Glycopyrrolate is a medication that belongs to a class of drugs known as antimuscarinics or anticholinergics. It works by blocking the action of acetylcholine, a neurotransmitter that plays a role in various bodily functions, including the regulation of smooth muscle contraction.

Glycopyrrolate (Cuvposa) or Glycopyrronium is an anticholinergic medicine that does not cross the blood-brain barrier and hence does not cause central nervous system-related adverse effects. It is used to control respiratory secretion as in the perioperative settings and in patients with chronic drooling of the saliva. It is also used to reverse the cholinergic side effects of anesthetic agents and muscarinic agents like neostigmine and pyridostigmine.

Glycopyrrolate Uses:

• Chronic drooling (Cuvposa only):
  • Glycopyrronium is used in management to decrease chronic, severe drooling in the child age group of patients from 3 to 16 years with CNS abnormalities (eg includes cerebral palsy).
• Reduction of secretions (injection only):
  • It is also used during the induction of anesthesia via reducing tracheobronchial and pharyngeal secretions. It is also helpful in reducing the volume and pH of gastric secretions thus reducing the chances of aspiration during intubation.
• Reversal of bradycardia, vagal reflexes (injection only):
  • This drug can also be used to inhibit negative feedback reflexes from the vagus nerve to the cardiac plexus during the induction phase of Anesthesia.
  • Intraoperative cardiac arrhythmias secondary to drugs or surgically induced or from vagal reflexes can also be controlled.
• Reversal of muscarinic effects of cholinergic agents (injection only):
  • Bradycardia and excessive secretions can be protected by using Glycopyrronium.
  • In short, it helps to antagonize muscarinic effects of cholinergic agents (like pyridostigmine and neostigmine).
  • Muscarinic agonists are usually given to reverse neuromuscular blockade caused by non-depolarizing muscular relaxants.
• Off Label Use of Glycopyrrolate in Adults:
  • For excessive facial, palm, and axillary sweating.

Glycopyrrolate (Cuvposa) Dose in Adults

Glycopyrrolate (Cuvposa) Dose in the treatment of primary focal hyperhidrosis (off- label): 

• Common effective dosage range is 1 to 2 mg taken orally once or twice a day.
• Doctors may adjust the dose based on how well it works for the individual and how well the person can tolerate it.
• Some patients have been given doses as high as 6 to 8 mg per day, divided into 2 or 3 doses, but this depends on the specific case and the doctor's judgment.

Glycopyrrolate (Cuvposa) Dose in the treatment of Reduction of secretions (preoperative):

• For reducing secretions before surgery, the typical dose of glycopyrrolate is administered intramuscularly (IM) at a rate of 4 micrograms per kilogram of body weight.
• This is usually given 30 to 60 minutes before the administration of anesthesia or alongside preanesthetic opioids and/or sedatives.
• The goal is to limit excessive secretions during the surgical procedure.

Glycopyrrolate (Cuvposa) Dose in the treatment of Reversal of bradycardia, vagal reflexes (intraoperative):

• Glycopyrrolate is typically administered intravenously (IV) at a dose of 0.1 mg as a single dose.
• If necessary, this dose may be repeated at 2- to 3-minute intervals as needed.
• The purpose of using glycopyrrolate in this scenario is to counteract slow heart rate (bradycardia) and excessive stimulation of the vagus nerve during surgical procedures.

Glycopyrrolate (Cuvposa) Dose in the treatment of Reversal of muscarinic effects of cholinergic agents:

• To counteract the effects of certain medications that affect muscles, like neostigmine or pyridostigmine, glycopyrrolate is given through a vein (IV).
• The typical dose is 0.2 mg of glycopyrrolate for every 1 mg of neostigmine or 5 mg of pyridostigmine that has been given.
• This helps balance out the impact of these muscle-affecting medications and is done to prevent excessive stimulation.
• The exact amount may be adjusted based on the specific situation and what the healthcare provider determines is best for the patient.

