Drug Interactions between Anoro Ellipta and olanzapine

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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GENERALLY AVOID: The potential exists for additive anticholinergic effects such as mydriasis, blurred vision, heat intolerance, fever, dry mouth, tachycardia, urinary retention, constipation, and glaucoma (onset or exacerbation) when topical or inhaled anticholinergic agents are used with each other or with other agents that possess anticholinergic properties. The risk of systemic anticholinergic effects following topical administration depends on variables such as strength of the product, size of the application area, frequency of application, and use of occlusive dressing. Systemic effects are uncommon following oral inhalation or nasal administration due to the poor absorption of quaternary ammonium compounds from gastrointestinal and nasal mucosa. However, worsening of urinary retention or angle-closure glaucoma has been reported with the use of orally inhaled anticholinergic agents. Increased intraocular pressure and precipitation or exacerbation of angle-closure glaucoma may also occur due to inadvertent contact of the eye with aerosolized or nebulized drug.

MANAGEMENT: Topical and inhaled anticholinergic preparations should preferably not be used in combination with other anticholinergic agents or agents with significant anticholinergic effects such as antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, and class IA antiarrhythmics (especially disopyramide). Caution is advised if concomitant use cannot be avoided, particularly in the elderly and those with significantly impaired renal and/or hepatic function. Measures should be taken whenever possible to minimize ocular exposure to these drugs, such as keeping eyes closed during oral inhalation, use of a mouthpiece rather than face mask during nebulization, and not touching the eyes following topical application until hands are washed with soap and water. Patients should be advised to contact their physician if they experience excessive anticholinergic adverse effects or signs and symptoms of angle-closure glaucoma (e.g., eye pain or discomfort; blurred vision; visual halos; colored images in association with red eyes from conjunctival congestion or corneal edema).

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