Foradile
Foradile - General Information
Foradile is a long-acting beta2-agonist used in the management of asthma and/or chronic obstructive pulmonary disease (COPD). Inhaled formoterol works like other beta2-agonists, causing bronchodilatation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma.
Pharmacology of Foradile
Foradile is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1- receptors. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10%-50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2- agonists may have cardiac effects.
Foradile for patients
INFORMATION FOR THE PATIENT OR GUARDIAN
Information for the Patient or Guardian about PrFORADIL® inhalation powder capsules
Before using FORADIL, please read these instructions carefully. It contains information about FORADIL and itís use for the treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Additional information specific to the treatment of asthma is presented separately in the section "USE IN ASTHMA"
This information may add to the specific advice from your doctor and pharmacist. If, after reading this material, you have further questions, ask your doctor or pharmacist.
USE IN ASTHMA AND COPD
What is FORADIL and how does it work?
FORADIL is the brand name for a medication called formoterol fumarate. FORADIL is a new type of drug known as a long-acting bronchodilator. FORADIL is used for the treatment of breathing problems in asthma and also other airway diseases such as chronic bronchitis and emphysema, which may also be referred to as chronic obstructive pulmonary disease (COPD). It makes breathing easier by opening the small air passages in the lungs, and helps them remain opened and relaxed for about 12 hours.
What is in FORADIL?
FORADIL comes as gelatin capsules containing a dry powder. The dry powder is INHALED into the lungs using the inhaler provided. Each capsule contains 12 micrograms of formoterol fumarate. The capsules also contain lactose. FORADIL comes in blister packs containing 60 capsules.
What should I tell my doctor before taking FORADIL?
Tell your doctor :
- about all the health problems you have now or have had in the past - especially heart disease, diabetes, overactive thyroid; - about other medications you take including ones you can buy without a prescription especially medications used to treat depression or sad mood (monoamine oxidase inhibitors and tricyclic antidepressants), sympathomimetic agents, antihistamines, water pills (diuretics), · -blockers for high blood pressure and certain eye drops for the treatment of glaucoma, drugs containing quinidine, disopyramide, procainamide, phenothiazine or xanthine derivatives (theophylline or aminophylline); - if you are severely allergic to milk or have ever had any unusual or allergic reaction to FORADIL; - if you are pregnant, plan to become pregnant, or are breast-feeding.
Are there any side effects?
Like any medication, FORADIL may cause unwanted side effects in some people. The side effects that do occur are usually mild and go away a short time after starting FORADIL.
FORADIL may occasionally cause mild side effects such as tremor, fast and irregular heart beat, headache, dizziness or irritation of the mouth or throat. Rarely, more serious side effects, such as muscle cramps and pain, agitation, feeling nervous or tired, difficulties in sleeping, and, very rarely, bronchospasm (an attack of asthma) can occur. In isolated cases allergic reactions with severe drop of blood pressure and swelling of the face, eyelids, lips have been reported. You should check with your doctor if:
- the mild side effects persist
- the more serious ones occur
- you notice any other effects not listed here.
What if you are pregnant, plan to become pregnant or are breast-feeding?
You should tell your doctor if you are pregnant, plan to become pregnant or are breast-feeding. Avoid using FORADIL during pregnancy. Mothers who are breast-feeding should not use FORADIL.
How do I take FORADIL properly?
Your doctor will have explained that you are to take this drug twice daily regularly. Follow your doctorís directions carefully. They may differ from the information outlined here.
ASTHMA: The regular dose for adults, (including elderly patients), and children 6 years of age and older is 1 or 2 capsules twice a day, once in the morning and again in the evening.
COPD: The regular dose for adults, including elderly patients, is 1 or 2 capsules twice a day, once in the morning and again in the evening.
FORADIL should not be taken more than twice daily. If you have difficulty breathing, tightness, wheezing or coughing and need relief, use the short-acting bronchodilator medication your doctor has prescribed for that purpose.
It is important that you take FORADIL correctly. The exact instructions for using FORADIL capsules with the inhaler are outlined in detail in this insert. If you have any questions or problems, ask your doctor or pharmacist.
The capsules are not to be swallowed; like most asthma and COPD medications, FORADIL is inhaled. Exact directions for using the inhaler are in this insert. Once your doctor and or your pharmacist has shown you how to use FORADIL, the diagrams and directions in this insert will serve as a reminder of the technique. It is suggested that you display it wherever you usually administer FORADIL.
