GLENISPERA CO

Indications

• Chronic asthma
• Chronic obstructive pulmonary disease (COPD)
• Reversible airways obstruction
• Prophylaxis of exercise-induced bronchospasm

Dosage

Children: Child 6–11 years: 12 micrograms twice daily (maximum daily dose 24 micrograms). Child 12–17 years: 12 micrograms twice daily, may

Adults: 6–12 micrograms by inhalation 1–2 times a day, increased if necessary up to 24 micrograms twice daily (max. per dose 36 micrograms), with a maximum daily dose of 48 micrograms.

Mechanism of action

Formoterol fumarate acts as an agonist at beta-2 adrenergic receptors located on bronchial smooth muscle. Upon binding, it activates adenylate cyclase, increasing intracellular cyclic AMP (cAMP) levels, leading to relaxation of bronchial smooth muscle and bronchodilation. This mechanism results in improved airflow and reduced resistance in the airways.

Pharmacodynamics

The pharmacodynamic effect of formoterol fumarate includes bronchodilation and relief of bronchospasm associated with asthma and COPD. The duration of action is approximately 12 hours, allowing for twice-daily dosing in many cases. Formoterol also exhibits some anti-inflammatory effects, although its primary role is as a bronchodilator.

Pharmacokinetics

Formoterol fumarate is well-absorbed following inhalation, with peak plasma concentrations typically occurring within 15 to 30 minutes. It undergoes extensive metabolism in the liver, primarily via the cytochrome P450 system. The elimination half-life is approximately 10 hours. Renal impairment may necessitate dose adjustments, especially in severe cases, while hepatic impairment is advised against due to the risk of unpredictable conversion to terbutaline.

Contra-indications

• Hypersensitivity to formoterol or any component of the formulation
• Severe impairment or cirrhosis of liver
• Rapidly deteriorating asthma

Adverse effects

• Anxiety
• Abnormal behaviour
• Muscle cramps
• Sleep disorders
• Akathisia
• Angioedema
• Bronchospasm
• Circulatory collapse
• Dizziness
• Hypokalaemia
• Hypotension
• Myocardial ischaemia
• Nausea
• Skin reactions

Interactions

• Concomitant use with theophylline and its derivatives may potentiate hypokalaemia
• Corticosteroids may also increase the risk of hypokalaemia
• Diuretics can lead to additive effects on serum potassium levels

Precautions

• Caution in patients with a history of cardiovascular disease
• Monitor potassium levels in patients on high doses
• Use with caution in patients with severe asthma or those requiring high doses of beta-agonists

Pregnancy

Manufacturer advises to avoid use due to lack of information on safety during pregnancy.

Breast-feeding

Manufacturer advises to avoid use due to lack of information on safety during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Inhalation powder (various dosage forms including 6 micrograms, 12 micrograms, and 24 micrograms per dose)

Indications

• Hyperhidrosis (excessive sweating)
• Premedication in anesthetic procedures

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Apply once daily to the affected area for hyperhidrosis, using the liquid formulation at body temperature.

Mechanism of action

Glycopyrronium bromide acts as a competitive antagonist of muscarinic acetylcholine receptors. By blocking these receptors, it inhibits glandular secretion and reduces the activity of smooth muscle, leading to a decrease in sweating and other secretory functions.

Pharmacodynamics

The pharmacodynamic effects of glycopyrronium bromide include a reduction in salivary, bronchial, and sweating secretions. The onset of action is generally rapid, with effects typically noted within 30 minutes after administration. These actions are particularly beneficial in managing conditions characterized by excessive secretion, such as hyperhidrosis.

Pharmacokinetics

Glycopyrronium bromide is poorly absorbed when applied topically, which minimizes systemic effects. When used systemically, it is well absorbed, with peak plasma concentrations achieved within 1-2 hours. The drug undergoes hepatic metabolism and has a half-life of approximately 1-2 hours. Renal excretion is a significant pathway for elimination, and thus caution is advised in patients with renal impairment.

Contra-indications

• Infections affecting the treatment site

Adverse effects

• Skin reactions
• Pain
• Paraesthesia

Precautions

• Avoid contact with eyes
• Avoid contact with mucous membranes
• Avoid use on broken or irritated skin
• Do not shave axillae or use depilatories within 12 hours of application

Pregnancy

Manufacturer advises caution, as specific studies on use during pregnancy are limited.

Breast-feeding

Manufacturer advises avoiding application to the breast area; no information available on presence in milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• 0.05% solution for topical use
• Powder for dry skin application

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on age and weight.

Adults: Refer to BNF for specific dosing guidance, typically involving the use of metered-dose inhalers or nebulizers.

