Tiotropium Bromide Monohydrate is the monohydrate bromide salt form of tiotropium, a quaternary ammonium derivative of atropine and a long-acting muscarinic receptor antagonist, with bronchodilating activity. Upon inhalation, tiotropium binds to and blocks mainly muscarinic M3 receptors located on smooth muscle cells, thereby preventing smooth muscle contraction.

Tiotropium bromide is a long-acting, 24-hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). It is a long-acting, 24 hour, the anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium is a muscarinic receptor antagonist, on the topical application, it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.

Mechanism of Action of Tiotropium Bromide

Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on the topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies prevention of methacholine-induced bronchoconstriction effects were dose-dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site-specific effect.

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Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on the topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.

Indications of Tiotropium Bromide

• Chronic obstructive pulmonary disease (COPD).
• COPD, Maintenance
• Asthma, Maintenance
• Emphysema
• Acute Exacerbation of Chronic Obstructive Pulmonary Disease
• Asthma Bronchial
• Chronic Obstructive Pulmonary Disease (COPD)
• Long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema; to reduce exacerbations in COPD patients.
• Used in the management of chronic obstructive pulmonary disease (COPD).

To use the inhaler, follow these steps

• Use the diagram in the patient information that came with your medication to help you learn the names of the parts of your inhaler. You should be able to find the dust cap, mouthpiece, base, piercing button, and center chamber.
• Pick up one blister card of tiotropium capsules and tear it along the perforation. You should now have two strips that each contain three capsules.
• Put away one of the strips for later. Use the tab to carefully peel back the foil on the other blister strip until the STOP line. This should fully uncover one capsule. The other two capsules on the strip should still be sealed in their packaging. Plan to use those capsules in the next 2 days.
• Pull upward on the dust cap of your inhaler to open it.
• Open the mouthpiece of the inhaler. Remove the tiotropium capsule from the package and place it in the center chamber of the inhaler.
• Close the mouthpiece firmly until it clicks, but do not close the dust cap.
• Hold the inhaler so that the mouthpiece is on top. Press the green piercing button once, then let it go.
• Breathe out completely without putting any part of the inhaler in or near your mouth.
• Bring the inhaler up to your mouth and close your lips tightly around the mouthpiece.
• Hold your head upright and breathe in slowly and deeply. You should breathe just fast enough to hear the capsule vibrate. Continue to breathe in until your lungs are full.
• Hold your breath for as long as you can comfortably do so. Take the inhaler out of your mouth while you are holding your breath.
• Breathe normally for a short time.
• Repeat steps 8-11 to inhale any medication that may be left in your inhaler.
• Open the mouthpiece and tilt the inhaler to spill out the used capsule. Discard the used capsule out of the reach of children and pets. You may see a small amount of powder remaining in the capsule. This is normal and does not mean that you did not get your full dose.
• Close the mouthpiece and dust cap and store the inhaler in a safe place.

Contra-Indications of Tiotropium Bromide

• Closed-angle glaucoma
• Blockage of Urinary Bladder
• Enlarged Prostate
• Cannot Empty Bladder
• Chronic kidney disease stage 3A (moderate)
• Chronic kidney disease stage 3B (moderate)
• Chronic kidney disease stage 4 (severe)
• Chronic kidney disease stage 5 (failure)
• Allergies to Anticholinergics – Quaternary & Ipratropium Analogues

The dosage of Tiotropium Bromide

Strengths: 18 mcg; 2.5 mcg/inch; 1.25 mcg/inh

Chronic Obstructive Pulmonary Disease

Tiotropium inhalation powder, hard capsule

• 18 mcg (2 inhalations) orally once a day using the HandiHaler device

Tiotropium, solution for inhalation

• 5 mcg (2 inhalations) orally once a day

Asthma 

• 2.5 mcg (2 inhalations of 1.25 mcg) orally once a day

Pediatric Asthma 

• Less than 12 years: safety and efficacy have not been established.

12 years or older

• 2.5 mcg (2 inhalations of 1.25 mcg) orally once a day

Side Effects of Tiotropium Bromide

The most common

• dry mouth
• a sore throat
• a cough
• constipation
• blurred vision or vision changes
• pain with urination
• stomach pain or cramping
• diarrhea
• a headache
• dizziness
• confusion
• stomach pain;
• back pain, joint or muscle pain.
• problems with your vision (including color vision);
• sudden chest pain or trouble breathing;
• pain or swelling in one or both legs;
• a migraine headache;
• pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

More common

• Abdominal or stomach pain, discomfort, or tenderness
• chills or fever
• difficulty with moving
• a headache, severe and throbbing
• joint or back pain
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in the chest
• discomfort in arms, shoulders, neck or upper back
• excessive sweating
• feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
• sudden tingling or coldness in an arm or leg
• sudden slow or difficult speech
• sudden drowsiness or need to sleep
• fast breathing
• sharp pain when taking a deep breath
• fast or slow heartbeat
• coughing up blood
• rust colored urine
• decreased amount of urine

Rare

• Anxiety
• change in vision
• chest pain or tightness
• confusion
• a cough
• Agitation
• arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• fainting
• hallucinations
• a headache
• irritability
• lightheadedness
• mood or mental changes
• muscle pain or cramps
• muscle spasm or jerking of all extremities
• nervousness

Drug Interactions of Tiotropium Bromide

Tiotropium bromide may interact with the following drugs, supplements & may change the efficacy of drugs

• antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• beta 2 agonists (e.g., salbutamol, formoterol, terbutaline)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• long-acting beta agonists (e.g., indacaterol, salmeterol)
• citalopram
• decongestant cold medications (e.g., phenylephrine, pseudoephedrine)
• decongestant eye drops and nose sprays (e.g., naphazoline, oxymetazoline, xylometazoline)
• diuretics (e.g., furosemide, hydrochlorothiazide)
• domperidone
• escitalopram
• ipratropium
• macrolide antibiotics (e.g., clarithromycin, erythromycin, telithromycin)
• methadone
• mirabegron
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• quinolone antibiotics (e.g., levofloxacin moxifloxacin ofloxacin)
• serotonin antagonists (anti-emetic medications; e.g., ondansetron granisetron, )
• theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
• thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
• tolterodine
• topiramate
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)

Pregnancy Catagory

FDA Pregnancy Risk  Category C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

It is not known if tiotropium passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children.

References