Glycopyrrolate (Cuvposa) Dose in Childrens

Glycopyrrolate (Cuvposa) Dose in the treatment of Chronic drooling:

• For kids aged 3 years and older, and teenagers up to 16 years, who have a problem with chronic drooling, glycopyrrolate is often given in a liquid form called oral solution (Cuvposa).
• The typical starting dose is 20 micrograms per kilogram of body weight, three times a day. The doctor may adjust the dose, increasing it by 20 micrograms per kilogram every 5 to 7 days based on how well the child can tolerate it and how well it's working, up to a maximum of 100 micrograms per kilogram, three times a day.
• But the total dose per administration should not go beyond 1,500 to 3,000 micrograms.
• This helps manage the drooling issue in a way that is safe and effective for each child.

Glycopyrrolate (Cuvposa) Dose to control respiratory secretions, palliative care: 

• In palliative care, when trying to manage excessive respiratory secretions, glycopyrrolate is sometimes used in children.
• The typical dose is between 40 to 100 micrograms per kilogram of body weight, and it's taken by mouth every 4 to 8 hours.

Glycopyrrolate (Cuvposa) Dose in the treatment of Reduction of secretions (preoperative):

• For little ones under 2 years old, if the goal is to decrease secretions before a procedure, glycopyrrolate is typically given as a shot in the muscle (IM). The dose ranges from 4 to 9 micrograms per kilogram of body weight, and it's administered 30 to 60 minutes before the procedure.
• For children older than 2 years and adolescents, the typical dose is 4 micrograms per kilogram, also given as an injection 30 to 60 minutes before the procedure. The exact amount might be adjusted based on the specific needs of the child and what the healthcare team decides is best for the situation.

Glycopyrrolate (Cuvposa) Dose in the reversal of bradycardia, vagal reflexes (intraoperative):

• If a child or adolescent experiences slow heart rate (bradycardia) during surgery, glycopyrrolate might be given through a vein (IV) to reverse it.
• The typical dose is 4 micrograms per kilogram of body weight, with a maximum of 100 micrograms per dose.
• This can be repeated every 2 to 3 minutes if needed.
• The goal is to quickly adjust the heart rate and address any excessive stimulation of the vagus nerve during the surgery.

Glycopyrrolate (Cuvposa) Dose in the reversal of muscarinic effects of cholinergic agents:

• If a child or adolescent is experiencing side effects from certain medications affecting muscles, like neostigmine or pyridostigmine, glycopyrrolate might be given through a vein (IV).
• The dose is usually 0.2 milligrams of glycopyrrolate for every 1 milligram of neostigmine or 5 milligrams of pyridostigmine that has been given.
• This helps balance out the effects of these medications.

Pregnancy Risk Factor B (injection)

• It seems that glycopyrrolate, a medication, doesn't pass through the protective barrier around the baby in the womb in significant amounts.
• Even when given in doses of 0.004 milligrams per kilogram, there doesn't appear to be a significant impact on the baby's heart rate or the variation in the heart rate.
• This suggests that, at this dose, glycopyrrolate is not causing notable effects on the developing baby during pregnancy.

Glycopyrrolate use during breastfeeding:

• It's uncertain whether glycopyrrolate, a medication, is found in breast milk.
• The advice from the manufacturer is that if a mother is using this medication, she should consider the potential risk to the baby, the advantages of breastfeeding for the baby, and the benefits of the treatment for herself.
• It's also mentioned that glycopyrrolate might have an effect on the production of breast milk.
• So, if a woman is thinking about breastfeeding while using this medication, it's important to talk to a healthcare provider to make the best decision for both the mother and the baby.

Dose in Kidney disease: 

• The manufacturer's instructions don't give specific details about adjusting the dosage of the medication in certain situations, like when someone has kidney problems.
• However, it's noted that if a person has kidney failure, the removal of the medication from the body is significantly affected.
• In such cases, using the medication cautiously is recommended, and the dosage might need to be adjusted based on individual circumstances.

