Issues
Sound-alike/look-alike issues:

Chlor-Trimeton may be confused with Chloromycetin

Older Adult: High-Risk Medication:

Beers Criteria: Chlorpheniramine, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) because of its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided because of reduced clearance with advanced age and tolerance associated with use as a hypnotic (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Chlorpheniramine, as a single agent or as part of a combination (excludes OTC products), is identified as a high-risk medication in patients 65 years and older on the PQA's Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Drowsiness (slight to moderate)

Respiratory: Thickening of bronchial secretions

1% to 10%:

Central nervous system: Dizziness, excitability, fatigue, headache, nervousness

Endocrine & metabolic: Weight gain

Gastrointestinal: Abdominal pain, diarrhea, increased appetite, nausea, xerostomia

Genitourinary: Urinary retention

Neuromuscular & skeletal: Arthralgia, weakness

Ophthalmic: Diplopia

Renal: Polyuria

Respiratory: Pharyngitis

Contraindications

OTC labeling: When used for self-medication, do not use to make a child sleep.

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).

Special populations:

• Pediatric: Antihistamines may cause excitation in young children.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider prior to use if you have breathing problems (eg, chronic bronchitis, emphysema), glaucoma, difficultly in urination due to enlargement of the prostate gland, or are currently taking sedatives, tranquilizers.

Warnings: Additional Pediatric Considerations

Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported. Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. The FDA does not recommend OTC uses for these products in pediatric patients <2 years of age and recommends to use with caution in pediatric patients ≥2 years of age. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018; CDC 2007; FDA 2017; FDA 2018).

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

Substrate of CYP2D6 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

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

Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

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

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

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

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: Chlorpheniramine may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

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

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Isoproterenol: Chlorpheniramine may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: Chlorpheniramine may enhance the arrhythmogenic effect of Thioridazine. Thioridazine may increase the serum concentration of Chlorpheniramine. Management: Avoid this combination when possible. If used, monitor closely for arrhythmia as well as general toxicity of chlorpheniramine. Risk D: Consider therapy modification

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Pregnancy Considerations

Maternal chlorpheniramine use has generally not resulted in an increased risk of birth defects (Aselton 1985; Gilboa 2009; Heinonen 1977; Jick 1981).

Antihistamines may be used for the treatment of rhinitis, urticaria, and pruritus with rash in pregnant women. Although second generation antihistamines may be preferred, chlorpheniramine may be used when a first generation antihistamine is needed during pregnancy. The lowest effective dose should be used (BSACI [Powell 2015]; BSACI [Scadding 2017]; Murase 2014; Zuberbier 2018).

Breastfeeding Considerations

Chlorpheniramine is present in breast milk.

Drowsiness and irritability have been reported in breastfed infants exposed to antihistamines (Ito 1993). In general, if a breastfed infant is exposed to a first generation antihistamine via breast milk, they should be monitored for irritability or drowsiness (Butler 2014).

When treatment with an antihistamine is needed in a patient who is breastfeeding a child, second generation antihistamines are preferred. Maternal use of chlorpheniramine should be avoided (Butler 2014; BSACI [Powell 2015]).

Antihistamines may temporarily decrease maternal serum prolactin concentrations when administered prior to the establishment of breastfeeding (Messinis 1985).

Mechanism of Action

Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract

Pharmacokinetics

Note: Data from chlorpheniramine maleate:

Distribution: Vd: Children and Adolescents 6 to 16 years: 7 ± 2.8 L/kg (Simons 1982); Adults: 6-12 L/kg (Paton 1985)

Protein binding: 33% (range: 29% to 37%) (Martínez-Gómez 2007)

Metabolism: Hepatic via CYP450 enzymes (including CYP2D6 and other unidentified enzymes) to active and inactive metabolites; significant first-pass effect (Sharma 2003)

Half-life elimination: Serum: Children and Adolescents 6 to 16 years: 13.1 ± 6.6 hours (range: 6.3 to 23.1 hours) (Simons, 1982); Adults: 14-24 hours (Paton 1985)

Time to peak: Children and Adolescents 6 to 16 years: Oral : 2.5 ± 1.5 hours (range: 1 to 6 hours) (Simons 1982); Adults: 2-3 hours (Sharma 2003)

Excretion: Urine (Sharma 2003)

Pricing: US

Syrup (Chlor-Trimeton Oral)

2 mg/5 mL (per mL): $0.04

Tablet, controlled release (Chlor-Trimeton Allergy Oral)

