Desloratadine

R06A - Antihistamines for systemic use ATC R06AX27 Small molecule approved 2001 Oral Natural product

JFDA label: Aeriallerg

Mechanism of Action

Antagonist of Histamine H1 receptor — Histamine H1 receptor antagonist

Target	Action	Gene / class
Histamine H1 receptor efficacy	ANTAGONIST	HRH1

Indications

Approved

Allergic rhinitis
Urticaria

Off-label

NSAID-associated urticaria (prophylaxis)

Contraindications

Source: Lexicomp

Hypersensitivity to desloratadine, loratadine, or any component of the formulation 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 (7)

Very Common Headache · irritability

Common dizziness · Drowsiness · emotional lability · fatigue · insomnia

Renal and urinary disorders (2)

Common dysmenorrhea · Urinary tract infection

Gastrointestinal disorders (7)

Very Common Diarrhea

Common anorexia · dyspepsia · increased appetite · nausea · Vomiting · xerostomia

Skin and subcutaneous tissue disorders (2)

Common Erythema · maculopapular rash

Musculoskeletal and connective tissue disorders (1)

Common Myalgia

Ear and labyrinth disorders (1)

Common Otitis media

Infections and infestations (2)

Common parasitic infection · Varicella

General disorders and administration site conditions (1)

Very Common Fever

Other (11)

Not Known Frequency reported in children · Hepatitis (rare) · hyperbilirubinemia · hypersensitivity reactions (including anaphylaxis, dyspnea, edema, pruritus, rash, urticaria) · increased liver enzymes · movement disorder (including dystonia, tics, and extrapyramidal symptoms) · palpitations · psychomotor agitation · seizure · tachycardia · unless otherwise noted

Respiratory, thoracic and mediastinal disorders (6)

Very Common cough · Upper respiratory tract infection

Common Bronchitis · epistaxis · pharyngitis · rhinorrhea

Dosing

Source: Lexicomp

Chronic idiopathic urticaria: Oral: 5 mg once daily. In one clinical trial, the titrated use of higher doses (up to 10 mg twice daily) in adults demonstrated clinical improvement (Staevska 2010). Seasonal or perennial allergic rhinitis: Oral: 5 mg once daily NSAID-associated urticaria, prophylaxis (off-label use): Oral: 5 mg 30 minutes before intake of a strong COX-1 inhibitor (Trautmann 2016).

(For additional information see "Desloratadine: Pediatric drug information") Perennial allergic rhinitis, chronic idiopathic urticaria: Oral: Children: 6 to 11 months: 1 mg once daily 12 months to 5 years: 1.25 mg once daily 6 to 11 years: 2.5 mg once daily Children ≥12 years and Adolescents: Refer to adult dosing. Seasonal allergic rhinitis: Oral: Children: 2 to 5 years: 1.25 mg once daily 6 to 11 years: 2.5 mg once daily Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

Adults: Mild to severe impairment: 5 mg every other day. Children: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

Hypersensitivity reactions (including anaphylaxis) have been reported with use; discontinue therapy immediately with signs/symptoms of hypersensitivity. Disease-related concerns:

Hepatic impairment

Use with caution in patients with hepatic impairment; dosage adjustment needed.

Renal impairment

Use with caution in patients with renal impairment; dosage adjustment needed. Concurrent drug therapy issues:

Sedatives

Effects may be potentiated when used with other sedative drugs or ethanol. Special populations:

Slow metabolizers

Use with caution in patients known to be slow metabolizers of desloratadine (incidence of side effects may be increased). 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.

Phenylalanine

Some products may contain phenylalanine.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies; therefore, the manufacturer classifies desloratadine as pregnancy category C. The use of antihistamines for the treatment of rhinitis during pregnancy is generally considered to be safe at recommended doses. Information related to the use of desloratadine during pregnancy is limited; therefore, other agents may be preferred. Desloratadine is the primary metabolite of loratadine; refer to the Loratadine monograph for additional information.

