The P-I-E-N-O Parkinsn's List Drug Database
selegiline / EldeprylTM , DeprenylTM
ANTIPARKINSON:
MAO-B INHIBITOR: HIGH RISK
Description: Selegiline (also commonly known as deprenyl or deprenil) is an oral agent used in the treatment of idiopathic Parkinson's disease, in combination with levodopa or levodopa and carbidopa. Due to its selectivity for MAO type B, selegiline is purported to possess fewer drug interactions and a lower risk of hypertension than phenelzine (NardilTM ). In controlled clinical trials, selegiline caused slight improvement in motor performance at the start of therapy and worsening at its discontinuance; it also delayed the development of disability that requires the addition of levodopa. Selegiline was approved by the FDA in June 1989. A transdermal delivery system is currently under investigation.
Mechanism of Action: Selegiline is a noncompetitive antagonist of monoamine oxidase type B (MAO-B), the main form of this enzyme in the human brain. Monoamine oxidase type B is responsible for the oxidative deamination of dopamine in the brain. Blockade of this enzyme reduces the metabolism of dopamine, decreases free radical production, and potentiates the effects of administered levodopa. It is unknown whether the benefits seen in Parkinson's disease occur from increased dopaminergic transmission or from a decreased rate of neuronal death due to free radicals. Selegiline doses of 10 mg/day block essentially all the MAO-B in the adult brain. Selegiline's duration of action depends on the time required to regenerate MAO type B. At higher selegiline doses (e.g., 20-40 mg/day), brain MAO is blocked nonselectively, predisposing patients to the risks of traditional MAOIs that block MOA type A (e.g., hypertension). Like phenelzine, the effects of selegiline are cumulative, with beneficial effects seen in a few days to several months.
Pharmacokinetics: Selegiline is administered orally and is readily absorbed from the GI tract and crosses the blood/brain barrier. Peak serum concentrations are found in 0.5-2 hours. The drug is rapidly and completely metabolized to three active derivatives with the following half-lives: N-desmethyldeprenyl, 2 hours; 1-amphetamine, 17.7 hours; and 1-methamphetamine, 20.5 hours. Selegiline is eliminated slowly by the kidneys; about 45% of a single 10 mg dose is eliminated in the urine as the three active metabolites in 48 hours.
CONTRAINDICATIONS/PRECAUTIONS: Selegiline is relatively contraindicated in patients with profound dementia, severe psychosis, tardive dyskinesia, or excessive tremor because these conditions can be exacerbated.
Selegiline is relatively contraindicated in patients with peptic ulcer disease due to possible reactivation of ulcers. This effect is believed to be caused by stimulation of the histamine receptors in the stomach or by the inhibition of MAO in the stomach, preventing the breakdown of gastric histamine.
Selegiline should be used cautiously in pregnant women. The effects on the fetus during pregnancy are not known.
DRUG INTERACTIONS: Selegiline is a monoamine oxidase inhibitor. In general, tricyclic antidepressants should be used cautiously, if at all, in patients receiving drugs with monoamine oxidase inhibitor (MAOI) activity. Although at low doses selegiline is selective for MAO type B, in doses above 30-40 mg/day, this selectivity is lost. Selegiline, despite its selectivity, can provoke serious CNS reactions in patients receiving either tricyclic antidepressants (clomipramine, desipramine, etc.) or fluoxetine. Concomitant administration of selegiline and fluoxetine can cause mania and the development of a serotonin syndrome (characterized by hyperthermia, diaphoresis, shivering, tremor, myoclonus, seizures, ataxia, delirium, restlessness). Concurrent use of selegiline with fluoxetine is not recommended because of this rare, but serious reaction. At least 2 weeks should pass between the last dose of a MAO inhibitor and the first dose of fluoxetine. However, at least a 5-week interval is needed between the last dose of fluoxetine and initiation of MAO-inhibitor therapy because of the prolonged elimination of fluoxetine. It is unclear if selegiline interacts similarly with other member of the selective serotonin reuptake inhibitors (SSRIs).
Administration of levodopa to patients receiving drugs that inhibit monoamine oxidase (MAO) can produce a hypertensive response. While traditional MAOIs such as phenelzine inhibit MAO type A and selegiline is selective for MAO type B, at doses above 30-40 mg/day, this selectivity is lost. Selegiline can increase levodopa-induced dyskinesias, nausea, orthostatic hypotension, confusion, and hallucinations. Reductions in levodopa dosage may be necessary within a few days after the start of selegiline treatment. Even though Parkinson's disease is an indication for both selegiline and levodopa, and these 2 drugs may be administered together safely in some cases, patients should be monitored closely for hypertensive responses, especially if selegiline doses higher than 10 mg/day are used.
Administration of meperidine to patients receiving drugs that inhibit monoamine oxidase (MAO) can cause excitation, sweating, severe hypertension, and rigidity. In some patients, hypotension, respiratory depression, coma, vascular collapse, and death have occurred. Meperidine may block reuptake of serotonin; other drugs that block serotonin reuptake, such as fluoxetine, have caused a similar reaction when administered concomitantly with selegiline. In addition, meperidine is not to be used within 2-3 weeks of MAO-inhibitor therapy. Since selegiline also inhibits MAO (albeit type B), concomitant use of meperidine with selegiline should be avoided.
