SELEGILINE
Drugs in Pregnancy and Lactation.
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Name: SELEGILINE
Class: Antiparkinsonian Agent
Risk Factor: CM
Fetal Risk Summary
Selegiline (L-deprenyl; MAO-B), a selective irreversible inhibitor of monoamine oxidase type B, is used as an adjunct in the management of parkinsonian patients being treated with levodopa/carbidopa. The drug has no beneficial effect when used alone (1,2).
Reproduction studies in pregnant rats and rabbits at doses up to 35 and 95 times the human therapeutic dose on a body surface area basis (HTD), respectively, did not reveal any evidence of teratogenicity (1,2). At the highest doses tested, however, rat fetal body weight was decreased, and the number of resorptions and postimplantation losses in rabbits increased, resulting in fewer live fetuses. An increase in the number of stillbirths and decreases in pup survival and body weight (at birth and throughout the lactation period) were observed when rats were given doses up to 15 and 62 times the HTD during late gestation and throughout lactation (1,2). At 62 times the HTD, no pups born alive survived to day 4 postpartum.
In a 1994 study, rats were treated daily throughout gestation with a combination of SC selegiline (3 mg/kg) and clorgyline, a monoamine oxidase-A inhibitor (3 mg/kg) (3). In another treatment group, the same doses of the drugs were administered to pregnant females throughout gestation but, at birth, the daily injections of the drugs were administered to the pups until sacrifice. Saline control groups were used for comparison. Pregnancy duration was significantly longer in the treated groups than in controls, but the litter sizes were the same. Other developmental milestones (eye opening, incisor eruption, or olfactory responses) were similar to that of controls. Pup weight gain in both treatment groups was significantly slower than their controls. The decreased weight gain may have been due to less frequent nursing, a condition that was not resolved even when the pups were cross-fostered with control dams. None of the exposed offspring had changes in the development of the dopamine system (as indicated by dopamine terminal density). Moreover, monoamine oxidase (MAO) activity in the brain tissue of pups exposed to the drugs only during gestation was not significantly different from that of controls at 5 days of age. In contrast, MAO activity in pups continually exposed to the drugs was significantly less than controls. Compared with controls, the treatment groups were very aggressive, frequently biting the investigators. In addition, significant deficits in passive avoidance were observed at 24 days of age, and open field activity was significantly increased at 30 days of age. These two results were thought to be a measure of impulsivity (3). Major alterations of the serotonin system were also observed (as indicated by serotonin terminal density) in the hippocampus (higher density), caudate (higher density), and cortex (less density at 5 and 30 days, but increased at 15 days). Seizures and visual impairment were noted in pups that received the drugs during pregnancy and after birth, but not in those exposed only in utero.
It is not known if selegiline crosses the placenta to the fetus. The molecular weight (about 224 for the hydrochloride salt) is low enough, however, that passage to the fetus should be expected.
Human pregnancy experience with selegiline is limited. A 1998 report described a case involving a 34-year-old woman with an 8-year history of Parkinson's disease who became pregnant while under treatment with selegiline (10 mg/day), levodopa (450 mg/day), and benserazide (128.25 mg/day) (4). Because of insufficient pregnancy safety information, selegiline was discontinued (gestational time not specified). A normal healthy, 3050-g, 49-cm-long male infant was delivered at term with Apgar scores of 9, 10, and 10 at 1, 5, and 10 minutes, respectively.
In a second case, a 39-year-old woman with a 5-year history of Parkinson's disease took selegiline (10 mg/day), levodopa (400600 mg/day), and benserazide (100150 mg/day) throughout gestation (5). She was advised to stop selegiline but continued it against medical advice. She delivered a healthy 3800-g male infant at term with Apgar scores of 10 at 1 and 10 minutes. She breast-fed the infant for 3 days and then changed to bottle-feeding out of concern over drug transfer into her breast milk. The boy, monitored closely by a pediatrician and a neurologist, was doing very well at 10 years of age with normal somatic and mental development, and was excelling at school and in sports.
In summary, only two cases of exposure to selegiline during human pregnancy have been located, and only one of them involved exposure throughout gestation. Although there is no indication of physical teratogenicity in animal studies or the two human cases, selegiline did result in significant neurochanges in rats when combined with another monoamine oxidase inhibitor. Until additional human data are available, the use of selegiline during pregnancy should be avoided if possible (4,5).
Breast Feeding Summary
Except for the one case above (breast feeding for 3 days), no reports have described the use of selegiline during human lactation. The molecular weight (about 224 for the hydrochloride salt) is low enough that excretion into breast milk should be expected. The effects of this exposure on a nursing infant are unknown. However, significant neurotoxicity was observed in rat pups administered the combination of selegiline and clorgyline directly (see above) (3). Although, in that study, two MAO inhibitors were used and the dose of selegiline was high, the safest course is to avoid selegiline during breast feeding, at least until the amount of the drug in human milk has been determined.
References
- Product information. Carbex. Endo Pharmaceuticals, 2000.
- Product information. Eldepryl. Somerset Pharmaceuticals, 2000.
- Whitaker-Azmitia PM, Zhang X, Clarke C. Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies. Neuropsychopharmacology 1994;11:12532.
- Hagell P, Odin P, Vinge E. Pregnancy in Parkinson's disease: a review of the literature and a case report. Mov Disord 1998;13:348.
- Kupsch A, Oertel WH. Selegiline, pregnancy, and Parkinson' disease. Mov Disord 1998;13:17594.
Q&A about Selegiline
Selegiline is used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease. It is also used to treat the same muscular conditions when they are caused by drugs such as chlorpromazine (Thorazine), fluphenazine (Prolixin), perphenazine (Trilafon), and others
My dog had five seizures after he went on anipryl and SAM-e.
I was prescribed Emsam (Selegiline transdermal patch) for depression ~1 week ago. It is an MAO inhibitor. According to my doc, it could take up to 3 weeks to start working. A study I found online (http://www.ajp.psychiatryonline.org/cgi/... shows minimal effects over placebo after one week, but it really doesn't start working until 3-4 weeks or even longer. What is the chemical/physiological reason for this delay?
My 12 year old Rat Terrier has been taking Selegiline 5 mg for the past five years. He was prescribed this medicine by a vet when I expressed my concern over severe anxiety in my dog. I now would like to switch to something more homeopathic or natural. Does anyone have any suggestions? This is for an anxiety problem that is not merely situational (i.e. fireworks, riding in a car, etc.) but pretty much all the time.
http://www.rescueremedy.com/pets/