Long-acting beta-agonist formoterol (Perforomist, Foradil) relaxes the smooth muscles in the airways. It is used to treat individuals with chronic obstructive lung disease and asthma on a long-term maintenance basis.

Formoterol (Perforomist, Foradil) Uses:

• US labeling:

  • Asthma:
    • Treatment of nocturnal asthma symptoms in patients with reversible obstructive pulmonary disease (only as simultaneous therapy with an inhaled corticosteroid) (Foradil Aerolizer).
  • Chronic obstructive pulmonary disease (COPD):
    • Patients with COPD receiving maintenance therapy for bronchoconstriction (Foradil Aerolizer, Perforomist).
  • Exercise-induced bronchospasm:
    • When used on an as-needed basis, monotherapy may be explored for patients without persistent asthma for the prevention of exercise-induced bronchospasm (Foradil Aerolizer).

• Canadian labeling:

  • Asthma:
    • Treatment of nocturnal asthma symptoms in patients with reversible obstructive pulmonary disease (only as simultaneous therapy with an inhaled corticosteroid) (Foradil, Oxeze Turbuhaler).
  • COPD:
    • Maintenance treatment of COPD (Foradil).
  • Exercise-induced bronchospasm:
    • When used on an as-needed basis, monotherapy may be explored for patients without persistent asthma for the prevention of exercise-induced bronchospasm (Oxeze Turbuhaler).

Read: GINA Asthma Guidelines 2020 including GINA asthma severity assessment guidelines and GINA Asthma evaluation and diagnosis guidelines.

Formoterol (Perforomist, Foradil) Dose in Adults

Note: In the US, Foradil Aerolizer is no longer available.

Formoterol (Perforomist, Foradil) Dosage in the treatment of Asthma: Inhalation:

Note:.Long-acting beta-agonists (LABAs) should not be used alone for the treatment of asthma; rather, they should be used in conjunction with inhaled corticosteroids.

• US labeling:

  • Foradil Aerolizer: Dry powder inhaler:
    • 12 mcg every twelve hours (maximum: 24 mcg in a day)

• Canadian labeling:

  • Foradil: Dry powder inhaler:
    • 12 mcg every twelve hours; in serious situations, 24 mcg every twelve hours (maximum: 48 mcg daily)
  • Oxeze Turbuhaler:
    • Dry powder inhaler:
      • 6 or 12 micrograms every twelve hours (maximum: 48 mcg daily)

Formoterol (Perforomist, Foradil) Dosage in the treatment of COPD: Inhalation:

• US labeling:

  • Foradil Aerolizer: Dry powder inhaler:
    • Every 12 hours, 12 mcg (maximum dose: 24 mcg per day)
  • Perforomist: Nebulization solution:
    • 20 mcg two times each day (maximum dose: 40 mcg per day)

• Canadian labeling:

  • Foradil: Dry powder inhaler:
    • 12 or 24 micrograms twice a day (maximum dose: 48 mcg per day)

Formoterol (Perforomist, Foradil) Dosage in the treatment of Exercise-induced bronchospasm: Inhalation:

Note:

• If you are currently taking the medication to treat your asthma, you shouldn't need to take any more of it to treat exercise-induced bronchospasm.
• The Asthma Guidelines advise against using LABAs frequently or chronically to treat exercise-induced bronchospasm because they may mask poorly managed persistent asthma.

• US labeling:

  • Foradil Aerolizer: Dry powder inhaler:
    • Occasionally, "as required," 12 mcg at least 15 minutes prior to exercise; no extra doses should be taken for the following 12 hours.

• Canadian labeling:

  • Oxeze Turbuhaler: Dry powder inhaler:
    • Occasionally, "as needed," 6 mcg or 12 mcg at least 15 minutes prior to exercise (maximum: 48 mcg per day)

Formoterol (Perforomist, Foradil) Dose in Children

Note:

• More than a year has passed since Foradil Aerolizer was withdrawn.
• Perforomist and Foradil Aerolizer are distinct products.

Formoterol (Perforomist, Foradil) Dosage in the maintenance treatment of Asthma:

Note: Long-acting beta-agonists (LABAs) should not be used alone to treat asthma; rather, they should be used in conjunction with inhaled corticosteroids.

