Search The Medical Knowledge Base

Drug Details

Eldepryl 10mg Tablets

• Drug Class Description
  Monoamine-oxidase-B inhibitors.
• Generic Name
  Selegiline Hydrochloride
• Presentation
  Tablets for oral administration.
• Description
  Selegiline hydrochloride 10 mg
• Indications
  

  Selegiline is indicated for the treatment of Parkinson's disease, or symptomatic parkinsonism. It may be used alone in early Parkinson's disease for symptomatic relief to delay the need for levodopa (with or without decarboxylase inhibitor) or as an adjunct to levodopa (with or without decarboxylase inhibitor). Selegiline in combination with maximal levodopa therapy is indicated particularly in patients who experience fluctuations in their condition such as 'end-dose' type fluctuations, 'on-off' symptoms or other dyskinesias.

• Adult Dosage
  

  10 mg daily either alone or as an adjunct to levodopa or levodopa/peripheral decarboxylase inhibitor. Selegiline may be administered either as a single dose in the morning or in two divided doses of 5 mg, taken at breakfast and lunch. When selegiline is added to a levodopa regimen it is possible to reduce the levodopa dosage by an average of 10 -30%. Reduction of the levodopa dose should be gradual in steps of 10% every 3 to 4 days.

  No dosage adjustment is required for patients with renal or hepatic impairment.

• Contra Indications
  

  Eldepryl is contra-indicated in patients with known hypersensitivity (including severe dizziness or hypotension) to selegiline or any of the excipients used in this product.

  Eldepryl is contra-indicated in patients receiving treatment with serotonin-agonists (e.g. sumatriptan, naratriptan, zolmitriptan and rizatriptan).

  Selegiline is also contra-indicated for concomitant use with pethidine and other opioids.

  Selegiline should not be used in patients who are being treated with antidepressant drugs, including MAO inhibitors tricyclic antidepressants, serotonin noradrenalin reuptake inhibitors (venlafaxine) and selective serotonin reuptake inhibitors (e.g citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline).

  Selegiline should also not be used with other drugs which are also monoamine oxidase inhibitors, e.g. linezolid.

  Selegiline should not be used in combination with sympathomimetics.

  Selegiline should not be used in patients with active duodenal or gastric ulcer.

  Selegiline should not be used in patients with other extrapyramidal disorders not related to dopamine deficiency.

  Selegiline in combination with levodopa is contra-indicated in severe cardiovascular disease, arterial hypertension, hyperthyroidism, phaeochromocytoma, narrow-angle glaucoma, prostatic adenoma with appearance of residual urine, tachycardia, arrhythmias, severe angina pectoris, psychoses, advanced dementia and thyrotoxicosis.

• Special Precautions
  

  The precise dose at which selegiline becomes a non-selective inhibitor of all MAO has not been determined, but with doses higher than 10 mg/day there is a theoretical risk of hypertension after ingestion of tyramine-rich food.

  Concomitant treatment with medicines which inhibit MAO-A, (or non-selective MAO inhibitors) can cause hypotensive reactions. Hypotension, sometimes sudden in onset, has been reported with conventional selegiline.

  Special care should be taken when administering selegiline to patients who have labile hypertension, cardiac arrhythmias, severe angina pectoris, psychosis or a history of peptic ulceration as aggravation of these conditions may occur during treatment.

  Although serious hepatic toxicity has not been observed, caution is recommended in patients with a history of hepatic dysfunction. Transient or continuing abnormalities with a tendency for elevated plasma concentrations of liver enzymes have been described during long-term therapy with conventional tablets of selegiline.

  Selegiline should be used with caution in severe liver or kidney dysfunction.

  Caution should be exercised in patients receiving MAO inhibitors during general anaesthesia in surgery.

  Some studies concluded in an increased risk of mortality in patients receiving selegiline and levodopa compared to those receiving levodopa only. However, it is noteworthy that multiple methodological bias were identified in these studies and that a meta analysis and large cohort studies concluded that there was no significant difference in mortality in patients treated with selegiline to those treated with comparators or with the association selegiline/levodopa.

  Studies have related the risk of an increased hypotensive response to concomitant administration of selegiline and levodopa, in patients with cardiovascular risk.

