landiolol 280 MG Injection

INDICATIONS AND USAGE RAPIBLYK is indicated for the short-term reduction of ventricular rate in adults with supraventricular tachycardia including atrial fibrillation and atrial flutter, and pediatric patients with supraventricular tachycardia. RAPIBLYK is a beta adrenergic blocker indicated for the short-term reduction of ventricular rate in: adults with supraventricular tachycardia including atrial fibrillation and atrial flutter ( 1 ), and pediatric patients with supraventricular tachycardia. ( 1 )

DOSAGE AND ADMINISTRATION Administer as an intravenous infusion in a monitored setting. ( 2.1 ) Titrate according to ventricular rate. ( 2.1 ) In adults with normal cardiac function, start at 9 mcg/kg/min; adjust dose in 10-minute intervals as needed in increments of 9 mcg/kg/min to a maximum of 36 mcg/kg/min. ( 2.1 ) In adults with If impaired cardiac function, start at 1 mcg/kg/min; adjust dose in 15-minute intervals as needed in increments of 1 mcg/kg/min to a maximum of 36 mcg/kg/min. ( 2.1 ) In pediatric patients, start at 9 mcg/kg/min; adjust dose in 10-minute intervals as needed in increments of 9 mcg/kg/min to a maximum of 36 mcg/kg/min. (2.1) 2.1 Recommended Dosage Administer RAPIBLYK as a continuous intravenous infusion in a monitored setting, titrating as needed for heart rate control. There are limited data beyond 24 hours of use. Adults Pediatric patients Normal cardiac function Impaired cardiac function Normal cardiac function* Starting dose 9 mcg/kg/min 1 mcg/kg/min 9 mcg kg/min Titration interval 10 min 15 min 10 min Titration step 9 mcg/kg/min 1 mcg/kg/min 9 mcg kg/min Maximum dose 36 mcg/kg/min 36 mcg/kg/min 36 mcg kg/min *There are no data to guide dosage recommendations in pediatric patients with impaired cardiac function. 2.2 Transitioning from RAPIBLYK Injection Therapy to Alternative Medications When transitioning to alternative medications consider the pharmacodynamics of the medication to which the patient is being transitioned and monitor clinical response. If switched to an oral beta-blocker, the dosage of RAPIBLYK can be reduced as follows: Ten minutes after administration of the oral beta-blocker, reduce the infusion rate of RAPIBLYK by 50%. If satisfactory control is maintained for at least one hour, discontinue RAPIBLYK. 2.3 Instructions for Preparation Use appropriate aseptic technique for reconstitution. Reconstitute each 280 mg vial of RAPIBLYK with 50 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Gently swirl to dissolve contents. Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be a clear, colorless solution. Use immediately. The reconstituted RAPIBLYK solution storage conditions are described in Table 2. Discard unused portion. Table 2: Reconstituted RAPIBLYK Solution Storage and Use Conditions Diluent used to Prepare Solution Reconstituted RAPIBLYK Solution Storage and Use Conditions 50 mL of 0.9% Sodium Chloride Injection, USP Use within 4 hours at room temperature (25°C, 77°F) 50 mL of 5% Dextrose Injection, USP Use within 48 hours at room temperature (25°C, 77°F) 2.4 Administration Following reconstitution, the product contains 280 mg landiolol/50 mL = 5.6 mg/mL. The infusion rate can be calculated as: Infusion rate (mL/hour) = target dose (mcg/kg/min) × body weight (kg) / 93