• Foradil Aerolizer (12 mcg/inhalation):

  • Children of 5 years or more than 5 years and Adolescents: Oral inhalation:
    • 12 mcg every 12 hours;
    • maximum every day dose: 24 mcg per day

• Canadian labeling: Foradil 12 mcg/inhalation [Canadian product]: Oral inhalation:

  • Children ≥6 years and Adolescents ≤16 years:
    • 12 mcg every 12 hours;
    • maximum daily dose: 24 mcg per day
  • Adolescents ≥17 years:
    • 12 mcg every 12 hours; in severe cases, 24 mcg every 12 hours may be necessary;
    • maximum daily dose: 48 mcg per day

• Canadian labeling: Oxeze Turbuhaler 6 mcg/inhalation and 12 mcg/inhalation [Canadian products]: Oral Inhalation:

  • Children ≥6 years and Adolescents ≤16 years:
    • 6 mcg or 12 mcg every 12 hours;
    • maximum daily dose: 24 mcg per day
  • Adolescents ≥17 years:
    • 6 mcg or 12 mcg every 12 hours;
    • in severe cases, 24 mcg every 12 hours may be necessary; maximum daily dose: 48 mcg per day

Formoterol (Perforomist, Foradil) Dosage in the prevention of Exercise-induced bronchospasm:

Note:

• Patients should not be considered to take additional doses of formoterol if they are already taking it for asthma maintenance.
• The NAEPP and GINA Asthma Guidelines advise against using long-acting beta-agonists (LABAs) frequently or chronically for exercise-induced bronchospasm since they may mask poorly-controlled persistent asthma.

• Foradil Aerolizer (12 mcg/inhalation):

  • Children ≥5 years and Adolescents: Oral Inhalation:
    • 12 mcg on occasion, "as needed," 15 minutes before activity; further doses should not be taken for 12 hours;
    • The daily maximum dose is 24 mcg.

• Canadian labeling: Oxeze Turbuhaler 6 mcg per inhalation and 12 mcg/inhalation [Canadian products]:

  • Children ≥6 years and Adolescents: Oral Inhalation:
    • maximum daily dose: 6 or 12 mcg, occasionally "as required" before activity.
    • 24 mcg daily

Formoterol Pregnancy Risk Category: C

• In some studies on animal reproduction, adverse events were reported.
• If administered during labor, beta-agonists can cause uterine contractions to be disrupted.

Formoterol use during breastfeeding:

• It is unknown if formoterol can be found in breast milk.
• According to the manufacturer of the product, when deciding whether to continue or stop breastfeeding during therapy, it should consider the risks to infant exposure, the benefits to the infant and the benefits to the mother.

Formoterol (Perforomist, Foradil) Dose in Kidney disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Formoterol (Perforomist, Foradil) Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied)

Less Common Side Effects of Formoterol (Perforomist, Foradil):

• Cardiovascular:

  • Chest Pain

• Central Nervous System:

  • Anxiety
  • Dizziness
  • Insomnia
  • Voice Disorder
  • Headache

• Dermatologic:

  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Xerostomia
  • Vomiting
  • Abdominal Pain
  • Dyspepsia
  • Diarrhea
  • Gastroenteritis

• Neuromuscular & Skeletal:

  • Muscle Cramps
  • Tremor

• Respiratory:

  • Respiratory Tract Infection
  • Exacerbation Of Asthma
  • Bronchitis
  • Pharyngitis
  • Sinusitis
  • Dyspnea
  • Tonsillitis

• Miscellaneous:

  • Fever

Contraindications to Formoterol (Perforomist, Foradil):

• Treatment of status asthmaticus, other acute episodes of COPD or asthma;
• Hypersensitivity to formoterol and any component of the formulation (Foradil Aerolizer only); (Foradil Aerolizer only).
• Monotherapy is a treatment for asthma that does not require the use of long-term medication to control the condition.
• Prevalence of tachyarrhythmias.

