- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyWhen prescribed as monotherapy for the first time in the early stage of Parkinson's disease or as an adjuvant to levodopa, the dose of Zelapar is one 1.25 mg unit per day.When Zelapar adjunctive therapy is prescribed a reduction (10 to 30%) in the dose of levodopa is usually required. Reduction of the levodopa dose should be gradual in steps of 10% every 3 to 4 days.
Hepatic impairmentNo data are known on dose adjustment in patients with mild hepatic impairment.
Renal impairmentNo data are known on dose adjustment in patients with mild renal impairment.
Method of administrationThe unit should be placed on the tongue in the morning, at least five minutes before breakfast and allowed to dissolve. The unit will dissolve rapidly (in less than 10 seconds) in the mouth. The patient should not eat, drink, rinse or wash-out out their mouth for five minutes after taking their medicine to enable selegiline to be absorbed pre-gastrically.Do not push the Zelapar tablet through the foil blister. Peel back the foil and carefully remove the unit.Unused tablets must be disposed of after three months of a sachet opening.
Patients with hepatic or renal dysfunctionSelegiline should be used with caution in severe hepatic or renal dysfunction. 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.
Patients taking other MAO inhibitorsThe selectivity for MAO-B following administration of conventional selegiline tablets may be diminished with doses above 10 mg/day. A non-selective dose of Zelapar above 10 mg/day has not been determined. 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.Caution should be exercised in patients receiving MAO inhibitors during general anaesthesia in surgery. MAO inhibitors, including selegiline may potentiate the effects of CNS depressants used for general anaesthesia. Transient respiratory and cardiovascular depression, hypotension and coma have been reported (see section 4.5).
Patients taking levodopaSome 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.Since selegiline potentiates the effects of levodopa, the adverse effects of levodopa may be increased especially if patients are receiving levodopa therapy with high doses. These patients should be monitored. When selegiline is added to the maximum tolerated dose of levodopa, involuntary movements and agitation may occur. These undesirable effects disappear after levodopa doses reduction. Levodopa should be reduced by about 10 to 30% when selegiline is added to the treatment (see section 4.2 Posology and Method of Administration). When an optimum dose of levodopa is reached, adverse effects from the combination are less than those observed with levodopa on its own.The addition of selegiline to levodopa may not be beneficial in those patients who experience fluctuations in response which are not dose dependent.
Doping screening testsThe use of selegiline may produce a positive result in doping screening tests.
OtherMouth ulcers may occur during treatment with Zelapar 1.25 mg oral lyophilisate.Although conventional tablets of selegiline, at doses of 5 to 10 mg/day, have been in widespread use for many years, the full spectrum of possible responses to Zelapar may not have been observed to date. Therefore patients should be observed closely for atypical responses.
Concomitant use contraindicated (see section 4.3)
Serotonin agonistsPatients receiving treatment with serotonin-agonists (e.g. sumatriptan, naratriptan, zolmitriptan and rizatriptan).
AntidepressantsSelegiline should not be administered with any type of antidepressant.Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs)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 serotonin syndrome, concomitant administration of selegiline and SSRIs or SNRIs is contraindicated.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. 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.
Tricyclic antidepressantsSevere CNS toxicity 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.
MAO inhibitorsSelegiline should not be given in conjunction with non-specific MAO inhibitors, e.g. linezolid. Concomitant administration of selegiline and MAO inhibitors may cause central nervous and cardiovascular system disorders (see section 4.4).Four patients receiving altretamine and a monamine oxidase inhibitor experienced symptomatic hypotension after four to seven days of concomitant therapy.
SympathomimeticsBecause of the risk of hypertension, co-administration of selegiline and sympathomimetics, including nasal decongestants is contraindicated.
PethidineInteractions between non-selective MAO-inhibitors and pethidine as well as selegiline and pethidine have been described. The mechanism of this interaction is not fully understood and therefore, use of pethidine concomitantly with selegiline should be avoided (see section 4.3).
Concomitant use not recommended
DopaminePatients 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.
Oral contraceptives or drugs for hormone replacement therapyThe 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 such as digitalis and/or anticoagulants.Concomitant use of hypertensive or anti-hypertensive agents, psychostimulants, central suppressant drugs (sedatives, hypnotics) and alcohol should be avoided.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.
Food interactionsAs 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.
|System Organ Class||Frequency||Undesirable effects|
|Psychiatric disorders||common||confusion, depression, hallucinations, insomnia,|
|uncommon||abnormal dreams, agitation, anxiety, psychoses|
|Nervous system disorders||common||dizziness, dyskinesia (including akinesia, bradykinesia), headache, impaired balance, tremor,|
|Ear and labyrinth disorders||common||vertigo|
|Cardiac disorders||uncommon||angina pectoris|
|Vascular disorders||common||hypertension, hypotension|
|Respiratory, thoracic and mediastinal disorders||common||nasal congestion, sore throat|
|Gastrointestinal disorders||very common||stomatitis|
|common||constipation, diarrhoea, dry mouth, mouth ulceration, nausea|
|Skin and subcutaneous tissue disorders||common||sweating increased|
|Musculoskeletal and connective tissue disorders||common||arthralgia, back pain, muscle cramps|
|General disorders and administration site conditions||common||fatigue|
|uncommon||chest pain, irritability|
|Injury, poisoning and procedural complications||common||fall|
|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||uncommon||mood change, mild transient sleep disorder|
|Eye disorders||uncommon||blurred vision|
|uncommon||Arrhythmias, palpitations, supraventricular tachycardia|
|Vascular disorders||uncommon||orthostatic hypotension|
|Skin and subcutaneous tissue disorders||uncommon||hair loss, skin eruptions|
|Musculoskeletal and connective tissue disorders||uncommon||myopathy|
|Renal and urinary disorders||uncommon||micturition disorders|
|not known||urinary retention|
|General disorders and administration site conditions||uncommon||ankle oedema|
|Investigations||common||mild hepatic enzymes increased|
|uncommon||transient transaminase increase (ALAT), transient increase in liver enzyme values|
Cephalon (UK) Limited
Teva UK Limited, Field House, Station Approach, Harlow, Essex, CM20 2FB
+44 (0) 207 4507349
+44 (0) 207 5407117
+44 (0) 207 5407117