Generic Name
Salmeterol
Brand Name
Salozix®
Dosage Form
Metered-dose inhaler
Strength
25 mcg/dose
Indication
Salmeterol is a long-acting beta-2 adrenergic receptor agonist used to treat asthma and COPD.
Salmeterol is indicated in the treatment of asthma with an inhaled corticosteroid, prevention of exercise induced bronchospasm, and the maintenance of airflow obstruction and prevention of exacerbations of chronic obstructive pulmonary disease.
Recommended Dose:
Adults and children 12 years or older; 25 mcg (2 inhalation) orally twice a day.
Missed Dose
Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.
Get your prescription refilled before you run out of medicine completely.
Route of Elimination
Salmeterol is 57.4% eliminated in the feces and 23% in the urine. Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.
Half- life
The half-life of salmeterol is 5.5h.
Clearance
The average clearance of salmeterol in a group of asthmatic patients was 392L/h. Further data regarding the clearance of salmeterol is not readily available.
Toxicity
Patients experiencing an overdose have presented with metabolic acidosis, hyperlactatemia, anxiety, palpitations, chest pain, sinus tachycardia, ST depression, hypokalemia, hypophosphatemia. Though patients may also present with seizures, angina, hypertension or hypotension, arrhythmia, headache, tremor, muscle cramps, dry mouth, nausea, dizziness, fatigue, malaise, insomnia, and hyperglycemia. Patients should be given symptomatic and supportive treatment which may include intravenous fluids, potassium supplementation, a cardioselective beta-blocker, and cardiac monitoring.
Data regarding the LD50 of salmeterol is not readily available.
Pregnancy and Lactation
-Available data from studies and case reports have not found a drug-associated increase in major birth defects, miscarriage, or adverse fetal or maternal outcomes.
-There are clinical considerations for asthma during pregnancy; poorly or moderately controlled asthma is associated with pre-eclampsia, prematurity, low birth weight, and small for gestational age infants.
-Severe asthma is associated with maternal mortality, fetal mortality, or both.
-Closely monitor pregnant patients and adjust medications to optimize asthma control.
-Beta-agonists, including this drug, may potentially interfere with uterine contractility due to a relaxant effect on uterine smooth muscle; use this drug during labor only if benefits clearly outweigh the risks.
Animal studies of oral doses approximately 50 times the maximum recommended human daily inhalation dose (MRHDID) caused teratogenicity characteristic of beta-adrenoreceptor stimulation, including precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of frontal cranial bones; no such effects occurred at oral doses 20 times the MRHDID. Doses 973 times the MRHDID was fetotoxic and decreased fertility in survivors. This drug crossed the placenta following oral administration to rodents. Published data in humans do not definitively establish absence of risk, but have not established an association with major birth defects, miscarriage, or adverse fetal or maternal outcomes. The background birth defect and miscarriage risk for the indicated population is not known. In the US general population, the estimated major birth defect risk is 2 to 4% and the miscarriage risk is 15 to 20%.
-There is no information regarding this drug on the presence in human milk, the effects on a breastfed infant, or effects on milk production.
-Drug concentrations in human plasma after inhalation are low; concentrations in breast milk are expected to be low.
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.
Animal studies of oral doses of 10,000 mg/kg/day salmeterol showed measurable levels in the milk.
Interactions with medicines
Interaction reports for salmeterol and the medicines listed below;
· Acetylsalicylic Acid (aspirin)
· Fluticasone / Salmeterol
· Ipratropium
· Amoxicillin / clavulanate
· Rosuvastatin
· Duloxetine
· Heparin Sodium (heparin)
· Escitalopram
· Atorvastatin
· Paracetamol (acetaminophen)
· Clopidogrel
· Montelukast
· Tiotropium
· Budesonide / Formoterol
· Albuterol
· Vitamin B12 (cyanocobalamin)
· Vitamin C (ascorbic acid)
· Vitamin D3 (cholecalciferol)
· Alprazolam
Precautions
This medicine should not be used if you are having a severe COPD attack, or if symptoms of COPD attack has already started. Your doctor may prescribe another medicine for you to use in case of an acute COPD attack. If the other medicine does not work as well, tell your doctor right away.
