Salmeterol @ ( *** ) - Sympathomim- Bronchodilators- (FDC- List )- (Feb 1994)
Drug Interaction:
Bronchodilators- include
Albuterol, Biotolterol, Ephedrine,Ephinephrine, Ethylnorepinephrine, Isoetharine, Isoproterrenol, Metaproterenol, Pirbuterol, Salmeterol, Terbutaline
Refer- Ephedrine- Inhalation
Effects are antagonised by nonselective beta-blockers and less so by cardioselective beta-blockers. Additive cardio-vascular and metabolic effects with methylxanthines eg. theophylline and aminophylline (parentrally). Hypokalemia with steroids and diuretics. Potentiation of vascular effects with MAOI and tricyclic antidepressants.
Indication:
Bronchodilators- include
Albuterol, Biotolterol, Ephedrine,Ephinephrine, Ethylnorepinephrine, Isoetharine, Isoproterrenol, Metaproterenol, Pirbuterol, Salmeterol, Terbutaline
Refer- Ephedrine- Inhalation
Approved by FDA on February 4, 1994
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing (Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Salmetrol Xinofate Bronchodilator December 1993
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
1.Salmeterol as Xinefoate 25mcg /25mcg/25mcg+ 05-07-2001
Fluticasone Proionate BP 30mcg/125mcg/250mcg
per actuation inhaler
Bronchial asthma where use of bronchodilator and
an inhaled Corticosteriod are appropiate
2.Salmeterol Xinafoate eq.to Sameterol 25mcg + 09-11-2000
Fluticasone Propionate 125mcg/250mcg
per acuation Inhaler
For regular treatment of bronchial asthma where
the use of a bronchodilator and an Inhaled
Corticosteroid is appropiate
Patent Expiry Date of drugs (Ref - IDMA Publication)
Chemical Category Manufacturer/ US Patent
Ingredient- Marketer Expiration Date
Salmeterol Respiratry Glaxo Wellcome 12-02-2002
xinofoate
Adverse Reaction:
Albuterol-
CNS- CNS stimulation, malaise, emotional lability, fatigue, nightmates, aggresive behaviour,
lightheadedness, disturbed sleep, irritability,
Respiratory- bronchitis, nasal congestion, sputum increase, epistaxis, hoarseness
Miscellaneous- increased appetite, muscle carmps, pallor, conjuntivitis, anorexia, teeth discoloration, dilated pupils, epigastric apin, micturition difficulty, mauclespasm, voicechanges, urticaria, angioedema, rash, bronchospasm,prophyyngeal edema.
Bitolterol-
Lightheadedness, elevationsof AST, decrease in platelet and WBC counts and proteinuria,
clinical relevance of relationship unknown.
Ephedrine-
precordial pain, contact dermitis after topical appication.
Parentral- vesical sphnicter spasm may result in difficult and painful urination, urinary retention may develop in males with prostatism.Confusion, delirium, and hallucinations have been reported, excessive doses may cause asharp rise in blood pressure suficient to produce cerebral hemorrhage.
Epinephrine-
Anxiety, fear, pallor.
Parentral- cerbral haemorrhage caused by rapid rise in bloodpressure, particularly in elderly patients with cerebrovascular disease. Parentral use may induce or aggravate psychomotoragitation, disorientation,impairment of memory, assaultive behaviour, panic, hallucinations, suicidal or hormicidal tendencies.schizophrenic -type thought disorders or paraoid delusions, hemiplegia and subarchinoid and cerbral hemorrhage. Patients with Parkinsons disease may experience a temporary increase in rigidity and tremor.
Ethylnorepinephrine- elevated pulse rate.
Isoethane- anxiety
Isoproterenol-
Cardiovascular- Adams Stroke attacks, cardiac arrest, hypotension,precordial ache/distress. In a few patients presumbly, with organic disease of the AV node and its branches, isoproterenol has recipitated Adams Stroke seizures during normal sinus rhythm or transcient heart block.
Respiratory- bronchitis, sputum increase, bronchial edema, and inflammatoion, pulmonary edema.
Miscellaneous- swelling of the parotoid glands with prolonged use
Metaproterenol-
Respiratory- asthma exacerbation, hoarseness , nasal congestion,
Miscellaneous- rash, backache, fatigue, skin reaction.