Where should I keep FORADIL?
Keep this medication AT ROOM TEMPERATURE, IN A DRY PLACE. Your car or the bathroom are not good choices.
The capsules should be removed from the blister pack just before use. Keep this medicine out of the reach of children because it may harm them. Do not use FORADIL after the expiry date marked on the carton.
USE IN ASTHMA:
Your doctor will have explained that this drug is to be taken twice daily regularly, in addition to the drug which reduces the inflammation of the lungs due to asthma (also known as a preventive medication). A short-acting bronchodilator (also known as a quick reliever) should also be used when you are aware of the shortness of breath, tightness, coughing and wheezing of your asthma.
Can my child take FORADIL for the treatment of breathing problems in asthma?
FORADIL inhalation powder is suitable for children aged 6 years or more. Children should only use FORADIL if they are able to handle the inhaler correctly,. They should only use the inhaler with the help of an adult.
The severity of asthma changes with age. Your child should therefore be periodically re-examined by a physician. It is important to make sure that your child also understands and properly follows the asthma therapies prescribed to him/her. These will include in addition to FORADIL, a drug which reduces the inflammation in the lung due to asthma (also known as a preventive medication) and a short-acting bronchodilator (also known as a quick reliever).
You must continue to regularly take the anti-inflammatory medications (e.g., inhaled steroids) your doctor has prescribed. Your anti-inflammatory medications and FORADIL are designed to act together to best treat your asthmatic condition. Even though you feel better, DO NOT STOP or reduce your doses of FORADIL or your anti-inflammatory medications.
Important Notes:
It is very important that you take FORADIL exactly as your doctor tells you. If the relief of your asthma is not as good as usual or does not last as long as usual, TELL YOUR DOCTOR RIGHT AWAY. A change from "usual" includes more wheezing, coughing, tightness or shortness of breath.
If you are using more of your short-acting bronchodilating medication or if you feel that it is less effective TELL YOUR DOCTOR RIGHT AWAY. Your doctor may adjust your treatment.
If your symptoms are waking you up at night TELL YOUR DOCTOR RIGHT AWAY. Your doctor may adjust your treatment.
If you have taken all your medication and an hour at rest has not relieved your symptoms, YOU MAY NEED EMERGENCY TREATMENT.
Nothing in this material should stop you from calling your doctor or pharmacist with any questions or concerns you may have about using FORADIL.
Information for the Patient/Guardian about Administering FORADIL® inhalation powder capsules
Before using FORADIL, please read these instructions carefully. They contain information about FORADIL which may add to the specific advice from your doctor and pharmacist. If, after reading this material, you have further questions, ask your doctor or pharmacist.
Your doctor will have explained that you are to take this drug regularly, as well as the drug which reduces the inflammation of the lungs due to your asthma or COPD. You will also probably have a short-acting bronchodilator to use when you are aware of the tightening, coughing and wheezing of your asthma.
How do I use the FORADIL inhaler and capsules?
1. Pull off cap
2. To open, hold base of the inhaler firmly and turn the mouthpiece in the direction of the arrow.
3. Remove the capsule from the blister pack. It is important to keep the capsule in the blister pack until you are ready to use it. Place the capsule in the capsule shaped compartment in the base of the inhaler.
4. Return the mouthpiece to the closed position.
5. Keeping the inhaler upright, firmly squeeze the two blue buttons fully ONLY ONCE. This will pierce the capsule. Release the buttons. Although the capsule is now pierced, the powder will not be released until you inhale it.
Please note that the capsule might splinter at this step and small fragments of gelatin might reach your mouth and throat. This gelatin is edible and is therefore not harmful. You can minimize the tendency of the capsule splintering by:
- piercing the capsule only once
- keeping the capsules stored in a dry place at room temperature
- keeping the capsule in the blister pack until you are ready to use it.
6. Breathe out fully.
7. Place the mouthpiece in your mouth and tilt your head slightly backward. Close your lips around the mouthpiece and breathe in steadily as deeply as you can. As you breathe in, you will inhale the medication into your lungs.
You should hear a whirring noise as you breathe in because inhalation causes the capsule to spin around in the inhaler. Please note if you do not hear the whirring noise, the capsule may be stuck in the capsule-shaped compartment. If this occurs, re-open the inhaler carefully and pry the capsule out. You cannot loosen the capsule by repeatedly pressing the buttons.