This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse. Paradoxical bronchospasm may be life-threatening. Check with your doctor right away if you or your child are having a cough, difficulty with breathing, shortness of breath, or wheezing after using this medicine.
If you or your child develop a skin rash, hives, or any allergic reaction (including anaphylaxis) to this medicine, check with your doctor right away.
Check with your doctor right away if you or your child have chest pain, a fast heartbeat, nervousness, shaking of the hands or feet, noisy breathing, a feeling of choking, or tightness or irritation of the throat while using this medicine.
Hypokalemia (low potassium in the blood) may occur while you are using this medicine. Check with your doctor right away if you or your child have more than one of the following symptoms: convulsions (seizures), decreased urine, dry mouth, increased thirst, irregular heartbeat, loss of appetite, mood changes, muscle pain or cramps, nausea or vomiting, numbness or tingling in the hands, feet, or lips, shortness of breath, or unusual tiredness or weakness.
This medicine may affect blood sugar levels. If you or your child are diabetic and notice a change in the results of your blood or urine sugar tests, check with your doctor.
Side effects
The most common adverse reactions of salmeterol (incidence ≥3%) in asthmatics include upper respiratory infection or inflammation, oral candidiasis, pharyngitis, bronchitis, dysphonia, headaches, cough, nausea, and vomiting. In patients with chronic obstructive pulmonary disease, the most common adverse effects include pneumonia, throat irritation, viral respiratory infections, oral candidiasis, dysphonia, headaches, and musculoskeletal pains.
Immediate hypersensitivity reactions may occur. Patients may present with urticaria, rash, angioedema, bronchospasm, headache, tremor, or anaphylaxis.
More severe adverse effects, associated with salmeterol overdose, are characterized by excessive beta-adrenergic stimulation to the heart. Although salmeterol is a highly selective beta-2 agonist, it still exhibits some beta-1 effects and thus cardiac effects.
These symptoms include angina, tachycardia, hypertension, hypotension, arrhythmia, palpitation, and fatigue. These undesirable pharmacologic effects are predominantly a result of reflex activation in response to peripheral vasodilation, hypoxemia, hypokalemia, and direct stimulation of cardiac beta-adrenoceptors.
Paradoxical bronchospasm, laryngeal spasm, and throat swelling can occur. In COPD patients, long-acting beta-agonists (LABA) have shown to increase the risk of cardiac failure.
Contraindications
Hypersensitivity is a contraindication for salmeterol. It is contraindicated in patients with a known hypersensitivity to any ingredient in the preparation, including lactose and milk protein.
Salmeterol is contraindicated in patients who have had adverse reactions to salmeterol in the past. It should not be used for status asthmaticus or other acute asthma episodes. Salmeterol should not be used in combination with other long-acting beta-agonists. Studies have shown an increased risk for death in asthma patients taking salmeterol vs. placebo; this risk was highest for African-American patients.
There is an FDA black box warning for asthma patients due to the increased incidence of asthma-related deaths with this medication. Salmeterol should not be used as a monotherapy in asthma patients. Clinicians should only use it as an adjunct medication in patients who have failed other asthma therapies such as low to medium dose inhaled steroids or who have severe asthma necessitating two maintenance therapies.
While not strictly contraindications, salmeterol use requires caution in patients with an existing cardiovascular disorder, convulsive disorder, hepatic impairment, diabetes mellitus, hyperthyroidism/thyrotoxicosis, or using other CYP3A inhibitors, as this may increase toxicity and prolong the patient’s QT interval. There is a (usually transient) risk of hypokalemia; therefore, salmeterol use merits caution in patients with hypokalemia.
Storage
Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.