Drug information of Selegiline

Mechanism of effect

Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain.

Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monoamine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.

Pharmacodynamic

Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine.

Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells.

Pharmacokinetics

• Bioavailability:4% (oral, fasted), 20% (oral, after food), 73% (patch)
• Protein binding: ≥85–90% 

• Metabolism:

Extensive in liver

Metabolites include: N-desmethylselegiline, L-amphetamine and L-methamphetamine

• Half-Life:

10 hours (oral), 18–25 hours (transdermal)
Excretion : 

Urine (main route) 

Dosage

Usual Adult Dose for Parkinson's Disease

Oral tablet:
Recommended dose: 5 mg orally twice a day
Maximum dose: 10 mg orally per day

Oral disintegrating tablet:
Initial dose: 1.25 mg orally once a day for at least 6 weeks.
Maintenance dose: 1.25 to 2.5 mg orally once a day
Maximum dose: 2.5 mg orally once a day

Drug contraindications

phaeochromocytoma

Side effects

anemia , Anxiety , Insomnia , Diarrhea , Headache , weight decrease , nausea , dry mouth , dizziness , vertigo , hallucinations , tiredness , Abdominal pain , urinary retention

Interactions

Expectorant , Doxepin , Ephedrine , Sibutramine , Citalopram , fentanyl , Tapentadol , Pethidine , safinamide , teriflunomide , rasagiline , Diethylpropion , Phenylpropanolamine , apraclonidine , Benzatropine , lisdexamfetamine , Lorcaserin , Methohexital , Alphagan , Nitrous oxide , Desvenlafaxine , Xylometazoline , Propylhexedrine , Milnacipran , acrivastine+pseudoephedrine , Doxylamine , Dexfenfluramine , chlorcyclizine + pseudoephedrine , chlorcyclizine + phenylephrine , Butorphanol , Benzphetamine , Acetaminophen and benzhydrocodone , Dipipanone , Difenoxin , Levomilnacipran , Guanadrel , 5-hydroxytryptophan , Ethchlorvynol , phendimetrazine , tropisetron , Cannabidiol , chlorcyclizine , Netupitant , Nesiritide

Alerts

• Selegiline should not be used at daily doses exceeding those recommended (10 mg/day) because of the risks associated with non-selective inhibition of MAO.
• Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of
• Some patients given Selegiline may experience an exacerbation of levodopa associated side effects, presumably due to the increased amounts of dopamine reaction with super sensitive, post-synaptic receptors. These effects may often be mitigated by reducing the dose of levodopa/carbidopa by approximately 10 to 30%.
• Patients should be advised of the possible need to reduce levodopa dosage after the initiation of Selegiline therapy.
• Patients (or their families if the patient is incompetent) should be advised not to exceed the daily recommended dose of 10 mg. The risk of using higher daily doses of Selegiline should be explained, and a brief description of the `cheese reaction' provided. Rare hypertensive reactions with Selegiline at recommended doses associated with dietary influences have been reported.

Points of recommendation

Tell your doctor if:

- If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.

- If you have taken fluoxetine within the last 5 weeks. Do not start this medicine (selegiline capsules and tablets) if you have taken fluoxetine within the last 5 weeks.

- If you have any of these health problems: Kidney disease or liver disease.

- If the patient is a child. This medicine is not approved for use in children.

- If you are breast-feeding or plan to breast-feed.

• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine (selegiline capsules and tablets) affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this medicine (selegiline capsules and tablets), you will want to slowly stop it as ordered by your doctor.
• Avoid drinking alcohol while taking this medicine (selegiline capsules and tablets).
• A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take this medicine (selegiline capsules and tablets) with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine (selegiline capsules and tablets) while you are pregnant.
• Before using this medication, tell your doctor or pharmacist your medical history, especially of: a certain kind of adrenal gland tumor (pheochromocytoma), cerebrovascular disease (e.g., stroke), heart problems (e.g., congestive heart failure, heart attack), bleeding problems, history of severe/frequent headaches, peptic ulcer, diabetes, personal/family history of mental/mood disorders (e.g., schizophrenia, bipolar disorder), personal/family history of high blood pressure, liver disease, overactive thyroid (hyperthyroidism).

Pregnancy level

C

Related drugs

Phenelzine , isocarboxazid , safinamide , rasagiline , Apomorphine