Tiotropium and olodaterol
Tiotropium and olodaterol Uses, Dosage, Side Effects, Food Interaction and all others data.
Olodaterol is a novel, long-acting beta2-adrenergic agonist (LABA) that exerts its pharmacological effect by binding and activating beta2-adrenergic receptors located primarily in the lungs. Beta2-adrenergic receptors are membrane-bound receptors that are normally activated by endogenous epinephrine whose signalling, via a downstream L-type calcium channel interaction, mediates smooth muscle relaxation and bronchodilation. Activation of the receptor stimulates an associated G protein which then activates adenylate cyclase, catalyzing the formation of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevation of these two molecules induces bronchodilation by relaxation of airway smooth muscles. It is by this mechanism that olodaterol is used for the treatment of chronic obstructive pulmonary disease (COPD) and the progressive airflow obstruction that is characteristic of it. Treatment with bronchodilators helps to mitigate associated symptoms such as shortness of breath, cough, and sputum production. Single doses of olodaterol have been shown to improve forced expiratory volume in 1 sec (FEV1) for 24 h in patients with COPD, allowing once daily dosing. A once-a-day treatment with a LABA has several advantages over short-acting bronchodilators and twice-daily LABAs including improved convenience and compliance and improved airflow over a 24-hour period. Despite similarities in symptoms, olodaterol is not indicated for the treatment of acute exacerbations of COPD or for the treatment of asthma.
Olodaterol is a potent agonist of the human beta2-adrenergic receptor in vitro, and is highly selective for this receptor, with much lower levels of activity at the b1- and b3-adrenergic receptors that are commonly expressed on cardiac smooth muscle and adipose tissue, respectively. Binding to the receptor causes smooth muscle relaxation in the lungs and bronchodilation. It has also been shown to potently reverse active bronchoconstriction.
Tiotropium is a long-acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation. The bronchodilation following inhalation of Tiotropium is predominantly a site-specific effect.
Tiotropium is a long acting antimuscarinic that causes bronchodilation. The effects of tiotropium last over 24 hours and there is a wide therapeutic index as overdoses are uncommon even at doses well above the recommended maximum.
| Trade Name | Tiotropium and olodaterol |
| Generic | olodaterol + tiotropium |
| Type | Inhalation |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Olodaterol is a long-acting beta2-adrenergic agonist used in the management of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Olodaterol is indicated for use in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is not indicated for the treatment of acute exacerbations of COPD or for the treatment of asthma.
Tiotropium is used for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Tiotropium and olodaterol is also used to associated treatment for these conditions: Chronic Obstructive Pulmonary Disease (COPD)Asthma, Bronchitis, Bronchoconstriction, Chronic Bronchitis, Chronic Obstructive Airways Disease Exacerbated, Chronic Obstructive Pulmonary Disease (COPD), Chronic Obstructive Respiratory Diseases, Emphysema
How Tiotropium and olodaterol works
Olodaterol is a long-acting beta2-adrenergic agonist (LABA) that exerts its pharmacological effect by binding and activating beta2-adrenergic receptors located primarily in the lungs. Beta2-adrenergic receptors are membrane-bound receptors that are normally activated by endogenous epinephrine whose signalling, via a downstream L-type calcium channel interaction, mediates smooth muscle relaxation and bronchodilation. Activation of the receptor stimulates an associated G protein which then activates adenylate cyclase, catalyzing the formation of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevation of these two molecules induces bronchodilation by relaxation of airway smooth muscles.
Tiotropium is an antagonist of muscarinic receptors M1 to M5. Inhibition of the M3 receptor in the smooth muscle of the lungs leads to relaxation of smooth muscle and bronchodilation.
Dosage
Tiotropium and olodaterol dosage
Adults and adolescents 12 years and older: The recommended dosage of Tiotropium bromide is the inhalation of 2 puffsonce daily.
Side Effects
The most commonly reported adverse drug reaction was dry mouth. Dry mouth was usually mild and often resolved during continued treatment. Other reactions reported in individual patients and consistent with possible anticholinergic effects included constipation, increased heart rate, blurred vision, glaucoma, urinary difficulty, and urinary retention.
Toxicity
Adverse drug reactions that occurred at a frequency greater than 2% include nasopharyngitis (11.3%), upper respiratory tract infection (8.2%), bronchitis (4.7%), urinary tract infection (2.5%), cough (4.2%), dizziness (2.3%), rash (2.2%), diarrhea (2.9%), back pain (3.5%), and arthralgia (2.1%).
