tasimelteon

Action and Spectrum

Actions and Spectrum: 

tasimelteon is a medication used to regulate the sleep-wake cycle in individuals with a specific sleep disorder called non-24-hour sleep-wake disorder (Non-24) or irregular sleep-wake rhythm disorder. Here’s some information about the action and spectrum of tasimelteon: 

Action: tasimelteon is a selective agonist of melatonin receptors, explicitly targeting the MT1 and MT2 receptors in the brain. Melatonin is a hormone that naturally produced by pineal gland in the brain, plays a vital role in regulating the sleep-wake cycle. tasimelteon mimics melatonin’s effects, helping regulate the sleep-wake cycle in individuals with Non-24. It acts as a melatonin receptor agonist, which binds and activates these receptors, leading to the desired effects. 

Spectrum: tasimelteon is primarily indicated for the treatment of Non-24, a disorder that affects individuals who are blind. In Non-24, the sleep-wake cycle is not synchronized with the 24-hour day-night cycle due to disrupting the body’s internal clock. This disorder can lead to significant difficulties in maintaining a regular sleep pattern, causing excessive daytime sleepiness and nighttime wakefulness. 

tasimelteon helps to regulate the sleep-wake cycle in individuals with Non-24 by entraining the circadian rhythm. It specifically targets the melatonin receptors in the brain, which are involved in regulating the sleep-wake cycle. By activating these receptors, tasimelteon helps to promote sleep at appropriate times and reduce nighttime wakefulness, thus aligning the sleep pattern with the desired 24-hour cycle. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache (17%) 

1-10% 

Nightmares or abnormal dreams (10%) 

Increased ALT (10%) 

URT infections (7%) 

Urinary tract infections (7%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: tasimelteon should not be used in individuals with known hypersensitivity or allergy to tasimelteon or its components. Allergic reactions can range from mild-severe and may include symptoms such as rash, itching, swelling, dizziness, or difficulty breathing. 
• Severe Hepatic Impairment: tasimelteon is primarily metabolized in the liver, and its use is not recommended in individuals with severe hepatic impairment. The safety and efficacy of tasimelteon in this patient population have not been established, and it may lead to an enhanced risk of adverse effects. 
• CYP1A2 Inhibitors: tasimelteon is metabolized by the CYP1A2 enzyme pathway in the liver. Co-administration of tasimelteon with strong inhibitors of CYP1A2, such as fluvoxamine, may increase tasimelteon concentrations. Therefore, concurrent use of tasimelteon with strong CYP1A2 inhibitors should be avoided or carefully monitored. 

Caution 

• Hepatic Impairment: tasimelteon is metabolized in the liver, and caution should be exercised when administering the medication to individuals with mild to moderate hepatic impairment. Close monitoring of tasimelteon’s effects and potential adverse reactions may be necessary in this population. 
• Renal Impairment: tasimelteon is primarily metabolized in the liver, and renal impairment is not expected to significantly impact its clearance. However, limited information is available regarding tasimelteon use in individuals with severe renal impairment. Caution should be exercised when using tasimelteon in such cases. 
• Drug Interactions: tasimelteon may interact with certain medications, including potent CYP1A2 inhibitors (such as fluvoxamine) and inducers (such as rifampin). Co-administration of tasimelteon with these medications may alter tasimelteon’s metabolism and lead to potential side effects or reduced efficacy. Close monitoring and potential dose adjustments may be necessary when tasimelteon is used concomitantly with other medications. 
• Pregnancy and Lactation: There is limited information available on the use of tasimelteon in pregnant women. It is unknown if tasimelteon is excreted in human milk, so caution is advised when using it while breastfeeding. 
• Pediatric Use: The safety and efficacy of tasimelteon have not been established in children and adolescents under 18. Therefore, tasimelteon is not recommended for use in this population. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

tasimelteon is a melatonin receptor agonist with a high affinity for the MT1 and MT2 receptors in the brain. By selectively binding to these receptors, tasimelteon mimics the effects of endogenous melatonin, a hormone that regulates the sleep-wake cycle. It acts as a circadian regulator by entraining the body’s internal clock and promoting sleep onset at appropriate times.

tasimelteon’s pharmacological action helps to synchronize the sleep-wake cycle in individuals with non-24-hour sleep-wake disorder characterized by a disrupted circadian rhythm. By restoring a more regular sleep pattern, tasimelteon can alleviate excessive daytime sleepiness and improve overall sleep quality in affected individuals. 

