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 as a maintenance treatment for COPD patients with emphysema and/or chronic bronchitis.

Tiotropium and Olodaterol (Spiolto) Dose in Adults

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

• Oral inhalation: Soft mist inhaler:
  • Tiotropium 2.5 mcg/olodaterol 2.5 mcg per actuation, twice day (maximum: twice daily), inhalations

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:

  • It is not advised to treat asthma with long-acting beta-2 antagonist (LABA) monotherapy.
  • Salmeterol was found to increase the risk of death from asthma in a significant, randomised, placebo-controlled US clinical investigation. This is regarded as a LABA class effect.
  • When LABAs are coupled with inhaled Corticosteroids, significant increases in major asthma-related events have not been observed in large clinical trials.
  • According to current guidelines, inhaled corticosteroids should not be taken before adding a LABA.
  • In a more recent multicenter, randomised, double-blinded trial, the use of salmeterol in combination with an inhaled corticosteroid (i.e., fluticasone) in a single inhaler in a significant number of children, adolescents, and adults with persistent asthma (nonlife-threatening and stable) patients did not increase the risk of serious asthma-related events compared to fluticasone alone; additionally, patients receiving fluticasone/salmetero
  • 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

  • This drug should not be used by people who have moderate to severe renal impairment (creatinine clearance of 60 mL/min). Adverse effects of anticholinergic drugs need to be constantly watched.

• 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
• Anticholinergic adverse reactions 
• 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.
• Point the inhaler toward the ground and activate it until an aerosol cloud appears. Repeat this three more times before using. Prime the inhaler before the first usage or if it hasn't been used in more than 3 weeks.
• Activate once before use if not used for more than three days (but less than 21 days). When the dose is ready to be given, slowly inhale through your mouth while pressing the dose-release button. After doing this for as long as you can, hold your breath for 10 seconds or as long as it feels comfortable. For the second inhalation, repeat.

Mechanism of action of Tiotropium and Olodaterol (Spiolto):

Tiotropium:

• Induces bronchodilation by inhibiting the acetylcholine (M3) receptors' competitive and reversible activity in the bronchial smooth muscles.

Olodaterol

• LABA (long-acting beta-2 receptor agonist) is a long-acting beta-2 receptor antagonist that promotes intracellular Adenyl Cyclase while also activating beta 2 airway receptors.
• Consequently, cyclic3'-5' adenosine monophosphate production rises (cAMP).
• The airway smooth muscle cells relax as cAMP levels rise, resulting in bronchodilation.
• 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.