Glycopyrronium

R03B - Other agents for obstructive airway diseases, inhalants ATC A03AB02 Small molecule approved 1961 Oral Parenteral Topical Natural product

JFDA label: Goprat 0.2mg/1ml solution for injection

Mechanism of Action

12.1 Mechanism of Action Glycopyrronium is a competitive inhibitor of acetylcholine receptors that are located on certain peripheral tissues, including sweat glands. In hyperhidrosis, glycopyrronium inhibits the action of acetylcholine on sweat glands, reducing sweating.

Indications

Off-label

Asthma
Hyperhidrosis
Pulmonary Disease, Chronic Obstructive
Severe Acute Respiratory Syndrome

Contraindications

Source: openFDA

Qbrexza is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of Qbrexza (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome). Qbrexza is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of Qbrexza (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome) ( 4 ). Absolute

Adverse Reactions

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

Cardiac disorders (2)

Uncommon Atrial fibrillation · Palpitations

Vascular disorders (1)

Very Common Flushing

Nervous system disorders (1)

Very Common Headache

Renal and urinary disorders (2)

Very Common Urinary retention

Uncommon Dysuria

Metabolism and nutrition disorders (1)

Uncommon Hyperglycaemia

Gastrointestinal disorders (5)

Very Common Constipation · Dry mouth · Gastroenteritis · Vomiting

Uncommon Dyspepsia

Skin and subcutaneous tissue disorders (2)

Uncommon Dermatitis · Rash

Musculoskeletal and connective tissue disorders (1)

Uncommon Musculoskeletal chest pain

Psychiatric disorders (1)

Very Common Insomnia

Infections and infestations (6)

Very Common Nasopharyngitis · Sinusitis · Upper respiratory tract infection · Urinary tract infection

Uncommon Cystitis noninfective · Rhinitis

General disorders and administration site conditions (9)

Uncommon Asthenia · Bladder pain · Cystitis · Dental caries · Fatigue · Hypoaesthesia · Pain in extremity · Sinus congestion

Rare Ageusia

Respiratory, thoracic and mediastinal disorders (4)

Very Common Nasal congestion

Uncommon Epistaxis · Productive cough · Throat irritation

Dosing

Source: openFDA

For topical use only. Qbrexza is for topical use in the underarm area only and not for use in other body areas. Qbrexza is administered by a single-use pre-moistened cloth packaged in individual pouches. Qbrexza should be applied to clean dry skin on the underarm areas only. Qbrexza should not be used more frequently than once every 24 hours. Tear open the pouch and pull out the cloth, unfold the cloth, and wipe it across one entire underarm once. Using the same cloth, wipe the other underarm once. A single cloth should be used to apply Qbrexza to both underarms. After applying Qbrexza, discard the cloth in the household trash out of reach of children and others. Wash hands immediately with soap and water after applying and discarding the Qbrexza cloth. Qbrexza may cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes. Avoid transfer of Qbrexza to the periocular area [see Warnings and Precautions ( 5.3 )] . Do not apply Qbrexza to broken skin. Avoid using Qbrexza with occlusive dressings. For topical use only. Apply Qbrexza once daily to both axillae using a single cloth ( 2 ).

Warnings & Precautions

Source: openFDA

Warnings & Precautions

New or worsening urinary retention: Use with caution in patients with a history of documented urinary retention ( 5.1 ). Control of body temperature: In the presence of high ambient temperature, heat illness may occur; avoid use if patients develop generalized lack of sweating when exposed to hot or very warm environmental temperatures ( 5.2 ). Operating machinery or an automobile: Transient blurred vision may occur with use of Qbrexza. If blurred vision occurs, discontinue use of Qbrexza until symptoms resolve; avoid operating a motor vehicle or other machinery until symptoms resolve ( 5.3 ).

New or Worsening Urinary Retention New or worsening signs and symptoms

New or Worsening Urinary Retention New or worsening signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder) have occurred in patients taking Qbrexza with or without a history of documented urinary retention. Instruct patients to discontinue use immediately and consult a physician should any of these signs or symptoms develop. Qbrexza should be used with caution in patients with prostatic hypertrophy or bladder-neck obstruction.

