Ventrax Metered-Dose Inhaler (MDI)

Glycopyrrolate, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA) indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

Limitation of Use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma.

Glycopyrrolate: Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methylcholine and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted more than 12 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site specific effect.

Formoterol Fumarate: Formoterol fumarate is a long-acting selective beta2-adrenergic agonist (beta2-agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1-receptors. The in vitro binding selectivity to beta2- over beta1 adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta2-selectivity ratio than formoterol. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2 receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects.

This inhaler should be administered as two inhalations taken twice daily in the morning and in the evening by the orally inhaled route only. Do not take more than two inhalations twice daily.

This inhaler contains 120 inhalations per canister. The canister has an attached dose indicator, which indicates how many inhalations remain. The dose indicator display will move after every tenth actuation. When nearing the end of the usable inhalations, the color behind the number in the dose indicator display window changes to red. This inhaler should be discarded when the dose indicator display window shows zero.

Priming this inhaler is essential to ensure appropriate drug content in each actuation. Prime this inhaler before using for the first time. To prime this inhaler, release 4 sprays into the air away from the face, shaking well before each spray. This inhaler must be re-primed when the inhaler has not been used for more than 7 days. To re-prime this inhaler, release 2 sprays into the air away from the face, shaking well before each spray.

• Other adrenergic drugs may potentiate effect: Use with caution
• Xanthine derivatives, steroids, diuretics or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with
• caution.
• Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non-potassium sparing diuretics may
• worsen with concomitant beta2-agonists.
• Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol fumarate on cardiovascular system.
• Beta-blockers: Use with caution and only when medically necessary.
• Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administrations of this inhaler with other anticholinergic-containing drugs.

• All LABAs are contraindicated in patients with asthma without use of a long-term asthma controller medication. This inhaler is not indicated for the treatment of asthma.
• Hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of this product.

Common side effects include:

• urinary tract infection
• cough

Pregnancy Category C. There are no adequate and well-controlled trials of this inhaler or its individual components, glycopyrrolate and formoterol fumarate, in pregnant women. Because animal reproduction studies are not always predictive of human response, this inhaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking this inhaler.

It is not known whether this inhaler is excreted in human milk. Because many drugs are excreted in human milk and because formoterol fumarate, one of the active ingredients in this inhaler, has been detected in the milk of lactating rats, caution should be exercised when this inhaler is administered to a nursing woman. Since there are no data from controlled trials on the use of this inhaler by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue this inhaler, taking into account the importance of this inhaler to the mother.

• Do not initiate in acutely deteriorating COPD or to treat acute symptoms.
• Do not use in combination with an additional medicine containing a LABA because of risk of overdose.
• If paradoxical bronchospasm occurs, discontinue this inhaler and institute alternative therapy.
• Use with caution in patients with cardiovascular disorders.
• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.
• Be alert to hypokalemia and hyperglycemia.
• Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a physician immediately if symptoms occur.
• Worsening urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a physician immediately if symptoms occur.

Combined bronchodilators

Pressurized canister, do not puncture, break or incinerate even when empty as canister may explode. Avoid exposure to direct sunlight or heat. Clean your inhaler regularly as per direction. Do not store above 30° C. Keep in a dry place. Protect from light and keep out of the reach of children. Keep away from eyes. Discard within three months after removing from the foil pouch. For best results, the canister should be at room temperature before use. Shake well before each use.