Dose in Liver disease:

• The manufacturer's instructions don't offer specific details on adjusting the dosage of the medication for people with liver problems.
• However, it's advised to use the medication cautiously in individuals with liver impairment, and the possibility of reducing the dose should be considered.

Side effects of Glycopyrrolate (Cuvposa):

• Cardiovascular:
  • Flushing
  • Pallor
  • Cardiac Arrhythmias
  • Heart Block
  • Hypertension
  • Hypotension
  • Palpitation
  • Tachycardia
• Central Nervous System:
  • Headache
  • Aggressiveness
  • Agitation
  • Crying
  • Irritability
  • Mood Changes
  • Pain
  • Restlessness
  • Confusion
  • Dizziness
  • Drowsiness
  • Excitement
  • Insomnia
  • Nervousness
• Dermatologic:
  • Dry Skin
  • Pruritus
  • Rash
  • Hypohidrosis
  • Urticaria
• Endocrine & Metabolic:
  • Dehydration
• Gastrointestinal:
  • Vomiting
  • Xerostomia
  • Constipation
  • Abdominal Distention
  • Abdominal Pain
  • Flatulence
  • Retching
  • Intestinal Obstruction
  • Loss Of Taste
  • Nausea
  • Pseudo-Obstruction
• Genitourinary:
  • Urinary Retention
  • Urinary Tract Infection
  • Decreased Lactation
  • Impotence
  • Urinary Hesitancy
• Neuromuscular & Skeletal:
  • Weakness
• Ophthalmic:
  • Nystagmus
  • Blurred Vision
  • Cycloplegia
  • Increased Intraocular Pressure
  • Mydriasis
• Respiratory:
  • Nasal Congestion
  • Sinusitis
  • Upper Respiratory Tract Infection
  • Bronchial Secretion
  • Nasal Dryness
  • Pneumonia

Contraindications to Glycopyrrolate (Cuvposa):

• Glycopyrrolate should not be used if there is a known hypersensitivity to glycopyrrolate or any component of the formulation.
• It is also contraindicated in certain medical conditions that make the use of anticholinergic medication unsafe.
• These conditions include severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, paralytic ileus, obstructive diseases of the gastrointestinal tract (such as achalasia, pyloroduodenal stenosis), intestinal atony in elderly or debilitated patients, unstable cardiovascular status in acute hemorrhage, glaucoma, obstructive uropathy (such as bladder neck obstruction due to prostatic hypertrophy), and myasthenia gravis.
• Additionally, for the oral solution, there is an extra contraindication, which is the simultaneous use of potassium chloride in a solid oral dosage form.

Warnings and precautions

CNS effects

• Glycopyrrolate can have effects on the central nervous system (CNS), potentially leading to drowsiness and/or blurred vision.
• These effects could affect a person's ability to perform tasks that require mental alertness, such as operating machinery or driving.
• Therefore, individuals taking glycopyrrolate should be cautioned about engaging in activities that demand focus and quick reactions.
• It's important for patients to be aware of these potential side effects and to avoid activities that could be unsafe while taking this medication.

Transit GI:

• Glycopyrrolate can slow down the movement of muscles in the gastrointestinal (GI) tract, which may lead to constipation or a condition that looks like a blockage in the intestines (intestinal pseudo-obstruction).
• Constipation is a frequent side effect and may limit the dosage that can be taken.
• Intestinal pseudo-obstruction can cause symptoms like a swollen belly, pain, nausea, or vomiting.
• If these symptoms develop or get worse while using glycopyrrolate, it's important to stop the medication and seek medical attention.

Heat prostration:

• Heat prostration, a condition where the body overheats, may happen when using glycopyrrolate, especially in the presence of fever, high environmental temperature, or during physical exercise.
• This risk is higher in children and the elderly.
• It's important to be cautious in hot weather and during exercise while using this medication.
• It is advisable to avoid exertion and exposure to high environmental temperatures after taking glycopyrrolate to reduce the risk of heat-related issues.
• If someone experiences symptoms of heat prostration, such as excessive sweating, weakness, dizziness, or nausea, they should seek shade, hydrate, and inform their healthcare provider.

