potassium. Use Caution/Monitor. levalbuterol and salmeterol both decrease sedation. Use Caution/Monitor. levalbuterol and salmeterol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.salsalateMonitor Closely (1)salsalate increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.saquinavirMonitor Closely (1)levalbuterol, saquinavir. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Increased risk of hypokalemia, QT prolongation, and cardiac arrhythmias.scullcapMonitor Closely (1)scullcap increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.secobarbitalMonitor Closely (1)secobarbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.serdexmethylphenidate/dexmethylphenidateMonitor Closely (1)levalbuterol and serdexmethylphenidate/dexmethylphenidate both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.shepherd's purseMonitor Closely (1)shepherd's purse increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycolMonitor Closely (1)levalbuterol and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.solriamfetolMonitor Closely (1)levalbuterol and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.sotalolMonitor Closely (2)sotalol decreases effects of levalbuterol by pharmacodynamic antagonism. Use Caution/Monitor. sotalol increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.spironolactoneMonitor Closely (1)spironolactone increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.succinylcholineMonitor Closely (1)succinylcholine increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.sufentanilMonitor Closely (1)sufentanil increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.sulfasalazineMonitor Closely (1)sulfasalazine increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.sulindacMonitor Closely (1)sulindac increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.tapentadolMonitor Closely (1)tapentadol increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.temazepamMonitor Closely (1)temazepam increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.terbutalineMonitor Closely (3)levalbuterol and terbutaline both decrease serum potassium. Use Caution/Monitor. levalbuterol and terbutaline both decrease sedation. Use Caution/Monitor. levalbuterol and terbutaline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.thioridazineMonitor Closely (1)thioridazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thiothixeneMonitor Closely (1)thiothixene increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.timololMonitor Closely (2)timolol decreases effects of levalbuterol by pharmacodynamic antagonism. Use Caution/Monitor. timolol increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.tolfenamic acidMonitor Closely (1)tolfenamic acid increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.tolmetinMonitor Closely (1)tolmetin increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.tolvaptanMonitor Closely (1)tolvaptan increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.torsemideMonitor Closely (1)levalbuterol and torsemide both decrease serum potassium. Use Caution/Monitor.Minor (1)levalbuterol, torsemide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.tramadolMonitor Closely (1)tramadol increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.tranylcypromineSerious - Use Alternative (1)tranylcypromine increases effects of levalbuterol by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.trazodoneMonitor Closely (1)trazodone increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trazodone, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triamtereneMonitor Closely (1)triamterene increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.triazolamMonitor Closely (1)triazolam increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trimipramineMonitor Closely (1)trimipramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triprolidineMonitor Closely (1)triprolidine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.valbenazineMonitor Closely (1)valbenazine and levalbuterol both increase QTc interval. Use Caution/Monitor.xylometazolineMonitor Closely (2)levalbuterol and xylometazoline both decrease sedation. Use Caution/Monitor. levalbuterol and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.yohimbineMonitor Closely (2)levalbuterol and yohimbine both decrease sedation. Use Caution/Monitor. levalbuterol and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.ziconotideMonitor Closely (1)ziconotide increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. >10% Headache (8-12%) Viral infection (7-12%) Rhinitis (3-11%) 1-10% Pharyngitis (3-10%) Tremor (7%) Sinusitis (1-4%) Flu (1-4%) Dyspepsia (1-3%) Leg cramps (<3%) Generalized pain (2.8%) Nasal edema (2.8%) Nervousness (2.8%) Tachycardia (2.8%) Postmarketing Reports Dysphonia Gastroesophageal reflux disease, nausea Angioedema, anaphylaxis, rash, urticaria Chest pain, tachycardia, arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) Asthma, increased cough, dyspnea, dysphonia Metabolic acidosis Nervousness, tremor Contraindications Hypersensitivity to levalbuterol or racemic albuterol Cautions Risk of paradoxical bronchospasm; this should be distinguished from inadequate response; discontinue and treat with alternate therapy if it occurs Has higher affinity for beta1- and beta2-adrenergic receptors than racemic albuterol has Risk of hypersensitivity reactions Use caution in hyperthyroidism; may increase thyroid activity Use with caution in diabetes mellitus (beta2 agonists may increase glucose) Risk of hypokalemia (usually transient); use with caution in hypokalemia Use with caution in patients with history of seizure disorders; therapy may increase CNS activity/excitation Exceeding the recommended dose may result in serious adverse effects, including fatalities Cardiovascular effects Use with caution