Tasimelteon - Indications, Contraindications, Side Effects, Precautions, and Drug Interactions

Overview

Tasimelteon is used for the treatment of various sleep disorders. The drug was approved by the FDA (Food and Drug Administration) in January 2014 for dyssomnia, especially non-24-hour sleep-awake disorders. The drug was initially invented for the treatment of insomnia and other sleep disorders, and after the third phase of a clinical trial, it was approved for the treatment of non-24-hour sleep-awake disorders. The article talks in detail about drug indications, adverse effects, drug interactions, and clinical pharmacology.

Indications

1. Non-24-hour sleep-wake disorder in adults.

2. Night-time sleep disturbance in pediatric patients due to Smith -Magenis Syndrome (SMS), and in adults.

Dose and Administration

Tasimelteon capsules and oral suspensions are not interchangeable, as they are both drug forms and are not substitutes for each other.

The adult recommended dose for non-24-hour sleep-awake disorder is the drug capsule 20 mg (milligram), once daily after a meal, one hour before bedtime, and every night at the same time.

The drug dosage (capsule) remains the same for patients 16 years and above, for SMS, and the dosage for oral suspension in patients between three to 15 years of age, is usually based on their body weight. But the drug administration is one hour before bedtime, every night at the same time.

For Patients:

When Is Tasimelteon Prescribed to a Person?

Tasmileteon is prescribed for the treatment of dyssomnia or sleep disorders in people, such as non-24-hour sleep-wake disorders in blind people, who have a natural clock of the body out of sync with the regular day-night cycle. In addition, the drug is also used to treat sleep disorders associated with some developmental disorders, such Smith-Magenis syndrome, in children below three years of age. The drug also treats nighttime sleep issues in adults. The drug works similarly to melatonin, which is a natural brain chemical responsible for sleep.

How Should the Drug Be Used?

The drug is available as a capsule or oral suspension to be taken via mouth. The drug is prescribed to be taken once a day, one hour before bedtime but after a meal. The drug should be taken at regular timings daily by children and adults or as prescribed by the doctor. The directions given on the doctor’s prescription and label of the drug should be followed cautiously. The doctor and pharmacist should be asked to repeat the instructions in case a person does not understand any part of it. The capsule should not be chewed or crushed; it should be swallowed as a whole.

If a patient (children or adults) is taking oral suspensions of the drug, the following steps should be taken for dose preparation and measurement.

• Take out the drug’s bottle, adapter, and dosing syringe from the packing.

• The bottle should be shaken well for 30 seconds to mix the drug well before taking the dose.

• To open the bottle of the drug, the child-resistant cap should then be pressed counterclockwise. The cap should not be discarded.

• Before opening the drug bottle for the very first time, the seal must be removed, and the bottle adapter must be pressed in and fitted properly on the top of the bottle. The cap can then be removed by turning clockwise, and the drug should be mixed thoroughly again for 30 seconds.

• The oral dosing syringe’s plunger is then pressed into the via bottle adapter up to the maximum depth, and the bottle is then turned upside down to fill the dosing syringe up to the level or amount of drug prescribed by the physician. In case air bubbles are found in the dosing syringe, the syringe must be fully pressed into the bottle to get rid of the bubbles and fill the syringe again.

• The dosing syringe is then taken out slowly by turning the bottle upright and placing the child-resistant cap again.

• The dosing dispenser is then taken out, and the dose should be placed in the mouth, preferably the corner of the cheek of adults or children. The drug should be given in the exact amount, and a person should get enough time to swallow the drug dose.

• The plunger of the syringe and the barrel should be washed thoroughly with water, and then after drying, should be put back into the oral dosing syringe. A person should be restricted from washing the oral dosing syringe in the dishwashing machine.

• The dose of the drug should always be measured with the oral dosing syringe given along with the drug bottle, and hence the syringe should not be discarded after use.

• The syringe must be refrigerated after each use.

• A person starts feeling sleepy after taking the drug. Therefore, they should directly go to bed after taking the dose and should not get involved in any other activities.

What Are the Precautions Needed Before Taking this Drug?

• The doctor and pharmacist should be informed about any allergic reactions to any medications, tasimelteon, or any other ingredient present in the drug.

• The doctor should also be informed about all the non-prescription, prescription, nutritional supplements, and herbal products; a person is taking to avoid any drug interactions after taking Tasimelteon.

• If a person has any history of past or present liver disease, a doctor should be informed.

• In case of pregnancy, breastfeeding, or planning to conceive, the doctor must be informed. Also, if a woman gets pregnant while taking this drug, inform the doctor immediately.

• The drug causes sleep and makes a person drowsy. Therefore, driving and operating heavy machinery should be restricted.

• The side effects of the drug can worsen with alcohol consumption. Therefore, a doctor should be consulted for the safe use.

• Also, smoking cigarettes can reduce the effectiveness of the drug; therefore, inform the doctor if a person is using any tobacco product.

What Are the Side Effects of the Drug?

Tasimelteon causes symptoms such as

• Headache.

• Unusual dreams and nightmares.

• Fever.

• Difficulty in urinating or frequent urination.

• Shortness of breath.

• Cold.

If these symptoms become severe, consult the doctor immediately.

Dietary Instructions:

A person can continue taking their normal regular diet unless advised otherwise by the doctor. In case of any confusion, a person should ask the doctor about their diet plan or any particular food that needs to be avoided while taking the drug.

Overdose:

In case of a drug overdose, consult the healthcare provider immediately if a person collapses or has seizures and breathing issues.

Missed Dose:

In case of missed doses, skip the dose missed, and continue with the regularly scheduled dose to avoid double doses. Do not make up for the missed one.

