Drug Interaction Report

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).

The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown.

The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category:

• darifenacin
• Spiriva (tiotropium)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.