Incomplete mechanical obstruction

• Diarrhea could be an initial indicator of an incomplete mechanical intestinal obstruction, particularly in patients with an ileostomy or colostomy.
• Therefore, it is advised to avoid using glycopyrrolate in such patients.
• If there's suspicion of incomplete mechanical intestinal obstruction or if diarrhea develops, the treatment should be stopped, and medical attention should be sought.

Cardiovascular disease

• In individuals with cardiovascular conditions like coronary artery disease, arrhythmias, heart failure, hypertension, or rapid heart rate (tachycardia), glycopyrrolate should be used cautiously.
• It's important to assess the heart rate before giving the medication, especially in cases of tachycardia.
• This cautious approach helps ensure the safety of individuals with cardiovascular disease.

Hepatic impairment

• For individuals with liver problems, glycopyrrolate should be used with caution.
• It is advisable to consider a reduction in dosage in such cases.
• The liver plays a crucial role in processing medications, and if it's not functioning properly, adjustments may be necessary to ensure the medication is used safely and effectively.

Hiatal hernia

• In individuals with a hiatal hernia and reflux esophagitis, glycopyrrolate should be used with caution.
• It is advisable to consider a reduction in dosage for these patients.
• Hiatal hernia can contribute to gastroesophageal reflux, and using glycopyrrolate cautiously, along with a potential dosage adjustment, helps manage the medication's impact in individuals with this condition.

Hyperthyroidism:

• In individuals with hyperthyroidism (an overactive thyroid), glycopyrrolate should be used with caution.
• Hyperthyroidism can affect various bodily functions, and the use of glycopyrrolate requires careful consideration in such cases.

Neuropathy:

• For individuals with autonomic neuropathy, the use of glycopyrrolate should be approached with caution.
• Autonomic neuropathy involves damage to the nerves that control involuntary bodily functions, and caution is necessary because glycopyrrolate affects these functions.
• Considering a dosage reduction may be advisable in such cases.

Bladder neck obstruction/prostatic hyperplasia:

• In individuals with prostatic hyperplasia (enlarged prostate) or bladder neck obstruction, the use of glycopyrrolate should be approached with caution.
• This medication may potentially worsen symptoms such as urinary retention in individuals with these conditions.
• Therefore, it's important to use glycopyrrolate cautiously in such cases, and considering a dosage reduction might be advisable.

Renal impairment

• For individuals with renal impairment (kidney problems), glycopyrrolate should be used with caution.
• In cases of renal failure, the elimination of glycopyrrolate from the body is significantly impaired.
• Therefore, caution is warranted, and dosage adjustments may be necessary in individuals with compromised kidney function.

Ulcerative colitis

• In individuals with ulcerative colitis, the use of glycopyrrolate should be approached with caution.
• Large doses of glycopyrrolate have the potential to suppress intestinal motility, and caution is advised to avoid the risk of precipitating or exacerbating an ileus (intestinal obstruction) or toxic megacolon.
• It's important to consider a dosage reduction in these cases.
• Furthermore, the use of glycopyrrolate is contraindicated in individuals with severe ulcerative colitis, indicating that it should not be used in such cases.

Glycopyrrolate (glycopyrronium): Drug Interaction

Monitoring parameters:

Heart Rate:

• Glycopyrrolate may affect your heart rate.
• If you have heart conditions, like coronary artery disease or arrhythmias, or if you're experiencing a fast heart rate, use this medication with caution.
• It's important to evaluate your heart rate before taking glycopyrrolate.

Anticholinergic Effects:

• Glycopyrrolate has anticholinergic effects, which can cause side effects like blurred vision and drowsiness.
• Be cautious when performing tasks that require mental alertness, such as driving or operating machinery.
• If you experience drowsiness or blurred vision, discuss it with your healthcare provider.

Bowel Sounds:

• Glycopyrrolate can affect the sounds in your stomach (bowel sounds).
• If you notice changes or discomfort in your stomach, inform your healthcare provider.

