Tiotropium and Olodaterol (Spiolto) is a combination of anticholinergic medicine and a long-acting bronchodilator. It is used in the treatment of patieints with chronic obstructive pulmonary disease. It reduces phlegm formation and improves airflow by reducing bronchoconstriction in patients with emphysema and chronic bronchitis.

Tiotropium and Olodaterol (Spiolto) Uses:

• COPD:

  • Used for maintenance treatment of patients with COPD, including chronic bronchitis and/or emphysema.

Tiotropium and Olodaterol (Spiolto) Dose in Adults

Tiotropium and Olodaterol (Spiolto) Dose in the treatment of COPD:

• Oral inhalation: Soft mist inhaler:
  • Two inhalations (tiotropium 2.5 mcg/olodaterol 2.5 mcg per actuation) once a day (maximum: 2 inhalations/day)

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• This combination has not been used in animal reproduction studies. Beta-agonists may cause uterine contractions if administered during labor. Refer to individual monographs.

Use during breastfeeding:

• It is unknown if breast milk secretes hormones.
• These are the recommendations of the manufacturer. When deciding whether to continue breastfeeding or not during therapy, the following should be remembered:
  • Infant exposure is a risk
  • Breastfeeding is good for the infant
  • Treatments for the mother: Benefits
• You can view individual monographs.

Dose in Kidney Disease:

• CrCl >60 mL/minute: Dosage adjustment not necessary.
• CrCl ≤60 mL/minute: Dosage adjustment not necessary; anticholinergic adverse effects should be closely monitored.

Dose in Liver disease:

Dosage adjustment is not necessary.

Common Side Effects of Tiotropium and Olodaterol (Spiolto):

• Respiratory:

  • Nasopharyngitis
  • Cough

• Neuromuscular & skeletal:

  • Back pain
  •  

Contraindications to Tiotropium and Olodaterol (Spiolto):

• Hypersensitivity to ipratropium or tiotropium (or any other component of the formulation).
• It can be used as a monotherapy for the treatment of asthma without the need to use an inhaled corticosteroid.

Canadian labeling: Additional contraindications not in US labeling

• Atropine hypersensitivity.

There is limited documentation on allergenic cross-reactivity between sympathomimetics and sympathomimetics. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Asthma-related Deaths:

  • Monotherapy with long-acting beta-2 antagonist (LABA), is not recommended for asthma treatment.
  • A large, randomized, placebo controlled US clinical trial found an increase in asthma-related death rates when salmeterol was added to regular asthma therapy. This is considered a class effect for all LABAs.
  • Large clinical trials have not shown a significant increase in serious asthma-related events when LABAs are combined with inhaled Corticosteroids.
  • According to current guidelines, inhaled corticosteroids should not be taken before adding a LABA.
  • In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol combined with an inhaled corticosteroid (ie, fluticasone) in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (nonlife-threatening and stable), the risk of serious asthma-related events did not increase compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol experienced a fewer severe asthma exacerbation as compared to patients who received fluticasone alone.
  • There no indication of tiotropium/olodaterol for the treatment of asthma.
  • The risk of death in patients suffering from chronic obstructive lung disease (COPD) is not increased by the use of LABA, according to data.

• Bronchospasm

  • Inhaled beta-2 agonists can cause life-threatening paradoxical and potentially fatal bronchospasm. This should be distinguished from inadequate treatment.
  • Paradoxical bronchospasm should be treated with alternative therapies.

• CNS effects

  • Use can cause blurred vision and dizziness. Patients should be warned about driving or operating machinery that requires mental alertness.

• Hypersensitivity reactions

  • It may cause anaphylaxis and angioedema. Urticaria, pruritus, rash and anaphylaxis are all possible signs/symptoms.

• Serious effects/fatalities:

  • Avoid exceeding the recommended dosage or frequency of use when taking LABA-containing medications. Excessive use of sympathomimetics inhaled can cause serious adverse reactions, including death.

• Cardiovascular disease

  • Patients with heart disease, such as arrhythmias and hypertension, should be cautious about using beta-agonists. Blood pressure and heart rate can be increased by the use of betaagonists.
  • Beta2 agonists (eg, T wave flattening, QTc lengthening, ST-segment depression) may also cause ECG changes.

• Diabetes:

  • Be cautious with diabetes mellitus. Beta-2 agonists can increase serum glucose levels and pre-existing diabetes mellitus, and ketoacidosis could be exacerbated.

• Glaucoma:

  • Patients with narrow-angle Glaucoma should be cautious; intraocular pressure could be raised.

• Hyperthyroidism:

  • Patients with hyperthyroidism should be cautious. Thyroid activity could be stimulated.

• Hypokalemia

  • Hypokalemia patients should be cautious; transiently, serum potassium may be reduced.

• Renal impairment

  • Patients with moderate to severe kidney impairment (creatinine clearance of 60mL/minute) should not use this medication. Anticholinergic adverse reactions should be closely monitored.

• Seizures:

  • Should be used cautiously in patients with seizure disorders; CNS stimulation/excitation may occur.

• Urinary retention

  • Patients with urinary retention should be cautious.
  • Patients with bladder neck obstruction or prostatic hyperplasia should monitor for signs and symptoms of urinary retention.

Tiotropium and olodaterol: Drug Interaction

Monitoring parameters:

• FEV-1, peak flow, and/or other pulmonary function tests
• Anticholinergic adverse reactions (patients with CrCl ≤60 mL/minute)
• Serum K+ levels
• Serum glucose
• Blood pressure
• Pulse rate
• CNS stimulation
• Signs and symptoms of glaucoma
• Hypersensitivity reactions
• Urinary retention.

How to administer Tiotropium and Olodaterol (Spiolto)?

Oral inhalation: Soft mist inhaler:

• For inhalation via oral route only. Should be administered at the same time each day.
• Prime inhaler before initial use or if not in use for more than 3 weeks; point inhaler toward the ground and actuate until you see an aerosol cloud, then repeat 3 additional times before use.
• If not used for more than 3 days (but ≤21 days), actuate once prior to use. When the dose is ready to be administered, slowly breathe in via mouth & press the dose-release button; continue to slowly breathe in as long as possible, then hold breath for 10 seconds or for as long as comfortable. Repeat for 2nd inhalation.

Mechanism of action of Tiotropium and Olodaterol (Spiolto):

Tiotropium:

• Inhibits the competitive and reversible action of acetylcholine (M3) receptors in the bronchial smooth muscles and causes bronchodilation.

Olodaterol

• LABA (long-acting beta-2 receptor agonist) is a long-acting beta-2-receptor antagonist that activates beta 2 airway receptors and stimulates intracellular Adenyl Cyclase.
• This then causes an increase in cyclic3'-5' adenosine monophosphate synthesis (cAMP). 
• The elevation of cAMP levels causes bronchodilation through relaxation of the airway smooth muscles cells. 
• It is more apt to beta 2 receptors than it is for beta 1 and beta 3 receptors.

See individual agents:

• Tiotropium (Spiriva)
• Olodaterol (Striverdi Respimat)

International Brand Names of Tiotropium and olodaterol:

• Spiolto
• Spiolto Respimat
• Vahelva Respimat

Tiotropium and Olodaterol Brand Names in Pakistan:

No Brands Available in Pakistan.