Lactation

Desloratadine is excreted into breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Chemistry & Properties

Formula	C19H19ClN2
Molecular weight	310.83 g/mol
IUPAC name	13-chloro-2-piperidin-4-ylidene-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
CAS	100643-71-8
PubChem CID	124087
InChIKey	`JAUOIFJMECXRGI-UHFFFAOYSA-N`
logP	4.02 (XLogP 4.5)
Polar surface area	24.92 Å²
H-bond acceptors / donors	2 / 1
Drug-likeness (QED)	0.79
Lipinski violations	0

SMILES

Clc1ccc2c(c1)CCc1cccnc1C2=C1CCNCC1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

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

Receptor binding (top 1)

Target	Action	Affinity
H1 receptor (HRH1)	Antagonist	pKi 9.0

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (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 (11, DDInter)

Interacting drug	Severity	Management
Candida albicans	moderate
Coccidioides immitis spherule	moderate
Histamine	moderate
Iodide I-123	moderate
Iodide I-131	moderate
Pitolisant	moderate
Trichophyton mentagrophytes	moderate
Tuberculin purified protein derivative	moderate
Erythromycin	minor
Hyaluronidase	minor
Ketoconazole	minor

Registered Products (37)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Dislara 2.5 mg ODT	Tablet 2.5 mg	10 tab pack varies	Al-Taqqadom Pharmaceutical Industries	1.100
Dislara 5mg ODT	Tablet 5 mg	10 tab pack varies	Al-Taqqadom Pharmaceutical Industries	1.100
ALES	Tablet 5 mg	10 tab pack varies	Itqan Pharmaceutical Industries/Jordan	1.250
Histacare	Tablet 5 mg	10 tab pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	1.340
Lorius	Tablet 5 mg	10 tab pack varies	SAVVY PHARMA/JORDAN	1.340
Rina 5mg F.C Tab	Film-Coated Tablet 5 mg	10 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.340
Rina-D 12 hours	Tablet 2.5 mg, 120 mg	10 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.140
Rina 5mg F.C Tab	Film-Coated Tablet 5 mg	20 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.530
Desmax Oral Solution	Solution Desloratadine 0.5 mg/ml	100 ml	Petra Pharmaceutical Industries	2.610
Iris syrup	Syrup 0.5 mg/ml	100 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	2.610
Rina Syrup	Syrup 2.5 mg/5 ml	100 ml	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.610
Dehist Syrup	Syrup 0.5 mg/1 ml	100 ml	Sukhtian Pharma Co. (SP)	2.730
Dehist Tablet	Tablet 5.0 mg	30 tab	Sukhtian Pharmaceutical Manufacturing (SP)	2.790
Dora	Tablet 5 mg	30 tab	Professional Drug Store	2.790
Dora	Solution 5 mg/10 ml	150 ml	Professional Drug Store	3.030
Noura	Tablet 2.5 mg	30 tab	Orient Montreal Drug Store	3.050
Dislara 2.5 mg ODT	Tablet 2.5 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	3.110
Dislara 5mg ODT	Tablet 5 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	3.110
Aeriallerg	Injection 0.5 mg/ml	125 ml	Pharma International Company/ Jordan	3.270
Allerest	Syrup 0.5 mg/ml	125 ml	Hayat Pharmaceutical Industries CO.PLC/JORDAN	3.270
Histacare Syrup	Syrup 0.5 mg/1 ml	125 ml pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	3.270
Deslora Oral Solution	Solution 0.05 % WT./VOL.	120.0 MILLILITER	JERASH PHARMACEUTICALS LTD.CO/JORDAN	3.440
ALES	Tablet 5 mg	30 tab pack varies	Itqan Pharmaceutical Industries/Jordan	3.550
Aerius Oral Solution	Solution 0.5 mg/ml	150 ml	Adatco Drug Store	3.740
Noura	Tablet 5 mg	30 tab	Orient Montreal Drug Store	3.740
Aeriallerg	Tablet 5 mg	30 tab	Pharma International Company/ Jordan	3.790
Allerest	Tablet 5 mg	30 tab	Hayat Pharmaceutical Industries CO.PLC/JORDAN	3.790
Histacare	Tablet 5 mg	30 tab pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	3.790
Iris 5mg F.C Tab	Film-Coated Tablet 5 mg	30 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	3.790
Lorius	Tablet 5 mg	30 tab pack varies	SAVVY PHARMA/JORDAN	3.790
Rina 5mg F.C Tab	Film-Coated Tablet 5 mg	30 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	3.790
Histacare Syrup	Syrup 0.5 mg/1 ml	150 ml pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	3.920
dilora	Suspension 2.5 mg/5 ml	150 ml	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	3.940
Aerius Tab	Tablet 5 mg	30 tab	Adatco Drug Store	3.990
Rina-D 12 hours	Tablet 2.5 mg, 120 mg	20 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	4.070
Rina-D 12 hours	Tablet 2.5 mg, 120 mg	30 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	6.030
Rina 5mg F.C Tab	Film-Coated Tablet 5 mg	500 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	54.960