Drug Class Description
Anticholinergics

Generic Name
Tiotropium

Drug Description
The delivered dose is 2.5 microgram tiotropium per puff (2 puffs comprise one medicinal dose) and is equivalent to 3.124 microgram tiotropium bromide monohydrate.The delivered dose is the dose which is available for the patient after passing the mouthpiece.

Presentation
Solution for inhalationClear, colourless, solution for inhalation

Indications
Tiotropium is indicated as a maintenance bronchodilator treatment to relieve symptoms of patients with chronic obstructive pulmonary disease (COPD).

Adult Dosage
The medicinal product is intended for inhalation use only. The cartridge can only be inserted and used in the Respimat inhaler.Two puffs from the Respimat inhaler comprise one medicinal dose.The recommended dose for adults is 5 microgram tiotropium given as two puffs from the Respimat inhaler once daily, at the same time of the day.The recommended dose should not be exceeded.Special Populations:Geriatric patients can use tiotropium bromide at the recommended dose.Renally impaired patients can use tiotropium bromide at the recommended dose. For patients with moderate to severe impairment (creatinine clearance 50 ml/min.Hepatically impaired patients can use tiotropium bromide at the recommended dose.Paediatric patients:Spiriva Respimat is not recommended for use in children and adolescents below 18 years due to lack of data on safety and efficacy.To ensure proper administration of the medicinal product, the patient should be shown how to use the inhaler by a physician or other health professionals.Patient's instructions for use and handling Spiriva Respimat inhaler and Spiriva Respimat cartridgeInserting the cartridge and preparation for useThe following steps 1-6 are necessary before first use:11 With the green cap (A) closed, press the safety catch (E) and pull off the clear base (G).2a 2b2 Take the cartridge (H) out of the box. Push the narrow end of the cartridge into the inhaler until it clicks into place. The cartridge should be pushed gently against a firm surface to ensure that it has gone all the way in (2b). Do not remove the cartridge once it has been inserted into the inhaler.33 Replace the clear base (G). Do not remove the clear base again.To prepare the Spiriva Respimat inhaler for first-time use44 Hold the Spiriva Respimat inhaler upright, with the green cap (A) closed. Turn the base (G) in the direction of the red arrows on the label until it clicks (half a turn).55 Open the green cap (A) until it snaps fully open.66 Point the Spiriva Respimat inhaler towards the ground. Press the dose release button (D). Close the green cap (A). Repeat steps 4, 5 and 6 until a cloud is visible. Then repeat steps 4, 5 and 6 three more times to ensure the inhaler is prepared for use. Your Spiriva Respimat inhaler is now ready to use. These steps will not affect the number of doses available. After preparation your Spiriva Respimat inhaler will be able to deliver your 60 puffs (30 medicinal doses).Using the Spiriva Respimat inhalerYou will need to use this inhaler ONLY ONCE A DAY.Each time you use it take TWO PUFFS.II Hold the Spiriva Respimat inhaler upright, with the green cap (A) closed, to avoid accidental release of dose. Turn the base (G) in the direction of the red arrows on the label until it clicks (half a turn).IIII Open the green cap (A) until it snaps fully open. Breathe out slowly and fully, and then close your lips around the end of the mouthpiece without covering the air vents (C). Point your Spiriva Respimat inhaler to the back of your throat. While taking in a slow, deep breath through your mouth, press the dose release button (D) and continue to breathe in slowly for as long as you can. Hold your breath for 10 seconds or for as long as comfortable. III Repeat steps I and II so that you get the full dose. You will need to use this inhaler only ONCE A DAY. Close the green cap until you use your Spiriva Respimat inhaler again. If Spiriva Respimat inhaler has not been used for more than 7 days release one puff towards the ground. If Spiriva Respimat inhaler has not been used for more than 21 days repeat steps 4 to 6 until a cloud is visible. Then repeat steps 4 to 6 three more times.When to get a new Spiriva Respimat inhalerThe Spiriva Respimat inhaler contains 60 puffs (30 medicinal doses). The dose indicator shows approximately how much medication is left. When the pointer enters the red area of the scale, there is, approximately, medication for 7 days left (14 puffs). This is when you need to get a new Spiriva Respimat inhaler prescription Once the dose indicator has reached the end of the red scale (i.e. all 30 doses have been used), the Spiriva Respimat inhaler is empty and locks automatically. At this point, the base cannot be turned any further. At the latest, two months after use the Spiriva Respimat inhaler should be discarded even if not all medication has been used.How to care for your inhalerClean the mouthpiece including the metal part inside the mouthpiece with a damp cloth or tissue only, at least once a week.Any minor discoloration in the mouthpiece does not affect your Spiriva Respimat inhaler performance.If necessary, wipe the outside of your Spiriva Respimat inhaler with a damp cloth.

Child Dosage
Paediatric patients: Safety and effectiveness of tiotropium bromide inhalation powder in paediatric patients have not been established and therefore it should not be used in patients under 18 years of age.

Elderly Dosage
Geriatric patients can use tiotropium bromide at the recommended dose.

