AZILECT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZILECT (AZILECT).
Irreversible selective inhibitor of monoamine oxidase type B (MAO-B), which inhibits the metabolism of dopamine in the brain, increasing dopaminergic activity.
| Metabolism | Metabolized primarily by CYP1A2, with minor contributions from CYP3A4 and CYP2C9; undergoes N-dealkylation to form active metabolite 1-(R)-aminoindan and inactive metabolites. |
| Excretion | Renal (approximately 60% of dose as metabolites, <1% unchanged); fecal (about 20%); small amount exhaled as CO2. Metabolites primarily excreted via urine. |
| Half-life | Terminal elimination half-life of rasagiline is approximately 3-4 hours; however, due to irreversible MAO-B inhibition, the pharmacological effect lasts longer than the elimination half-life. |
| Protein binding | Approximately 60-70% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | Approximately 1-2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: Absolute bioavailability is about 36% due to extensive first-pass metabolism. |
| Onset of Action | Oral: Clinical effect (MAO-B inhibition) begins within 1-2 hours; peak effect occurs within 1 week. |
| Duration of Action | MAO-B inhibition persists for about 2-3 weeks after discontinuation due to irreversible binding, requiring a washout period before starting serotonergic drugs. |
1 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for GFR ≥30 mL/min. Not recommended if GFR <30 mL/min due to lack of data. |
| Liver impairment | Child-Pugh Class A: 0.5 mg once daily. Child-Pugh Class B or C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dosage adjustment. Monitor for increased risk of hallucinations and other adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZILECT (AZILECT).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions, advise against breastfeeding during therapy. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, rasagiline increased fetal malformations at doses 3 times the MRHD. No adequate human studies. Use only if potential benefit justifies risk. First trimester: Avoid due to organogenesis. Second/third trimester: Limited data; monitor fetal growth. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concurrent use with other MAOIs (including MAO-A inhibitors) or within 14 days of their discontinuation","Concurrent use with meperidine or other opioid analgesics","Concurrent use with serotonergic drugs (e.g., SSRIs, SNRIs, TCAs, St. John's wort)","Pheochromocytoma"]
| Precautions | ["Risk of hypertensive crisis with tyramine-rich foods (cheese reaction) due to MAO-A inhibition at higher doses or if selectivity is lost","Serotonin syndrome when used with serotonergic drugs (e.g., SSRIs, SNRIs, TCAs, meperidine)","Increased risk of orthostatic hypotension","Potential for exacerbation of dyskinesia when used with levodopa","Avoid use with other MAOIs or within 14 days of their discontinuation"] |
| Food/Dietary | Avoid tyramine-rich foods to prevent hypertensive crisis: aged cheeses (cheddar, blue cheese), cured meats (salami, pepperoni), pickled or fermented foods (sauerkraut, kimchi), soy products (soy sauce, tofu), tap beers, red wine, and overripe avocados. Also avoid large amounts of caffeine (coffee, tea, energy drinks). |
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| Monitor for maternal hypertension, serotonin syndrome (especially with concomitant serotonergic drugs), and fetal growth via ultrasound in third trimester. |
| Fertility Effects | Animal studies showed no impairment of fertility at doses up to 26 mg/kg/day (about 30 times MRHD). Human data lacking. |
| Clinical Pearls | Initiate at 0.5 mg orally once daily for at least 2 weeks before increasing to 1 mg once daily if needed. Avoid use with opioids (especially meperidine, tramadol, methadone) due to serotonin syndrome risk. Monitor for severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS). Contraindicated with other MAOIs or selective serotonin reuptake inhibitors (SSRIs) within 14 days. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. · Avoid foods and beverages high in tyramine (e.g., aged cheese, cured meats, sauerkraut, soy sauce, tap beer, red wine) to prevent hypertensive crisis. · Notify your doctor immediately if you experience severe headache, chest pain, nausea, or vomiting, as these may be signs of hypertensive emergency. · Do not take any other medications, including over-the-counter drugs (especially cold medicines, antidepressants, or St. John's wort), without consulting your doctor. · Rash or skin reactions should be reported promptly as they could indicate a serious condition. |