  The addition of selegiline to levodopa may not be beneficial in those patients who experience fluctuations in response which are not dose dependent.

  Caution is advised when selegiline is taken in combination with other centrally acting medicinal products and substances. The concomitant intake of alcohol should be avoided.

  Since selegiline potentiates the effects of levodopa, the adverse effects of levodopa may be increased. When selegiline is added to the maximum tolerated dose of levodopa, involuntary movements and agitation may occur. Levodopa should be reduced by about 10 to 30% when selegiline is added to the treatment. When an optimum dose of levodopa is reached, adverse effects from the combination are less than those observed with levodopa on its own.

   

• Interactions
  

  Association contra-indicated

  Sympathomimetics

  Because of the risk of hypertension, co-administration of selegiline and sympathomimetics is contraindicated.

  Pethidine

  The concomitant administration of the selective MAO-B inhibitor selegiline and pethidine is contraindicated.

  Selegiline should not be administered with any type of antidepressant.

  Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs)

  When selegiline is used at its recommended dose, it selectively inhibits MAO-B. The combined use of the SSRI, fluoxetine and Eldepryl, should only be used under clinical supervision.

  Serious reactions with signs and symptoms that may include diaphoresis, flushing, ataxia, hyperthermia, hyper/hypotension, seizures, palpitation, dizziness and mental changes that include agitation, confusion and hallucinations progressing to delirium and coma have been reported in some patients receiving a combination of selegiline and fluoxetine. Similar experience has been reported in patients receiving selegiline and two other serotonin reuptake inhibitors, sertraline and paroxetine. There is a potential risk of interaction with fluvoxamine and venlafaxine.

  Because of the risk of confusion, hypomania, hallucination and manic episodes, agitation, myoclonus, hyperreflexia, incoordination, shivering, tremor, convulsion, ataxia, diaphoresis, diarrhea, fever, hypertension, which can be part of the serotonine syndrome, concomitant administration of selegiline and SSRIs or SNRIs is contraindicated.

  Use of Eldepryl beyond the recommended dose could lead to non-selectivity and serious adverse effects.

  Death has been reported to occur following the initiation of therapy with non-selective MAO inhibitors shortly after discontinuation of fluoxetine. Fluoxetine should not be used less than 14 days after discontinuation of selegiline. Since fluoxetine has a very long elimination half life, at least 5 weeks should be allowed after stopping fluoxetine and before starting selegiline.

  Selegiline should not be started until 2 weeks after stopping sertraline. For all other serotonin reuptake inhibitors, a time interval of 1 week is recommended between discontinuation of the serotonin reuptake inhibitor and initiation of selegiline. In general, selegiline should not be introduced after a drug that is known to interact with selegiline, until after 5 half lives of that drug have elapsed.

  At least 14 days should lapse between the discontinuation of selegiline and initiation of treatment with any drug known to interact with selegiline.

  A time interval of 24 hours is recommended between the discontinuation of selegiline and initiation of serotonin agonists.

  Patients being treated with selegiline currently or within the past 2 weeks should receive dopamine only after careful risk-benefit assessment, as this combination enhances the risk of hypertensive reactions.

  Tricyclic antidepressants

  Severe CNS toxicity (serotonin syndrome) has been reported in patients with the combination of tricyclic antidepressants and selegiline. In one patient receiving amitriptyline and selegiline this included hyperpyrexia and death, and another patient receiving protriptyline and selegiline experienced tremor, agitation, and restlessness followed by unresponsiveness and death two weeks after selegiline was added.

  Other adverse reactions occasionally reported in patients receiving a combination of selegiline with various tricyclic antidepressants include hyper/hypotension, dizziness, diaphoresis, tremor, seizures and changes in behavioural and mental status. Therefore, the concomitant use of selegiline and tricyclic antidepressants is contraindicated.

  Associations not recommended

  MAO inhibitors

  Concomitant administration of selegiline and MAO inhibitors may cause severe hypotension.

  Oral contraceptives

  The combination of selegiline and oral contraceptives or drugs for hormone replacement therapy, should be avoided, as this combination may multiply the bioavailability of selegiline.