Bowel Movements:

• Glycopyrrolate may slow down bowel movements, leading to constipation.
• If you have concerns about your bowel habits or experience constipation, talk to your healthcare provider.
• In some cases, diarrhea could be a sign of incomplete intestinal obstruction; if this happens, discontinue the medication and seek medical advice.

Effects on Drooling:

• If you're using glycopyrrolate for chronic drooling, the typical dosage for children is based on their weight.
• It's important to follow the prescribed dosage, and the healthcare provider may adjust it based on the child's response.

How to administer Glycopyrrolate (Cuvposa)?

Intramuscular (IM) Administration:

• Glycopyrrolate can be given directly without dilution if administered through the muscle (IM).

Intravenous (IV) Administration:

• For IV use, glycopyrrolate can be given without dilution, or it may be diluted in a compatible solution.
• In perioperative settings, it's typically administered over 1 to 2 minutes, for instance, in adults, 0.2 mg over 1 to 2 minutes.
• It can also be administered via the tubing of an ongoing IV infusion of normal saline (NS).
• Glycopyrrolate may be given in the same syringe with neostigmine or pyridostigmine for reversing neuromuscular blockade.

Oral Administration:

• For oral administration, the oral solution should be given 1 hour before or 2 hours after meals.
• Measure the oral solution accurately, using a proper measuring device such as a dosing cup or an oral syringe.

Mechanism of action of Glycopyrrolate (Cuvposa):

• Glycopyrrolate works by blocking the effects of acetylcholine in certain parts of the body, including smooth muscle, glands that produce secretions, and the central nervous system (CNS).
• By doing this, it indirectly decreases the rate of salivation by preventing the stimulation of acetylcholine receptors.
• In simpler terms, it helps reduce the production of saliva by interfering with the signals that tell the body to make more saliva.

Onset of Action:

• IM (Intramuscular): 15 to 30 minutes
• IV (Intravenous): Within 1 minute

Peak Effect:

• IM: Within approximately 30 to 45 minutes

Duration:

• Vagal Effect: 2 to 3 hours
• Inhibition of Salivation: Up to 7 hours
• Parenteral: 7 hours

Absorption:

• Oral Tablet: Poor absorption (about 3%)
• Oral Solution: 23% lower absorption compared to the tablet; absorption is variable and erratic
• A high-fat meal significantly reduces the oral bioavailability.

Distribution:

• Volume of Distribution (V): IV:
  • Children and Adolescents (≤14 years): 1.3 to 1.8 L/kg (range: 0.7 to 3.9 L/kg)
  • Adults: 0.42 ± 0.22 L/kg

Bioavailability:

• Tablet: 3%

Half-life Elimination:

• IV:
  • Infants: 21.6 to 130 minutes
  • Children: 19.2 to 99.2 minutes
• IM: Adults: 0.55 to 1.25 hours
• IV: 0.83 ± 0.27 hour
• Oral Solution: Adults: 3 hours

Time to Peak, Plasma:

• 3.1 hours

Excretion:

• Urine: More than 80% for IM, 85% for IV (as unchanged drug)
• Bile: Less than 5% (as unchanged drug)

Clearance:

• Children and Adolescents (≤14 years): Mean range: 1.01 to 1.41 L/kg/hour (range: 0.32 to 2.22 L/kg/hour)
• Adults: 0.54 ± 0.14 L/kg/hour

International Brand Names of Glycopyrrolate:

• Cuvposa
• Glycate
• Glyrx-PF
• Robinul
• Robinul-Forte
• Androl
• Glyco-P
• Glycopyrrola
• Glyprolate
• Pyrolate
• Robinul
• Robinul Forte
• Robinunl
• Supotaria
• Tabinul

Glycopyrrolate Brand Names in Pakistan:

Correct Spellings: Glycopyrrolate, Cuvposa Incorrect spellings: Glycopyrolate, Cuposa, Glycopyrolat, Cvpos