Triprolidine

R01B - Nasal decongestants for systemic use ATC R01BA52 Small molecule approved 1982 Oral Natural product

JFDA label: Unifed Syrup

Mechanism of Action

Triprolidine is an H1-receptor antagonist, which provides dose-related suppression of histamine-induced wheel and flare reactions (Simmons 1986). It is useful for the prevention and suppression of the signs and symptoms of allergic rhinitis and other upper respiratory allergies.

Indications

Approved

Upper respiratory allergies

Contraindications

Source: Lexicomp

OTC labeling: When used for self-medication, do not use if you are taking sedatives or tranquilizers. Documentation of allergenic cross-reactivity for Antihistamines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Dosing

Source: Lexicomp

Upper respiratory allergies: Oral: 2.5 mg every 4 to 6 hours (maximum 10 mg/day)

Upper respiratory allergies: Oral: Triprolidine 0.625 mg/mL: Children 6 to Children ≥12 years and Adolescents: 2.5 mg every 6 hours (maximum: 10 mg/day) Triprolidine 0.938 mg/mL: Infants and Children 4 months to Children 2 to Children 4 to Triprolidine 1.25 mg/mL: Infants and Children 4 months to Children 2 to Children 4 to Triprolidine 2.5 mg/5 mL: Children 6 to Children ≥12 years and Adolescents: 2.5 mg every 4 to 6 hours (maximum: 10 mg/day)

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Pediatric

Antihistamines may cause excitation in young children. Other warnings/precautions:

Appropriate use

Prior to self-medication (OTC use), contact health care provider if you have breathing problems (eg, chronic bronchitis, emphysema), glaucoma, or difficulty urinating because of enlarged prostate. Discontinue use and contact health care provider if new symptoms develop; if symptoms do not improve within 7 days or are accompanied by fever; or if nervousness, dizziness or sleeplessness occur. Do not exceed recommended dosage.

Pregnancy & Lactation

Pregnancy

Information related to the use of triprolidine in pregnancy is limited (Aldridge 2014; Gilboa 2009). Antihistamines may be used for the treatment of rhinitis in pregnant women, although agents other than triprolidine may be preferred (Wallace 2008).

Lactation

Triprolidine is excreted in breast milk. Based on data from three cases, the estimated exposure to the nursing infant is

Chemistry & Properties

Formula	C19H22N2
Molecular weight	278.4 g/mol
IUPAC name	2-[(E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridine
CAS	486-12-4
PubChem CID	5282443
InChIKey	`CBEQULMOCCWAQT-WOJGMQOQSA-N`
logP	3.92 (XLogP 3.9)
Polar surface area	16.13 Å²
H-bond acceptors / donors	2 / 0
Drug-likeness (QED)	0.84
Lipinski violations	0

SMILES

Cc1ccc(/C(=C\CN2CCCC2)c2ccccn2)cc1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.786 h
Volume of distribution	4.084 L/kg
Protein binding	89.7%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 2)

Target	Action	Affinity
H1	Binding	pKi 9.1
HISTAMINE H1 (HRH1)	Binding	pKi 8.8

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT(unspecified) (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
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
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
Buspirone	moderate
Butabarbital	moderate

Showing 40 of 100+.

Registered Products (17)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Tripofed	Suspension 1.25 mg/5 ml, 30 mg/5 ml	100 ml	Sun Set Drug Store	0.630
Trifed Expectorant	Suspension 100 mg/5 ml, 1.25 mg/5 ml, 30 mg/5 ml	100 ml	Hikma Pharmaceuticals Co.Ltd/Jordan	0.650
Bronchofed Expectorant	Solution 30 mg, 100 mg, 1.25 mg	100 ml	Dar Al Dawa Development and Investment Co Ltd/Jordan	0.740
Trifed Expectorant	Suspension 30 mg/5 ml, 100 mg/5 ml, 1.25 mg/5 ml	120 ml	Hikma Pharmaceuticals Co.Ltd/Jordan	0.750
Newfed	Suspension 1.25 mg/5 ml mg, 30 mg/5 ml mg	100 ml	Al-Gadeed Pharmaceutical Industries	0.810
Bronchofed Syrup	Syrup 30 mg, 1.25 mg	100 ml	Dar Al Dawa Development and Investment Co Ltd/Jordan	0.840
Trifed Syrup	Syrup 1.25 mg/5 ml, 30 mg/5 ml	100 ml	Hikma Pharmaceuticals Co.Ltd/Jordan	0.840
Trifed PLUS Syrup	Syrup 125 mg/5 ml, 1.25 mg/5 ml, 25 mg/5 ml	100 ml	Hikma Pharmaceuticals Co.Ltd/Jordan	0.880
Trifed Tablets	Tablet 2.5 mg, 60 mg	20 tab pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	0.890
Unifed Tablets	Tablet 60 mg, 2.5 mg	20 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.040
Unifed Expectorant Syrup	Syrup 100 mg/5 ml, 1.25 mg/5 ml, 30 mg/5 ml	120 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.050
Trifed Plus Tablets	Tablet 300 mg, 2.5 mg, 50 mg	20 tab	Hikma Pharmaceuticals Co.Ltd/Jordan	1.100
Unifed Syrup	Syrup 1.25 mg/5 ml, 30 mg/5 ml	120 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.210
Unifed DM Syrup	Syrup 30 mg/5 ml, 1.25 mg/5 ml, 10 mg/5 ml	120 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.370
Unifed Extra Syrup	Syrup 50 mg, 1.25 mg, 10 mg, 7.5 mg	120 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.440
Trifed Tablets	Tablet 2.5 mg, 60 mg	1000 tab pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	33.060
Unifed Tablets	Tablet 60 mg, 2.5 mg	1000 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	33.060