Meptin Inhalation Solution

Procaterol HCl.

Meptin Inhalation Solution also contains the following excipients: Anhydrous citric acid, sodium hydroxide (pH adjuster) and purified water. It has a pH of 3-4.
Procaterol hydrochloride is chemically 8-hydroxy-5-[(1RS,2SR)-1-hydroxy-2-isopropylamino-butyl]-quinolin-2(1H)-one monohydrochloride hemihydrate. Its molecular formula is C₁₆H₂₂N₂O₂HCl·½H₂O with a molecular weight of 335.83.
Procaterol hydrochloride occurs as white to pale yellow-white crystals or crystalline powder. It is soluble in water, formic acid and methanol, slightly soluble in ethanol (95), and practically insoluble in diethyl ether. The pH of its aqueous solution (1-100) is 4-5. Its aqueous solution (1-20) shows no optical rotation. It gradually changes in color when exposed to light. Melting point: Approximately 195°C (decomposition).

Pharmacology: Bronchodilative Action: The bronchodilative action of procaterol HCl was comparable to or more potent than that of isoproterenol, and more potent than that of salbutamol and orciprenaline, as determined by inhibition on increased pulmonary resistance in dogs, cats and guinea pigs.
The onset of the bronchodilative action is observed 1-5 min after inhalation in conscious guinea pigs and anesthesized dogs, indicating much faster onset of action than the tablet formulation.
Inhaled procaterol HCl dilates not only the central airway but also peripheral airways in pediatric asthma patients.
Duration of Bronchodilative Action: Procaterol HCl had a longer duration of brochodilative action than isoproterenol, trimetoquinol, orciprenaline, and salbutamol in dogs, cats and guinea pigs.
The potency with which procaterol HCl at 10 mcg by inhalation inhibits the increase in airway resistance due to histamine is equal to that of salbutamol at 200 mcg by inhalation in anesthesized dogs. However, procaterol is longer-acting than salbutamol.
Selectivity for β₂-Adrenergic Receptors (Organ Selectivity): The selectivity of procaterol HCl for β-adrenergic receptors in the respiratory system was greater than that for such receptors in the cardiovascular system, as compared to isoproterenol, trimetoquinol, orciprenaline, and salbutamol in dogs, cats and guinea pigs.
Antiallergic Action: Procaterol HCl exhibited a definite antiallergic action by inhibiting antigen-induced increase in airway resistance, the passive cutaneous anaphylaxis (PCA) reaction, and histamine release from sensitized lung tissues in guinea pigs and rats, as well as allergen-induced skin reactions, and increases in asthmatic responses to allergen inhalation in bronchial asthma patients, as compared to isoproterenol, trimetoquinol, orciprenaline and salbutamol.
Effects on the Respiratory Tract System: Procaterol HCl accelerated ciliary movement in airways of pigeons.
Effect on Exercised-Induced Asthmatic Attacks: Procaterol HCl suppressed treadmill exercise-induced asthmatic attacks in patients with bronchial asthma.
Pharmacokinetics: Plasma Concentrations: When Meptin Air was administered by inhalation to 6 healthy male subjects as 4 doses (40 mcg per subject as procaterol HCl*), a peak plasma concentration of 128 pg/mL was attained at 15 min post-dosing followed by a gradual decline.
Urinary Excretion: When Meptin Air was administered by inhalation as 4 doses (40 mcg per subject as procaterol HCl), 14.36% of the dose was excreted in the urine within 24 hrs post-dosing.
Cytochrome (CYP)-450 Isoenzyme for Hepatic Oxidized Metabolism of Drugs: The enzyme is mainly CYP3A4 (in vitro).
*The approved dose for a single administration of Meptin Air is 20 mcg.

Remission of various symptoms caused by respiratory obstructive disturbances due to moderate acute asthma.

Adults: Usual Dose: 30-50 mcg (0.3-0.5 mL) via a nebulizer with deep breathing.
Children: The amount should be reduced to 10-30 mcg (0.1-0.3 mL).
The dosage may be adjusted according to the patient's age and severity of symptoms.
Patients and parents should be cautioned about the possible risk of serious adverse reactions, including arrhythmia and cardiac arrest, that may result from excessive use of Meptin Inhalation Solution. The following information or other appropriate instruction should be given to patients receiving this drug or their families (see Overdosage).
Take Meptin Inhalation Solution exactly as directed, 0.3-0.5 mL per dose for adults and 0.1-0.3 mL per dose for children.
Administration: Take hold of the unit-dose ampoule at the top and, bend back and forth to break off the unit from the ampoule strip. To avoid accidental opening of the unit-dose ampoule, do not begin breaking it off the ampoule strip from the bottom.
Shake the unit-dose ampoule gently so that the drug solution settles downward away from the opening and then twist off the upper part of the ampoule.

