Dulamet

Approved Indications:

• Asthma (Maintenance Therapy):
  Indicated in patients ≥12 years for the long-term maintenance treatment of asthma, where use of both an inhaled corticosteroid (ICS) and a long-acting beta2-agonist (LABA) is appropriate.
  It is not indicated for relief of acute bronchospasm.
• Chronic Obstructive Pulmonary Disease (COPD):
  In some regions (e.g., Canada, EU), used for the maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.
  (Note: This is off-label in the United States.)

Important Off-label/Clinically Accepted Use:

• Step-up Therapy in Moderate to Severe Asthma:
  As an escalation from ICS monotherapy when asthma is inadequately controlled.

Formulation:
Inhalation aerosol; pressurized metered-dose inhaler (pMDI)

Strengths Available (per actuation):

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

Asthma (Adults and Adolescents ≥12 years):

• Usual Dose:
• 100/5 mcg: 2 inhalations twice daily (morning and evening)
• 200/5 mcg: 2 inhalations twice daily for more severe asthma
• Maximum Dose: 400 mcg of mometasone + 20 mcg of formoterol per day

Pediatric Use (<12 years):

• Not approved; safety and efficacy not established

Elderly:

• No dose adjustment required; use with standard precautions

Renal/Hepatic Impairment:

• No formal dose adjustment; however, use cautiously and monitor, especially in hepatic impairment due to possible systemic corticosteroid effects

Administration Instructions:

• Inhale deeply through the mouth while activating the inhaler
• Rinse mouth with water after each dose (to prevent oropharyngeal candidiasis)
• Shake well before use
• Prime before first use or if not used for >5 days
• Not for use with a spacer

This combination product provides synergistic control of asthma symptoms via two complementary mechanisms:

• Mometasone Furoate: A potent inhaled corticosteroid (ICS) that binds glucocorticoid receptors in airway epithelial cells, downregulating inflammatory cytokine production, reducing eosinophilic infiltration, and suppressing airway hyperresponsiveness and mucosal edema.
• Formoterol Fumarate: A long-acting β2-adrenergic receptor agonist (LABA) that stimulates intracellular adenylate cyclase, increasing cyclic AMP levels in bronchial smooth muscle, resulting in bronchodilation. It has a rapid onset of action (within minutes) and a prolonged duration of ≥12 hours.

Together, the combination targets both inflammation and bronchoconstriction, improving lung function and reducing exacerbation frequency.

Mometasone Furoate:

• Absorption: Low systemic bioavailability due to extensive first-pass metabolism and inhaled route
• Peak Plasma Time: 1–2 hours
• Metabolism: Primarily via CYP3A4 to inactive metabolites
• Elimination: Mainly fecal (via bile); negligible renal excretion
• Half-life: 5.8 hours

Formoterol Fumarate:

• Absorption: Rapid absorption from lungs
• Peak Plasma Time: ~1 hour post-inhalation
• Metabolism: Hepatically metabolized via glucuronidation and O-demethylation (CYP2D6, CYP2C19, CYP2C9)
• Elimination: Primarily via urine (60–70%) and feces
• Half-life: 10–14 hours

Onset of Action:

• Formoterol provides bronchodilation within 3 minutes, suitable for symptom control.
• Mometasone's full anti-inflammatory benefit may require several days of consistent use.

• Pregnancy:
  Classified as Category C (prior to FDA’s phasing out of pregnancy letter categories).
  Use only if potential benefit outweighs the potential fetal risk. Animal studies showed adverse effects at high doses.
• Lactation:
  Unknown whether mometasone or formoterol is excreted in human milk.
  Systemic absorption is low, but caution is advised. Use only if clearly necessary.
• Recommendation:
  Monitor infants for possible corticosteroid or beta-agonist side effects (e.g., growth suppression, jitteriness).

• Primary Class: Combination Respiratory Agent
• Subclass:
• Inhaled Corticosteroid (ICS)
• Long-Acting Beta2-Adrenergic Agonist (LABA)

• Hypersensitivity to mometasone, formoterol, or any excipient in the formulation
• Primary treatment of status asthmaticus or acute asthma episodes
• Concomitant use of other LABA-containing drugs (increased risk of overdose)
• Untreated systemic fungal, viral, or bacterial infections
• Use with caution in patients with QT prolongation history or tachyarrhythmias

• Asthma-Related Death (LABA Class Effect): LABAs may increase the risk of asthma-related death if not used in combination with ICS
• Paradoxical Bronchospasm: May occur after inhalation; discontinue immediately if suspected
• Systemic Corticosteroid Effects: Includes adrenal suppression, growth suppression in children, osteoporosis, and Cushingoid features with long-term use
• Cardiovascular Risk (Formoterol): Use cautiously in patients with heart disease, arrhythmias, or hypertension
• Immunosuppression: Avoid exposure to chickenpox or measles; increased infection risk
• Hypokalemia and Hyperglycemia: LABAs may cause dose-dependent effects on serum potassium and glucose

Common Side Effects:

• Respiratory:
• Hoarseness, dysphonia
• Cough, sore throat
• Oropharyngeal candidiasis
• Systemic (Corticosteroid Effects):
• Headache, sinusitis
• Dry mouth
• Nervous System:
• Tremor, dizziness (from formoterol)

Less Common / Rare Side Effects:

• Palpitations, chest pain, hypertension
• Allergic reactions including rash and anaphylaxis
• Growth suppression in children with long-term ICS use

Serious Adverse Effects:

• Asthma-related death (LABA monotherapy)
• Paradoxical bronchospasm
• Adrenal suppression, Cushing’s syndrome with long-term use

Onset:

• Inhalation-related effects may occur within days; systemic corticosteroid effects may take weeks or months of prolonged use.

Major Interactions:

• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Increase mometasone systemic exposure, enhancing risk of corticosteroid toxicity
• Beta-blockers (e.g., propranolol): May reduce formoterol effectiveness; avoid in asthma
• MAO Inhibitors and TCAs: Potentiate cardiovascular effects of formoterol; avoid concomitant use
• Diuretics: Increased risk of hypokalemia when used with formoterol
• Other LABAs: Risk of overdose and cardiovascular complications

Enzyme Systems Involved:

• Mometasone: CYP3A4
• Formoterol: CYP2D6, CYP2C19, CYP2C9 (minor involvement)

• Global Initiative for Asthma (GINA 2024): Recommends ICS/LABA combinations (including mometasone/formoterol) for stepwise asthma therapy starting from Step 3
• FDA Label Updates: Reinforced black box warning on LABA monotherapy; mandates combination with ICS
• EMA Safety Monitoring: Continues to monitor systemic corticosteroid risks, including growth suppression in children
• COPD Use: Formally approved in select countries (not FDA-approved for COPD in the U.S.)

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions allowed from 15°C to 30°C (59°F to 86°F)
• Humidity: Protect from moisture
• Light: Store in original container, away from direct sunlight
• Handling Instructions:
• Do not freeze
• Shake well before each use
• Do not puncture or incinerate canister
• Discard when labeled number of inhalations is used
• Keep out of reach of children