Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Association contra-indicated (see section 4.3)
Sympathomimetics
Because of the risk of hypertension, co-administration of selegiline and sympathomimetics is contraindicated.
Pethidine tramadol, buprenorphine and other opioids
The concomitant administration of the selective MAO-B inhibitor selegiline and pethidine and other opioids is contraindicated. Tramadol and buprenorphine are also potential interacting medicaments.
Selgin should be used cautiously when co-administered with buprenorphine/opioids as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
Selegiline should not be administered with any type of antidepressant.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) When selegiline is used at its recommended dose, it selectively inhibits MAO-B. The combined use of the SSRI, fluoxetine and Selgin, 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 Selgin 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 ofselegiline. 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.

MAO inhibitors
Concomitant administration of selegiline and MAO inhibitors may cause central nervous and cardiovascular system disorders (see section 4.4).

Associations not recommended
Oral contraceptives
The combination of selegiline and oral contraceptives or drugs for hormone replacement therapy, should be avoided, as this combination may increase 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 / index, 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 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.