Administrations of Meptin Inhalation Solution to patients in excess of the recommended doses can cause ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation and other symptoms), cardiac arrest, and other severe adverse reactions. Patients should be properly instructed on the dose and method of administration of Meptin Inhalation Solution (see Dosage & Administration and Precautions).
Overdosage with Meptin Inhalation Solution has been associated with tachycardia, tachycardiac arrhythmia, hypotension, nervousness, tremor, hypokalemia and hyperglycemia.
In the event any overdosage-related abnormalities are observed, Meptin Inhalation Solution should be discontinued and if required, gastric lavage should be performed to remove any unabsorbed drug. Emergency treatment and general maintenancy therapy should also be provided if needed.
In the event serious tachycardiac arrhythmia has developed, β-blockers eg, propranolol may be effective but administration of these drugs to asthma patients should be performed with care because β-blockers may increase airway resistance in these patients.

History of hypersensitivity to any of the components of Meptin Inhalation Solution.

Patients with hyperthyroidism (the disease may be exacerbated); hypertension (blood pressure may be further increased); heart disease (palpitation, arrhythmia, exacerbation of heart disease and other symptoms may occur); diabetes mellitus (the disease may be exacerbated).
Important Precautions: Continuous use of excessive amounts of Meptin Inhalation Solution may cause cardiac arrhythmia and cardiac arrest. Special care should be taken in order not to exceed the recommended dose; in case of an asthma episode.
If the desired therapeutic effect is not achieved at recommended levels, Meptin Inhalation Solution should be discontinued. Special care should be discontinued. When Meptin Inhalation Solution is administered to children, they should be properly instructed on the method of use of this drug and adequately observed for any effects.
Patients and their families should be instructed to consult a physician for emergency treatment, and reassessment of therapy when the recommended dosing schedule is not effective in relieving severe episodes of asthma.
Effects on Laboratory Tests: Meptin Inhalation Solution tends to inhibit skin reactions in allergen tests. The drug should be withdrawn 12 hrs prior to such tests.
Other Precautions: Tissue damage in cardiac muscle was noted in oral toxicity study of procaterol HCl using rats and dogs, similar to other β₂-adrenergic agonists.
Dietary administration of procaterol HCl for 104 weeks was reported to cause mesovarian leiomyoma in SD rats. However, this tumor is rat species-specific and tends to develop during long-term administration of β₂-adrenergic agonists.
Use in pregnancy & lactation: Meptin Inhalation Solution should be administered to pregnant or possibly pregnant women only if the expected therapeutic benefit is thought to outweigh any possible risk. The safety of Meptin Inhalation solution during pregnancy has not been established.
Nursing should be interrupted before starting treatment with Meptin Inhalation Solution. Rat studies showed that procaterol HCl is excreted in breast milk.
Use in children: The safety of Meptin Inhalation Solution in low birth weight infants, neonated and suckling infants has not been established.
Use in the elderly: Dosage adjustment or other appropriate measures should be considered when prescribing Meptin Inhalation Solution to elderly patients because they may be physiologically more sensitive to the drug than younger patients.

Meptin Inhalation Solution should be administered to pregnant or possibly pregnant women only if the expected therapeutic benefit is thought to outweigh any possible risk. The safety of Meptin Inhalation solution during pregnancy has not been established.
Nursing should be interrupted before starting treatment with Meptin Inhalation Solution. Rat studies showed that procaterol HCl is excreted in breast milk.

