Drug Interactions between AlleRx Dose Pack PE (AM Dose) and olodaterol / tiotropium

MONITOR: The pressor response to phenylephrine may be potentiated by the vagolytic effect of atropine, which inhibits the reflex bradycardia that would normally accompany any increases in blood pressure induced by phenylephrine. Other antimuscarinic agents may also participate in this interaction, although clinical data are lacking. In one report, pseudo-pheochromocytoma (i.e., significant increases in blood pressure and tachycardia) occurred in seven patients who underwent eye surgery and were given phenylephrine 10% ophthalmic solution and systemic atropine, three of whom subsequently developed left ventricular failure and pulmonary edema that required intensive care monitoring. Two patients had preexisting hypertension, while others had no known history of cardiovascular disease. All had received general anesthesia with propofol, phenoperidine, and vecuronium. Since phenylephrine use alone may be associated with cardiovascular toxicities including hypertension, arrhythmia, myocardial infarction and cardiac failure, the extent of involvement by atropine is uncertain. The authors reported no further cardiovascular events following implementation of various measures that reduced phenylephrine dosage and systemic exposure, including: use of a milder strength of phenylephrine ophthalmic solution; swabbing to minimize drainage into the nasolachrymal duct to the nasal mucosa; and use of a cannula to reduce drop size. In a study of six healthy volunteers, diastolic and systolic blood pressure increased by 4 mmHg following administration of phenylephrine (0.42 mcg/kg/min), compared to 17 mmHg when phenylephrine was given after three doses of atropine (0.02, 0.01 and 0.01 mg/kg at 30 minute intervals).

MANAGEMENT: Caution is advised if phenylephrine (systemic or ophthalmic) is used in combination with atropine or other antimuscarinic agents. Cardiovascular status, including blood pressure and heart rate, should be closely monitored. When using ophthalmic formulations, measures to minimize systemic absorption should be employed, such as digital compression of the lacrimal sac or lid closure after instillation. A milder strength (< 10%) is preferable if phenylephrine ophthalmic solution is given.

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MONITOR: Coadministration of beta-2 adrenergic agonists with other adrenergic agents may potentiate the risk of cardiovascular side effects. Beta-2 adrenergic agonists can produce clinically significant cardiovascular effects including increases in pulse rate and systolic or diastolic blood pressure as well as ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The risk is lower when beta-2 adrenergic agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is advised if beta-2 adrenergic agonists are used concomitantly with other adrenergic agents, particularly in patients with cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, hypertrophic obstructive cardiomyopathy, or hypertension. Blood pressure and heart rate should be closely monitored.

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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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