Tasimelteon is a medication primarily used to treat Non-24-Hour Sleep-Wake Disorder (Non-24). Non-24 is a circadian rhythm disorder where a person's internal body clock is not synchronized with the typical 24-hour day, leading to difficulties in falling asleep and waking up at consistent times.
Tasimelteon works by mimicking the action of melatonin, a hormone that regulates the sleep-wake cycle. It binds to melatonin receptors in the brain, helping to regulate the sleep-wake cycle in individuals with Non-24. It's important to note that Tasimelteon is not a cure for Non-24, but it can help manage the symptoms.
Tasimelteon (Hetlioz) is a novel drug and the first of its kind that has been approved by the FDA for the treatment of non-24-hour sleep-wake disorder. The Europeans have approved it for the treatment of non-24-hour sleep-wake disorder only in totally blind people. It has not been approved in Europe in sighted people. Non-24 hour sleep-wake disorder is only seen in totally blind patients. However, it may rarely affect sighted individuals as well.
The symptoms of non-24-hour sleep-wake disorder include:
- Difficulty to fall asleep at night.
- Sleep time gradually gets delayed.
- Getting up later in the morning
- The sleep does not relieve fatigue and is not restful.
- This also results in daytime sleepiness.
- The sleep pattern may be disturbed or the patient may develop insomnia
- Depression and anxiety
Other hypnotic drugs used to treat insomnia include:
Benzodiazepines, zolpidem, zaleplon, and zopiclone.
Tasimelteon (Hetlioz) dose in adults
Tasimelteon is a medicine for Non-24-Hour Sleep-Wake Disorder. It helps fix the body clock so people can sleep better. It might take weeks or months to see the effects because everyone's body clock is different.
Tasimelteon (Hetlioz) dose in the treatment of non-24-hour sleep-wake disorder:
- The usual dose of Tasimelteon is 20 mg taken once daily. It's important to take it at the same time every night before bedtime.
- This consistency helps in regulating the sleep-wake cycle.
Tasimelteon (Hetlioz) dose in Children
It has not been studied in children.
Pregnancy Risk Factor C
- Tasimelteon is classified as Pregnancy Risk Factor C, meaning there's a potential risk to the fetus based on animal studies, but there may be situations where the benefits of the medication outweigh the potential risks.
- Adverse events were noted in some animal studies related to reproduction.
Tasimelteon use during breastfeeding:
- The excretion of tasimelteon into breast milk is not well understood, so it's uncertain whether it passes into breast milk.
- As a precaution, the manufacturer recommends exercising caution if tasimelteon is administered to a breastfeeding woman.
- This means that the potential risks and benefits should be carefully considered before deciding whether to use tasimelteon while breastfeeding.
Tasimelteon (Hetlioz) dose in Kidney Disease:
- Adjustment in the dose is not necessary.
Tasimelteon (Hetlioz) dose in Liver Disease:
- In patient with mild or moderate liver problem, no dosage adjustment is necessary when taking Tasimelteon.
- In patient with severe liver problem, the manufacturer's labeling does not provide specific dosage adjustments because it has not been studied in this population. Therefore, the use of Tasimelteon is not recommended for individuals with severe liver impairment.
Tasimelteon (Hetlioz) side effects (common):
- Central nervous system:
- Headache
(Tasimelteon) Hetlioz Side Effects (Less common):
- Central nervous system:
- Abnormal dreams
- Genitourinary:
- Urinary tract infection
- Hepatic:
- Increased serum ALT
- Respiratory:
- Upper respiratory tract infection
Contraindication to Tasimelteon (Hetlioz) include:
- According to the manufacturer's labeling, there are no contraindications listed for Tasimelteon.
Warnings and Precautions
CNS depression:
- Tasimelteon may lead to CNS (central nervous system) depression, which can affect both physical and mental abilities.
- Patients should be warned about engaging in activities that require mental alertness, such as operating machinery or driving, as their abilities may be impaired while taking the medication.
Hepatic impairment:
- In cases of severe hepatic impairment, the use of Tasimelteon is not recommended.
- This caution is due to the lack of specific dosage adjustments provided in the manufacturer's labeling, as Tasimelteon has not been studied extensively in this population.