In clinical trials involving 6655 subjects, a total of 101 patients (1.52%) showed adverse reactions including abnormal laboratory values. The following summary of data includes adverse reactions reported after marketing without data on the incidence.
Clinically Significant Adverse Reactions (Incidence Unknown*): Shock, Anaphylactoid Reactions: Shock or anaphylactoid reactions may occur. Patients should therefore be closely monitored. If abnormal findings are observed, Meptin Inhalation Solution should be discontinued and appropriate measures taken.
Significant decreases in serum potassium levels have been reported in patients receiving procaterol hydrochloride. If xanthine derivatives, corticosteroids or diuretics are co-administered with Meptin Inhalation Solution to patients with severe asthma, extreme care is necessary to minimize the possibility of aggravating the decrease in serum potassium levels induced by β₂-adrenergic agonists. Serum potassium levels should be closely monitored for hypoxic patients, in view of the possible aggravation of cardiac arrhythmias secondary to a decrease in serum potassium levels.
Other Adverse Reactions: Cardiovascular: >5%; ≥0.1%: Palpitation and tachycardia. <0.1%: Abnormal electrocardiogram (ECG), increased blood pressure, facial flushing, etc.
Incidence Unknown*: Supraventricular extrasystole and tachycardia, ventricular extrasystole, etc, facial pallor and decreased blood pressure.
Psychoneurologic: 5%>; ≥0.1%: Tremor, headache and dull headache. <0.1%: Muscle cramp, numbness of hands, dizziness, cold sweat, sleepiness, etc. Incidence Unknown*: Nervousness.
Gastrointestinal: 5%>; ≥0.1%: Nausea, vomiting, etc.
Respiratory: <0.1%: Abnormal tracheal or pharyngolaryngeal sensation, nasal obstruction, dyspepsia, etc.
Hypersensitivity (if symptoms of hypersensitivity occur, Meptin Inhalation Solution should be discontinued immediately): <0.1%: Skin rash, pruritus, etc.
Other: <0.1%: Generalized malaise, weakness, impaired hearing, thrombocytopenia, etc.
Incidence Unknown*: Transient decrease in serum potassium (1-2 hr after dosing).
*The incidences of adverse reactions reported voluntarily after marketing or those reported in foreign countries are not known.

Meptin Inhalation Solution should be administered with care when co-administered with the following drugs: Catecholamines (eg, Epinephrine and Isoproterenol): Signs, Symptoms and Treatment: The combined use of Meptin Inhalation Solution with catecholamines may cause arrhythmias or in some cases, cardiac arrest.
Mechanism or Risk Factors: Epinephrine, isoproterenol and other catecholamines potentiate adrenoreceptor-stimulating action of Meptin Inhalation Solution, possibly resulting in the induction of arrhythmias.
Xanthine Derivatives (eg, Theophylline, Aminophylline and Diprophylline): Signs, Symptoms and Treatment: The combined use Meptin Inhalation Solution with xanthine derivatives may aggravate hypokalemia and cardiovascular adverse reactions (eg, tachycardia, arrhythmias) due to β-adrenergic stimulations. If any of these abnormalities are observed, appropriate measures eg, dose reduction or treatment discontinuation should be taken.
Mechanism and Risk Factors: Xanthine derivatives potentiate adrenoreceptor-stimulationg action of Meptin Inhalation Solution, possibly resulting in a decreased serum potassium and aggravating cardiovascular adverse reactions. The mechanism responsible for inductions of hypokalemia is not known.
Corticosteroids (eg, Betamethasone, Prednisolone and Hydrocortisone sodium succinate), and Diuretics (eg, Furosemide): Signs, Symptoms and Treatment: The combined use of Meptin Inhalation Solution with corticosteroids and diuretics may cause a decreased serum potassium levels, resulting in arrhythmias. If any of these abnormalities are observed, appropriate measures eg, dose reduction or treatment discontinuation should be taken.
Mechanism and Risk Factors: Corticosteroids and diuretics augment the excretion of potassium from renal tubules, possibly resulting in an excessive decresae in serum potassium levels.

Precautions Concerning Use: At Time of Dispensing: Patients or the guardians should be instructed to keep Meptin Inhalation Solution out of reach of children to avoid accidental ingestions.
Patients receiving Meptin Inhalation Solution should be advised to rinse the mouth after inhalation whenever feasible.
Do not open unit-dose ampoules until immediately before use, since Meptin Inhalation Solution does not contain preservatives.
Patients should be instructed to use the entire content of a unit-dose ampoule at one time and not to use for dose adjustment.
Avoid contact with eyes.
Use Meptin Inhalation Solution only with a nebulizer.
Do not reuse any drug solution remaining in the nebulizer.
Store Meptin Inhalation Solution protected from direct sunlight eg, in a medicine envelope.

Store below 25°C. Protect from light.

Antiasthmatic & COPD Preparations

R03AC16 - procaterol ; Belongs to the class of adrenergic inhalants, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.

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