Mechanism of action

Formoterol selectively binds to and activates beta2-adrenergic receptors, predominantly located in bronchial smooth muscle. This activation stimulates adenylyl cyclase, leading to increased levels of cyclic AMP (cAMP). Elevated cAMP causes relaxation of bronchial smooth muscle and dilation of the airways. Additionally, formoterol inhibits the release of hypersensitivity mediators, such as histamine and leukotrienes, from mast cells, further contributing to its bronchodilator effect.

Pharmacodynamics

As a bronchodilator, formoterol works locally in the lungs to relax smooth muscle and open the airways. It provides both a rapid onset of action and a prolonged duration, making it suitable for the management of chronic respiratory conditions. However, it should not be used as monotherapy in asthma management due to an associated increased risk of asthma-related death when not combined with inhaled corticosteroids.

Pharmacokinetics

Formoterol is administered via inhalation, allowing for direct delivery to the lungs. It has a rapid onset of action, typically within 2-3 minutes, and is characterized by a long duration of action, up to 12 hours. The pharmacokinetics of formoterol may vary based on individual patient factors, including age, lung function, and concurrent medications.

Contra-indications

• Hypersensitivity to formoterol or any of its components
• Severe uncontrolled asthma
• Acute bronchospasm
• Cardiovascular disorders
• Use of monoamine oxidase inhibitors (MAOIs) within 14 days

Adverse effects

• Tachycardia
• Palpitations
• Tremor
• Headache
• Nervousness
• Dizziness
• Nausea
• Muscle cramps
• Hypokalemia
• Hyperglycemia

Interactions

• Other sympathomimetics
• Beta-blockers (may reduce effectiveness of formoterol)
• Diuretics (may increase the risk of hypokalemia)
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic antidepressants

Precautions

• Caution in patients with cardiovascular disorders
• Caution in patients with diabetes mellitus
• Use with caution in patients with hyperthyroidism
• Monitor for worsening of asthma symptoms
• Avoid use as a rescue medication

Pregnancy

Formoterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider.

Breast-feeding

It is not known whether formoterol is excreted in human milk. Caution should be exercised when prescribing to nursing women.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Aerosol inhaler
• Dry powder inhaler
• Nebuliser solution

Indications

• Reduction of salivation and secretions during surgery
• Management of peptic ulcers
• Treatment of chronic obstructive pulmonary disease (COPD)
• Preoperative medication to decrease bronchial secretions
• Management of hyperhidrosis

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific adult dosing recommendations depending on the indication.

Mechanism of action

Glycopyrrolate acts as a competitive antagonist at muscarinic acetylcholine receptors. By inhibiting the binding of acetylcholine, it reduces the activity of the parasympathetic nervous system, which leads to decreased secretion of glands, such as salivary and bronchial glands, as well as a reduction in gastrointestinal motility.

Pharmacodynamics

Glycopyrrolate exhibits antimuscarinic properties, which result in decreased secretions from salivary and bronchial glands. This effect can be beneficial in various clinical situations where excessive secretions can lead to complications. The drug also has a mild effect on inhibiting gastric acid secretion, contributing to its use in peptic ulcer management.

Pharmacokinetics

Glycopyrrolate is well absorbed following oral administration. It has a bioavailability of approximately 10% due to significant first-pass metabolism. The drug is widely distributed in body tissues and has a relatively long half-life, allowing for prolonged effects. Glycopyrrolate is primarily excreted unchanged in the urine, with renal clearance being a significant route for elimination.

Contra-indications

• Hypersensitivity to glycopyrrolate or any of its components
• Myasthenia gravis
• Glaucoma
• Obstructive uropathy
• Severe ulcerative colitis

Adverse effects

• Dry mouth
• Constipation
• Blurred vision
• Urinary retention
• Tachycardia
• Nausea
• Dizziness
• Anxiety

Interactions

• Anticholinergic drugs may enhance the effects of glycopyrrolate
• Concurrent use with other drugs that may cause anticholinergic side effects can increase the risk of adverse effects
• Potassium chloride may cause gastrointestinal irritation when administered with glycopyrrolate

Precautions

• Caution in patients with cardiovascular disease
• Caution in elderly patients
• Use with caution in patients with hepatic or renal impairment
• Monitor for signs of increased heart rate

Pregnancy

Glycopyrrolate should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Glycopyrrolate is excreted in breast milk, caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 1 mg, 2 mg
• Injectable solution: 0.2 mg/mL

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma (as an adjunct therapy)
• Pre-operative medication to reduce secretions
• Management of excessive salivation

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric patients.

Adults: Refer to the BNF for specific dosing information based on the indication and patient characteristics.

Mechanism of action

Glycopyrronium has the highest affinity for M1 muscarinic receptors, followed by M3, M2/M4, and M5. By antagonizing these receptors, particularly M3 which is responsible for bronchoconstriction and secretions, glycopyrronium decreases airway resistance and reduces the secretion of mucus in the airways, thereby facilitating easier breathing. It also decreases salivary and gastric secretions, contributing to its therapeutic effects in various conditions.

