Glycopyrronium Bromide 1mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Glycopyrronium Bromide 1mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1mg of Glycopyrronium bromide (or Glycopyrrolate).
Contains lactose monohydrate
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablets.
White to off-white, round flat beveled tablet (nominal diameter 5.5mm) debossed “1” on one side and break line on other side without any visible defects.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For use in adults as add-on therapy in the treatment of peptic ulcer
4.2 Posology and method of administration
Posology
Use in adults:
One tablet three times daily (in the morning, early afternoon and at bedtime)
The dosage of Glycopyrronium Bromide 1mg tablets should be adjusted to the need of the individual patient to assure symptomatic control with a minimum of adverse reactions. The recommended maximum daily dose of Glycopyrronium bromide is 8mg.
Dose adjustment may be required in elderly and in patients with renal impairment
Dosage needs to be adjusted as needed as tolerated
Glycopyrronium Bromide tablets are not recommended for use in children.
Method of administration
Glycopyrronium bromide 1mg tablets are administered orally
4.3 Contraindications
Glycopyrronium bromide tablets must not be used
• In Glaucoma, obstructive uropathy (for example bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasis, pyloroduodenal stenosis, etc.); paralytic ileus; intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis.
• In those patients with a hypersensitivity to Glycopyrronium bromide or, any other excipient(s) listed in section 6.1.
• In patients taking solid oral dosage forms of potassium chloride. Slower gastrointestinal time produced by Glycopyrronium bromide may increase the risk of hyperkalemia from potassium chloride products.
4.4 Special warnings and precautions for use
Warnings
In the presence of a high environmental temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with use of Glycopyrronium bromide.
Diarrhea may be an early symptom of incomplete intestinal obstruction, specially in patients with ileostomy or colostomy. If incomplete mechanical intestinal obstruction is suspected, treatment should be discontinued and patient examined for intestinal obstruction.
Precautions
Use Glycopyrronium bromide with caution in the elderly and in all patients with: o Autonomic neuropathy o Hepatic or renal disease
o Ulcerative colitis- large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate “toxic mega colon,” a serious complication of the disease.
o Hyperthyroidism
o Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition.
o Cardiac or coronary artery disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia and hypotension.
4.5 Interaction with other medicinal products and other forms of interaction
The concurrent use of Glycopyrronium bromide with other anticholinergics or medications with anticholinergic activity, such as phenothiazines, antiparkinson drugs, or tricyclic antidepressants, may intensify the antimuscarinic effects and may result in an increase in anticholinergic side effects.
Concomitant administration of Glycopyrronium bromide and potassium chloride may increase the severity of potassium chloride-induced gastrointestinal lesions as a result of a slower gastrointestinal transit time.
Slower gastrointestinal time produced by Glycopyrronium bromide may increase the risk of hyperkalemia from potassium chloride products.
Glycopyrronium bromide may increase serum levels of digoxin (from slow release digoxin formulations). Patients should be monitored for digoxin toxicity or use of other dosage forms of digoxin should be considered.
The anticholinergic effects of Glycopyrronium bromide maybe increased with concomitant administration of amantadine. Dose adjustment should be considered.
Atenolol‘s bioavailability may be increased with co-administration of Glycopyrronium bromide, dose adjustment may be required.
Metformin plasma levels may be elevated with co-administration of Glycopyrronium bromide. Clinical response to metformin should be monitored or dose reduced if warranted.
Haloperidol serum levels may be decreased when co-administered with Glycopyrronium bromide resulting in worsening of schizophrenic symptoms and development of tardive dyskinesia.
Levodopa’s therapeutic effect may be reduced with Glycopyrronium bromide administration. Dose adjustment should be considered.
Concurrent use of Glycopyrronium bromide with codeine or methadone may produce paralytic ileus
Concurrent use of Reserpine with Glycopyrronium bromide may antagonize the inhibitory action of Glycopyrronium bromide on gastric acid secretion.
Monoamine oxidase (MAO) inhibitors block detoxification of Glycopyrronium bromide thus potentiating its action.
4.6 Fertility, pregnancy and lactation
There are no or limited amount of data from the use of Glycopyrronium bromide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). . Glycopyrronium bromide tablets are not recommended during pregnancy and in women of childbearing potential not using contraception. Glycopyrronium bromide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Glycopyrronium Bromide tablets are administered to nursing mothers.
4.7 Effects on ability to drive and use machines
Glycopyrronium Bromide tablets have moderate influence on the ability to drive and use machines. Glycopyrronium bromide may produce drowsiness or blurred vision. Patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking this drug.
4.8 Undesirable effects
Based on data from clinical studies and post-marketing experience, the following table presents the adverse reaction profile for Glycopyrronium bromide.