Pharmacodynamics: 

Mechanism of action: The action of tasimelteon is primarily based on its activity as a selective agonist of melatonin receptors, explicitly targeting the MT1 and MT2 receptors in the brain. 

Melatonin levels increase in the evening, promoting sleep onset, and decrease in the morning, signaling wakefulness. 

tasimelteon acts as a melatonin receptor agonist, binding to and activating the MT1 and MT2 receptors. By binding to these receptors, tasimelteon mimics the effects of endogenous melatonin, promoting sleep-wake cycle regulation. 

Pharmacokinetics: 

Absorption 

tasimelteon is well-absorbed after oral administration. The peak plasma concentration (Cmax) is reached within 1 to 2 hours following ingestion. Taking tasimelteon with a high-fat meal may slightly decrease its absorption, but the clinical significance of this effect is considered minimal. 

Distribution 

tasimelteon has a high protein binding capacity, primarily binding to albumin. It has a moderate volume of distribution, indicating that it is distributed throughout the body. 

Metabolism 

tasimelteon undergoes extensive metabolism in the liver. It is mainly metabolized by the cytochrome P450 enzyme CYP1A2. The primary metabolites formed are hydroxylated derivatives of tasimelteon. These metabolites are also pharmacologically active but have lower potency than the parent drug. 

Elimination and Excretion 

The metabolites of tasimelteon and a small portion of the unchanged drug are eliminated primarily through urine. The elimination half-life of tasimelteon ranges from 0.8 to 1.5 hours. Approximately 40-50% of the administered dose is excreted in urine, while a smaller proportion is excreted in feces. 

Adminstartion

Administration: 

Oral administration 

tasimelteon is available in oral capsule form and should be taken according to a healthcare professional’s prescribed dosage and administration instructions.  

• Dosage: The recommended dosage of tasimelteon may vary depending on the specific sleep disorder being treated and individual patient factors. It is key to follow the dosage prescribed by your healthcare professional. Do not adjust the dose or stop taking tasimelteon without consulting your doctor. 
• Timing of Administration: tasimelteon should be taken orally, usually once daily, at the same time each day. It is typically taken before bedtime. 
• Swallowing: Take the tasimelteon capsule whole with water. Do not chew, crush/break the capsule before swallowing, which may affect the drug’s effectiveness and release profile. 
• Food Intake: tasimelteon can be taken with or without food. However, it is generally recommended to take it without food, as taking it with a meal high in fat may slightly decrease its absorption. 
• Compliance: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.
• Follow-up: Regularly follow up with your healthcare professional to monitor your response to tasimelteon and adjust the treatment plan as necessary. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tasimelteon 

Pronounced: [ TAS-i-MEL-tee-on ] 

Why do we use tasimelteon? 

tasimelteon is primarily used to treat a specific sleep disorder called non-24-hour sleep-wake disorder (Non-24) or irregular sleep-wake rhythm disorder. Here are the primary uses of tasimelteon: 

• Non-24-Hour Sleep-Wake Disorder: This disorder primarily affects individuals who are blind and is characterized by an irregular sleep-wake cycle that is not synchronized with the 24-hour day-night cycle. tasimelteon helps regulate the sleep-wake cycle by mimicking the effects of melatonin. 
• Non-24 can lead to significant difficulties in maintaining a regular sleep pattern, resulting in excessive daytime sleepiness, nighttime wakefulness, and disrupted daily functioning. tasimelteon helps align the sleep pattern with the desired 24-hour cycle, reducing the impact of Non-24 symptoms and improving sleep quality.