8. If you have heard the whirring noise, HOLD YOUR BREATH for as long as you comfortably can while removing the inhaler from your mouth. Then breathe out.
9. After use, open the inhaler. Check that the capsule is empty. If it is not close the inhaler and re-inhale following steps 6, 7 and 8. Remove the empty capsule. Close the mouthpiece. Replace the cap.
What if I miss a dose?
FORADIL should not be used more often than twice a day. If you forget to take a dose, take it as soon as possible. However, if it is almost time for your next dose, do not take the missed one, just go back to your regular dosing schedule. Never take a double dose.
What if you have taken an overdose?
If you accidentally used a lot more FORADIL than your doctor has prescribed, tell your doctor immediately or go to your nearest Poison Control Centre or hospital. If you develop nausea and/or vomiting, shakiness, headache, fast or irregular heartbeat, or sleepiness, your dose of FORADIL may be too high. Tell your doctor immediately.
How do I clean the inhaler?
To remove any powder residues, wipe the mouthpiece and capsule compartment with a DRY cloth or a small, soft, clean brush.
PHARMACOLOGY
The principal therapeutic effect of formoterol is to relieve and prevent bronchoconstriction by relaxing airway smooth muscle via specific interaction with ß2-adrenoreceptors. Numerous studies have confirmed that formoterol is highly potent and possesses high intrinsic activity and very high affinity at the ß2-adrenoreceptor.
HUMAN PHARMACOKINETICS
Absorption
As reported for other inhaled drugs, it is likely that about 90% of formoterol administered from an inhaler will be swallowed and then absorbed from the gastrointestinal tract. This means that the pharmacokinetic characteristics of the oral formulation largely apply also to the inhalation powder.
Oral doses of up to 300 m g formoterol fumarate are readily absorbed from the gastrointestinal tract. Peak plasma concentrations of the unchanged substance are reached 0.5 to 1 hour after administration. The absorption of an oral 80m g dose is 65% or more.
The pharmacokinetics of formoterol appear linear in the range of oral doses investigated, i.e. 20 to 300m g. Repeated oral administration of 40 to 160m g daily does not lead to significant accumulation of the drug.
Following inhalation of therapeutic doses, formoterol cannot be detected in the plasma using earlier analytical methods. However, analysis of urinary excretion rates suggests that inhaled formoterol is rapidly absorbed. The maximum excretion rate after administration of 12 to 96m g is reached within 1 to 2 hours of inhalation.
Cumulative urinary excretion of formoterol after administration of the inhalation powder (12 to 24m g) and two different aerosol formulations (12 to 96m g) showed the amount of formoterol available in the circulation to increase in proportion to the dose.
Distribution
The plasma protein binding of formoterol is 61 to 64% (34% to albumin). There is no saturation of binding sites in the concentration range reached with therapeutic doses.
Biotransformation
Formoterol is eliminated primarily by metabolism, direct fold glucuronidation being the major pathway of biotransformation. O-demethylation followed by glucuronidation is another pathway.
Elimination
Elimination of formoterol from the circulation seems to be polyphasic; the apparent half-life depends on the time interval considered. On the basis of plasma or blood concentrations up to 6, 8 or 12 hours after oral administration, an elimination half-life of about 2 to 3 hours was determined. From urinary excretion rates between 3 and 16 hours after inhalation, a half-life of about 5 hours was calculated.
The drug and its metabolites are completely eliminated from the body; about two-thirds of an oral dose appear in the urine and one-third in the feces. After inhalation about 6 to 9% of the dose on average is excreted unchanged in the urine. Renal clearance of formoterol is 150 mL/min.
PHARMACODYNAMICS AND CLINICAL TRIALS
ASTHMA: The efficacy of formoterol dry powder was evaluated in controlled cli nical studies using 12m g and 24m g b.i.d. in adults and children. Formoterol sh owed superior efficacy compared to salbutamol dry powder (400m g b.i.d.). Formoterol significantly improved lung function, reduced nocturnal and daytime asthma symptoms and reduced the need for additional short-acting relief bronchodilators.