Symptoms of overdose include altered mental status, tremors, abdominal pain, and severe constipation. However, doses of up to 282µg did not lead to systemic anticholinergic effects in a trial of 6 patients. In case of overdose, stop tiotropium and being symptomatic and supportive therapy.
Precaution
As an anticholinergic drug, Tiotropium may potentially worsen symptoms and signs associated with narrow angle glaucoma, prostatic hyperplasia or bladder-neck obstruction and should be used with caution in patients with any of these conditions. As a predominantly renally excreted drug, patients with moderate to severe renal impairment treated with Tiotropium should be monitored closely.
Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow angle glaucoma. Should any of these signs and symptoms develop, consult a physician immediately. Miotic eye drops alone are not considered to be effective treatment.
Interaction
Tiotropium has been used concomitantly with other drugs commonly used in COPD without increases in adverse drug reactions. These include sympathomimetic bronchodilators, methylxanthines, and oral and inhaled steroids. However, the co-administration of Tiotropium with other anticholinergic-containing drugs (e.g., ipratropium) has not been studied and is therefore not recommended.
Volume of Distribution
The volume of distribution is high (1110 L), suggesting extensive distribution into tissue.
The volume of distribution of tiotropium is 32L/kg.
Elimination Route
Olodaterol reaches maximum plasma concentrations generally within 10 to 20 minutes following drug inhalation. In healthy volunteers, the absolute bioavailability of olodaterol following inhalation was estimated to be approximately 30%, whereas the absolute bioavailability was below 1% when given as an oral solution. Thus, the systemic availability of olodaterol after inhalation is mainly determined by lung absorption, while any swallowed portion of the dose only negligibly contributes to systemic exposure.
33% of an inhaled solution reaches systemic circulation, while oral solutions have a bioavailability of 2-3%. A dry powder for inhalation is 19.5% bioavailable. Tiotropium metered spray for inhalation reaches a maximum concentration in 5-7 minutes.
Half Life
The terminal half-life following intravenous administration is 22 hours. The terminal half-life following inhalation in contrast is about 45 hours, indicating that the latter is determined by absorption rather than by elimination processes.
The terminal half life of tiotropium is 24 hours in patients with COPD and 44 hours in patients with asthma.
Clearance
Total clearance of olodaterol in healthy volunteers is 872 mL/min, and renal clearance is 173 mL/min.
The total clearance of tiotropium is 880mL/min in healthy subjects receiving 5µg daily. The renal clearance of tiotropium was 669mL/min. Patients 2 This decreased clearance is not associated with increased AUC or Cmax.
Elimination Route
Following intravenous administration of [14C]-labeled olodaterol, 38% of the radioactive dose was recovered in the urine and 53% was recovered in feces. The amount of unchanged olodaterol recovered in the urine after intravenous administration was 19%. Following oral administration, only 9% of olodaterol and/or its metabolites was recovered in urine, while the major portion was recovered in feces (84%).
74% of intravenous tiotropium was excreted unchanged in urine. 14% of a dry powder inhalation dose was excreted unchanged in the urine. 24 hour urinary excretion after 21 days of 5µg once daily inhalation in patients with COPD is 18.6% and in patients with asthma is 12.8%.
Pregnancy & Breastfeeding use
Pregnancy Category C. Tiotropium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Labor and Delivery: The safety and effectiveness of Tiotropium has not been studied during labor and delivery.
Nursing Mothers: Clinical data from nursing women exposed to Tiotropium are not available. caution should be exercised if administered to a nursing woman.
Contraindication
Tiotropium is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, including ipratropium, or to any component of this product.
Special Warning
Pediatric Use: The safety and effectiveness of Tiotropium in pediatric patients have not been established.
Geriatric use: No adjustment of Tiotropium dosage in geriatric patients is warranted.
Acute Overdose
High doses of Tiotropium may lead to anticholinergic signs and symptoms. Acute intoxication by inadvertent oral ingestion of Tiotropium Bromide unlikely since it is not well-absorbed systemically.
Storage Condition
The inhaler should be stored in a dry, cool place away from direct sunlight and heat. The canister should not be broken, punctured or burnt, even when apparently empty. Keep away from eyes. Keep out of reach of children.
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