Landiolol Hydrochloride (Monograph)

Brand name: Rapiblyk
Drug class: beta-Adrenergic Blocking Agents

Introduction

Landiolol is a beta-1 adrenergic receptor antagonist.

Uses for Landiolol Hydrochloride

Landiolol Hydrochloride has the following uses:

Landiolol is indicated for the short-term reduction of ventricular rate in adults with supraventricular tachycardia including atrial fibrillation and atrial flutter.

Landiolol Hydrochloride Dosage and Administration

General

Landiolol hydrochloride is available in the following dosage form(s) and strength(s):

For injection: 280 mg of landiolol (equivalent to 300 mg of landiolol HCl) as a lyophilized powder in a single-dose vial for reconstitution.

Dosage

Adults

Dosage and Administration

Reconstitute lyophilized powder prior to administration.
Administer as a continuous IV infusion in a monitored setting.
Titrate according to ventricular rate. There are limited data beyond 24 hours of use.
In patients 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.
In patients with 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.

Cautions for Landiolol Hydrochloride

Contraindications

Severe sinus bradycardia, sick sinus syndrome, heart block greater than first degree.
Decompensated heart failure.
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.

Warnings/Precautions

Warnings

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 landiolol infusion for hypotension then expect the blood pressure effect to wane within 30 minutes.

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 landiolol. Reduce or stop the landiolol infusion for bradyarrhythmia.

Cardiac Failure

Beta-blockers, like landiolol, 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 landiolol infusion and start supportive therapy.

Reactive Airways Disease

Patients with reactive airways disease should, in general, not receive beta-blockers. Because of its relative beta¬1 selectivity and titratability, landiolol 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.

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 children. Monitor for signs and symptoms of hypoglycemia in patients receiving landiolol.

Infusion Site Reactions

Infusion site reactions such as pain, swelling and erythema have occurred with the use of landiolol. 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.

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.

Use in Patients with Pheochromocytoma

If landiolol is used in the setting of pheochromocytoma, administer the drug 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.

Use in Patients with Peripheral Circulatory Disorders

Landiolol may exacerbate peripheral circulatory disorders, such as Raynaud’s disease or syndrome, and peripheral occlusive vascular disease.

Abrupt Discontinuation of Landiolol 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 landiolol.

Hyperkalemia

Beta-blockers, including landiolol, can cause increases in serum potassium and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. IV administration of beta-blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with landiolol.

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.

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.

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.

Specific Populations

Pregnancy

The available published data on landiolol use in pregnant women are insufficient to inform a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Landiolol exposure was limited to a single injection at the time of Cesarean delivery in a small clinical trial. Neonatal bradycardia, hypoglycemia, and respiratory depression have been observed with use of beta-blockers in pregnancy near the time of delivery.

Administration of landiolol to pregnant rats showed distribution of landiolol to the placenta and the fetus. In animal reproduction studies, no embryo-fetal toxicity was observed in rats or rabbits during the period of organogenesis at landiolol exposure in rats approximately 2.7 times human exposure at the maximum recommended human dose (MRHD). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Landiolol crosses the placenta in rats. Neonates born to mothers who are receiving landiolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. Monitor neonates exposed to landiolol during pregnancy and labor for hypotension, hypoglycemia, bradycardia, and respiratory depression and manage accordingly.

Lactation

There are no data on the presence of landiolol and its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. However, other drugs in this class are detected in human milk.

Landiolol was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk, but the concentration of landiolol in animal milk does not necessarily predict the concentration of drug in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for landiolol and any potential adverse effects on the breast fed infant from the drug or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of landiolol in pediatric patients have not been established.

Geriatric Use

Clinical studies of landiolol did not include sufficient numbers of subjects 65 years of age and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting greater frequency of decreased renal or cardiac function and of concomitant disease or other drug therapy.

Hepatic Impairment

More conservative dose titration is recommended in patients with mild hepatic impairment (Child-Pugh A). The effect of moderate or severe hepatic impairment (Child-Pugh B or C) on landiolol pharmacokinetics is unknown. Avoid use of landiolol in patients with moderate or severe hepatic impairment (Child-Pugh B or C).

Common Adverse Effects

The most common adverse reaction (9.9%) is hypotension.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Negative Inotropes and Chronotropes: Avoid concomitant use.
Sympathomimetics, Positive Inotropes and Vasoconstrictors: Avoid use.
Catecholamine Depleting Drugs: Monitor blood pressure and heart rate.

Actions

Mechanism of Action

Landiolol 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.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.