Adults: sustained bronchodilator and bronchoprotective effect of formoterol inhaled twice daily for six months in moderate asthma
A 6-month randomized double-blind trial was conducted in 271 patients with moderate asthma to compare the effect on bronchial hyperresponsiveness (as measured by the methacholine challenge) of three treatments; twice daily
formoterol dry powder capsules (12m g b.i.d.), four times daily salbutamol dry powder capsules (200m g q.i.d.), or salbutamol MDI on-demand. All patients were taking inhaled corticosteroids (400 to 1200m g beclomethasone or equivalent). Mean baseline FEV1 was 2.73 L (80% of predicted). Mean age was 36. Geometric means of PC20 were comparable between treatment groups, at baseline (0.7 to 0.8 mg/mL), but increased during double-blind period to values between 4.1 and 5.1 in the formoterol group, 2.6 and 3.6 in the regular salbutamol group, and 1.3 and 1.7 in the on-demand salbutamol group. Formoterol achieved significantly better protection against methacholine-induced bronchial hyperreactivity at the beginning of treatment, at 3 months, at 6 months, and achieved significantly better control of the disease as measured by spirometry, peak flow, symptom scores, and rescue medication compared to on-demand salbutamol. In all treatment groups there was no rebound effect measured 2 days after cessation of treatment: (PC20 between 2.0 and 2.2 mg/mL). Formoterol treated patients experienced fewer exacerbation days compared to patients treated with on-demand salbutamol. A similar trend between Formoterol and regular salbutamol did not reach statistical significance.
Children: sustained bronchodilator and bronchoprotective effect of formoterol inhaled twice daily for twelve months in asthma
A 12-month, double-blind, placebo-controlled trial was conducted in 518 children (aged 5 - 12 years) with asthma to determine if 12m g or 24m g of formoterol dry powder capsules for inhalation delivered by a single-dose breath actuated inhaler (AerolizerTM) administered b.i.d. were superior to placebo with respect to lung function measurements over a 12-month period.
Patients had baseline FEV1 of 50 - 85% of normal and 15% increase in FEV 1 within 30 mins after inhaling 200m g salbutamol.
The area under the FEV1 curve measured over 12 hours was significantly greater than placebo for both formoterol 12m g b.i.d. and 24m g b.i.d after twelve weeks of treatment. No difference was seen between the doses. Similar results were seen after the first dose and after 12 months treatment, for FEF 25-75%, FVC for the 24m g dose and for morning and evening premedication PEFR. Symptom scores were significantly lower than placebo in the 12m g b.i.d.group but not in the 24m g b.i.d group at the three month efficacy time point, but were no longer significant at 12 months for either dose. Rescue medication was used significantly less at night-time for both formoterol doses, but was only significantly less for the lower dose during the night-time over the twelve month period.
Non-pulmonary Effects
Potentially serious ECG changes (such as increased QTc interval) and hypokalemia may result from ß2-agonist therapy. Although clinically not significant, a small increase in QTc interval and/or decrease in serum potassium has been reported at therapeutic doses of formoterol. The effects of single doses of formoterol at 12 to 96µg were studied in 22 adult asthmatics, all of whom were receiving inhaled cor ticosteroids and an inhaled short-acting ß2- agonist prior to entering the trial. The number of patients whose longest measured QTc in this trial was >440 msec was greater for placebo (3 patients) than it was for formoterol 12 µg (no patient), 24 µg (2 patients), and 48 µg (2 patients). Five patients treated with formoterol 96µg showed QTc prolongations >440 msec. Six patients had clinically meaningful ([K+] <3.2 mmol/L) hypokalemia at 96 µg, compared with one each at 12 and 48 µg.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE:
The efficacy of formoterol dry powder was evaluated in two placebo-controlled and comparator-controlled clinical studies.
A12-week randomized double-blind trial was conducted in 780 patients with COPD to assess the efficacy of inhaled formoterol fumarate dry powder capsules (12µg b.i.d. and 24µg b.i.d.) compared with placebo or ipratropium bromide MDI (40µg q.i.d.). Patients were male or female out-patients over or equal to 40 years old. Their FEV1 was expected to be less than 70% of the predicted value and at least 0.75 litres, with the FEV1 /VC being less than 88% for men and less than 89% for women. Fomoterol at both 24 µg and 12 µg b.i.d. produced statistically and clinically significant improvements in lung function, as measured by FEV1 area under the curve, when compared to placebo after 12 weeks of treatment. The estima ted improvement was 194 mL and 223 mL for 24 µg and 12 µg b.i.d., respectively.Formoterol was also statistically significant when compared to ipratropium bromide.
