Contents

Salbutamol sulfate 100 mcg, beclometasone dipropionate 50 mcg

Indication

Salbutamol + Beclometasone dipropionate (Ibicar S) is intended for the treatment of bronchial asthma and COPD (chronic obstructive pulmonary disease), with asthmatic component.

Dosage / Direction For Use

Adult 2 puffs every 6 hr (qid) or every 4 hr (6 times daily). Max daily dose: 12 puffs/day. If patient take 2 puffs at once do not use again before 4 hr. Childn (>6 yr) 1-2 puffs every 12 hr (bid) or every 8 hr (tid) or every 6 hr (qid). Max daily dose: 8 puffs/day.

Overdosage

At high doses, some patients may experience transient side effects (slight increase in heart rate, mild muscle tremors) that disappear after the first day of treatment, reducing the dose if needed.If a patient uses a quantity greater than that indicated for this medication, tachycardia, muscle tremors, restlessness, nausea, etc. may occur.In this case, besides the monitoring of clinical signs and symptoms of the patient, the use of a cardioselective beta-blocker may be necessary.

Administration

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Contraindication

Salbutamol + Beclometasone dipropionate (Ibicar S) inhaler is contraindicated in patients sensitive to any of the active substances or other components of the formulation.Use of the product should be avoided in patients with pulmonary tuberculosis or viral infections.This drug is contraindicated for children less than 6 years of age.

Special Precaution

Should be used only during the initial period of treatment & not recommended for continuous use in excess of 10 days. Prolonged use may lead to sensitization phenomena. Do not exceed recommended dose in case of persistent bronchospasm. Adrenal suppression, including growth retardation in childn & adolescents, decrease in bone mineral density, cataract & glaucoma may occur after treatment w/ inhaled corticosteroids in high doses for long periods. Trauma, surgery, infection & rapid dose reduction may result in adrenal crisis. Gradually reduce dose & monitor adrenal function in patients receiving high doses of steroids. Patients sensitive to sympathomimetic effects. Patients w/ coronary heart disease, arrhythmia, HTN, glaucoma, hyperthyroidism, pheochromocytoma, diabetes & prostatic hypertrophy. Pregnancy & lactation.

Adverse Reactions

There were no reported serious side effects related to the use of Salbutamol + Beclometasone dipropionate (Ibicar S) at the recommended dose, only a few patients complained of hoarseness or dysphonia.Candidiasis in the mouth or throat may occasionally occur. The incidence increases with doses greater than 400 mcg per day of product. This can be reduced or prevented by rinsing the mouth with water after each dose. This infection should be treated with topical antifungal medication and it is not necessary to interrupt the treatment.At high doses, some patients may experience transient side effects (slight increase in heart rate, mild muscle tremors), which disappear after the first day of treatment, reducing the dose if needed.Systemic side effects are extremely unlikely. However, their occurrence is related to extended use. Special care should be taken when using the drug for prolonged periods; the patient should be monitored to establish any systemic side effects (osteoporosis, peptic ulcer, signs of secondary adrenal insufficiency).At high doses, used for long periods can occur adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.Very rarely cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles) and myocardial ischemia has been reported.Very common reaction (> 1/10): Candidiasis in the mouth and throat.Common reaction (> 1/100 and <1/10): paradoxical bronchospasm.Unusual reaction (> 1/1,000 and <1/100): slight increase in heart rate, mild muscle tremors.Rare reaction (> 1/10,000 and <1,000): adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.Very rare reaction (1/10,000): systemic side effects (osteoporosis, peptic ulcer, signs of secondary adrenal insufficiency) and arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles), myocardial ischemia.

Drug Interaction

There is a theoretical potential for interaction in particularly sensitive patients using disulfiram or metronidazole because Salbutamol + Beclometasone dipropionate (Ibicar S) inhaler contains ethanol and its interaction with disulfiram can result in redness and with metronidazole redness, vomiting and tachycardia can occur.Salbutamol + Beclometasone dipropionate (Ibicar S) inhaler will interact with beta blockers (eg propranolol).Patients should be advised that the drug contains a small percentage of alcohol. In normal doses, there is no risk to patients.There are no known interactions with alcohol and nicotine to date. There were no changes to date in laboratory tests, possibly because it is a drug of local action with little systemic absorption.

Storage

Store at temperatures not exceeding 30°C. Do not freeze.

Description

Salbutamol is a direct-acting sympathomimetic agent which demonstrates relatively selective action on beta-2 adrenergic receptors. Beclometasone dipropionate is a synthetic glucocorticoid with a potent anti-inflammatory activity and weak mineralocorticoid activity. This combination of salbutamol and Beclometasone dipropionate is specially provided for those patients who require regular doses of both drugs for treatment of their obstructive airways disease.Each actuation delivers: Salbutamol Sulfate, BP equivalent to Salbutamol 100 mcg, Beclometasone Dipropionate Anhydrous 50 mcg.Excipients: Ethanol BP 3.5 % w/w (5.23 % v/v), Oleic Acid USP NF, Propellant 1,1,1,2-Tetrafluoroethane (HFA 134a).