in cardiovascular disorder (eg, arrhythmias, hypertension, coronary insufficiency) May cause elevation in blood pressure and heart rate; may cause CNS stimulation or excitation May increase risk of arrhythmia and electrocardiogram changes, including ST segment depression, prolongation of the QTc interval, or flattening of the T wave Drug interaction overview Short-acting bronchodilators Avoid use If additional adrenergic drugs are to be administered by any route, use with caution to avoid deleterious additive cardiovascular effects Beta-blockers Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-adrenergic agonists, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. Under certain circumstances, cardioselective beta-blockers should be considered and may be used with caution Diuretics ECG changes or hypokalemia that may result from the administration of non-potassium-sparing diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded Digoxin Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose IV and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days Monoamine oxidase inhibitors or tricyclic antidepressants Use extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of levalbuterol on the vascular system may be potentiated Consider alternative therapy in patients taking MAO inhibitors or tricyclic antidepressants Pregnancy There are no adequate and well-controlled studies in pregnant women; there are clinical considerations with use in pregnant women Pregnancy exposure registry Monitors pregnancy outcomes in women exposed to asthma medication during pregnancy To enroll in MotherToBaby Pregnancy Studies’ Asthma & Pregnancy Study or for more information about the registry, call 1-877-311-8972 or visit www.mothertobaby.org/ongoing-study/asthma Clinical considerations In women with poorly or moderately controlled asthma, there is increased risk of preeclampsia in mother and prematurity, low birth weight, and small for gestational age in neonate Closely monitor and adjust medication as necessary to maintain optimal control Lactation There are no available data on presence of levalbuterol in human milk, effects on breastfed child, or effects on milk production Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Beta2-receptor agonist with some beta1 activity; relaxes bronchial smooth muscle Absorption Peak plasma concentration Single levalbuterol 1.25 mg solution: 1.1 ng/mL ([R]-albuterol) Cumulative levalbuterol 5 mg solution: 4.5 ng/mL ([R]-albuterol) Levalbuterol inhaler 90 mcg: 199 pg/mL Peak plasma time Single levalbuterol 1.25 mg solution: 0.2 hr ([R]-albuterol) Cumulative levalbuterol 5 mg solution: 0.2 hr ([R]-albuterol) AUC Single levalbuterol 1.25 mg: 3.3 ng⋅hr/mL ([R]-albuterol) Cumulative levalbuterol 5 mg: 17.4 ng⋅hr/mL ([R]-albuterol) Levalbuterol inhaler 90 mcg: 695 ng⋅hr/mL Metabolism Published literature suggests that the primary enzyme responsible for the metabolism of albuterol enantiomers in humans is SULT1A3 (sulfotransferase) Elimination Primary route of elimination of albuterol enantiomers is through renal excretion (80% to 100%) of either the parent compound or the primary metabolite Excretion: Feces (< 20%) Following IV administration of racemic albuterol, between 25% and 46% of the (R)-albuterol fraction of the dose was excreted as unchanged (R)-albuterol in the urine Half-time Single levalbuterol 1.25 mg: 3.3 hr ([R]-albuterol) Cumulative levalbuterol 5 mg: 4 hr Oral Inhalation Preparation Aerosol inhaler Priming Prime inhaler before using for the first time and when inhaler has not been used for more than 3 days by releasing 4 test sprays into the air, away from the face Cleaning Wash the actuator with warm water and air-dry thoroughly at least once a week; may cease to deliver levalbuterol tartrate if not properly cleaned and dried thoroughly Keep plastic actuator clean to prevent medication build-up and blockage If actuator becomes blocked with levalbuterol tartrate, wash actuator to remove the blockage The canister is fitted with a dose indicator, which indicates how many inhalations remain When nearing the end of the usable inhalations, the color behind the number in the dose indicator window changes to red Discard inhaler when dose indicator displays zero, corresponding to the use of 200 actuations Oral Inhalation Administration Oral inhalation only Aerosol inhaler Shake well before use Avoid spraying in the eyes Check inside the mouthpiece of the actuator for objects Shake the inhaler well for 5 seconds before use Breathe out through mouth and push out as much air from lungs as possible While breathing in deeply and slowly, press down on the center of the targeting rings until a spray of medicine has been released Close your mouth and hold your breath for 10 seconds if possible; then breathe out gently Wait about 1 min before next dose Nebulizer solution Administer by nebulization using with a standard jet nebulizer (with a face mask or mouthpiece) connected to an air compressor Drug compatibility (physical and chemical), efficacy, and safety of nebulizer solution when mixed with other drugs in a nebulizer have not been established Safety and efficacy of nebulizer solution have been established in clinical trials when administered using the PARI LC Jet and PARI LC Plus nebulizers, and the PARI Master® Dura-Neb® 2000 and Dura-Neb® 3000 compressors Storage Aerosol inhaler Store canister at 20-25ºC (68-77ºF) Protect from freezing temperatures and direct sunlight Do not use or store inhaler near heat or open flame; do not throw into a fire or an incinerator Temperatures >120ºF may cause the canister to burst Nebulizer solution Store in the protective foil pouch at 20-25ºC (68-77ºF) Protect from light and excessive heat Once foil pouch is opened, contents of the vial should be used immediately;