Both doses of formoterol, when compared to placebo, produced statistically and clinically significant improvement or this variable in both reversible and irreversible sub-groups of patients. (Reversibility is defined as 15% increase in forced expiratory volume in one second (FEV1) 30 minutes after inhalation of 200 µg salbutamol). For reversible patients the improvement seen was 244 mL and 241 mL for fo rmoterol 24 µg and 12 µg b.i.d., respectively. For irreversible patients the improvement seen was 137 mL and 213 mL for formoterol 24 µg and 12µg b.i.d., respectively.
Formoterol (24 µg and 12 µg b.i.d.) when compared to placebo showed statistically significant improvements in all the lung function measurements: FEV1 AUC on day 1 of treatment, FEV1 at each time-point over 12 hours, IVC, FVC AUC and morning pre-medication PEF. Statistically significant improvements were also seen in clinical measures: total score on the patient diary, number of puffs of rescue medication and the percentage of bad days. Quality of Life, as measured by the St. Georgeís Respiratory Questionaire (SGRQ), was both statistically and clinically signficantly improved in all areas (total, symptoms, activity and impacts) for formoterol (12 µg b.i.d.) when compared to placebo with statistically improvements for the 24 µg b.i.d. dose for the total, symptoms and activity scores.
The primary objective of the 12-month randomized between patient trial was to assess the efficacy of inhaled formoterol fumarate dry powder capsules (12 µg b.i.d. and 24 µg b.i.d.) compared with placebo with respect to FEV1 AUC (after 12 weeks). The secondary objective was to compare formoterol with placebo (with respect to FEV1 AUC at 6 and 12 months) and with oral SR theophylline after 3, 6 and 12 months (FEV1 pre-dose at all visits and post-dose after 3, 6 and 12 months). The two formoterol and the placebo groups were compared in a double-blind mode, while the theophylline group was open-label. A total of 854 male or female out-patients over or equal to 40 years old patients with COPD were randomized. Their FEV1 was expected to be less than 70% of the predicted value and at least 0.75 litres, with the FEV1/VC being less than 88% for men and less than 89% for women.
Formoterol at both 24 µg and 12 µg b.i.d. produced statistically and clinically significant improvements in lung funation, as measured by FEV1 area under the curve, when compared to placebo after 12 weeks of treatment. The estimated improvement was 208 mL and 200 mL for 24 µg and 12 µg b.i.d., respectively. Formoterol was also statistically significant when compared to theophylline. Both doses of formoterol, when compared to placebo, produced statistically and clinically significant improvement or this variable in both reversible and irreversible sub-groups of patients. (Reversibility is defined as 15% increase in forced expiratory volume in one second (FEV1) 30 minutes after inhalation of 200 µg salbutamol). For reversible patients the improvement seen was 271 mL and 331 mL for formoterol 24 µg and 12 µg b.i.d., respectively. For irreversible patients the improvement seen was 166 mL and 109 mL for formoterol 24 µg and 12µg b.i.d., respectively.
Formoterol (24 µg and 12 µg b.i.d.) when compared to placebo showed statistically significant improvements in the other lung function measurements: FEV1 AUC after 6 and 12 months of treatment, FEV1 at each time-point over 12 hours, FVC AUC and morning pre-medication PEF after 3, 6 and 12 months of treatment. Statistically significant improvements between both doses of formoterol when compared with placebo were also seen in the number of puffs of rescue medication taken. Quality of Life, as measured by the St. Georgeís Respiratory Questionaire (SGRQ), was statistically signficantly improved in all areas (total, symptoms, activity and impacts) for formoterol (12 µg b.i.d.) when compared to placebo after 6 months of treatment, and for both impact and total scores for 24 µg b.i.d. Clinically relevant improvement in the symptoms scores were seen in the formoterol 12 µg b.i.d. treatment group at both 6 and 12 months and in the impacts score for the formoterol 24 µg b.i.d. treatment group at 12 months.
In conclusion, FORADIL administered by the AerolizerTM at doses of 12 µg b.i.d. and 24 µ g b.i.d. provides rapid onset of bronchodilation in patients with stable COPD that was maintained over at least 12 hours.
