Chlorpheniramine

Pharmacologic Category

Alkylamine Derivative; Histamine H₁ Antagonist; Histamine H₁ Antagonist, First Generation

Dosing: Adult

Allergic symptoms, allergic rhinitis, urticaria, pruritus: Oral: Chlorpheniramine maleate:

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

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

Motion sickness (off-label use): Immediate release: 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.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Avoid use (Beers Criteria [AGS 2019]).

Dosing: Renal 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

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: Oral:

Immediate release:

Oral liquid (2 mg/5 mL):

Children 2 to <6 years: 1 mg every 4 to 6 hours; maximum daily dose: 6 mg/day.

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: Renal 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.

Use: Labeled Indications

Allergic symptoms, allergic rhinitis, urticaria, pruritus: Perennial and seasonal allergic rhinitis and other allergic symptoms including urticaria, pruritus

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Motion sicknessLevel of Evidence [C]

Data from a limited number of patients studied suggests that chlorpheniramine may be beneficial in the treatment of motion sickness ^Ref. Additional data may be necessary to further define its role in this condition.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Antihistamines

Administration: Oral

May be administered with food or water. Timed release oral forms are to be swallowed whole, not crushed or chewed. If used for motion sickness, administer 3 hours before stimulus.

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.

Storage/Stability

Protect from light.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to ease allergy signs.

Frequently reported side effects of this drug

• Fatigue

• Anxiety

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• A significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Geriatric Patients: High-Risk Medication:

Contraindications

Hypersensitivity to chlorpheniramine maleate or any component of the formulation; narrow-angle glaucoma; bladder neck obstruction; symptomatic prostate hypertrophy; during acute asthmatic attacks; stenosing peptic ulcer; pyloroduodenal obstruction. Avoid use in premature and term newborns due to possible association with SIDS.

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).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).

• Increased intraocular pressure: Use with caution in patients with increased intraocular pressure.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Respiratory disease: Use with caution in patients with asthma or other chronic breathing disorders.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Pediatric: Antihistamines may cause excitation in young children. Not for OTC use in children <2 years of age.

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).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Anticholinergic action may cause significant confusion, constipation, or problems voiding urine. If an antihistamine is indicated, a second generation nonsedating antihistamine would be a more appropriate choice.

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).

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) (Angier 2010; Murase 2014; Wallace 2008; Zuberbier 2014). Antihistamines are not recommended for treatment of pruritus associated with intrahepatic cholestasis in pregnancy (Ambros-Rudolph 2011; Kremer 2011).

Breast-Feeding 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 (Butler 2014; Powell 2015; Zuberbier 2014).

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

Lexicomp Pregnancy & Lactation, In-Depth

• Chlorpheniramine

Briggs' Drugs in Pregnancy & Lactation

• Chlorpheniramine

Adverse Reactions

>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

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• H₁ Antihistamine Allergy

Toxicology

• Histamine H₁ Antagonists, First Generation

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 Open Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

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

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

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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of 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

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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

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

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

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

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. 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. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

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

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

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

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

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

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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. 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

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

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

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

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. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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 D: Consider therapy modification

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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

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

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

Test Interactions

May suppress the wheal and flare reactions to skin test antigens.

Genes of Interest

• Cytochrome P450 3A4

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, propylene glycol, saccharin sodium, sodium benzoate; cotton candy flavor]

Syrup, Oral, as maleate:

Aller-Chlor: 2 mg/5 mL (120 mL [DSC]) [contains alcohol, usp, fd&c yellow #6 (sunset yellow), menthol, methylparaben, propylene glycol, propylparaben]

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

Ed Chlorped Jr: 2 mg/5 mL (118 mL [DSC], 473 mL) [alcohol free, sugar free; contains fd&c red #40, methylparaben, propylene glycol, propylparaben; cherry flavor]

Tablet, Oral, as maleate:

Aller-Chlor: 4 mg [scored; contains fd&c yellow #10 aluminum lake]

Allergy: 4 mg [scored; contains corn starch, fd&c yellow #10 aluminum lake]

Allergy Relief: 4 mg [contains fd&c yellow #10 aluminum lake]

Allergy-Time: 4 mg [contains fd&c yellow #10 aluminum lake]

Chlor-Trimeton: 4 mg [scored]

Ed-Chlortan: 4 mg [DSC] [scored; contains fd&c yellow #10 aluminum lake]

Pharbechlor: 4 mg

Generic: 4 mg

Tablet Extended Release, Oral, as maleate:

Chlor-Trimeton Allergy: 12 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]

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

Generic: 12 mg

Anatomic Therapeutic Chemical (ATC) Classification

• R06AB04

Generic Available (US)

May be product dependent

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 - $0.05

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.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Note: Data from chlorpheniramine maleate:

Distribution: V_d: 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)

Dental Use

Treatment of histamine-induced allergic symptoms

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Chronic use of antihistamines will inhibit salivary flow, particularly in elderly patients; this may contribute to periodontal disease, tooth decay, and oral discomfort.

Effects on Bleeding

No information available to require special precautions

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Oral Medications That Should Not Be Crushed or Altered

Pharmacotherapy Pearls

Not effective for nasal stuffiness.

Index Terms

Chlorphenamine; Chlorpheniramine Maleate; CTM

References

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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); 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); 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); Niramine (TW); 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)

Last Updated 3/14/20