Control of Body Temperature In the presence of high ambient temperatur

Control of Body Temperature In the presence of high ambient temperature, heat illness (hyperpyrexia and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as Qbrexza. Advise patients using Qbrexza to watch for generalized lack of sweating when in hot or very warm environmental temperatures and to avoid use if not sweating under these conditions.

Operating Machinery or an Automobile Transient blurred vision may occu

Operating Machinery or an Automobile Transient blurred vision may occur with use of Qbrexza. If blurred vision occurs, the patient should discontinue use until symptoms resolve. Patients should be warned not to engage in activities that require clear vision such as operating a motor vehicle or other machinery, or performing hazardous work until the symptoms have resolved.

Risk of Accidental Exposure Cases of accidental exposure resulting in

Risk of Accidental Exposure Cases of accidental exposure resulting in mydriasis, anisocoria, and blurred vision have been reported in postmarketing surveillance of Qbrexza. The exposures occurred when children accessed Qbrexza wipes discarded in trash or when patients touched the periocular area after using Qbrexza. In most cases, the mydriasis, anisocoria, and blurred vision were temporary and resolved within one week following exposure. The risk of accidental exposure was increased in these cases by not adhering to recommendations for the appropriate use of Qbrexza. Strict adherence to the recommended hand washing after use and disposal instructions is of the utmost importance to prevent accidental exposure. [see Dosage and Administration (2) ].

Pregnancy & Lactation

Pregnancy

Chemistry & Properties

Formula	C19H28NO3+
Molecular weight	318.44 g/mol
IUPAC name	(1,1-dimethylpyrrolidin-1-ium-3-yl) 2-cyclopentyl-2-hydroxy-2-phenylacetate
CAS	740028-90-4
PubChem CID	3494
InChIKey	`ANGKOCUUWGHLCE-UHFFFAOYSA-N`
logP	2.46 (XLogP 3.1)
Polar surface area	46.53 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.69
Lipinski violations	0

SMILES

C[N+]1(C)CCC(OC(=O)C(O)(c2ccccc2)C2CCCC2)C1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MATE1 (Substrate)OCT2 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Potassium chloride	major
Potassium citrate	major
Topiramate	major
Zonisamide	major
Acebutolol	moderate
Acetylcholine	moderate
Aclidinium	moderate
Acrivastine	moderate
Alfentanil	moderate
Alimemazine	moderate
Amantadine	moderate
Ambenonium	moderate
Amitriptyline	moderate
Amoxapine	moderate
Arbutamine	moderate
Aripiprazole	moderate
Asenapine	moderate
Atenolol	moderate
Atropine	moderate
Azatadine	moderate
Belladonna	moderate
Benzatropine	moderate
Benzhydrocodone	moderate
Betaxolol	moderate
Bethanechol	moderate
Biperiden	moderate
Bisoprolol	moderate
Botulinum Toxin Type B	moderate
Botulinum toxin type A	moderate
Brexpiprazole	moderate
Brompheniramine	moderate
Buprenorphine	moderate
Butorphanol	moderate
Carbamoylcholine (ophthalmic)	moderate
Carbinoxamine	moderate
Cariprazine	moderate
Carteolol	moderate
Carvedilol	moderate
Cevimeline	moderate
Chlorcyclizine	moderate

Showing 40 of 100+.

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Seebri Breezhaler	Capsule 50 mcg	1 Inhaler + 30 Hard Capsule	The Jordan Drugstore Co	35.620
Enerzair Breezhaler 150 mcg/50 mcg/160 mcg Inhalation powder	Powder 160 mcg, 150 mcg, 50 mcg	30 Hard Capsules + 1 inhaler	The Jordan Drugstore Co	39.740
Breztri Aerosphere pressurised inhalation, suspension	Suspension 160 mcg, 5 mcg, 7.2 mcg	120 Actuations	Shawi & Rushedat Drug Store	51.610
Ultibro Breezhaler	Capsule 110 mcg, 50 mcg	30 Hard Capsules + 1 Inhaler	The Jordan Drugstore Co	52.700
Goprat 0.2mg/1ml solution for injection	Injection 0.2 mg/1 ml	5 vial	MS PHARMA/JORDAN	—