Since the bronchodilator effect of Foradil is still significant 12 hours after inhalation, twice-daily maintenace therapy controls bronchoconstriction associated with chronic conditions both during the day and at night.
SELECTED BIBLIOGRAPHY
ARVIDSSON P, LARSSON S, LÖ FDAHL CG, et al. Formoterol, a new long-acting bronchodilator for inhalation. Eur Respir J 1989; 2: 325-330
DAUGBERG P, NIELSEN KG, SKOV M, BISGAARD H.
Duration of action of formoterol and salbutamol dry-powder inhalation in prevention of exercise-induced asthma in children.
Acta Paediatr 1996; 85 (6): 684-7.
DE BLIC J, KUUSELA AL.
Formoterol dry powder capsules for inhalation in children with asthma treated over one year. Eur Respir J 1995; 8 Suppl. 19: 14S.
DEVOY MAB, FULLER RW, and PALMER JBD.
Are there any detrimental effects of the use of inhaled long-acting ß2-agonists in the treatment of asthma?
Chest 1995; 107: 1116-1124
KESTEN S, CHAPMAN KR, BRODER I, et al.
A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.
Am Rev Respir Dis 1991; 144: 622-625
KESTEN S, CHAPMAN KR, BRODER I, et al.
Sustained improvement in asthma with long-term use of formoterol fumarate. Ann Allergy 1992; 69 (5): 415-420
LÖ FDAHL GC, and CHUNG KF.
Long-acting ß2-adrenoceptor agonists: a new perspective in the treatment of asthma.
Eur Respir J 1991; 4: 218-226
NATIONAL INSTITUTE OF HEALTH
Global Strategy for Asthma Management and Prevention NHLBI / WHO Workshop Report, March 1993 Publication #95-3659, January 1995
NIELSEN KG, SKOV M, KLUG B, IFVERSEN M, BISGARRD H.
Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer(r). Eur Respir J 1997;10: 2105-9.
PATALANO F, TITMANN U, BARAN D, BERDEL D, BONER A.
Foradil(r) (formoterol fumarate) 12 (Fg BID is an effective and safe treatment in childhood asthma.
Ann. Allergy Asthma Immunol 1998; 80: 129.
SEARS MR, TAYLOR DR, PRING CG, et al.
Regular inhaled ß-agonist in the treatment in bronchial asthma. Lancet 1990; 336: 1391-1396
SPITZER WO, SUISSA S, ERNST P, et al.
The use of ß-agonists and the risk of death from asthma. N Engl J Med 1992; 328 (8): 501-506
TATTERSFIELD AE.
Clinical pharmacology of long-acting ß-receptor agonists. Life Sci 1993; 52: 2161-2169
THE 1996 CANADIAN ASTHMA CONSENSUS CONFERENCE Canadian Respiratory Journal 1996; 3(2): 89-100.
WALLIN A, MELANDER B, ROSENHALL L, et al.
Formoterol, a new long-acting b 2-agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.
Thorax 1990; 45: 259-261
YATES DH, SUSSMAN HS, SHAW MJ, et al.
Regular formoterol treatment in mild asthma: effect on bronchial responsiveness during and after treatment.
Am J Resp Crit Care Med 1995; 152: 1170-1174
Foradile Interactions
Short-Acting ß2-agonists: Aerosol bronchodilators of the short-acting adrenergic stimulant type may be used for relief of breakthrough symptoms while using formoterol. However, increasing use of such preparations to control symptoms indicates deterioration of asthma control and the need to reassess the patientís therapy.
Concomitant administration of other sympathomimetic agents may potentiate the undesirable effects of FORADIL.
Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: FORADIL should be administered with extreme caution in patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants because the action of formoterol on the cardiovascular system may be potentiated by these agents.
Corticosteroids, Methylxanthines and Diuretics: Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalemic effect of ß2-agonists. Hypokalemia may increase susceptibility to cardiac arrhythmias in patients treated with digitalis.
ß-adrenergic Blockers: ß-adrenergic blockers may weaken or antagonise the effect of FORADIL. Therefore FORADIL should not be given together with ß-adrenergic blockers (including eye drops) unless there are compelling reasons for their use.
Other Drugs:Drugs such as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, and tricyclic antidepressants may be associated with QT-interval prolongation and an increased risk of ventricular arrhythmia.
