a, dizziness, fatigue, malaise, and insomnia.
Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associatedwith abuse of ProAir Digihaler.
Treatment consists of discontinuation of ProAir Digihaler together with appropriate symptomatic therapy.
The judicioususe of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can producebronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of ProAir Digihaler.
11 DESCRIPTION
The active ingredient of ProAir Digihaler inhalation powder is albuterol sulfate, a racemic salt of albuterol. Albuterolsulfate is a beta2-adrenergic agonist. It has the chemical name α1
-[(tert-butylamino) methyl]-4-hydroxy-m-xylene-α,α'-
diol sulfate (2:1) (salt), and the following chemical structure:The molecular weight of albuterol sulfate is 576.7, and the empirical formula is (C13H21NO3)2•H2SO4. Albuterol sulfateis a white to off-white crystalline powder. It is soluble in water and slightly soluble in ethanol. Albuterol sulfate is theofficial U.S. Adopted Name in the United States, and salbutamol sulfate is the recommended World Health Organizationinternational nonproprietary name.
ProAir Digihaler is inhalation-driven, multi-dose inhalation powder (dry powder inhaler) for oral inhalation only. Itcontains a formulation blend of albuterol sulfate with alpha-lactose monohydrate. Each actuation provides a metered doseof 2.6 mg of the formulation containing 117 mcg of albuterol sulfate (equivalent to 97 mcg of albuterol base) and lactosefrom the device reservoir. Under standardized in vitro test conditions with fixed flow rates ranging from 58 to 71 L/min,and with a total air volume of 2 L, ProAir Digihaler inhaler delivers 108 mcg of albuterol sulfate (equivalent to 90 mcg ofalbuterol base) with lactose from the mouthpiece. The actual amount of drug delivered to the lung will depend on patientfactors, such as inspiratory flow profile. In a study that investigated the peak inspiratory flow rate (PIFR) in asthma (n=27,ages 12 to 17 years old and n=50, ages 18 to 45 years old) and COPD (n=50, over 50 years old) patients, the mean PIFRachieved by subjects was >60 L/min (range = 31 to 110 L/min.), indicating that patients would be able to achieve therequired inspiratory flow to operate the MDPI device correctly. The inhaler is provided for 200 actuations (inhalations).
ProAir Digihaler contains a QR code on the electronic module which is built-in to the top of the inhaler and automaticallydetects, records and stores data on inhaler events, including peak inspiratory flow rate (L/min). ProAir Digihaler may pairwith and transmit data to the mobile App where inhaler events are categorized.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Albuterol sulfate is a beta2-adrenergic agonist. The pharmacologic effects of albuterol sulfate are attributable to activationof beta2-adrenergic receptors on airway smooth muscle. Activation of beta2-adrenergic receptors leads to the activation ofadenylcyclase and to an increase in the intracellular concentration of cyclic-3',5’-adenosine monophosphate (cyclic AMP).
This increase of cyclic AMP is associated with the activation of protein kinase A, which in turn inhibits thephosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle rela |