Contra Indications
Spiriva Respimat is contraindicated in patients with hypersensitivity to tiotropium bromide, atropine or its derivatives, e.g. ipratropium or oxitropium or to any of the excipients

Special Precautions
Tiotropium bromide, as a once daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy.Immediate hypersensitivity reactions may occur after administration of tiotropium bromide solution for inhalationConsistent with its anticholinergic activity, tiotropium bromide should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.Inhaled medicines may cause inhalation-induced bronchospasm.As plasma concentration increases with decreased renal function in patients with moderate to severe renal impairment (creatinine clearance 50 ml/min) tiotropium bromide should be used only if the expected benefit outweighs the potential risk. There is no long term experience in patients with severe renal impairment.Patients should be cautioned to avoid getting the spray into their eyes. They should be advised that this may result in precipitation or worsening of narrow-angle glaucoma, eye pain or discomfort, temporary blurring of vision, visual halos or coloured images in association with red eyes from conjunctival congestion and corneal oedema. Should any combination of these eye symptoms develop, patients should stop using tiotropium bromide and consult a specialist immediatelyDry mouth, which has been observed with anti-cholinergic treatment, may in the long term be associated with dental caries.Tiotropium bromide should not be used more frequently than once daily

Interactions
Although no formal drug interaction studies have been performed, tiotropium bromide has been used concomitantly with other drugs commonly used in the treatment of COPD, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids without clinical evidence of drug interactions.The co-administration of tiotropium bromide with other anticholinergic containing drugs has not been studied and therefore is not recommended.

Adverse Reactions
a) General descriptionMany of the listed undesirable effects can be assigned to the anticholinergic properties of tiotropium bromide.In combined one-year and three month studies of 849 patients receiving tiotropium bromide, the most commonly observed undesirable effect was dry mouth which occurred in approximately 6% of patients.b) Table of Undesirable effects according to the MedDRA terminologyThe frequencies assigned to the undesirable effects listed below are based on crude incidence rates of adverse drug reactions (i.e. events attributed to tiotropium by study investigators) observed in the tiotropium group (849 patients) pooled from two three-month and two one-year phase III placebo-controlled clinical trials. While some of the undesirable effects listed may in reality occur at lower frequencies than indicated below, the size of the source database did not allow for the assignment of frequency categories lower than the category 'uncommon'( 1/1,000, < 1/100).System Organ Class / MedDRA Preferred TermFrequency1Nervous system disorders DizzinessUncommonHeadacheUncommonEye disorders Vision blurredUncommonIntraocular pressure increasedNot known*GlaucomaNot known*Cardiac disorders PalpitationsUncommonSupraventricular tachycardiaUncommonAtrial fibrillationUncommonTachycardiaNot known*Respiratory, thoracic and mediastinal disorders CoughUncommonPharyngitis and other application site irritationUncommonDysphoniaUncommonBronchospasmNot known*EpistaxisNot known*SinusitisNot known*Gastrointestinal DisordersDry Mouth2CommonOral candidiasisUncommonGastrooesophageal reflux diseaseUncommonDysphagiaUncommonDental cariesNot known*Constipation2Not known*Intestinal obstruction, including ileus paralytic2Not known*NauseaNot known*Skin and subcutaneous tissue disorders, Immune system disordersPruritusUncommonNot known*RashNot known*UrticariaNot known*Other Hypersensitivity (including immediate reactions)Not known*Renal and urinary Disorders DysuriaUncommonUrinary retention2UncommonUrinary tract infectionNot known*1 common 1/100, < 1/10; uncommon 1/1,000, < 1/100 according to frequency convention2 see section c)* frequency not known, no adverse drug reaction observed in 849 patientsc) Information characterising individual serious and/or frequently occurring undesirable effects The most common anticholinergic adverse reaction reported by COPD patients was dry mouth. Dry mouth was mild in the majority of cases. In general, dry mouth had an onset between 3 and 5 weeks. Dry mouth commonly resolved while patients continued to receive tiotropium bromide, but led to discontinuation from the combined one-year and 3-month trials by 2 of 849 (0.2%) patients in the active treatment group.Serious undesirable effects consistent with anticholinergic effects include constipation, intestinal obstruction including ileus paralytic and urinary retention, though none were reported in the tiotropium Respimat development program.d) Pharmacological class - undesirable effects Several organ systems and functions are under control of the parasympathetic nervous system and thus can be affected by anticholinergic agents. Possible adverse events attributable to systemic anticholinergic effects include dry mouth, dry throat, tachycardia, blurred vision, increased intraocular pressure, glaucoma, urinary difficulty, urinary retention, and constipation. Urinary retention, when reported in the overall tiotropium data base, was usually observed in elderly men with predisposing factors, (e.g. prostatic hyperplasia). Increased incidences of dry mouth and constipation may occur with increasing age. In common with all inhaled medications, tiotropium bromide may cause inhalation-induced bronchospasm. Local upper airway irritant phenomena have also been observed in patients receiving tiotropium bromide.

Manufacturer
Boehringer Ingelheim

Drug Availability
(POM)

Updated
12 August 2009