Pirbuterol-
CNS- anxiety, confusion, depressin, fatigue, syncope
Dermatologic- alopecia, edema, pruritus, rash, bruising
GI- abdominal pain/cramps, glossitis, stomatitis
Miscellaneous- hypotension, numbness inextremities, weight gain
Salmeterol-
Respiratory- upper respiratory tract infection, nasopharyngitis, nasal cavity/ sinus disease, sinus headache, lower respiratory tract infection, allergic ehinitis, rhinitis, laryngitis, tracheitis/bronchitis
Miscellaneous- joint/back pain, muscle cramp/contracton,myalgia/myositis, muscular soreness, giddiness, influenza,viral gastroenteritis, urticaria, dental pain,malaise/fatigue, rash/skin eruption, dysmenorhea
Terbutaline-
ECG changes such as sinus pause, artrial premature beats, AV blcok,ventricular premature beats, ST-T wave depresion, Y-wave inversion, sinus bradycardia, and atrial escape beat with aberrant conduction, increased heart rate,muscle cramps, central stimulation, pain at injection site., elevations in liver enzymes and hypersentivity vasculitis
Contra-Indications:
Acute bronchiospasm, hypersens, thyrotoxicosis.
Special precautions:
Salmetrol is not a replacement for oral or inhaled corticosteroids.Patients with coronary
insufficiency arrhythmias, hypertension, seizure disorders and hyperthyroidism. Hypokalemia , pregnancy, lactation., children less than 2 years.
Tolerance- may occur with prolonged use of sympathomimetics agents, but temporary cessatin of the drug restores its original effectiveness.
Hypokalemia- decrease in serum potassium levels have occured, possibly through intracellular shunting which can produce adverse cardiovascular effects. The decraese is usually transcient not requiring supplemenation.
Parkinsons disease- ephinephrine may temporarily increase rigidity and tremor.
Parentral use- avoid intraneural or intravascular injection of ethylorephinephrine.
Administer epinehrine with great caution and incarefully circimscribed quantities in areas of the body served by end atreries or with otherwise limited blood supply (eg finger, toes, nose, ears, genitals) or if peripoheral vascular disease is present to avoid vaso-constriction induced tissue sloughing.
Combined therapy- concomitant use with other sympathomimitics agents is not recommened. as it may lead to deleterious cardiovascular effects.
Patients should be warned not to stop or reduce corticosteroid therapy without medical advice, even if they feel better when they are being treated with B2 agonists.
Sulfites- some productscontain sulfites that may cause allergic-type reactions including anaphylactic symptoms and life-threatening /less severe asthmatic episodes
Drug abuse and dependence- prolonged drug abuse of ephedrine can lead to symptoms of paranoid schizophtrenia. With all sympathomimetics aerosols, cardiac arrest and even death may be associated with abuse.
Warnings-
Special risk patients- administer with caution to patients with dibetes mellitus, hyperthyroidism, prostatic hypertrophy, (ephedrine) or history of seizures, elderly, psychoneurotic individuals, patients with long standing bronchial asthma, and emphysema who have developed gegenerative heart disease (epinephrine)
Diabetes- large dose of IV albuterol may aggravate preexisting mellitus and ketoacidosis. diabetes patients receiving any of these agents may require an increase in dosage of insulin or oral hypoglycemic agents.
Cardiovascular effects- use with caution in patients with cardiovascular disorders. including coronary insufficiency, ischemic heart disease, history of stroke, coronary heart disease, cardiac arrhthmias, CHF and hypertension.
Closely monitor patients receiving epinephrine.
Ephedrine may cause hypertension resulting in intracranial hemorhage.
Large doses of inhaled or oral salmetrol (12 to 20 times ) the recommended dose ) have been associated with clinically significant prolongation of QTc interval, which has the potential for producing ventricular arrhythmias.
Parodoxical bronchospasm- occasional patients have developed severe pardoxical airway resistence with repeated excessive use of inhalation preparations, the cause is unknown. Discontinue the drug immediately and institute alternative therapy, since patients may not respond to other therapy until the drug is withdrawn.
Excessive dose of inhalants- deaths have been reported , the exact cause is unknown, but cardiac arrest following an unexpected severe acute asthmatic crisis and subequent hypoxia is suspected.
Usual dose response- advice patients to contact a physician if they do not respond to their dose of a sympathomimetic amine.
CNS effects- sympathomimetics may produce CNS stimulation.
Long term use- prolonged use of ephedrine may produce a syndrome resembling an anxiety state, many patients develop nervousness, a sedative may be needed.
Acute symptoms- do not use salmeterol to relieve acute asthma symptoms. If the patients short acting inhaled B2 agonists becomes less efective (eg the patient needs more inhalations than usual ) medical evaluatin must be obtained immediately and increasing the use of salmetrol in this situation is inappropiate.
Use with short acting B2 agonists- when patient begin treatment with salmeterol advice those who have been taking short-acting inhaled B2 agonists on a regular daily basis to discontinue their regular daily-dosing regimen and clearly instruct them to use short-acting inhaled B2 agonists only for symptomatic relief if they develop asthma symptoms while taking salmeterol.
