ONRIVA PLUS BEXICAP

Indications

• Chronic obstructive pulmonary disease (COPD)
• Maintenance treatment of obstructive airway disease

Dosage

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

Adults: 150 to 300 micrograms once daily by inhalation.

Mechanism of action

Indacaterol stimulates adrenergic beta-2 receptors located in the smooth muscle of the airways. This stimulation leads to muscle relaxation, increasing airway diameter in conditions like asthma and COPD. The drug exhibits a high affinity for lipid raft domains in the airway membrane, allowing it to dissociate slowly from the receptors and providing long-acting effects. Additionally, indacaterol increases intracellular cyclic AMP levels through the activation of adenyl cyclase, contributing to bronchodilation.

Pharmacodynamics

Indacaterol is classified as an ultra-long-acting beta-2 agonist, demonstrating a duration of action of approximately 24 hours, allowing for once-daily administration. Its pharmacological profile indicates that it has more than 24-fold greater activity at beta-2 receptors compared to beta-1 and 20-fold more than beta-3 receptors, which enhances its bronchodilatory effects. Cough is the most common adverse effect associated with indacaterol, occurring shortly after inhalation but generally not leading to discontinuation of therapy.

Pharmacokinetics

Indacaterol is well absorbed when inhaled, with a rapid onset of action occurring within 5 minutes. Its long duration of action is attributed to its slow dissociation from beta-2 receptors, which allows for sustained bronchodilation. The pharmacokinetic parameters such as half-life and clearance may vary based on individual patient factors, but the drug is designed to maintain therapeutic levels for the entire 24-hour dosing period.

Contra-indications

• Hypersensitivity to indacaterol or any of its excipients
• Severe acute asthma exacerbation

Adverse effects

• Cough
• Headache
• Pharyngitis
• Nausea
• Dizziness
• Tachycardia
• Palpitations
• Muscle cramps

Interactions

• Beta-blockers may reduce the effectiveness of indacaterol
• Concurrent use with other adrenergic drugs may enhance cardiovascular side effects
• Caution with monoamine oxidase inhibitors

Precautions

• Caution in patients with cardiovascular disorders
• Use with caution in patients with convulsive disorders
• Not recommended for use in patients with a history of seizures
• Monitor patients with hepatic impairment

Pregnancy

Manufacturer advises avoiding use during pregnancy due to lack of adequate human studies.

Breast-feeding

Manufacturer advises caution; indacaterol is present in milk in animal studies.

Storage

Store in a cool, dry place below 30 degrees Celsius. Keep out of reach of children.

Formulations

• {'name': 'Onbrez Breezhaler', 'strength': '150 micrograms', 'form': 'Inhalation powder capsules with device'}
• {'name': 'Onbrez Breezhaler', 'strength': '300 micrograms', 'form': 'Inhalation powder capsules with device'}

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

Dosage

Children: Specific dosing information is not applicable without a defined drug.

Adults: Specific dosing information is not applicable without a defined drug.

Indications

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Allergic Rhinitis
• Cystic Fibrosis
• Pulmonary Hypertension

Dosage

Children: Refer to specific inhaled medication guidelines for paediatric dosing.

Adults: Refer to specific inhaled medication guidelines for adult dosing.

Mechanism of action

Inhaled medications can have various mechanisms of action depending on the specific drug. For example, beta-2 adrenergic agonists stimulate beta-2 receptors on bronchial smooth muscle, leading to bronchodilation. Corticosteroids inhibit the expression of inflammatory mediators and reduce airway inflammation, while anticholinergics block acetylcholine from binding to its receptors, resulting in decreased bronchoconstriction.

Pharmacodynamics

The pharmacodynamics of inhaled medications involve their interaction with specific receptors or pathways in the lungs. Bronchodilators cause relaxation of the bronchial smooth muscle, leading to increased airflow. Corticosteroids effectively reduce inflammation and mucus production in the airways, thereby improving respiratory function and reducing exacerbations of asthma and COPD. The rapid delivery of these drugs to the site of action enhances their efficacy.

Pharmacokinetics

Inhaled medications have distinct pharmacokinetic properties. The onset of action can be very rapid, often within minutes, due to direct delivery to the lungs. The bioavailability depends on factors such as particle size, inhalation technique, and the type of inhaler used. Systemic absorption is generally lower than with oral medications, which minimizes systemic side effects. The duration of action varies based on the specific drug class; for example, short-acting beta agonists provide quick relief, while long-acting agents offer prolonged effects.

Pregnancy

Consult healthcare provider for risk assessment and guidance, as safety data may vary depending on the specific inhalation formulation.

Breast-feeding

Consult healthcare provider, as some inhalation medications may be excreted in breast milk and could affect the infant.

Storage

Store in a cool, dry place away from direct sunlight. Check specific product guidelines for temperature and humidity requirements.

Mechanism of action

Indacaterol works by stimulating adrenergic beta-2 receptors in the smooth muscle of the airways. This causes relaxation of the muscle, thereby increasing the diameter of the airways, which become constricted in asthma and COPD. It is also long acting due to its high affinity to the lipid raft domains in the airway membrane so it slowly dissociates from the receptors. Indacaterol also has a high intrinsic efficacy so it is also very rapid acting - onset of action occurs within 5 minutes. The pharmacological effects of beta2-adrenoceptor agonist drugs, including indacaterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’, 5’-adenosine monophosphate (cyclic monophosphate). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle. In vitro studies have shown that indacaterol has more than 24-fold greater agonist activity at beta2-receptors compared to beta1-receptors and 20-fold greater agonist activity compared to beta3-receptors. This selectivity profile is similar to formoterol. The clinical significance of these findings is unknown.

Pharmacodynamics

Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are β(2) -agonists and anticholinergics, either alone or in combination. Currently available β(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration. Indacaterol is considered an ultra-long-acting β(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Furthermore, this chiral compound it is given as the R-enantiomer and acts as a full agonist. Cough was the most commonly reported adverse effect with use of indacaterol. Compared to salmeterol, it has 35% more agonist activity. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators. [PMID: 22499359]