  Concomitant administration of amantadine and anticholinergic drugs can lead to an increased occurrence of side-effects.

  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 margin such as digitalis and/or anticoagulants.

  Four patients receiving altretamine and a monamine oxidase inhibitor experienced symptomatic hypotension after four to seven days of concomitant therapy.

  Concomitant treatment with medicinal products, with a narrow therapeutic index such as digitalis and/or anticoagulants, requires caution and careful monitoring.

  Concomitant use of hypertensive agents, antihypertensives, psychostimulants, central suppressant drugs (sedatives, hypnotics) and alcohol should be avoided.

  Food interactions

  As selegiline is a specific MAO-B inhibitor, foods containing tyramine have not been reported to induce hypertensive reactions during selegiline treatment at recommended dosage (i.e., it does not cause the so-called “ cheese-effect ”). Therefore, no dietary restrictions are required. However, in case of combination of selegiline and conventional MAO inhibitors or MAO-A, dietary restrictions (i.e. avoidance of food with large amounts of tyramine such as aged cheese and yeast products) are recommended.

• Adverse Drug Reactions
  

  The following undesirable effects have been reported with selegiline during clinical trials and/or post-marketing use. They are listed below as MedDRA preferred term by system organ class and frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common ( 1/10); Common ( 1/100 to <1/10); Uncommon ( 1/1,000 to <1/100); Rare ( 1/10,000 to <1/1,000); Very rare (<1/10,000), Not known (cannot be established from the available data).

  System Organ Class	Frequency	Undesirable effects
  Infections and infestations	Uncommon	Pharyngitis
  Blood and lymphatic system disorders	Uncommon	Leucocytopenia, thrombocytopenia
  Metabolism and nutrition disorders	Uncommon	Loss of appetite
  Psychiatric disorders	Common	Sleeping disorders, confusion, hallucinations, depression
  	Uncommon	Abnormal dreams, agitation, anxiety, psychoses, mood change
  	Not known	Hypersexuality
  Nervous system disorders	Common	Abnormal movements (such as dyskinesias, akinesia, bradykinesia), dizziness, headache, impaired balance, tremor
  	Uncommon	mild transient sleep disorder
  Eye disorders	Uncommon	Blurred vision
  Ear and labyrinth disorders	Common	Vertigo
  Cardiac disorders	Common	Bradycardia
  	Uncommon	Arrhythmias, palpitations, angina pectoris, supraventricular tachycardia
  Vascular disorders	Common	hypotension, hypertension
  	Uncommon	Orthostatic hypotension
  	Rare	Postural hypotension
  Respiratory, thoracic and mediastinal disorders	Common	Nasal congestion, sore throat
  	Uncommon	Dyspnoea
  Gastrointestinal disorders	Very common	Stomatitis
  	Common	Nausea, constipation, diarrhoea, mouth ulceration
  	Uncommon	Dry mouth
  Hepato-biliary disordrers	Uncommon	Transient rise of serum alanine aminotransferase (ALAT)
  Skin and subcutaneous tissue	Common	Sweating increased
  	Uncommon	Hair loss, skin eruptions
  	Rare	Skin reactions
  Muskuloskeletal and lymphatic system disorders	Common	Arthralgia, back pain, muscle cramps
  	Uncommon	Myopathy
  Renal and urinary disorders	Uncommon	Micturition disorders
  	Not known	Urinary retention
  General disorders and administration site conditions	Common	Fatigue
  	Uncommon	Chest pain, irritability, ankle oedema
  Injury, poisoning and procedural complications	Common	Fall
  Investigations	Common	Mild hepatic enzymes increased

  As selegiline potentiates the effect of levodopa (levodopa should be usually given in association with a peripheral decarboxylase inhibitor), the side-effects of levodopa may be emphasised unless the dosage of levodopa is reduced. Selegiline combination therapy may permit further reduction of levodopa dose (even by 30 %).The most common undesirable effect reported for conventional tablets is dyskinesia (4% of patients) other side effects include restlessness, hyperkinesis, abnormal movements, agitation, confusion, hallucination, postural hypotension, cardiac arrhythmias . Once the optimum levodopa dose level has been established, the side-effects produced by the combination will usually be less than those caused by the levodopa therapy on its own.