Tasimelteon (Hetlioz): Drug Interaction
|
Abiraterone Acetate |
May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). |
|
Alcohol (Ethyl) |
CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). |
|
Alizapride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
|
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Broccoli |
May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). |
|
Bromopride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabis |
May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). |
|
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
|
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
|
CNS Depressants |
May enhance the adverse/toxic effect of other CNS Depressants. |
|
CYP1A2 Inducers (Moderate) |
May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). |
|
CYP1A2 Inhibitors (Moderate) |
May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Tasimelteon. |
|
Cyproterone |
May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Deferasirox |
May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). |
|
Dimethindene (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Doxylamine |
May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. |
|
Dronabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Esketamine |
May enhance the CNS depressant effect of CNS Depressants. |
|
HydrOXYzine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Kava Kava |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Lofexidine |
May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Magnesium Sulfate |
May enhance the CNS depressant effect of CNS Depressants. |
|
Melatonin |
May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). |
|
MetyroSINE |
CNS Depressants may enhance the sedative effect of MetyroSINE. |
|
Minocycline |
May enhance the CNS depressant effect of CNS Depressants. |
|
Mirtazapine |
CNS Depressants may enhance the CNS depressant effect of Mirtazapine. |
|
Nabilone |
May enhance the CNS depressant effect of CNS Depressants. |
|
Obeticholic Acid |
May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). |
|
Peginterferon Alfa-2b |
May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). |
|
Piribedil |
CNS Depressants may enhance the CNS depressant effect of Piribedil. |
|
Pramipexole |
CNS Depressants may enhance the sedative effect of Pramipexole. |
|
ROPINIRole |
CNS Depressants may enhance the sedative effect of ROPINIRole. |
|
Rotigotine |
CNS Depressants may enhance the sedative effect of Rotigotine. |
|
Rufinamide |
May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Selective Serotonin Reuptake Inhibitors |
CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Teriflunomide |
May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). |
|
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tobacco (Smoked |
May decrease the serum concentration of Tasimelteon. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Trimeprazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Risk Factor D (Consider therapy modification) |
|
|
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
|
Buprenorphine |
|
|
Chlormethiazole |
May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Droperidol |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
|
HYDROcodone |
CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Methotrimeprazine |
CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. |
|
Opioid Agonists |
CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
OxyCODONE |
CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
|
Pitolisant |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Suvorexant |
CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. |
|
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Vemurafenib |
May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. |
|
Zolpidem: |
CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. |
|
Risk Factor X (Avoid combination) |
|
|
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
|
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
|
CYP1A2 Inhibitors (Strong |
May increase the serum concentration of Tasimelteon. |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of Tasimelteon. |
|
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
|
Oxomemazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Paraldehyde |
CNS Depressants may enhance the CNS depressant effect of Paraldehyde. |
|
Sodium Oxybate |
Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. |
|
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
Monitor:
None required.
How to administer Tasimelteon (Hetlioz)?
How to Take Tasimelteon:
- Take Orally: Tasimelteon should be taken by mouth (orally) without food.
- Take at Bedtime: It's important to take Tasimelteon at the same time every night before bedtime.
- Swallow Whole: Swallow the Tasimelteon capsule whole, without crushing or chewing it.
- Prepare for Sleep: After taking Tasimelteon, limit activities to preparing for sleep to allow the medication to work effectively.
- Consistency Matters: If you can't take the dose at the usual time on a particular night, skip that dose. It's essential to maintain consistency in your dosing schedule.
Mechanism of action of Tasimelteon (Hetlioz):
- Tasimelteon works by activating melatonin receptors, specifically the MT₁ and MT₂ receptors.
- It has a higher affinity for the MT₁ receptor than the MT₂ receptor.
- When it activates the MT₁ receptor, it's believed to make you feel sleepier, while activating the MT₂ receptor helps regulate your body's internal clock, influencing your sleep-wake cycle.
Onset:
- The effect of Tasimelteon may not be felt for weeks or even months due to differences in individual circadian rhythms.
Absorption:
- High-fat meals can delay Tasimelteon absorption, reducing the maximum concentration in the blood by 44%.
Protein Binding:
- Approximately 90% of Tasimelteon binds to proteins in the blood.
Distribution:
- Tasimelteon has a volume of distribution ranging from approximately 59 to 126 liters.
Metabolism:
- The liver extensively metabolizes Tasimelteon. It undergoes oxidative metabolism primarily through enzymes CYP1A2 and CYP3A4, with phenolic glucuronidation as the major phase II metabolic route.
Bioavailability:
- Around 38% of Tasimelteon is absorbed into the bloodstream when taken orally.
Half-life Elimination:
- The elimination half-life of Tasimelteon is approximately 1 to 2 hours.
Time to Peak:
- When taken on an empty stomach, Tasimelteon reaches its peak concentration in the blood within about 0.5 to 3 hours. This time increases by around 1.75 hours when taken with a high-fat meal.
Excretion:
- Tasimelteon is primarily excreted through urine (about 80%, with less than 1% as unchanged drug) and to a lesser extent through feces (about 4%).
International Brands of Tasimelteon:
- Hetlioz
Tasimelteon (Hetlioz) Brands in Pakistan:
Tasimelteon (Hetlioz) is not available in Pakistan.
 Injection.webp)