ZELAPAR

ZELAPAR- selegiline hydrochloride tablet, orally disintegrating
Bausch Health US, LLC

1 INDICATIONS AND USAGE

ZELAPAR is indicated as an adjunct in the management of patients with Parkinson’s disease being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that ZELAPAR has any beneficial effect in the absence of concurrent levodopa therapy [see Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

2.1 General Dosage Recommendations

Initiate treatment with 1.25 mg given once a day for at least 6 weeks. After 6 weeks, the dose may be increased to 2.5 mg given once a day if a desired benefit has not been achieved and the patient is tolerating ZELAPAR. There is no evidence that doses greater than 2.5 mg a day provide additional benefit, and they should ordinarily be avoided because of the potential increased risk of adverse events.

Take ZELAPAR in the morning before breakfast and without liquid. Patients should avoid ingesting food or liquids for 5 minutes before and after taking ZELAPAR.

Patients should not attempt to push ZELAPAR through the foil backing. Patients should PEEL BACK the backing of one or two blisters (as prescribed) with dry hands, and GENTLY remove the tablet(s). Patients should IMMEDIATELY place the ZELAPAR tablet(s) on top of the tongue where it will disintegrate in seconds.

2.2 Patients with Hepatic Impairment

In patients with mild to moderate hepatic disease (Child-Pugh score 5 to 9), the daily dose of ZELAPAR should be reduced (from 2.5 to 1.25 mg daily), depending on the clinical response. ZELAPAR is not recommended in patients with severe hepatic impairment (Child-Pugh score greater than 9) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.3 Patients with Renal Impairment

No dose adjustment of ZELAPAR is required in patients with mild to moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min). The maintenance dose of ZELAPAR (1.25 mg or 2.5 mg) is determined by the individual clinical response. ZELAPAR is not recommended in patients with severe renal impairment and patients with end-stage renal disease [ESRD] (creatinine clearance [CLcr] <30 mL/min) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

ZELAPAR Orally Disintegrating Tablets are pale yellow, imprinted with a stylized “V”, and contain 1.25 mg selegiline hydrochloride.

4 CONTRAINDICATIONS

ZELAPAR is contraindicated in patients with:

•

Concomitant use of opioid drugs (e.g., meperidine, tramadol, or methadone). Serotonin syndrome, a potentially serious condition, which can result in death, has been reported with concomitant use of meperidine (e.g., Demerol and other trade names). At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with these medications [see Warnings and Precautions (5.2)].

•

Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid), because of an increased risk for hypertensive crisis [see Warnings and Precautions (5.1)]. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with any MAO inhibitor.

•

Concomitant use of St. John’s wort or cyclobenzaprine (a tricyclic muscle relaxant).

•

Concomitant use of dextromethorphan, because of reported episodes of psychosis or bizarre behavior.

5 WARNINGS AND PRECAUTIONS

5.1 Hypertension

ZELAPAR should not be used at daily doses exceeding those recommended (2.5 mg/day) because of the risks associated with non-selective inhibition of MAO [see Drug Interactions (7.3) and Clinical Pharmacology (12.2)].

The selectivity of ZELAPAR for MAO-B may not be absolute even at the recommended daily dose of 2.5 mg daily. The selectivity of MAO-B inhibitors typically decreases, and it is ultimately lost as the dose is increased beyond recommended doses. Hypertensive reactions associated with ingestion of tyramine-containing foods have been reported even in patients taking the recommended daily dose of swallowed selegiline, a dose which is generally believed to be selective for MAO-B. Selectivity for MAO-B inhibition is gradually lost with increasing daily doses. An increase in tyramine sensitivity for blood pressure responses appears to begin at a dose of 5 mg ZELAPAR daily [see Drug Interactions (7.5)]. However, the precise dose at which ZELAPAR becomes a non-selective inhibitor of all MAO enzymes in individual patients is unknown.

Reports of hypertensive reactions have occurred in patients who ingested tyramine-containing consumables (i.e., food or drink) while receiving swallowed selegiline at the recommended dose (a dose believed to be relatively selective for MAO-B).

The safe use of ZELAPAR at doses above 2.5 mg daily without dietary tyramine restrictions has not been established.

A pharmacodynamic study showed increased tyramine sensitivity for increasing blood pressure and decreased selectivity for MAO-B with dosing above the recommended level (2.5 mg daily) [see Clinical Pharmacology (12.2)].

Uncontrolled hypertension has been reported when taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine).

After starting ZELAPAR, monitor patients for new onset hypertension or exacerbation of hypertension that is not adequately controlled.

5.2 Serotonin Syndrome

Serotonin syndrome and hyperpyrexia have been reported with the combined treatment of an antidepressant (e.g., selective serotonin reuptake inhibitors-SSRIs, serotonin-norepinephrine reuptake inhibitors-SNRIs, tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants) and a non-selective MAOI (e.g., phenelzine, tranylcypromine) or selective MAO-B inhibitors, such as selegiline (ELDEPRYL), rasagiline (AZILECT), and olanzapine (Zydis) selegiline (ZELAPAR).

Serotonin syndrome is a potentially serious condition, which can result in death. Typical clinical signs and symptoms include behavioral and cognitive/mental status changes (e.g., confusion, hypomania, hallucinations, agitation, delirium, headache, and coma), autonomic effects (e.g., syncope, shivering, sweating, high fever/hyperthermia, hypertension, hypotension, tachycardia, nausea, diarrhea), and somatic effects (e.g., muscular rigidity, myoclonus, muscle twitching, hyperreflexia manifested by clonus, and tremor).

In the post-marketing period, fatal and non-fatal cases of serotonin syndrome have been reported in patients treated with antidepressants concomitantly with ZELAPAR [see Contraindications (4) and Drug Interactions (7.1, 7.2, 7.3)].

Clinical studies of ZELAPAR did not allow concomitant use of any selective serotonin re-uptake inhibitor (e.g., fluoxetine-Prozac, fluvoxamine-Luvox, paroxetine-Paxil, sertraline, venlafaxine-Effexor, or nefazodone-Serzone) or any non-selective serotonin reuptake inhibiting antidepressant drug (except when taken at a low dose and only at night for the purpose of effective sleep) with ZELAPAR.

Because the mechanisms responsible for these reactions are not fully understood, avoid the combination of ZELAPAR with any antidepressant. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with a SSRI, SNRI, tricyclic, tetracyclic, or triazolopyridine antidepressant. In patients taking antidepressants with a long half-life (e.g., fluoxetine and its active metabolite), allow at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) to elapse between discontinuation of fluoxetine and initiation of ZELAPAR [see Drug Interactions (7.6)].