Warnings and precautions

• Deaths due to asthma: [US Boxed Warn]

  • The likelihood of dying from asthma increases with the use of long-acting betaagonists (LABAs).
  • It is not known if formoterol is safe or effective in treating asthma patients.
  • Patients with asthma who have not been prescribed a long-term asthma control medication are advised to avoid all LABAs, except formoterol.
  • In the treatment of asthma, monotherapy with a LABA is not recommended.
  • Salmeterol was linked to a rise in asthma-related death rates, according to a sizable, randomised, placebo-controlled US clinical research (SMART 2006). (when used as an adjunct to regular asthma therapy). For all LABAs, this risk is regarded as a class effect.
  • No information is available to say whether adding an injectable corticosteroid lowers the elevated risk of death associated with LABA use.
  • But according to current recommendations, LABA should be added after an inhalation corticosteroid has been administered.
  • It is not known if formoterol causes an increase in asthma-related deaths.
  • In a more recent multicenter, randomised, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (i.e., fluticasone) combined in a single inhaler in a significant number of kids, teens, and adults with persistent asthma (non-life threatening and stable) patients did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeter (Peters 2016; Stempel 2016a; Stempel 2016b).
  • There is no evidence to suggest that LABA use increases the risk of death for patients suffering from COPD.

• Bronchospasm

  • When inhaled bronchodilating medicines are administered, paradoxical bronchospasm, which can be fatal, may occur. It is important to distinguish this reaction from a weak response.
  • When paradoxical bronchospasm happens, stop medication right once and look for alternate treatments.

• Hypersensitivity reactions

  • There have been reports of immediate hypersensitivity reactions, including urticaria, angioedema and rash.

• Serious effects/fatalities:

  • Avoid using LABAs in excess. There have been fatalities and serious side effects associated with excessively taking sympathomimetics.

• Asthma

  • Use it in the right way:
    • Foradil Aerolizer: Avoid acute bronchospasm.
    • For acute symptoms or symptoms that occur between treatments, short-acting beta-agonists (eg albuterol) should not be used.
    • It is not recommended for patients suffering from severe or fatal asthma.
    • When formoterol is started, corticosteroids shouldn't be reduced or stopped.
    • Formoterol should not be used in monotherapy. It is not intended to replace systemic or inhaled corticosteroids.
    • Watch out for signs of worsening as you initiate treatment.
    • Asthma treatment with Perforomist is not FDA-approved. In people with asthma, neither safety nor efficacy have been established.

• Cardiovascular disease

  • Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, HF, or aneurysm); beta-agonists may cause an elevation in blood pressure and heart rate and result in CNS stimulation/excitation.
  • ECG changes can be caused by beta-agonists, including flattening the prolongation or T wave of the QTc interval and ST-segment depression.

• Chronic obstructive lung disease:

  • When chronic obstructive pulmonary disease is at an acute phase, avoid using (COPD).
  • Patients with COPD that is rapidly worsening or severely deteriorating should not be initiated.
  • There is no information available to say whether LABA use raises the risk of death in COPD patients.

• Diabetes:

  • Patients with diabetes mellitus should be cautious when using beta-agonists. They may raise serum glucose, but the effects are usually temporary.

• Exercise-induced bronchospasm

  • LABAs can conceal persistent asthma that is ill-controlled. As a result, the NIH Asthma guidelines advise against using LABAs frequently or for an extended period of time to treat exercise-induced bronchospasm.

• Hyperthyroidism:

  • Hyperthyroidism: Use caution. It may stimulate thyroid activity.

• Hypokalemia

  • Patients with hypokalemia should be cautious with beta-agonists as they can decrease serum potassium. However, the effect is often temporary.

• Pheochromocytoma:

  • Patients with pheochromocytoma should be cautious; it may worsen their symptoms.

• Seizures:

  • In individuals with seizure disorders, use with caution; beta-agonists may cause CNS stimulation or excitation.

Formoterol: Drug Interaction

Monitoring parameters:

• FEV-1
• peak flow
• pulmonary function tests
• shortness of breath
• blood pressure
• heart rate
• CNS stimulation
• serum glucose
• serum potassium

How to administer Formoterol (Perforomist, Foradil)?