12 mg (per each): $0.46

Tablet, controlled release (Chlorpheniramine Maleate ER Oral)

12 mg (per each): $0.63

Tablets (Chlor-Trimeton Oral)

4 mg (per each): $0.19

Tablets (Chlorpheniramine Maleate Oral)

4 mg (per each): $0.01

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Acira (BD);
  • Ahiston (IL);
  • Alergidryl (AR);
  • Alergitrat (AR);
  • Aller (MY);
  • Allerfin (BF, BJ, CI, ET, GH, GM, GN, JO, KE, LR, MA, ML, MR, MU, MW, NE, NG, QA, SA, SC, SD, SL, SN, TN, TZ, UG, ZM);
  • Allergex (ZA, ZW);
  • Allergyl (BF, BJ, CI, EG, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM);
  • Allermin (SG, TW);
  • Allermine (LK, VN);
  • Alleryl (MY);
  • Analer (PY);
  • Analerg (UY);
  • Anallerge (EG);
  • Antadex-H (MX);
  • Antamin (MY, PH, SG);
  • Benda (TW);
  • Bregamin (MX);
  • Cadistin (BF, BJ, CI, ET, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM);
  • Chlofen (LK);
  • Chloramine (MY, SG);
  • Chlorantine-M (EG);
  • Chlorohistal (AE);
  • Chlorohistan (KW);
  • Chlorohistol (QA);
  • Chlorpheniramine DHA (HK);
  • Chlorpheno (TH);
  • Chlorphenon (ID);
  • Chlorpyrimine (HK, MY, TH);
  • Chlortrimeton (ZA);
  • Cipium (ET);
  • Clomin (BD);
  • Clorfam (CO);
  • Cloro Trimeton (AR);
  • Cloro-Trimeton (MX);
  • Cloroalergan (PE);
  • Clorotrimeton (PE, VE);
  • Cohistan (ID);
  • Com-Trimeton (TW);
  • Derimeton (MX);
  • Heamin (TW);
  • Histafen (NZ);
  • Histal (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT);
  • Histalex (BD);
  • Histan (AE, BH);
  • Histant (SA);
  • Histat (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Histatapp (TH);
  • Histavil (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Histin (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Histon (LK);
  • Histop (BH, QA);
  • Horamine (HK);
  • Istamex (GR, JO);
  • Isticol Jarabe (CO);
  • Lergisina (PY);
  • Lorecare (PH);
  • Nipolen (CL);
  • Omvil (AE, BH, KW, QA);
  • Orphen (ID);
  • Peniramin (KR);
  • Pheneton 4 (LK);
  • Pheniram (AE, KW, QA, SA);
  • Pirafene (BG, EG);
  • Piriton (AE, BB, BM, BS, BZ, CY, GB, GY, IE, IQ, IR, JM, JO, KW, LB, LK, LY, NL, OM, PK, PR, QA, SA, SG, SR, SY, TT, YE);
  • Prodel (CL);
  • Sensitamine (ZW);
  • Sprinsol (HK);
  • Trimeton (IT);
  • Valemine (PH)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767. [PubMed 30693946]
  2. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  3. Aller-chlor syrup (chlorpheniramine maleate) [prescribing information]. Livonia, MI: Rugby Laboratories; March 2014.
  4. Aller-chlor tablets (chlorpheniramine maleate) [prescribing information]. Livonia, MI: Rugby Laboratories; March 2019.
  5. Allergy (chlorpheniramine maleate) [prescribing information]. Livonia, MI: Major Pharmaceuticals; March 2019.
  6. American Academy of Pediatrics (AAP). Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. Updated June 12, 2018. Available at http://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/
  7. Aselton P, Jick H, Milunsky A, et al, "First-Trimester Drug Use and Congenital Disorders," Obstet Gynecol, 1985, 65(4):451-5. [PubMed 3982720]
  8. Asero R. New-onset urticaria. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed November 23, 2021.
  9. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133(5):1270-1277. doi:10.1016/j.jaci.2014.02.036 [PubMed 24766875]
  10. Buckey JC, Alvarenga D, Cole B, Rigas JR. Chlorpheniramine for motion sickness. J Vestib Res. 2004;14(1):53-61. [PubMed 15156097]
  11. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: part II. Lactation. J Am Acad Dermatol. 2014;70(3):417.e1-10. [PubMed 24528912]
  12. Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56(1):1-4. [PubMed 17218934]
  13. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  14. Chlorpheniramine maleate extended-release tablets [prescribing information]. Dublin, OH: Cardinal Health, Inc; August 2012.
  15. Chlorpheniramine maleate tablets [prescribing information]. Valley Stream, NY: Reliable 1 Laboratories LLC; November 2015.
