Rasagiline: What Are Its Indications?

Rasagiline is indicated for the treatment of Parkinson’s disease. It can be used as adjuvant therapy with levodopa or as monotherapy. Discover its modes of administration and its contraindications.

Rasagiline is prescribed for the treatment of Parkinson’s disease. It can be used as adjuvant therapy with levodopa  – a dopamine precursor which started out as the treatment of choice for this disease – or as monotherapy without levodopa.

On the other hand, Parkinson’s disease is a type of movement disorder that occurs when neurons do not make enough of a chemical essential to the brain: dopamine. In this article, we will deepen the indications of rasagiline.

Mechanisms of action of rasagiline

This medicine is a selective MAO-B inhibitor. MAO-B inhibition protects dopamine from extra-neuronal degradation by increasing its concentration in the brain. This is why it was initially used as a supplement to levodopa. Nowadays, these two drugs are used in combination in patients with motor fluctuations.

Dosage and form of administration

This medication is administered orally. A dose of 1 mg every 24 hours is sufficient, alone or in combination with levodopa. Rasagiline can be taken with or without food. Also, in elderly patients, dose modification is not necessary.

In the case of the pediatric population,  rasagiline is not recommended due to the lack of data on the safety and efficacy in children and adolescents.

What are the contraindications for rasagiline?

Treatment with rasagiline is contraindicated in the following cases:

• When there is hypersensitivity to the active substance or to some of the excipients
• When there is already treatment with a monoamine oxidase (MAO) inhibitor. This includes drugs as well as natural products not subject to a medical prescription,  such as St. John’s Wort. At least 14 days must pass between stopping rasagiline and starting treatment with MAO inhibitors or pethidine
• In patients with moderate and severe hepatic impairment. In addition, special care should be taken when initiating the administration of rasagiline to patients with mild hepatic impairment. If hepatic impairment becomes moderate, discontinuation of treatment is necessary.

Interaction with other drugs and other forms of interaction

As we have already mentioned, administration of rasagiline  with other MAO inhibitors or antidepressants is contraindicated:

• Natural antidepressants like St. John’s Wort
• SSRIs –  Selective Serotonin Reuptake Inhibitors
• IRNS – Norepinephrine and serotonin reuptake inhibitors
• Tricyclic and tetracyclic antidepressants

It is also not recommended to take it simultaneously with sympathomimetic drugs. Such as those found in nasal and oral decongestants. Or in drugs with anticatarrhal properties that contain ephedrine or pseudoephedrine.

On the other hand, the concomitant administration of rasagiline and dextromethorphan is also contraindicated.

The enzyme cytochrome P450 (CYP450) participates in the metabolism of most drugs. In vitro metabolism studies  have indicated that  the cytochrome P450 1A2 isoenzyme (CYP1A2) is the major enzyme responsible for the metabolism of rasagiline.

Therefore, co-administration of rasagiline and ciprofloxacin – a CYP1A2 inhibitor – may alter plasma concentrations of rasagiline and should be prescribed with caution.

In addition,  there is a risk that the plasma levels of rasagiline in smoking patients may be reduced  due to induction of the metabolizing enzyme CYP1A2.

What are the side effects of rasagiline?

The following list details the most common side effects:

• Flu or infection caused by influenza virus
• Skin carcinoma
• Leukopenia
• Allergy, rhinitis or conjunctivitis
• Decreased appetite
• Depression, hallucinations
• Headache
• Fear of heights
• Angina pectoris
• Dermatitis
• Flatulence
• Urinary urgency
• Fever or discomfort
• Musculoskeletal pain, neck pain and arthritis

Is rasagiline contraindicated in pregnancy?

Currently, there are no clinical data on exposure to rasagiline during pregnancy. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonic and fetal development, childbirth or the postnatal process.

However,  extreme care should be taken when administering rasagiline to pregnant women.  Indeed, it can interfere with breastfeeding. According to some experimental data, rasagiline inhibits the secretion of prolactin.

However, it is not yet known whether rasagiline passes through breast milk. Precautions should therefore be more important when administered to nursing mothers.