01 2015 glycopyrronium drug assessment report bromide www.dtb.navarra.es @DTB_Navarre.es Seebri Breezhaler®, Enurev Breezhaler® in COPD. abstract Glycopyrronium bromide is an We´re not breathing anything inhaled long-acting muscarinic antagonist (LAMA) approved for new under the sun the relief of symptoms in adult patients with Chronic Obstruc- tive Pulmonary Disease (COPD).

The only head-to-head trial published to date showed non- inferiority vs tiotropium but not Indications1 Safety superiority. Glycopyrroium bromide is indicated as a main- Adverse reactions tenance bronchodilator treatment to relieve The most frequent adverse reactions descri- symptoms in adult patients with chronic obs- bed in clinical trials include: nasopharyngitis, The average change with respect tructive pulmonary disease (COPD). insomnia, cefalea, dry mouth, gastroenteritis to baseline FEV1 trough was 103 and urinary tract infections.1 mL (glycopyrronium) vs 99 mL Mechanism of action1 The trials also describe cases of atrial fi- (tiotropium), but there was no cli- Glycopyrromium is a long-acting muscarinic brillation at higher rates in the groups under nical relevance (120 mL). antagonist. It acts by blocking the bronchocons- glycopyrronium compared to the groups under trictor effect of acetylcholine on smooth mus- placebo.3,7 Safety profile remains inconclu- cle cells thus dilating the respiratory airways. sive given the short duration of the trials, the chronic nature of Posology and administration1 the disease and lack of data with The recommended dose consists of an inhala- regard to its cardiovascular tion of the contents of a capsule (liberating a No more effective safety profile. dose of 44 mcg of glycopyrronium) once daily by employing the Breezhaler inhaler, preferably than tiotropium and at the same time every day. unknown long-term CLASSIFICATION Clinical efficacy Two trials have been published comparing safety profile 2 IMPORTANT glycopyrronium compared to placebo (GLOW1 , THERAPEUTIC GLOW23) to evaluate lung function. Glycopyrro- INNOVATION nium proved significantly more effective than 4 placebo in FEV1 trough values after 12 weeks of MODEST THERAPEUTIC treatment, although clinical relevance remai- INNOVATION ned uncertain (difference with glycopyrronium The safety profile of glycopyrronium seems 3 of 108 mL in GLOW1 and 97mL in GLOW2). similar to that of tiotropium with a similar in- SOME ADDED Only one head-to-head non-inferiority trial cidence of overall adverse reactions (40.4% VALUE IN SPECIFIC lasting 12 weeks has been published (GLOW55) vs 40.6%, respectively). However, it should be 2 SITUATIONS which compared the efficacy and safety profile taken into account that the only comparative of glycopyrronium (50 mcg once daily) to tio- trial was of short duration and does not allow NO THERAPEUTIC tropium (18 mcg once daily). There were 657 for an adequate evaluation of the long-term INNOVATION participants (73.8% men) in the trial with an safety profile.5 1 average age of 63.5 years. The EMA Risk Management Plan recom- The results showed “non-inferiority” of glyco- mends post-marketing surveillance to moni- INSUFFICIENT EVIDENCE pyrronium vs tiotropium, with average changes tor both cardiovascular and cerebrovascular 7 0 with respect to baseline values in FEV1 trough events associated to glycopirronium. of 103 mL (glycopyrronium) and 99 mL (tiotro- pium), but with no clinical relevance (120 mL Contraindications1 according to the EMA criteria). Glycopyrronium bromide is contraindicated in With regard to the rate of exacerbations, cases of hypersensitivity to the active subs- The qualification assigned to the drug was reductions were similar in both groups under tance or to any of the excipients. As it contains agreed by the Drug Assessment Commit- glycopyrronium or tiotropium, with annual ra- lactose, patients with hereditary intolerance to tees of Andalusia, Basque Country, Catalonia tes of 0.38 and 0.35 respectively, although lon- galactose, Lapp lactase deficiency or problems Institute of Health, Aragon and Navarre. The current report is based on the available infor- ger trials (at least one year) are necessary to with the absorption of glucose or galactose mation and is susceptible to be updated ac- make an adequate evaluation.5 should not take this drug. cording to the latest evidence. Let us remind the reader about the importance of notifying the Pharmacovigilance Centre when there are suspicions of adverse reactions to drugs. Daily cost of treatment (E)

Formoterol 24 mcg 0.75 Salmeterol 100 mcg 1.19 Tiotropium, bromide 18 mcg 1.64 Aclidinium, bromide 644 mcg 1.59 Glycopyrronium , bromide 44 mcg 1.59

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80

Warnings and precautions1 Place in therapeutics recommended post-marketing follow-up. At Glycopyrronium bromide should be used Pharmacological management of COPD is present we are still awaiting results. with precaution in patients suffering from focused on reducing symptoms and/or com- Therefore taking into account the available narrow angle glaucoma, urinary retention plications. After diagnosis, treatment should data on efficacy and safety this agent cannot and with a history of cardiovascular disease. be initiated progressively in relation to the be considered as a first line option for the severity of the obstruction and the patient’s management of COPD. Use in special situations1 symptom profile, where bronchodilation re- Pregnancy and breastfeeding. There is no presents the first step in the management Presentations available information. Renal failure: it may of the disease. Inhaled bronchodilators such Seebri breezhaler®(Novartis), Enurev breez- be used in cases of mild to moderate renal as long-acting ß2-agonists (LABA) and haler® (Ferrer) 44 mcg 30 capsules+inhaler failure. Liver impairment: no information. long-acting muscarinic antagonists (LAMA) (47.61 €) Children: there are no recommendations constitute the basis of symptomatic mana- for specific use in children under 18 years. gement of COPD patients and permanent References symptoms.8,9 A complete report on Glycopyrronium bro- Interactions1 Glycopyrronium bromide is a new LAMA mide can be found at: www.bit.navarra.es Concomitant use of glycopyrronium bromi- for the management of COPD. There is one de with other anticholinergic agents is not only head-to-head trial (GLOW5)5 in which recommended. glycopyrronium has shown non inferiority but not superiority vs tiotropium on trough EMA Risk Management Plan7 FEV1 change. The EMA considers the need to carry out a Currently, the long-term profile of glyco- post-marketing safety trial on cardio and ce- pyrronium is still not defined as the duration rebrovascular events in order to clarify the of the trials was not long enough for evalua- safety profile of this drug. It also considers tion. Taking into account the potential for ad- the need for adequate representation in cli- verse cardiovascular reactions, and having nical trials of elderly patients with comor- excluded patients with cardio and cerebro- bidities or either liver or renal impairment. vascular risk from the trials, the EMA has

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