Dry powder inhaler:

• Foradil Aerolizer:
  • As soon as feasible prior to usage, remove the capsule from the foil blister.
  • Insert the capsule into the Aerolizer Inhaler's base's capsule chamber.
  • Capsules must only be used with the Aerolizer Inhaler; they cannot be ingested whole.
  • Just once, press and release both buttons.
  • Keep the blue buttons on the left and right of the inhaler level and horizontal (not up and down).
  • Fully exhale. Never breathe out into the inhaler.
  • tilted head back slightly and took a breath ( steadily, rapidly, and deeply).
  • Hold your breath for as long as you can.
  • Exhale, then take another breath if there is any powder still in the capsule.
  • When the capsule is emptied, repeat.
  • Remove the empty capsule from the inhaler and throw it away.
  • The Aerolizer Inhaler should not be used with a spacer.
  • Always keep your inhaler and capsules dry.
• Oxeze Turbuhaler [Canadian product]:
  • Inhaler should be held upright.
  • The inhaler is ready for use when a clicking sound can be heard after turning the coloured grip as far as it will go in one direction before returning to the original position.
  • Fully exhale. Exhale away from the inhaler's mouthpiece.
  • Put the mouthpiece to your lips and take a strong, deep breath.
  • Avoid biting or chewing on the mouthpiece.
  • Once a week, wipe the mouthpiece's outside with a dry tissue.
  • Keep your inhaler dry.
  • Unfortunately, the dose will be lost if the inhaler is dropped, disturbed, or if the patient exhales into the inhaler. A new dose should be administered.

Nebulization solution:

• Perforomist:
  • As soon as possible before usage, remove the unit dose vial from the foil packet.
  • Do not combine formoterol solution with other drugs; the solution does not need to be diluted before use.
  • After assembling the nebulizer in accordance with the manufacturer's instructions and turning it on, add the contents of the unit-dose vial to the reservoir. Continue breathing deeply and evenly until all of the medication has been inhaled.
  • An inhalation takes 9 minutes on average.
  • Do not consume the contents of the vial; instead, immediately discard any unneeded medication.
  • After use, clean the nebulizer.

Mechanism of action of Formoterol (Perforomist, Foradil):

• By selectively activating beta receptors, it relaxes the bronchial smooth muscles. It has little effect on heart beat.
• Formoterol is a long-acting drug.

The onset of action:

• Powder for inhalation: Within 3 minutes

Peak effect:

• Powder for inhalation: 80% of peak effect within 15 minutes;
• Solution for nebulization: 2 hours

Duration:

• Improvement in FEV observed for 12 hours in most patients

Absorption:

• Rapidly into plasma

Protein binding:

• 61 percent  to 64 percent  in vitro at higher concentrations than achieved with usual dosing

Metabolism:

• Hepatic via direct glucuronidation and O-demethylation; CYP2D6, CYP2C8/9, CYP2C19, CYP2A6 involved in O-demethylation

Half-life elimination:

• Powder: ~10-14 hours;
• Nebulized solution: ~7 hours

Time to peak:

• Maximum improvement in FEV in 1-3 hours

Excretion:

• Children 5-12 years: Urine (7 percent  to 9 percent  as direct glucuronide metabolites, 6 percent  as unchanged drug)
• Adults: Urine (15 percent  to 18 percent  as direct glucuronide metabolites, 2 percent  to 10 percent  as unchanged drug)

International Brand Names of Formoterol:

• Foradil Aerolizer
• Perforomist
• Foradil
• Oxeze Turbuhaler
• Acarol Dry Syrup
• Asmelor Novolizer
• Atimos
• Atimos Modulite
• Atock
• Broncoral
• EFO
• Fesema
• Fluir
• Foradil
• Foradil Aerolizer
• Foradil P
• Foradile
• Forasma
• Foratec
• Formatris
• Formoair
• Formohale
• Formorol
• Fortix
• Fortulin
• Kurovent
• Lexoma
• Neblik
• Newitock
• Oxis
• Oxis Turbuhaler
• Oxis turbuhaler
• Pneumera
• Tempus
• Zafiron

Formoterol Brand Names in Pakistan: