Chlorpheniramine

R06A - Antihistamines for systemic use Small molecule approved 1950 Oral Parenteral Natural product

Mechanism of Action

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

Indications

Approved

Allergic symptoms, allergic rhinitis, urticaria, pruritus

Off-label

Motion sickness

Contraindications

Source: Lexicomp

Hypersensitivity to chlorpheniramine maleate or any component of the formulation Absolute
bladder neck obstruction Absolute
during acute asthmatic attacks Absolute
narrow-angle glaucoma Absolute
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 Absolute
stenosing peptic ulcer Absolute
symptomatic prostate hypertrophy Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (6)

Very Common Drowsiness (slight to moderate)

Common Dizziness · excitability · fatigue · headache · nervousness

Renal and urinary disorders (2)

Common Polyuria · Urinary retention

Metabolism and nutrition disorders (1)

Common Weight gain

Gastrointestinal disorders (5)

Common Abdominal pain · diarrhea · increased appetite · nausea · xerostomia

Musculoskeletal and connective tissue disorders (2)

Common Arthralgia · weakness

Eye disorders (1)

Common Diplopia

Respiratory, thoracic and mediastinal disorders (2)

Very Common Thickening of bronchial secretions

Common Pharyngitis

Dosing

Source: Lexicomp

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.

(For additional information see "Chlorpheniramine: Pediatric drug information") Allergic symptoms, allergic rhinitis, urticaria, pruritus: Oral: Chlorpheniramine maleate: Immediate release: Children 6 to 11 years: 2 mg every 4 to 6 hours; do not exceed 12 mg/24 hours Children ≥12 years: Refer to adult dosing. Extended release: Children ≥12 years: Refer to adult dosing.

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

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

Warnings & Precautions

Source: Lexicomp

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 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.

Pregnancy & Lactation

Pregnancy

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).

Lactation

Chlorpheniramine is excreted into breast milk. In general, first generation antihistamines should be used with caution in breast-feeding women and nursing infants should be monitored for irritability or drowsiness. Second generation antihistamines are preferred (Butler 2014). Antihistamines may temporarily decrease maternal serum prolactin concentrations when administered prior to the establishment of nursing (Messinis 1985).

Chemistry & Properties

Formula	C16H19ClN2
Molecular weight	274.8 g/mol
IUPAC name	3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine
CAS	132-22-9
PubChem CID	2725
InChIKey	`SOYKEARSMXGVTM-UHFFFAOYSA-N`
logP	3.82 (XLogP 3.4)
Polar surface area	16.13 Å²
H-bond acceptors / donors	2 / 0
Drug-likeness (QED)	0.82
Lipinski violations	0

SMILES

CN(C)CCC(c1ccc(Cl)cc1)c1ccccn1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB 1.53)

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 6)

Target	Action	Affinity
HISTAMINE H1 (HRH1)	Binding	pKi 8.6
H1 receptor (HRH1)	Antagonist	pKi 8.1
5-HT Transporter (SLC6A4)	Binding	pKi 7.8
Dopamine Transporter (SLC6A3)	Binding	pKi 6.0
Norepinephrine transporter	Binding	pKi 5.8
HISTAMINE H4 (HRH4)	Binding	pKi 5.5

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Dextropropoxyphene	major
Potassium chloride	major
Potassium citrate	major
Sodium oxybate	major
Topiramate	major
Zonisamide	major
Abiraterone	moderate
Acetylcholine	moderate
Aclidinium	moderate
Acrivastine	moderate
Alfentanil	moderate
Alimemazine	moderate
Alprazolam	moderate
Amantadine	moderate
Amitriptyline	moderate
Amobarbital	moderate
Amoxapine	moderate
Apomorphine	moderate
Apraclonidine	moderate
Aripiprazole	moderate
Asenapine	moderate
Atropine	moderate
Azatadine	moderate
Azelastine (nasal)	moderate
Baclofen	moderate
Belladonna	moderate
Benzatropine	moderate
Benzhydrocodone	moderate
Berotralstat	moderate
Biperiden	moderate
Botulinum Toxin Type B	moderate
Botulinum toxin type A	moderate
Brexanolone	moderate
Brexpiprazole	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Brivaracetam	moderate
Bromocriptine	moderate
Brompheniramine	moderate
Buprenorphine	moderate

Showing 40 of 100+.

Registered Products (11)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Hatso Childrens cough	Suspension 100 mg/5 ml, 1 mg/5 ml, 15 mg/5 ml, 5 mg/5 ml	100 ml	Pharma International Company/ Jordan	0.800
Hatso Chlidrens Cold	Suspension 100 mg/5 ml, 1 mg/5 ml, 15 mg/5 ml	100 ml	Pharma International Company/ Jordan	0.800
SNIP TAB	Tablet 325 mg, 1 mg, 15 mg	20 tab pack varies	Al Hilal Drug Store	0.940
Rhinostop syrup	Syrup 100 mg/5 ml, Maleate 1 mg/5 ml, 20 mg/5 ml	100 ml	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	0.970
Fludrex Syrup	Syrup 120 mg, 0.75 mg/5 ml, 15 mg	120 ml	Sun Set Drug Store	1.050
Rhinostop tablet	Tablet 250 mg, Maleate 2.5 mg, 60 mg	20 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	1.250
SNIP TAB	Tablet 325 mg, 1 mg, 15 mg	30 tab pack varies	Al Hilal Drug Store	1.410
Revanin Cold & Flu Caplets	Tablet 500 mg, Maleate 2 mg, 30 mg	20 Caplet	The Arab Pharmaceutical Manufactruing Co.	1.520
Rhinostop tablet	Tablet 250 mg, Maleate 2.5 mg, 60 mg	30 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	1.880
Panadol Cold & Flu	Tablet 500 mg, 2 mg, 30 mg	24 tab	Sukhtian Group	2.290
Rhinostop tablet	Tablet 250 mg, Maleate 2.5 mg, 60 mg	1000 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	53.130