Rasagiline Mesilate

(rINNM)
Rasagiline Mesilate Chemical formula
Synonyms: Mesilato de rasagilina; Rasagiline, Mésilate de; Rasagiline Mesylate amine methanesulfonate.
Cyrillic synonym: Разагилина Мезилат.

💊 Chemical information

Chemical formula: C12H13N,CH4O3S = 267.3.
CAS — 136236-51-6 (rasagiline); 161735-79-1 (rasagiline mesilate).
ATC — N04BD02.
ATC Vet — QN04BD02.

💊 Adverse Effects and Precautions

Common adverse effects reported with rasagiline monotherapy include headache, flu-like syndrome, malaise, neck pain, angina pectoris, dyspepsia, anorexia, leucopenia, arthralgia, arthritis, depression, vertigo, rhinitis, conjunctivitis, skin rashes, melanoma, and urinary urgency. Cerebrovascular accidents and myocardial infarction have been reported rarely. Other adverse effects include orthostatic hypotension and hallucinations. Rasagiline should not be used in patients with severe hepatic impairment; use in moderate impairment should also be avoided. It should be used with caution in patients with mild hepatic impairment and therapy should be stopped in those who progress to moderate impairment.

💊 Interactions

As for Selegiline Hydrochloride. Unlike the non-selective MAOIs, such as phenelzine, rasagiline can be used safely without dietary tyramine restrictions, although these have been recommended in some countries. Rasagiline should not be given with other MAOIs because of the risk of non-selective MAO inhibition that may lead to hypertensive reactions. It is metabolised by the cytochrome P450 isoenzyme CYP1A2 and potent inhibitors of this enzyme such as ciprofloxacin may increase the plasma levels of rasagiline. UK licensed product information for rasagiline advises caution when such drugs are used with rasagiline whereas US licensed product information recommends that the dose of rasagiline be reduced to 0.5 mg daily when given with CYP1A2 inhibitors. Tobacco smoking induces hepatic metabolic enzymes and may decrease the plasma levels of rasagiline. Entacapone has been reported to increase the clearance of oral rasagiline by 28% when used together.

💊 Pharmacokinetics

Rasagiline is rapidly absorbed from the gastrointestinal tract, with peak plasma levels occurring in about 30 minutes to an hour. Bioavailability is reported to be about 36%. Rasagiline is about 60 to 70% bound to plasma proteins. It is extensively metabolised in the liver by N-dealkylation and hydroxylation, via the cytochrome P450 isoenzyme CYP1A2, and conjugation. 1-Aminoindan is a major metabolite and is stated to be active although it is not a monoamine oxidase B inhibitor. Metabolites are excreted mainly in the urine and partly in the faeces; less than 1% of a dose is excreted as unchanged drug in the urine. The terminal half-life is 0.6 to 2 hours.

💊 Uses and Administration

Rasagiline is an irreversible selective inhibitor of monoamine oxidase type B, an enzyme involved in the metabolic degradation of dopamine in the brain. It enhances the effects of levodopa and is used in the treatment of Parkinson’s disease, either alone or as an adjunct to levodopa therapy to reduce ‘end-ofdose’ fluctuations in response. Rasagiline is given orally as the mesilate and doses are expressed in terms of the base; rasagiline mesilate 1.56 mg is equivalent to about 1 mg of rasagiline. The usual dose is the equivalent of rasagiline 1 mg once daily. In the USA, an initial daily dose of 0.5 mg is recommended for adjunctive therapy. The dose of rasagiline may need to be reduced when given with drugs that inhibit the cytochrome P450 isoenzyme CYP1A2 (see Interactions, above for details) and in patients with hepatic impairment (see below).
1. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002; 59: 1937–43
2. Stern MB, et al. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patients. Mov Disord 2004; 19: 916–23
3. Thebault JJ, et al. Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. Pharmacotherapy 2004; 24: 1295–1305
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5. Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62: 241–8
6. Rascol O, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365: 947–54
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8. Chen JJ, et al. Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. J Clin Pharmacol 2005; 45: 878–94
9. Siderowf A, Stern M. Clinical trials with rasagiline: evidence for short-term and long-term effects. Neurology 2006; 66 (suppl 4): S80–S88
10. Oldfield V, et al. Rasagiline: a review of its use in the management of Parkinson’s disease. Drugs 2007; 67: 1725–47.

Administration in hepatic impairment.

UK licensed product information for rasagiline advises caution when used in patients with mild hepatic impairment whereas US licensed information recommends that the dose be reduced to 500 micrograms daily. Rasagiline should not be used in those with moderate or severe impairment.

💊 Preparations

Proprietary Preparations

Arg.: Elbrus; Belg.: Azilect; Cz.: Azilect; Denm.: Azilect; Fin.: Azilect; Fr.: Azilect; Ger.: Azilect; Gr.: Azilect; Irl.: Azilect; Israel: Azilect; Neth.: Azilect; Norw.: Azilect; Pol.: Azilect; Port.: Azilect; Spain: Azilect; UK: Azilect; USA: Azilect.
Published November 23, 2018.