INFORMATION TO BE PROVIDED TO THE PATIENT OR GUARDIAN
See illustrated Information For The Patient or Guardian section. It is important that patients understand how to use FORADIL® (formoterol fumarate) capsules with the supplied AerolizerTM inhalation device and how it should be used in relation to other asthma or COPD medications they are taking. Patients/Guardians should be given the following information:
i. The recommended dosage (one or two capsules twice daily, morning and evening) should not be exceeded.
ii. FORADIL is not meant to relieve acute asthma or COPD symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with a short-acting, inhaled ß2 -agonist such as salbutamol (the physician should provide the patient with such medication and instruct the patient in how it should be used).
iii. The physician should be notified immediately if any of the following situations occur, which may be a sign of seriously worsening asthma:
ï Decreased effectiveness of short-acting, inhaled ß2- agonists;
ï Need for more inhalations than usual of short-acting, inhaled ß2 -agonists.
iv. FORADIL should not be used as a substitute for oral or inhaled corticosteroids. The dosage of these medications should not be changed and they should not be stopped without consulting the physician, even if the patient feels better after initiating treatment with FORADIL.
v. Patients should be cautioned regarding potential adverse cardiovascular effects, such as palpitations or chest pain.
vi. In patients receiving FORADIL, other inhaled medications should be used only as directed by the physician.
vii. Guardians of children who have been prescribed FORADIL should be alerted to the general concern regarding asthma therapy compliance, especially neglect of anti-inflammatory therapy and overuse of short-acting ß2-agonists.
Foradile Contraindications
FORADIL® (formoterol fumarate) is contraindicated in patients with cardiac tachyarrhythmias. FORADIL contains lactose and is contraindicated in patients with an allergy to lactose, milk or in those who have ever had any unusual or allergic reaction to formoterol fumarate.
Additional information about Foradile
Foradile Indication: For use as long-term maintenance treatment of asthma in patients 6 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who are using optimal corticosteroid treatment and experiencing regular or frequent breakthrough symptoms requiring use of a short-acting bronchodilator.
Mechanism Of Action: The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Foradile also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown.
Drug Interactions: Acebutolol Antagonism
Atenolol Antagonism
Betaxolol Antagonism
Bevantolol Antagonism
Bisoprolol Antagonism
Carteolol Antagonism
Carvedilol Antagonism
Esmolol Antagonism
Labetalol Antagonism
Metoprolol Antagonism
Nadolol Antagonism
Oxprenolol Antagonism
Penbutolol Antagonism
Pindolol Antagonism
Practolol Antagonism
Propranolol Antagonism
Sotalol Antagonism
Timolol Antagonism
Food Interactions: Not Available
Generic Name: Formoterol
Synonyms: Formoterol fumarate; Formoterolum [Inn-Latin]
Drug Category: Bronchodilator Agents; Sympathomimetic; Adrenergic beta-Agonists
Drug Type: Small Molecule; Approved
Other Brand Names containing Formoterol: Foradil; Oxeze Turbuhaler; Oxeze Turbuhaler Foradil; Foradile; Oxis;
Absorption: Rapidly absorbed into plasma following administration by oral inhalation. It is likely that the majority of the inhaled formoterol delivered is swallowed and then absorbed from the gastrointestinal tract.
Toxicity (Overdose): An overdosage is likely to lead to effects that are typical of ß2-adrenergic stimulants: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.
Protein Binding: The binding of formoterol to human plasma proteins in vitro was 61%-64% at concentrations from 0.1 to 100 ng/mL. Binding to human serum albumin in vitro was 31%-38% over a range of 5 to 500 ng/mL. The concentrations of formoterol used to assess the plasma protein binding were higher than those achieved in plasma following inhalation of a single 120 µg dose.
Biotransformation: Metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. The most prominent pathway involves direct conjugation at the phenolic hydroxyl group. The second major pathway involves O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Four cytochrome P450 isozymes (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) are involved in the O-demethylation of formoterol.
Half Life: 10 hours
Dosage Forms of Foradile: Aerosol, metered Respiratory (inhalation)
Capsule Respiratory (inhalation)
Chemical IUPAC Name: N-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide
Chemical Formula: C19H24N2O4
Formoterol on Wikipedia: https://en.wikipedia.org/wiki/Formoterol
Organisms Affected: Humans and other mammals
