Drug interactions between Akineton HCl and levodopa

MONITOR: Anticholinergic agents may decrease the absorption and oral bioavailability of levodopa. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby increasing the gastric degradation of levodopa and reducing the amount available for absorption in the small intestine. In one study, pretreatment with trihexyphenidyl decreased the peak plasma concentration (Cmax) and delayed the time to peak concentration (Tmax) of levodopa in 3 of 6 healthy volunteers and 4 of 6 Parkinson patients. In another study, 42% of patients receiving levodopa with anticholinergic therapy developed abnormal involuntary movements compared to 19% of those treated with levodopa alone. Discontinuation or dosage reduction of anticholinergic therapy resulted in disappearance or amelioration of the symptoms in 9 of 10 cases, although subsequent aggravation of Parkinsonism necessitated resumption of anticholinergic therapy in 5 cases. There is also a case report describing a patient who required large doses of levodopa during concomitant therapy with homatropine. Following discontinuation of homatropine, the patient exhibited symptoms of levodopa toxicity and required a significant decrease in the levodopa dosage. Other studies have reported no effect of anticholinergic agents on levodopa blood levels or pharmacologic effects.

MANAGEMENT: Although certain anticholinergic agents may be used as adjunctive therapy in Parkinson's disease, clinicians should recognize their potential to reduce the oral bioavailability of levodopa in some patients. Pharmacologic response to levodopa should be monitored more closely whenever anticholinergic agents are added to or withdrawn from therapy, and the dosages of the drugs adjusted as necessary.