Brezu

Procaterol hydrochloride.

One mL contains 5 mcg of procaterol hydrochloride.
pH: 3.5 to 4.5.
Chemical name: 8-hydroxy-5-{(1RS,2SR)-1-hyrdoxy-2-[(1-methylethyl)amino]butyl}-quinolin-2-(1H)-one monohydrochloride hemihydrate.
Molecular formula: C₁₆H₂₂N₂O₃·HCl·½H₂O.
Molecular weight: 335.83.
Procaterol hydrochloride occurs as white to pale white yellowish 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 4.0-5.0. Its aqueous solution (1 → 20) shows no optical rotation. It gradually changes in color when exposed to light.
Melting point: Approx. 195°C (decomposition).
Excipients/Inactive Ingredients: Ethyl Paraben (Ethyl parahydroxybenzoate), butyl paraben (butyl parahydroxybenzoate), sodium benzoate, orange essence, sucrose, Alcohol (ethyl alcohol), anhydrous citric acid, sodium citrate, and purified water.

Pharmacology: Mechanism of Action: Procaterol hydrochloride selectively stimulates β2-adrenergic receptor of bronchial smooth muscle and develops bronchodilative action.
Bronchodilative Action: The bronchodilative action of procaterol hydrochloride was comparable to or more potent than that of isoprenaline and more potent than that of salbutamol sulfate, and orciprenaline sulfate as determined by inhibition of increased pulmonary resistance, in dogs, cats, and guinea pigs.
Duration of Bronchodilative Action: Procaterol hydrochloride had a longer duration of bronchodilative action than isoprenaline, trimetoquinol, orciprenaline sulfate, or salbutamol sulfate in dogs, cats, and guinea pigs.
Selectivity for β₂-Adrenergic Receptors (Organ Selectivity): The selectivity of procaterol hydrochloride for β₂-adrenergic receptors in the respiratory system was greater than that for such receptors in the cardiovascular system, as compared to isoprenaline, trimetoquinol, orciprenaline sulfate and salbutamol sulfate in dogs, cats, and guinea pigs.
Antiallergic Action: Procaterol hydrochloride exhibited definite anti-allergic action by inhibiting antigen-induced increases in airway resistance, the 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 isoprenaline, trimetoquinol, orciprenaline sulfate, and salbutamol sulfate. The drug also inhibited allergen-induced delayed-type and immediate-type bronchial responses.
Effects on Respiratory Tract System: Procaterol hydrochloride accelerated ciliary activity in the airway of pigeons.
Effect on Exercise-Induced Asthmatic Attacks: Procaterol hydrochloride suppressed treadmill exercise-induced asthmatic attacks in children with bronchial asthma.
Effect on Airway Hypersensitivity: Procaterol hydrochloride inhibited airway hypersensitivity induced by the inoculation of influenza virus C in dogs.
Effect on Vascular Permeability Increase: Procaterol hydrochloride inhibited vascular permeability increase and edema formation in dorsal subcutaneous air pouches induced by various inflammatory chemical agents in rats. Its potency was similar to that of isoprenaline. Procaterol hydrochloride also inhibited pulmonary edema induced by histamine inhalation in guinea pigs, with greater potency than salbutamol sulfate.
Effect on Cough: Procaterol hydrochloride inhibited substance P-induced cough in normal subjects with upper respiratory tract infection.
Clinical Studies: Procaterol Hydrochloride Syrup was studied in children. The clinical efficacy of the drug by single administration in those with bronchial asthma was 82.9% (34/41), the efficacy by repeated administration in those with bronchial asthma or asthma-like bronchitis was 50.7% (116/229), and the efficacy by repeated administration in those with acute bronchitis was 75.9% (104/137).
Pharmacokinetics: Plasma Concentrations: When Procaterol Hydrochloride Syrup was administered orally to 44 healthy male subjects at a single dose of 100 mcg/subject^Note as procaterol hydrochloride, in a fasting condition, the following plasma concentration curves and pharmacokinetic parameters were obtained. (See Figure and Table 1.)

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Urinary Excretion: When Procaterol Hydrochloride Syrup was administered orally as single doses of 50 and 100 mcg/subject^Note as procaterol hydrochloride, 9.93% and 11.65% of the dose were excreted into the urine within 24 hrs post-dosing, respectively.
Cytochrome P-450 Isozyme for Hepatic Oxidized Metabolism of Drugs: The enzyme is mainly CYP3A4 (in vitro).
^Note: The approved dose for a single administration of Procaterol Hydrochloride for adults is 50 mcg.

Relief of dyspnea and other symptoms caused by respiratory obstructive disturbance in the following disease: bronchial asthma, chronic bronchitis, and pulmonary emphysema. For the treatment of acute bronchitis.

The usual adult dosage is 50 mcg of procaterol hydrochloride [10 mL of Procaterol HCl (Brezu) Syrup 5 mcg/ml] once daily (at bed time) or twice daily (in the morning and at bed time) by the oral route.
The dose for children 6 years of age or older is 25 mcg of procaterol hydrochloride (5 mL of Procaterol hydrochloride) (Brezu) Syrup once daily (at bed time) or twice daily (in the morning and at bed time) by oral route.
The dose for children younger than 6 years of age 1.25 mcg of procaterol hydrochloride [0.25 mL of Procaterol hydrochloride (Brezu) Syrup] per kg body weight twice daily (in the morning and at bed time) or three times daily (in the morning, in the early afternoon and at bed time) by the oral route.
The dosage may be adjusted according to the patient's age and severity of symptoms. (See Table 2.)