Action

Pharmacology: Pharmacodynamics: Salbutamol + Beclometasone dipropionate (Ibicar S) is a combination of a bronchodilator, salbutamol, with a topical corticosteroid, beclomethasone dipropionate. Salbutamol is characterized by a rapid and safe anti-spasmodic bronchial action that determines an immediate improvement of respiratory function. The action of salbutamol occurs effectively in the bronchial muscles, without causing undesirable cardiocirculatory effect.Beclomethasone dipropionate controls the bronchial hyper-activity, reducing edema and hypersecretion, progressively inhibiting the onset of bronchospasm. Therefore, the two active principles complement and potentiate.The activity of beclomethasone dipropionate is predominantly within the lungs without causing systemic effects such as inhibition of the adrenal functions. In order to obtain successful treatment, it is important that patients carefully follow the instruction of use and learn to inhale the medicine correctly.Clinical Study: In a Phase III, randomized, open label, non-inferiority, comparative, multicentric, parallel group study of 10 days of treatment period Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation was compared with HFA propelled pMDI Salbutamol 100 mcg + Beclometasone 50 mcg (ClenilCompositum HFA spray) in patients with stable persistent asthma. Out of a total of 280 subjects, 140 subjects (mean age of 39.22 years) were randomized to Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation and 140 subjects (mean age of 38.85 years) were randomized to ClenilCompositum HFA spray group. All subjects were Asian with 60% male and 40% female.The results of the study showed that for the primary efficacy endpoint Forced expiratory volume in one second (FEV1) absolute value was comparable between Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation and ClenilCompositum HFA spray in patients with stable persistent asthma.The lower limit of the 95% confidence interval for the difference in FEV1 between groups was greater than the non-inferiority margin of -15% (on negative scale) of adjusted mean FEV1 of ClenilCompositum HFA spray in per protocol (PP) and intent to treat (ITT) population.Adverse events were reported for 5.0% (7/140) patients in Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation group and 2.1% (3/140) patients in the ClenilCompositum HFA spray group.All the adverse events were mild in severity in both treatment groups, there were no severe or moderate AEs reported in the study.Most of the AEs reported in this study were assessed by the investigator as not related to study drug. Adverse events considered to be related to study medication were reported for 1.4% (2/140) [wheezing and eosinophilia] of patients in Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation group. Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation was permanently withdrawn in subjects who experienced an adverse event of wheezing.There were no clinically significant changes observed from baseline to end of treatment in clinical laboratory evaluations, vital signs, ECG and physical examinations.There were no serious adverse events, deaths or unexpected safety findings or unexpected AEs reported during the study.The study concluded that Salbutamol and Beclometasone pressurized inhalation CFC free 100+50 mcg/actuation was safe, well tolerated and non-inferior in efficacy compared to ClenilCompositum HFA spray.Pharmacokinetics: After inhalation of salbutamol (0.04 to 0.10 mg), the peak plasma appears around 3 to 5 hours. About 83% of the inhaled dose is excreted in urine, 70% in the form of salbutamol and 30% as its metabolite salbutamol-o-phenyl-glucuronide. Kinetic studies showed that after an inhalation of a high dose of beclomethasone, only 20 to 25% of the drug is absorbed. One part of the dose is swallowed and excreted in the feces and the amount absorbed into the circulation is metabolized by the liver to alcohol and beclomethasone monopropionate and subsequently excreted as inactive metabolites in the bile and urine.Salbutamol + Beclometasone dipropionate (Ibicar S) due to the presence of active salbutamol, has rapid onset of action, within 3 to 5 minutes, which lasts on average 4 hours. In turn, the effects related to beclomethasone dipropionate are manifested in a longer term (1-2 weeks) after initiation of treatment, with significant action on the inflammatory process and preventing the occurrence of bronchoconstriction.Toxicology: Preclinical safety data: Acute Toxicity: LD50 (rats, by intratracheal): the highest possible dose (6.2 mg/kg of BDP + 12.4 mg/kg of S).The association does not present toxicity; LD50 (rat, by IV): 51.3 mg/kg of BDP + 102.7 mg/kg of S; LD50 (rat, oral): 1407 mg/kg of BDP + 2814 mg/kg of S.Chronic Toxicity: The administration of the association by inhalation in rats (n = 26) and dogs (n = 26) was well tolerated up to doses far above the expected in therapy.The administration of the aerosol for 14 days in dogs did not show any sign of local intolerance.Fetal toxicity and study of the effects on fertility: Studies in rats and rabbits have shown that the combination of drug Salbutamol and Beclometasone Pressurized Inhalation (100+50 micrograms/actuation) CFC FREE inhaler causes no adverse effect on breeding activity.Mutagenesis: The product is not mutagenic.Preclinical data on the propellant HFA-134a reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, reproductive toxicity and carcinogenic potential.