Breztri Aerosphere

Uses

Budesonide is a glucocorticoid used for the induction of remission in patients with active, mild to moderate ulcerative colitis.

Budesonide Nebuliser suspension is used for the maintenance treatment and as prophylactic therapy of asthma.

Budesonide Nasal Spray is used for-

• Prophylaxis and treatment of seasonal and perennial allergic rhinitis
• Prophylaxis and treatment of vasomotor rhinitis
• Symptomatic relief of nasal polyposis
• Prevention against nasal polyps after polypectomy

Budesonide Inhaler is used for the maintenance treatment of asthma as prophylactic therapy in adult and paediatric patients six years of age or older. It is also used for patients requiring oral corticosteroid therapy for asthma, many of those patients may be able to reduce or eliminate their requirement for oral corticosteroids over time. Budesonide inhaler is not used for the relief of acute bronchospasm.

In Anesthesia:

• As a pre-operative antimuscarinic agent to reduce salivary, tracheobronchial and pharyngeal sections and to reduce the acidity of the gastric contents.
• As a pre-operative or intra-operative antimuscarinic to attenuate or prevent intraoperative bradycardia with the use of suxamethonium or due to cardiac vagal reflexes.
• To protect against the peripheral muscarinic actions of anticholinesterases such as neostigmine and pyridostigmine, used to reverse residual neuromuscular blockade produced by non- depolarising muscle relaxants.

In Peptic Ulcer:

For use in adults as adjunctive therapy for the treatment of peptic ulcer when rapid anticholinergic effect is desired or when oral medication is not tolerated.

Hyperhidrosis, Sialorrhea, Cerebral palsy.

Breztri Aerosphere is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Allergies, Asthma, Chronic Obstructive Pulmonary Disease (COPD), Collagenous Colitis, Crohn's Disease (CD), Nasal Congestion, Oesophagitis, Eosinophilic, Polyps, Nasal, Pruritus, Rhinosinusitis, Ulcerative Colitis, Vasomotor Rhinitis, Corticosteroid-responsive dermatoses, Mild Crohn’s Disease, Moderate Crohn’s Disease

How Breztri Aerosphere works

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Dosage

Breztri Aerosphere dosage

Children 3 months to 12 years of age: 0.5 - 1 mg twice daily.Adults and elderly: 1 - 2 mg twice daily.

For IM/IV administration-

Pre-Anaesthetic Use:

• Adults:0.2 mg to 0.4 mg intravenously or intramuscularly before the induction of anesthesia. Alternatively, a dose of 0.004 to 0.005 mg/kg.
• Children (1 month to 12 years of age): 0.004 to 0.008 mg/kg up. Larger doses may result in profound and prolonged antisialogogue effect which may be unpleasant for the patient.

Intraoperative Use:

• Adults:A single dose of 0.2 to 0.4 mg (or 0.004 to 0.005 mg/kg) by intravenous injection should be used.
• Children: (1 month to 12 years of age) - A single dose of 0.004 to 0.008 mg/kg by intravenous injection should be used. This dose may be repeated if necessary.

Reversal of Neuromuscular Blockade:

• Adults:0.2 mg intravenously per 1 mg neostigmine or the equivalent dose of pyridostigmine.
• Children (1 month to 12 years of age) - 0.01 mg/kg intravenously with 0.05 mg/kg neostigmine or the equivalent dose of pyridostigmine. Supotaria may be administered simultaneously from the same syringe with the anticholinesterase; greater cardiovascular stability results from this method of administration.

For oral administration-

Initiate dosing at 0.02 mg/kg orally three times daily and titrate in increments of 0.02 mg/kg every 5-7 days based on therapeutic response and adverse reactions. The maximum recommended dosage is 0.1 mg/kg three times daily not to exceed 1.5-3 mg per dose based upon weight.

During the four-week titration period, dosing can be increased with the recommended dose titration schedule while ensuring that theanticholinergicadverse events are tolerable. Prior to each increase in dose, review the tolerability of the current dose level with the patient's caregiver.

Glycopyrrolate should be dosed at least one hour before or two hours after meals. The presence of high fat food reduces the oral bioavailability of Glycopyrrolate if taken shortly after a meal

Side Effects

●headache● nausea● upper abdominal pain● fatigue● acne● flatulence● joint pain● urinary tract infection● abdominal distension● constipation

Anticholinergic symptoms (mydriasis, hyperthermia, tachycardia, cardiac arrhythmia), Dry mouth, Dry skin, Anhidrosis, Flushing, Blurred vision, Cycloplegia, Photophobia, Palpitation, Xerophthalmia, Constipation, Urinary retention

Toxicity

Acute overdose of corticosteroids is rare, however prolonged high dosing of corticosteroids can lead to hypercorticism and adrenal axis suppression. In the case of overdose, reduce the dosage of corticosteroids temporarily.

