Topiramate
Tricyclic antidepressants
Hyoscyamine Interactions
Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include amantadine, amoxapine, bupropion, clozapine, cyclobenzaprine, disopyramide, maprotiline, olanzapine, orphenadrine, the sedating H1-blockers, most phenothiazines, and most tricyclic antidepressants. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. With many of the listed agents, additive drowsiness may also occur when combined with hyoscyamine.
Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
Drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Examples of drugs that significantly decrease GI motility include the antimuscarinics.
Oral formulations of digoxin can produce higher serum concentrations when administered concurrently with antimuscarinics (e.g., propantheline) because of decreased GI motility induced by the antimuscarinic agent. This interaction has mostly occurred in the literature with slowly-dissolving, large-particle formulations of digoxin tablets; the manufacture of oral digoxin products today, utilizing liquid formulations and/or smaller particle sizes, theoretically reduces the potential for absorption interactions. However, there is wide variability expected in individual responses to many digoxin-drug interactions. Other pharmacodynamic and pharmacokinetic systemic interactions are possible between digoxin and select antimuscarinic agents. Anticholinergics, because of their ability to cause tachycardia, can also antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if hyoscyamine is added. Furthermore, the antimuscarinic properties of hyoscyamine, by slowing GI transit, may decrease levodopa bioavailability however this mechanism appears to be of modest clinical significance.
The muscarinic actions of drugs known as parasympathomimetics (e.g., bethanechol), including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of hyoscyamine.
Ketoconazole requires an acidic pH for oral absorption. Medications that increase gastric pH or decrease acid output can cause a notable decrease in the bioavailability of ketoconazole. Medications that have this effect include antimuscarinics. Antimuscarinics have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction. An alternative imidazole antifungal should be considered if antimuscarinic medications are required.
Because hyoscyamine exhibits antimuscarinic properties that may slow GI motility, use with caution in patients receiving cisapride, erythromycin (when erythromycin is being administered to enhance GI motility), metoclopramide, or tegaserod. Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. The clinical significance of these potential interactions is uncertain.
Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
Through an additive effect, the use of topiramate (a weak carbonic anhydrase inhibitor) with agents that may increase the risk for heat-related disorders, such as antimuscarinics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
Antacids may inhibit the oral absorption of hyoscyamine and other antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
The adverse effects of antimuscarinics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered.
[ Last revised: 3/8/2005 1:09:00 PM ]
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