Morbidity/Mortality- it was previously suggested that an increased risk of death or near death from asthma may be associasted with the regular use of inhaled beta agonists. The report determined that te relationship between beta agonist use and death from asthma is of an extremely small magnitude , and may be restricted to the use of these agents via the nebulizer.
Overdosage or inadvertant IV injection -of conventional SC epinephrine doses may cause severe or fatal hypotension or cardiovascular hemorrhage resulting from sharp rise in blood pressure.
Respiratory depression- when compresed oxygen is used as the aerosol propellant, determine the percentage of oxygen by the patients individual requirement to avoid depression of respiratory drive.
Hypersentivity- reactions can occur after administration of bitolterol, albuterol, metaproterenol, terbutaline, ephedrine, salmeterol and possibly other bronchodilators.
Elderly- observe special caution whenusin inelderly patients who have concomittant cardiovascular disease that could be adversely aafected by this class of drug.
Pregnancy- use only when clearly needed and when potential benefits outweigh potential hazards to the fetus.
Lactation- decide whether to discontinue the drug or discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Children- safety and efficacy for use in children < 12 years of age have not been established.
Dosages/ Overdosage Etc:
Approved by FDA on February 4, 1994
Bronchial Constrictions and Bronchial Asthma
Dosage- Administer by orally inhaled route only
Overdosage- Symptoms Inhalation- Exaggeration of the effects of adverse reactions- seizures, hypkalemia,anginal pain, and hypotension may result.
Treatment
1. General supportive measures
2. Sedatives may be given for restlessness.
3. Judicious use of a cardioselective beta receptor blocker ie. metoprolol, atenol, is suggested, bearing in mind the danger of inducing an asthmatic attack.
4. Dialysis may not be adequate Systemic- Palpitations, tachcardia, bradycardia,extrasystoles, 1. Discontinuation of reduction in dosage will generally heart block, chest pain, hypokalemia, elevated blood control toxicity. pressure, fever, chills,cold prespiration, blaching of 2. Emesis, gastric lavage or charcoal may be useful the skin, nausea, vomting, mydraisis. Central actions following overdosage with oral agents. produce insomnia, anxiety and tremor. Delirium, 3. If pronounced, a beta adrenergic blocker (propranolol) convulsions, collapse and coma may occur. may be used, but consider the possibility of aggravation of airway obstruction. 4. Phenotolamine may be used to block strong alpha- adrenergic actions.
Missed dose-
1. If you using this medicine regularly, and you miss a dose, use it as soon as possible
2. Then use any remaining dose for that day at regularly spaced intervals 3. Do not double doses.
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Patient Information:
Bronchodilators- include
Albuterol, Biotolterol, Ephedrine,Ephinephrine, Ethylnorepinephrine, Isoetharine, Isoproterrenol, Metaproterenol, Pirbuterol, Salmeterol, Terbutaline
Refer- Ephedrine- Inhalation
1. Do not exceed the recommended dosage, excessive use may lead to adverse effect or loss of effectiveness.
2. Do not stop or adjust the dose.
3. Do not change brands without consulting the physician or the pharmacist.
4. If more than one inhaltion is necessary,wait for at least one full minute between inhalitions (administer the second inhalation at 3 to 5 minutes for isoproternol and epinephrine, 2 minutes for metoproternol ).
5. Notify physician of failure to respond to usual dosage or of dizziness or chest pain.
6. Isopreternol may cause the patients saliva to turn pinkish-red.
7. Allergies- tell your doctor if you have ever ha0d any unusual or allergic reaction to salmeterol. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.
8.Pregnancy - studies in rabbits have shown that that this medicine causes birth defects when given in doses many times higher than the usual inhalation dose.
9.Breast feeding- mothers who are using salmeterol and who wish to breast feed should discuss this with your doctor.
10.Children- although there is no specific information about the use of salmeterol innchildren younger than 12 years of age . this medicine is not expectedto cause different side effects or problems in children than it does in adults.
11.Elderly- this medicine is not expected to cause different side effects or problems in children than it does in adults.
12. Other medicines - Beta -blockers - these medicines may make your condition worse and prevent salmeterol from working properly
13. Other medical problems - Tell your doctor if you have any other medical problems especially - Heart or blood vessel disease - salmeterol may make this condition worse Overactive thyroid- chance of side efects may be increased in patients with this condition.
14. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.
13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Pharmacology- These agentsare used to produce bronchodilation.
Interaction with Food:
Refer symphomimetics -bronchodilators
Pregnancy and lactation:
Pregnancy-
Use only when clearly needed and when potential benefits outweigh potential hazards to the fetus.
Lactation-
Decide whether to discontinue the drug or discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Children-
Safety and efficacy for use in children < 12 years of age have not been established.