A 200mg oral dose is lethal to female mice while a 400mg oral dose is lethal to male mice.

Precaution

● Since budesonide is a glucocorticoid, general warnings concerning glucocorticoids should be followed.

● Risk of impaired adrenal function when transferring from glucocorticoid treatment with higher systemiceffects to glucocorticoid treatment with lower systemic effects, such as budesonide. Taper patients slowly fromsystemic corticosteroids if transferring to budesonide.

● Potential worsening of infections (e.g., chickenpox, measles, existing tuberculosis, fungal, bacterial, viral, orparasitic infection). Use with caution in patients with these infections.

● Reduced liver function affects the elimination of glucocorticoid, and increases systemic availability of oralbudesonide.

Antimuscarinics should be used with caution (due to increased risk of side effects) in Down's syndrome, in children and in the elderly.

They should also be used with caution in gastro-esophageal reflux disease, diarrhea, ulcerative colitis, acute myocardial infarction, hypertension, conditions characterized by tachycardia (including hyperthyroidism, cardiac insufficiency, cardiac surgery) because of the increase in heart rate produced by their administration, coronary artery disease and cardiac arrhythmias, pyrexia (due to inhibition of sweating), pregnancy and breastfeeding.

Because of prolongation of renal elimination, repeated or large doses of glycopyrronium bromide should be avoided in patients with uremia.

Large doses of quaternary anticholinergic compounds have been shown to block end plate nicotinic receptors. This should be considered before using glycopyrrolate in patients with myasthenia gravis.

It is known that the administration of anticholinergic agents during inhalation anesthesia can result in ventricular arrhythmias.

Lactation: Excretion in milk unknown; use with caution

Interaction

Avoid Cytochrome P450 3A4 inhibitors (e.g. ketoconazole, grapefruit juice). It may cause increased systemic corticosteroid effects. Budesonide does not affect the plasma levels of oral contraceptives.

Decreases levodopa effects. Effects may be enhanced by using drugs with antimuscarinic properties or MAOIs concurrently. May antagonise the Gl effects of cisapride, metoclopramide and dompeidone.

Volume of Distribution

The volume of distribution of budesonide is 2.2-3.9L/kg.

Elimination Route

Extended release oral capsules are 9-21% bioavailable. A 9mg dose reaches a C_max of 1.50±0.79ng/mL with a T_max of 2-8h and an AUC of 7.33ng*hr/mL. A high fat meal increases the T_max by 2.3h but otherwise does not affect the pharmacokinetics of budesonide.

180-360µg metered inhaled doses of budesonide are 34% deposited in the lungs, 39% bioavailable, and reach a C_max of 0.6-1.6nmol/L with a T_max of 10 minutes.

A 1mg nebulized dose is 6% bioavailable, reaching a C_max of 2.6nmol/L with a T_max of 20 minutes.

A 9mg oral extended release tablet reaches a C_max of 1.35±0.96ng/mL with a T_max of 13.3±5.9h and an AUC of 16.43±10.52ng*hr/mL.

Budesonide rectal foam 2mg twice daily has an AUC of 4.31ng*hr/mL.

Half Life

Budesonide has a plasma elimination half life of 2-3.6h. The terminal elimination half life in asthmatic children 4-6 years old is 2.3h.

Clearance

Budesonide has a plasma clearance of 0.9-1.8L/min. The 22R form has a clearance of 1.4L/min while the 22S form has a clearance of 1.0L/min. The clearance in asthmatic children 4-6 years old is 0.5L/min.

Elimination Route

Approximately 60% of a budesonide dose is recovered in the urine as the major metabolites 6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone, and their conjugates. No unchanged budesonide is recovered in urine.

Pregnancy & Breastfeeding use

Pregnancy Category CThere are no adequate and well-controlled studies in pregnant women. Budesonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Nursing mothers

Budesonide is secreted in human milk. So, a decision should be made whether to discontinue nursing or budesonide taking into account the clinical importance of the drug to the mother.

Use in childrenSafety and effectiveness of budesonide in pediatric patients have not been established.Use in Hepatic Impaired patientsMonitor patients for signs and/or symptoms of hypercorticism.

Pregnancy Category B. Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Contraindication

Hypersensitivity to any of the ingredients of Budesonide.

Angle-closure glaucoma; myasthenia gravis (large doses of quaternary ammonium compounds have been shown to block end plate nicotinic receptors); paralytic ileus; pyloric stenosis; prostatic enlargement. Anticholinesterase-antimuscarinic combinations such as neostigmine plus glycopyrronium should be avoided in patients with a prolonged QT interval.

Acute Overdose

If glucocorticoids are used at excessive doses for prolonged periods, systemic glucocorticoid effects such as hypercorticism and adrenal suppression may occur.

Symptoms: Decreased motor activity, piloerection, generalised oedema. Management: Immediate gastric lavage or emesis followed by supportive and symptomatic treatment.

Storage Condition

Innovators Monograph

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