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In view of the high degree of binding to plasma proteins by selegiline particular attention must be given to patients who are being treated with medicines with a narrow therapeutic marginindexsuch as digitalis and/or anticoagulants.
Selegiline should be used with caution in severe liver or kidney dysfunction.
This deteriorating response is currently interpreted as a manifestation of the inability of the ever decreasing population of intact nigrostriatal neurons to synthesize and release adequate amounts of dopamine.
No teratogenic effects were observed in a study of embryo-fetal development in Sprague-Dawley rats at oral doses of 412and 36 mg/kg or 412 and 35 times the human therapeutic dose on a mg/m 2 basisNo teratogenic effects were observed in a study of embryo-fetal development in New Zealand White rabbits at oral doses of 525and 50 mg/kg or 1048and 95 times the human therapeutic dose on a mg/m 2 basishoweverin this studythe number of litters produced at the two higher doses was less than recommended for assessing teratogenic potentialIn the rat studythere was a decrease in fetal body weight at the highest dose testedIn the rabbit studyincreases in total resorptions andpost-implantation lossand a decrease in the number of live fetuses per dam occurred at the highest dose testedIn a periand postnatal development study in Sprague-Dawley ratsoral doses of 416and 64 mg/kg or 415and 62 times the human therapeutic dose on a mg/m 2 basisan increase in the number of stillbirths and decreases in the number of pups per dampup survivaland pup body weightat birth and throughout the lactation periodwere observed at the two highest dosesAt the highest dose testedno pups born alive survived to Day 4 postpartumPostnatal development at the highest dose tested in dams could not be evaluated because of the lack of surviving pupsThe reproductive performance of the untreated offspring was not assessed.
The bioavailability of selegiline is increased 3 to 4 fold when it is taken with food.
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