Pharmacodynamics

As a quaternary ammonium compound, glycopyrronium is one of the most commonly prescribed LAMAs with a long duration of action due to its slow dissociation from muscarinic receptors. It has a wider therapeutic index compared to other anticholinergic medications. Patients may experience side effects such as urinary retention, risk of overheating, and transient blurred vision as a result of its anticholinergic properties.

Pharmacokinetics

Glycopyrronium is well-absorbed following inhalation, with peak plasma concentrations occurring within a few hours. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, and is excreted through both urine and feces. Its elimination half-life supports once-daily dosing in a clinical setting.

Adverse effects

• dry mouth
• blurred vision
• constipation
• urinary retention
• tachycardia
• confusion
• delirium

Interactions

• clozapine+glycopyrronium: Unknown (additive effect)
• antipsychotics, second generation+glycopyrronium: Unknown (additive effect)

Precautions

• use with caution in patients with urinary retention
• monitor for signs of overheating
• use with caution in elderly patients due to risk of confusion and delirium

Pregnancy

Glycopyrronium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if glycopyrronium is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• oral solution
• inhalation solution
• tablet

Mechanism of action

Formoterol is a relatively selective long-acting agonist of beta₂-adrenergic receptors, although it does carry some degree of activity at beta₁ and beta₃ receptors. Beta₂ receptors are found predominantly in bronchial smooth muscle (with a relatively minor amount found in cardiac tissue) whereas beta₁ receptors are the predominant adrenergic receptors found in the heart - for this reason, selectivity for beta₂ receptors is desirable in the treatment of pulmonary diseases such as COPD and asthma. Formoterol has demonstrated an approximately 200-fold greater activity at beta₂ receptors over beta₁ receptors. On a molecular level, activation of beta receptors by agonists like formoterol stimulates intracellular adenylyl cyclase, an enzyme responsible for the conversion of ATP to cyclic AMP (cAMP). The increased levels of cAMP in bronchial smooth muscle tissue result in relaxation of these muscles and subsequent dilation of the airways, as well as inhibition of the release of hypersensitivity mediators (e.g. histamine, leukotrienes) from culprit cells, especially mast cells. Formoterol is a long-acting selective stimulator of the beta2-adrenergic receptors in bronchial smooth muscle. This stimulation causes relaxation of smooth muscle fibers and produces bronchodilation. Formoterol stimulates beta2-adrenergic receptors and apparently has little or no effect on beta1- or alpha-adrenergic receptors. The drug's beta-adrenergic effects appear to result from stimulation of the production of cyclic adeno-3'-5'-monophosphate (cAMP)by activation of adenyl cyclase. Cyclic AMP mediate numerous cellular responses, increased concentrations of cAMP are associated with relaxation of bronchial smooth muscle and suppression of some aspects of inflammation, such as inhibition of release proinflammatory mast cell mediators(eg histamine, leukotrienes).

Pharmacodynamics

Formoterol works locally in the lungs as a bronchodilator, relaxing smooth muscle and opening up the airways. It possesses both a rapid onset of action (approximately 2-3 minutes) and a long duration of action (up to 12 hours). The use of long-acting beta-agonists (LABAs), such as formoterol, without concomitant inhaled corticosteroids in asthmatic patients should be avoided, as LABA monotherapy has been associated with an increased risk of asthma-related death.

Mechanism of action

Glycopyrronium is a muscarinic antagonist with the highest affinity for M1 receptors, followed by M3, M2/M4, and M5. Muscarinic receptors M1 to M4 are found in the lung, although M3 is predominantly responsible for bronchoconstriction and airway secretions. Secretions from salivary and sweat glands, as well as gastric acid secretions, are also predominantly mediated by the M3 receptor. Salivary and gastric acid secretions are also partially mediated by the M1 receptor. Antagonism of these receptors decreases the volume of their respective secretions, and in the case of the gastrointestinal system, reduces the acidity of the stomach. In the cardiovascular system, muscarinic receptors M1 to M5 are all present, however the function of M5 has not been described in literature. Under normal circumstances, stimulation of the vagal nerve lowers the heart rate, potentially leading to intraoperative bradycardia. Studies in mice suggest that this stimulation is predominantly mediated by the M3 receptor, and mutant knockout mice are not susceptible to these effects.

Pharmacodynamics

Glycopyrronium is a quaternary ammonium compound that is one of the most commonly prescribed long acting muscarinic antagonists. Glycopyrronium slowly dissociated from muscarinic receptors, leading to a long duration of action. It has a wider therapeutic index than other anticholinergic medications, such as [tiotropium]. Patients should be counselled regarding the risk of worsening urinary retention, risk of overheating, and transient blurred vision.