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Overdosage with Procaterol Hydrochloride Syrup has been associated with tachycardia, tachycardiac arrhythmia, hypotension, nervousness, tremor, hypokalemia, and hyperglycemia and lactic acidosis. In the event any overdosage-related abnormalities are observed, Procaterol Hydrochloride (Brezu) Syrup should be discontinued and, if required, gastric lavage should be performed to remove any unabsorbed drug. Emergency treatment and general maintenance therapy should also be provided, if needed. In the event serious tachycardiac arrhythmia has developed, β-blockers such as propranolol hydrochloride 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.

Careful Administration [Procaterol Hydrochloride (Brezu) Syrup should be administered with care in the following patients]: Patients with hyperthyroidism, where the disease may be exacerbated.
Patients with hypertension, where blood pressure may further increase.
Patients with heart disease (Palpitation, arrhythmia, exacerbation of heart disease and other symptoms may occur).
Patients with diabetes mellitus, where the disease may be exacerbated.
Patients during pregnancy or suspected of being pregnant (See Use in Pregnancy & Lactation).
Important Precautions: The mainstay of long-term management of bronchial asthma is anti-inflammatory agents such as inhaled corticosteroids.
Procaterol Hydrochloride (Brezu) Syrup should therefore be used only as additional therapy for patients whose symptoms are not adequately controlled by inhaled corticosteroids or other asthma medications, or whose disease severity clearly warrants initiation of treatment with Procaterol Hydrochloride (Brezu) Syrup. As Procaterol Hydrochloride (Brezu) Syrup is not a substitute for inhaled corticosteroids and other anti-inflammatory agents, the patient or their guardian or other legally authorized person should be instructed not to reduce the dosage of inhaled corticosteroids or to stop use of inhaled corticosteroids and switch to monotherapy with Procaterol Hydrochloride (Brezu) Syrup unless specifically instructed to do so by their physician, even if they have felt symptomatic improvement with the use of Procaterol Hydrochloride (Brezu) Syrup.
During the long-term management of bronchial asthma, chronic bronchitis and Pulmonary emphysema with Procaterol Hydrochloride (Brezu) Syrup, the patient may develop acute asthma episodes. The patient or their guardian or other legally authorized person should therefore be instructed to use adequate drugs other than Procaterol Hydrochloride (Brezu) Syrup, such as short-acting inhaled β₂ stimulants, if acute asthma episodes occur during treatment with Procaterol Hydrochloride (Brezu) Syrup. In addition, if the use of such drugs becomes more frequent or sufficient therapeutic effect is not observed with the initial dose of the drugs, the patient's asthma may not be adequately controlled. The patient or their guardian or other legally authorized person should be instructed to consult a physician as soon as possible and receive adequate medication in such cases. In addition, as such conditions may be life-threatening, anti-inflammatory therapy should be consolidated by adequate measures, such as increasing the dosage of inhaled corticosteroids.
If the desired therapeutic effect of Procaterol Hydrochloride (Brezu) Syrup cannot be achieved at the recommended dose, the drug should be discontinued.
Continuous administration of excessive amounts of this drug may cause cardiac arrhythmia and cardiac arrest. Special care should therefore be taken not to exceed the recommended dosage of this drug.
Effects on Laboratory Tests: This drug tends to inhibit skin reactions in allergen tests. The drug should be withdrawn 12 hours prior to such tests.
Other Precautions: Tissue damage in cardiac muscle was noted at 30 and 10 mg/kg/day or higher in the subacute and chronic toxicity studies, respectively, using rats. The damage was also observed in dog studies.
However, the damage has been reported with other β₂-adrenergic agonists in both rats and dogs.
Dietary administration of procaterol hydrochloride for 104 weeks was reported to cause mesovarian leiomyoma in SD rats. The tumor, however, is rat-specific and tends to develop during long-term use of β₂ adrenergic agonists.
Use in Children: The safety of this drug in low birth weight infants and neonates has not been established. (There is no clinical experience in low-birth weight infants and neonates.)
Use in the Elderly: Dosage adjustment or other appropriate measures should be considered when prescribing Procaterol Hydrochloride (Brezu) Syrup to elderly patients, because these patients may be physiologically more sensitive to the drug than younger patients.

This drug 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 this drug during pregnancy has not been established.)
Nursing should be interrupted before starting treatment with Procaterol Hydrochloride (Brezu) Syrup (Rat studies showed that procaterol is excreted in breast milk).

Japanese Data: In clinical trials involving 22,757 subjects, a total of 644 patients (2.83%) showed adverse reactions including abnormal laboratory values. The following summary of data includes adverse reactions reported after marketing without incidence.
Clinically significant adverse reactions (incidence unknown*): Shock, Anaphylactoid Reaction: Shock or anaphylactoid reaction may occur. Patients should therefore be closely monitored. If abnormal findings are observed, the drug should be discontinued and appropriate measures should be 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 Brezu in 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 in hypoxic patients, in view of the possible aggravation of cardiac arrhythmias secondary to a decrease in serum potassium levels.
Other Adverse Reactions: See Table 3.

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For coadministration [Procaterol Hydrochloride (Brezu) Syrup should be administered with care when coadministered with the following drugs]: See Table 4.

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At time of dispensing: Patients should be instructed to keep the drug out of the reach of children to avoid accidental ingestion.

Store at temperatures not exceeding 25°C. Procaterol hydrochloride (Brezu) Syrup should be protected from light.

Antiasthmatic & COPD Preparations

R03CC08 - procaterol ; Belongs to the class of adrenergics for systemic use, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.

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