Monobasic Sodium Phosphate + Dibasic Sodium Phosphate

Approved Indications:

• Asthma (Maintenance Treatment):
  Indicated for the long-term maintenance treatment of asthma in patients aged 12 years and older when use of both an inhaled corticosteroid (ICS) and a long-acting beta2-adrenergic agonist (LABA) is appropriate.
  Note: This combination is not indicated for the relief of acute bronchospasm.
• Chronic Obstructive Pulmonary Disease (COPD):
  In some regions (e.g., Europe, Canada), this combination is approved for the maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.
  Note: In the United States, this use is not FDA-approved.

Clinically Accepted Off-Label Use:

• As step-up therapy in moderate to severe asthma when monotherapy with inhaled corticosteroids is inadequate.

Available Strengths (per actuation):

• Mometasone Furoate 100 mcg + Formoterol Fumarate 5 mcg
• Mometasone Furoate 200 mcg + Formoterol Fumarate 5 mcg

Route of Administration: Inhalation via pressurized metered-dose inhaler (pMDI)

Asthma (Adults and Adolescents ≥12 years):

• 100/5 mcg: 2 inhalations twice daily (morning and evening)
• 200/5 mcg: 2 inhalations twice daily for patients with more severe asthma
• Maximum daily dose: Mometasone 400 mcg + Formoterol 20 mcg

Pediatric Use (<12 years):

• Safety and efficacy not established; not recommended

Elderly Patients:

• No dosage adjustment necessary; monitor for systemic effects

Renal or Hepatic Impairment:

• No specific dose adjustment recommended, but caution advised due to possible increased systemic exposure

Administration Instructions:

• Shake well before each use
• Prime the inhaler before first use or if not used for more than 5 days
• Inhale deeply through the mouth during actuation
• Rinse mouth with water after use to prevent oropharyngeal candidiasis
• Do not use a spacer device

This fixed-dose combination provides complementary therapeutic effects:

• Mometasone Furoate is a potent inhaled corticosteroid that exerts anti-inflammatory effects by binding to glucocorticoid receptors, suppressing the release of pro-inflammatory cytokines, reducing airway eosinophilia, and decreasing bronchial hyperresponsiveness.
• Formoterol Fumarate is a long-acting selective beta2-adrenergic agonist that activates adenylate cyclase in bronchial smooth muscle cells, increasing intracellular cyclic AMP levels. This leads to relaxation of airway smooth muscles and prolonged bronchodilation.

Together, these agents provide dual-action control of asthma symptoms by reducing airway inflammation and promoting sustained bronchodilation.

Mometasone Furoate:

• Absorption: Low systemic bioavailability due to extensive first-pass metabolism
• Time to Peak Concentration: 1–2 hours
• Metabolism: Primarily metabolized in the liver by CYP3A4
• Elimination: Mainly excreted in feces
• Half-life: Approximately 5.8 hours

Formoterol Fumarate:

• Absorption: Rapid pulmonary absorption after inhalation
• Time to Peak Concentration: Around 1 hour
• Metabolism: Extensively metabolized in the liver via multiple pathways, including CYP2D6, CYP2C19, and CYP2C9
• Elimination: Excreted via urine and feces
• Half-life: Approximately 10–14 hours

Pregnancy:

• Classified as Category C (prior FDA system).
• Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation:

• Unknown if either component is excreted in human breast milk.
• Given the low systemic absorption with inhaled administration, risk to the breastfed infant is likely low.
• Use with caution and monitor for adverse effects in nursing infants.

• Primary Class: Combination Respiratory Agent
• Subclasses:
• Mometasone Furoate: Inhaled Corticosteroid (ICS)
• Formoterol Fumarate: Long-Acting Beta2-Adrenergic Agonist (LABA)

• Known hypersensitivity to mometasone, formoterol, or any formulation excipients
• Primary treatment of status asthmaticus or acute asthma episodes
• Concomitant use of another LABA-containing medication
• Untreated systemic fungal, viral, or bacterial infections

• Asthma-Related Death (Black Box Warning): LABAs may increase the risk of asthma-related death if used without a corticosteroid; this risk is mitigated when combined with ICS
• Paradoxical Bronchospasm: May occur after inhalation; discontinue immediately if it occurs
• Systemic Corticosteroid Effects: Includes adrenal suppression, growth retardation in children, osteoporosis, and hypercorticism with prolonged use
• Cardiovascular Effects: Use with caution in patients with cardiac arrhythmias, hypertension, or coronary artery disease
• Immunosuppression: Increased risk of infections; avoid exposure to measles or varicella
• Ocular Effects: Prolonged use may increase intraocular pressure or lead to cataracts

Common Side Effects:

• Hoarseness, dysphonia
• Oropharyngeal candidiasis
• Headache
• Throat irritation
• Nasal congestion or sinusitis

Less Common or Serious Adverse Effects:

• Tachycardia or palpitations
• Hypertension
• Tremor, nervousness
• Allergic reactions including rash, angioedema
• Growth suppression in pediatric patients
• Adrenal suppression with long-term use

Onset & Severity:

• Local side effects (e.g., throat irritation, candidiasis) may appear within days
• Systemic side effects (e.g., adrenal suppression) are rare and occur with chronic high-dose use

Major Interactions:

• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): May increase systemic exposure to mometasone
• Beta-blockers: May antagonize the effects of formoterol
• MAO inhibitors and tricyclic antidepressants: May potentiate formoterol’s cardiovascular effects
• Diuretics: Increased risk of hypokalemia when used with formoterol
• Other LABAs: Avoid concomitant use due to additive sympathomimetic effects

Metabolic Pathways:

• Mometasone: CYP3A4
• Formoterol: CYP2D6, CYP2C19, CYP2C9

• Global Initiative for Asthma (GINA) 2024:
  Endorses use of ICS/LABA combinations, including mometasone/formoterol, as maintenance therapy in moderate to severe asthma (Step 3 and beyond)
• FDA Safety Updates:
  Emphasized requirement for ICS when prescribing LABA-containing products to reduce asthma-related mortality
• EMA Recommendations:
  Monitoring of growth velocity in pediatric patients using long-term corticosteroids remains advised

• Storage Temperature: 20°C to 25°C (68°F to 77°F)
• Allowable Excursions: 15°C to 30°C (59°F to 86°F)
• Humidity: Store in a dry place; avoid excessive moisture
• Light: Protect from direct sunlight; store in original container
• Handling Precautions:
• Do not freeze
• Shake well before each use
• Do not puncture or incinerate the canister
• Discard after labeled number of actuations
• Keep out of reach of children