Estimated frequencies of reactions are ranked according to the following convention: very common (>1/10); common (> 1/100, < 1/10); uncommon (> 1/1,000, < 1/100); rare (> 1/10,000, < 1/1,000); very rare (< 1/10,000)
Infections & Infestations
Common: Upper respiratory tract Infection, otitis media, urinary tract infection, influenza, pharyngitis streptococcal, pneumonia, sinusitis, gastroenteritis viral, nasopharyngitis, ear infection, cellulitis, oral herpes
Blood and lymphatic system disorders
Common: Hypokalemia, hypernatraemia
Uncommon: Metabolic acidosis
Metabolism and nutrition disorders
Common: Dehydration, dysgeusia
Psychiatric disorders
Common: Restlessness, agitation, crying, insomnia, drowsiness, intentional self-injury Rare:Impotence, mood alteration, aggression, nervousness, confusion Nervous system disorders
Common: Drowsiness, convulsion, somnolence, headache, disturbance in attention Eye disorders Common: Blurred vision
Rare: Pupil dilatation, cycloplegia, increased ocular tension
Ear and labyrinth disorders
Common: Ear infection
Cardiac disorders
Common: Tachycardia
Rare: Dizziness, feeling faint, lightheadedness Very rare: Palpitations
Respiratory, thoracic and mediastinal disorders Very common: Nasal congestion, dry nose Common: Cough
Gastrointestinal disorders
Very common: Vomiting, diarrhoea, dry mouth
Common: nausea, Abdominal pain, Constipation, chapped lips, abdominal distention Uncommon: Flatulence Hepatobiliary disorders
Uncommon: Alanine aminotransferase increased, blood albumin decreased, blood bilirubin increased, blood potassium decreased
Skin and subcutaneous tissue disorders
Very Common: Vascular disorders, flushing, dry skin,
Rare: Pallor, rash, urticaria,
Renal and urinary disorders
Common: Dysuria, urinary retention
Pregnancy, puerperium and perinatal conditions
Rare: Suppression of lactation
General disorders
Common: Decreased sweating
Rare: Weakness
Investigations
Common: Reduced urine output, heart rate increased Injury, poisoning and procedural complications Common: Feeding tube complication, fall Social circumstances
Uncommon: Abnormal behavior, irritability
“Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.”
4.9 Overdose
Glycopyrronium bromide is a quaternary ammonium agent and symptoms of overdosage are peripheral rather than central in nature. Symptoms of overdosage include hyperthermia, coma and seizures, jerky myoclonic movements or choreoathetosis leading to rhadomyolysis.
Excessive peripheral anticholinergic effects may be countermanded by giving intravenously a quaternary ammonium anticholinesterase such as neostigmine methylsulphate in increments of 0.25mg in adults. The dose may be repeated every 5 - 10 minutes until anticholinergic over-activity is reversed or up to a maximum of 2.5mg. Proportionately smaller doses should be used in children.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anticholinergic, ATC Code: A03AB02
Glycopyrronium bromide (or Glycopyrronium) inhibits the action of acetylcholine on peripheral acetylcholine (muscarinic) receptors on smooth muscle, cardiac muscle, the sinoatrial and atrioventricular nodes, exocrine glands, and to a lesser degree, autonomic ganglia.Thus, it diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions. Due to presence of highly polar quaternary ammonium group, its passage across the blood-brain barrier is limited.
5.2 Pharmacokinetic properties
Glycopyrronium bromide is poorly absorbed after oral administration with a range of bioavailabilty of 1-20%. Administration of a high fat meal further reduces oral absorption. Following oral administration, the anti-cholinergic effects of Glycopyrronium bromide may persist for up to 8-12 hours.
Glycopyrronium bromide is widely distributed with an average volume of distribution of 0.42 L/kg. Distribution volumes in children are 3-4 times to that in adults. The in vitro human plasma protein binding of Glycopyrronium bromide was 38% to 41% at concentrations of 1-10 ng/mL. After I.V. administration, Glycopyrronium bromide has a mean volume of distribution in children aged 1 to 14 years of approximately 1.3 to 1.8 L/kg, with a range from (0.7 to 3.9L/kg). In adults aged 60-75 years, the volume of distribution was lower (0.42 L/kg +/- 0.22). After IV injection of 0.006 mg/kg, the mean distribution phase half-life was 2.22 ± 1.26 minutes and with a mean elimination phase half-life of 0.83 ± 0.27 hours. Plasma levels 6 hours post dose were nearly 10-fold greater in uremic patients than in controls.
Only a small portion of absorbed Glycopyrronium bromide is metabolized and excreted as one or more metabolites.
Approximately 65-80% of orally administered Glycopyrronium bromide is recovered in urine as unchanged drug. The remaining portion is believed to be metabolized and excreted in bile. In adults, the average rate of clearance is 0.54 L/kg/hr. The clearance of Glycopyrronium bromide in patients with renal dysfunction is significantly delayed.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. Study in rats has shown decreased rate of conception and survival rate at weaning.
6.1 List of excipients
Lactose monohydrate,
Anhydrous calcium hydrogen phosphate, Magnesium stearate,
Povidone K-30,
Sodium starch glycolate.
6.2 Incompatibilities
None known
6.3 Shelf life
Unopened bottle: 3 Years
Do not use after five weeks of first opening
Blister: 2 Years
6.4 Special precautions for storage
Do not store above 25O C. Store in original container.
6.5 Nature and contents of container
HDPE bottle with screw-cap Pack sizes: 100 tablets
Alu-Alu Blister: packs of 10’s, 20’s, 30’s, 50’s, 60’s, 90’s, 100’s, 14’s, 28’s, 56’s, 84’s & 112’s (with or without calendar pack).
6.6 Special precautions for disposal
No special requirements
Any unused product or waste material should be disposed of in accordance with local requirements
7 MARKETING AUTHORISATION HOLDER
Dawa Limited 5, Sandridge Close,
Harrow, Middlesex,
HA11XD,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 30684/0125
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10/03/2015
10 DATE OF REVISION OF THE TEXT
26/06/2015