WARNINGS AND PRECAUTIONS Risk of hypotension, bradycardia, and cardiac failure: Monitor for signs and symptoms of cardiovascular adverse effects. Reduce or discontinue use ( 5.1 , 5.2 , 5.3 ) Risk of exacerbating reactive airway disease ( 5.5 ) Diabetes mellitus: May mask symptoms of hypoglycemia and alter glucose levels; monitor ( 5.6 ) Monitor for signs of myocardial ischemia when abruptly discontinuing in patients with coronary artery disease ( 5.10 ) 5.1 Hypotension Patients with hemodynamic compromise, hypovolemia, or on interacting medications are at increased risk of hypotension. Monitor blood pressure closely, especially if pretreatment blood pressure is low. Reduce or stop RAPIBLYK injection for hypotension then expect the blood pressure effect to wane within 30 minutes. 5.2 Bradycardia Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders are at increased risk of bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest. Monitor heart rate and rhythm in patients receiving RAPIBLYK injection. Reduce or stop RAPIBLYK injection for bradyarrhythmia. 5.3 Cardiac Failure Beta-blockers, like RAPIBLYK, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. At the first sign or symptom of impending cardiac failure, stop RAPIBLYK injection and start supportive therapy [see Overdosage ( 10 )] . 5.4 Reactive Airways Disease Patients with reactive airways disease should, in general, not receive beta-blockers. Because of its relative beta-1 selectivity and titratability, RAPIBLYK injection may be titrated to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta-2 stimulating agent may be administered with appropriate monitoring of ventricular rates. 5.5 Use in Patients with Diabetes Mellitus and Hypoglycemia Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus, patients who are fasting (i.e., surgery, not eating regularly, or are vomiting), or pediatric patients. Monitor for signs and symptoms of hypoglycemia in patients receiving RAPIBLYK. 5.6 Infusion Site Reactions Infusion site reactions such as pain, swelling and erythema have occurred with the use of RAPIBLYK injection. Avoid infusions into small veins or through a butterfly catheter. If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation. 5.7 Use in Patients with Prinzmetal’s Angina Beta-blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction. 5.8 Use in Patients with Pheochromocytoma If RAPIBLYK injection is used in the setting of pheochromocytoma, administer RAPIBLYK in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. Administration of beta-blockers without opposing alpha blockade in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta receptor-mediated vasodilation in skeletal muscle. 5.9 Use in Patients with Peripheral Circulatory Disorders RAPIBLYK injection may exacerbate peripheral circulatory disorders, such as Raynaud’s disease or syndrome, and peripheral occlusive vascular disease. 5.10 Abrupt Discontinuation of RAPIBLYK Injection Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta-blocker therapy. Observe patients for signs of myocardial ischemia when discontinuing RAPIBLYK injection. 5.11 Hyperkalemia Beta-blockers, including RAPIBLYK injection, can cause increases in serum potassium and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of beta-blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with RAPIBLYK injection. 5.12 Use in Patients with Metabolic Acidosis Beta-blockers have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may be associated with reduced cardiac contractility. 5.13 Use in Patients with Hyperthyroidism Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy. 5.14 Use in Patients at Risk of Severe Acute Hypersensitivity Reactions When using beta-blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions [see Drug Interactions ( 7 )] .

CONTRAINDICATIONS RAPIBLYK is contraindicated in patients with: Severe sinus bradycardia, sick sinus syndrome, heart block greater than first degree [see Warnings and Precautions ( 5.2 )] . Decompensated heart failure [see Warnings and Precautions ( 5.3 )] . Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest. Pulmonary hypertension: May precipitate cardiorespiratory decompensation. Hypersensitivity reactions, including anaphylaxis, to landiolol or any of the inactive ingredients 5.3 Severe sinus bradycardia ( 4 ) Sick sinus syndrome ( 4 ) Heart block greater than first degree ( 4 ) Decompensated heart failure ( 4 ) Cardiogenic shock ( 4 ) Pulmonary hypertension ( 4 ) Known hypersensitivity to landiolol ( 4 )

Mechanism of Action RAPIBLYK is a selective beta-1-adrenoreceptor antagonist that inhibits the positive chronotropic effects of the catecholamines, epinephrine and norepinephrine, on the heart, where beta-1-receptors are predominantly located. Landiolol does not exhibit any membrane-stabilizing activity or intrinsic sympathomimetic activity at the approved recommend dosage in vitro.