Drug Storage and Disposal:

The drug should be stored away from children’s reach in the air-tight container it came packed in. The drug should be stored in the refrigerator, and once the bottle is opened, it should be discarded within five weeks if it's a 48 milliliters bottle and in eight weeks if it’s a 158 milliliters bottle.

Expired and medications that are left unused should not be stored for a longer time should be disposed of to avoid accidental poisoning of pets and young children. Also, the drug should not be flushed in the toilets; rather, it should be discarded through take-back programs by contacting the nearest pharmacist or local recycling authorities. Instead, the drug can also be discarded according to the FDA’s (Food and Drug Administration) protocols for the safe disposal of medicine.

Drug Abuse and Dependence:

The clinical studies on Tasimelteon did not indicate any symptoms of abuse potential. Also, following the chronic administration of the drug, the discontinuation did not show any withdrawal signs as well.

For Doctors:

Clinical Pharmacology

Mechanism of Action:

The drug is an agonist at melatonin MT1 and MT2 receptors and therefore is believed to control cardiac rhythms. However, the exact mechanism of action of Tasimelteon for nighttime sleep disturbance and Non-24-hour sleep-awake is still unclear.

Pharmacodynamics:

The drug has more affinity for MT2 than MT1 receptors, but it is an antagonist for both of these receptors. The binding affinity of the drug is less than one-tenth of the parent molecule for both of these receptors.

Pharmacokinetics:

Absorption - The bioavailability of the drug is 38.3 percent, Tmax (capsule) is 0.5 to three hours, and Tmax (suspension) is 15 to 30 mins after oral administration, respectively.

Distribution - The oral volume of distribution of the drug is 59 to 126 litres, and the drug is 90 percent bound to proteins at therapeutic concentration.

Metabolism- The drug gets extensively metabolized and mainly consists of oxidation at various sites and oxidative dealkylation to open a dihydrofuran ring, followed by oxidation to form a carboxylic acid. The metabolism of Tasimelteon involves CYP1A2 and CYP3A4 isozymes.

Elimination- The oral dosage of the drug is eliminated or excreted 80 percent in urine, four percent in feces, and almost one percent is excreted in urine as a parent compound.

Ingredients

Active Ingredient: Tasimelteon

Inactive Ingredient:

• Capsule - Colloidal silicon dioxide, lactose anhydrous, microcrystalline cellulose, magnesium stearate, and croscarmellose sodium.

• Oral Suspension - Mannitol, ascorbic acid, microcrystalline cellulose, cherry flavor, polysorbate 80, sucrose, sucralose, sodium benzoate, and water.

Dose Form and Strength:

Capsule: 20 mg

Oral Suspension: 4mg/mL, in 48 mL and 158 mL bottles.

Adverse Effects:

The adverse effects caused by Tasimelteon are as follows:

• Headaches.

• Nightmares and unusual dreams.

• Urinary tract infections.

• Upper respiratory infections.

• Alanine aminotransferase.

Warnings and Precautions:

The doctor should advise the patient not to involve in any activities after taking the drug as it causes drowsiness and sleep. They should also guide the patient on drug administration and safe dose intake as recommended to avoid any drug overdose or any other adverse effects.

Drug Interactions

• Strong CYP1A2 Inhibitor: The drug should be avoided with CYP1A2 inhibitors, such as Fluvoxamine, as this combination can cause a greater risk of adverse effects due to a potential increase in Tasimelteon exposure.

• Beta-adrenergic Receptor Antagonists: It includes drugs, such as Metoprolol and Acebutolol, which can reduce melatonin production by inhibiting beta-1 adrenergic receptors. The efficacy of Tasimelteon can get reduced due to the administration of beta-adrenergic receptor antagonists at night.

• Strong CYP3A4 Inducer: The drugs such as Rifampin or other CYP3A4 inducers can reduce the efficacy and potential exposure of Tasimelteon. Therefore, this combination should also be avoided.

Use In Specific Populations

Pregnancy - Embryofetal developmental toxicity was not observed in pregnant rats at a higher dose of 50 mg/kg/day and almost 24 times higher than the human recommended dosage. Whereas the drug caused embryo-fetal toxicity in pregnant rats. Therefore, the case reports are not sufficient enough to evaluate the use of Tasimelteon in pregnant women and the associated miscarriages, fetal or maternal adverse outcomes, and fetal birth defects. Hence, the risk of birth defects for this group of population is unknown.

Lactation - No clinical data suggests the presence of the drug in animal or human milk or its effects on milk production or breastfed infants. Therefore, the clinical needs of the mother and the health and developmental defects of the infant should be considered while prescribing Tasimelteon to avoid any potential adverse effects.

Pediatric Use - The safety and efficacy of the drug for non-24-hour sleep-awake in children is not established. The safety and efficacy of Tasimelteon, oral suspension, is recommended in pediatric patients of age three years and older for the treatment of SMS or Smith-Magenis Syndrome. Also, drug usage safety and efficacy are not established for pediatric patients suffering from nighttime sleep disturbances.

Geriatric Use - The exposure to Tasimelteon is almost two times greater in adults as compared to young children. Therefore, the risk of adverse effects is also high in geriatric patients of 65 and above age.

Hepatic Impairment: Tasimelteon is not recommended in patients with mild to moderate hepatic impairment.

Smokers: The efficacy of the drug gets reduced withsmokingas it causes strong induction of CYP1A2 (cytochrome P450 family 1 subfamily A polypeptide 2) levels.

Patient Counseling Information:

The doctor should counsel the patient to read the FDA guidelines on labeling for oral suspensions to know the instructions to use. They should also be guided to read the description of the capsule before consuming it. In addition, they should be informed to take the drug dosage as guided do not alter the dose without asking the doctor.