Sumatriptan is an agonist at serotonin receptors while fluoxetine inhibits the reuptake of serotonin. A serious drug interaction has been described between selegiline and fluoxetine. Because both sumatriptan and fluoxetine potentiate serotonin (albeit by different mechanisms), it is possible that the serotonin syndrome described for fluoxetine-selegiline may also occur during concomitant use of sumatriptan and selegiline. Although no data are available on the combination of sumatriptran and selegiline, clinicians should consider this theoretical possibility.
Isolated reports suggest dextromethorphan may produce a severe, adrenergic response if administered to patients receiving MAOIs. It is unclear if selegiline and dextromethorphan produce a similar reaction.
At doses of 20 mg/day, selegiline can interact with foods and beverages containing high concentrations of pressor amines such as tyramine. Sudden and severe hypertensive reactions are possible. This reaction is believed to be a result of selegiline's effects on MAO type A, which occurs at higher doses. Dietary restrictions should be observed for at least 2 weeks after the last dose of any MAO inhibitor. Other catecholamine-releasing or sympathomimetic agents (e.g., ephedrine, phenylpropanolamine) may induce drug interactions with selegiline at higher doses.
ADVERSE REACTIONS: Selegiline therapy is adjunctive to levodopa and can potentiate dose-related adverse reactions to levodopa. A decrease in levodopa/carbidopa dosage may reduce the incidence of adverse reactions.
The incidence of adverse effects attributable to selegiline is difficult to ascertain. Reactions that led to discontinuation of therapy during pre-marketing studies were nausea/vomiting, hallucinations, confusion, mental depression, loss of balance, insomnia, orthostatic hypotension, increased akinetic involuntary movements, agitation, arrhythmias, bradykinesia, chorea, delusions, hypertension, new or increased angina pectoris, and syncope. Dyskinesias and mood lability (irritability, mood changes, agitation) are frequent side effects of selegiline therapy that require medical intervention. Extrapyramidal symptoms such as akathisia, or dystonia may occur. Tardive dyskinesia has been reported infrequently. During placebo-controlled trials dizziness was recorded in 7% of patients.
During placebo-controlled clinical trials the most common adverse effect produced by selegiline on the GI tract was nausea. Abdominal pain, anorexia, constipation, diarrhea, dysphagia, heartburn, rectal bleeding, and xerostomia, have also been reported in clinical studies. Incidence of GI bleeding may be attributable to exacerbation of existing peptic ulcer disease. Weight loss occurred infrequently.
MAOIs in general can predispose patients to develop a hypertensive crisis. Selegiline selectively inhibits MAO type B and at recommended dosage levels does not affect MAO type A which is the predominant MAO found in the gut. Patients taking selegiline can therefore consume foods containing tyramine, or medicines containing pharmacologically active amines with less risk of uncontrolled hypertension. The possibility of hypertension may still exist during selegiline therapy, especially at a dosage greater than 10 mg per day. Patients should be warned to report severe or continuing headache and any other symptoms of hypertension, such as angina, sinus tachycardia, sinus bradycardia, palpitations, mydriasis, diaphoresis, nausea/vomiting, stiff or sore neck, and fever.
Urinary retention occurred in clinical investigations using selegiline. Difficult or painful urination may occur from prostatic hypertrophy.
Selegiline may cause the feet and legs to swell because of peripheral edema.
Other adverse effects that have been reported with selegiline therapy are: anxiety or nervousness, bronchospasm, dysgeusia, drowsiness, paresthesias, sexual dysfunction, and tinnitus.
PATIENT INFORMATION:
What do selegiline tablets do?
Selegiline (EldeprylTM ) helps to increase or extend the effects of levodopa or carbidopa, and slow the progression of Parkinson's disease. Selegiline belongs to a class of drugs, called monoamine oxidase inhibitors (MAOIs), that block certain enzymes in the brain and change the balance of certain chemicals in the brain. Generic selegiline tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take selegiline?
They need to know if you have any of these conditions:
How should I take this medicine?
Take selegiline tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice. Do not take doses in the late afternoon or evening.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with selegiline?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking selegiline?
Serious side effects with selegiline include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with selegiline include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take selegiline?
Visit your doctor for regular checks on your progress. It can take up to 4 weeks to see the full effects of selegiline. Do not suddenly stop taking your medicine; this may make your condition worse or give you withdrawal symptoms. Ask your doctor for advice about gradually reducing your dosage. Even after you stop taking selegiline the effects can last for at least two weeks.
If your doctor increases the dose of selegiline to more than 10 mg a day, ask him/her about possible interactions with foods that contain tyramine. At higher doses, selegiline may interact with these foods to produce severe headaches, a rise in blood pressure, or irregular heart beat.
Call your doctor as soon as you can if you get frequent headaches or have palpitations.
You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how selegiline affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks. Selegiline can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.
Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects to selegiline.
If you are going to have surgery, tell your doctor or dentist that you are taking selegiline.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Throw away any unused medicine after the expiration date.
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