  16. Chlor-Trimeton (chlorpheniramine maleate) [prescribing information]. Whitehouse Station, NJ: Merck & Co; July 2013.
  17. deShazo RD, Kemp SF. Pharmacotherapy of allergic rhinitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 23, 2021.
  18. Ed ChlorPed (chlorpheniramine maleate) [prescribing information]. Ripley, MS: Edwards Pharmaceuticals, Inc: March 2011.
  19. Ed Chlorped Jr (chlorpheniramine maleate) [prescribing information]. Ripley, MS: Edwards Pharmaceuticals, Inc: August 2019.
  20. Fitzsimons R, van der Poel LA, Thornhill W, du Toit G, Shah N, Brough HA. Antihistamine use in children. Arch Dis Child Educ Pract Ed. 2015;100(3):122-131. doi:10.1136/archdischild-2013-304446
  21. Food and Drug Administration (FDA). Most young children with a cough or cold don't need medicines. July 18, 2017. Available at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm. Last accessed November 2, 2018.
  22. Food and Drug Administration (FDA). Use caution when giving cough and cold products to kids. Updated February 8, 2018. Available at https://www.fda.gov/drugs/resourcesforyou/specialfeatures/ucm263948.htm. Last accessed November 2, 2018.
  23. Gilboa SM, Strickland MJ, Olshan AF, et al, "Use of Antihistamine Medications During Early Pregnancy and Isolated Major Malformations," Birth Defects Res A Clin Mol Teratol, 2009, 85(2):137-50. [PubMed 19161158]
  24. Heinonen OP, Slone D, and Shapiro S, "Birth Defects and Drugs in Pregnancy," Publishing Sciences Group, Inc, Littleton, MA, 1977.
  25. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  26. Ito S, Blajchman A, Stephenson M, et al, "Prospective Follow-Up of Adverse Reactions in Breast-Fed Infants Exposed to Maternal Medication," Am J Obstet Gynecol, 1993, 168(5):1393-9. [PubMed 8498418]
  27. Jick H, Holmes LB, Hunter JR, et al, "First-Trimester Drug Use and Congenital Disorders," JAMA, 1981, 246(4):343-6. [PubMed 7241780]
  28. Khan DA. Chronic spontaneous urticaria: standard management and patient education. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 23, 2021.
  29. Martínez-Gómez MA, Villanueva-Camañas RM, Sagrado S, et al, "Evaluation of Enantioselective Binding of Antihistamines to Human Serum Albumin by ACE," Electrophoresis, 2007, 28(15):2635-43. [PubMed 17605150]
  30. Messinis IE, Souvatzoglou A, Fais N, et al, "Histamine H1 Receptor Participation in the Control of Prolactin Secretion in Postpartum," J Endocrinol Invest, 1985, 8(2):143-6. [PubMed 3928731]
  31. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: part I. Pregnancy. J Am Acad Dermatol. 2014;70(3):401.e1-14.
  32. Paton DM and Webster DR, "Clinical Pharmacokinetics of H1-Receptor Antagonists (The Antihistamines)," Clin Pharmacokinet, 1985, 10(6):477-97. [PubMed 2866055]
  33. Pharmacy Quality Alliance. Use of high-risk medications in the elderly (2017 update) (HRM-2017). https://www.pqaalliance.org/medication-safety. Published 2017. Accessed March 21, 2019.
  34. Powell RJ, Leech SC, Till S, et al. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy. 2015;45(3):547-565. [PubMed 25711134]
  35. Scadding GK, Kariyawasam HH, Scadding G, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised edition 2017; First edition 2007). Clin Exp Allergy. 2017;47(7):856-889. doi:10.1111/cea.12953 [PubMed 30239057]
  36. Sharma A and Hamelin BA, "Classic Histamine H1 Receptor Antagonists: A Critical Review of Their Metabolic and Pharmacokinetic Fate from a Bird's Eye View," Curr Drug Metab, 2003, 4(2):105-29. [PubMed 12678691]
  37. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.
  38. Simons FE, Luciuk GH, Simons KJ. Pharmacokinetics and efficacy of chlorpheniramine in children. J Allergy Clin Immunol. 1982;69(4):376-381.
  39. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
  40. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414. doi:10.1111/all.13397 [PubMed 29336054]
Topic 8860 Version 382.0