Drug information of Solriamfetol

Solriamfetol

Drug group:

Sunosi (solriamfetol) is a prescription medicine used to treat excessive daytime sleepiness in adults with narcolepsy or in those whose sleep is disrupted by sleep apnea.

Mechanism of effect

The specific mechanism of action is unknown but it may be through its activity as a dopamine and norepinephrine reuptake inhibitor

Pharmacodynamic

Solriamfetol binds to the dopamine transporter and norepinephrine transporter with low affinity (Ki=14.2 µM and 3.7 µM, respectively), and inhibits the reuptake of dopamine and norepinephrine with low potency (IC50 =2.9 μM and 4.4 μM, respectively). Solriamfetol has no appreciable binding affinity for the serotonin transporter (Ki=81.5 µM) and does not inhibit serotonin reuptake (IC50 > 100 μM). Solriamfetol has no appreciable binding affinity to dopamine, serotonin, norepinephrine, GABA, adenosine, histamine, orexin, benzodiazepine, muscarinic acetylcholine, or nicotinic acetylcholine receptors.

Pharmacokinetics

Absorption
Oral bioavailability of solriamfetol is approximately 95%Label. Peak plasma concentration is reached in 2 hours (with a range of 1.25 to 3 hours) in fasted patientsLabel. When solriamfetol is taken with a high fat meal, the time to peak plasma concentration increases to 3 hoursLabel.
Volume of distribution
199LLabel. Other studies have found the volume of distribution to be 158.2L ± 37.3L in fasted subjects and 159.8L ± 38.9L in fed subjects4.
Protein binding
13.3% to 19.4% protein bound over a plasma concentration range of 0.059 to 10.1mcg/mLLabel.
Metabolism
Solriamfetol does not undergo significant metabolism in humans, though less than 1% of solriamfetol is metabolized to N-acetyl solriamfetolLabel2.
Route of elimination
95% of solriamfetol is recovered in urine unchanged by metabolismLabel. Less than 1% of solriamfetol is recovered as N-acetyl solriamfetolLabel2.
Half-life
7.1 hoursLabel. Other studies have found the mean half life to be 6.1 ± 1.2 hours in fasted subjects and 5.9 ± 1.2 hours in fed subjects4.
Clearance
Renal clearance is 18.2L/h and total clearance is 19.5L/hLabel. Other studies have found clearance to be 18.4 ± 4.2L/h in fasted subjects and 18.8 ± 4.2L/h in fed subjects4.

Drug indications

Sunosi is indicated to improve wakefulness and reduce excessive daytime sleepiness in adult patients with narcolepsy (with or without cataplexy).

Sunosi is indicated to improve wakefulness and reduce excessive daytime sleepiness (EDS) in adult patients with obstructive sleep apnoea (OSA) whose EDS has not been satisfactorily treated by primary OSA therapy, such as continuous positive airway pressure (CPAP).

Dosage

Narcolepsy
The recommended starting dose is 75 mg once daily, upon awakening. If clinically indicated in patients with more severe levels of sleepiness, a starting dose of 150 mg may be considered.
Depending on clinical response, the dose can be titrated to a higher level by doubling the dose at intervals of at least 3 days, with a recommended maximum daily dose of 150 mg once daily.
OSA
The recommended starting dose is 37.5 mg once daily, upon awakening. Depending on clinical response, the dose can be titrated to a higher level by doubling the dose at intervals of at least 3 days, with a recommended maximum daily dose of 150 mg once daily.
Sunosi can be taken with or without food.
Taking Sunosi less than 9 hours before bedtime should be avoided as it may affect night time sleep.
Long-term use
The need for continued treatment and the appropriate dose should be periodically assessed during extended treatment in patients prescribed solriamfetol.
Special populations
Elderly (> 65 years)
Limited data are available in elderly patients. Consideration should be given to the use of lower doses and close monitoring in this population (see section 4.4). Solriamfetol is predominantly eliminated by the kidney and since elderly patients are more likely to have decreased renal function, dosing may need to be adjusted based on creatinine clearance in these patients.
Renal impairment
Mild renal impairment (creatinine clearance of 60-89 mL/min): No dose adjustment is required.
Moderate renal impairment (creatinine clearance of 30-59 mL/min): The recommended starting dose is 37.5 mg once daily. Dose may be increased to a maximum of 75 mg once daily after 5 days.
Severe renal impairment (creatinine clearance of 15-29 mL/min): The recommended dose is 37.5 mg once daily.
End stage renal disease (creatinine clearance <15 mL/min): Solriamfetol is not recommended for use in patients with end stage renal disease.
Paediatric population
The safety and efficacy of Sunosi in children and adolescents (<18 years old) have not yet been established. No data are available.
Method of administration
Sunosi is for oral use.
Administration of a 37.5 mg dose can be achieved by halving a 75 mg tablet using the score line.

Drug contraindications

 Hypersensitivity to the active substance or to any of the excipients
• Myocardial infarction within the past year, unstable angina pectoris, uncontrolled hypertension, serious cardiac arrhythmias and other serious heart problems.
• Concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days after MAOI treatment has been discontinued

Side effects

More common
  • Anxiety
Less common
  • Agitation
  • chest pain or discomfort
  • cough
  • fast, irregular, pounding, or racing heartbeat or pulse
  • feeling jittery
  • irritability
  • restlessness
  • tightness of the chest
  • tremor
  • trouble breathing
  • trouble sleeping

Interactions

Dexmethylphenidate , Rotigotine , lenvatinib , Levalbuterol , Cabozantinib , carbidopa , Droxidopa
Solriamfetol must not be administered concomitantly with MAOIs or within 14 days after MAOI treatment has been discontinued because it may increase the risk of a hypertensive reaction
Concomitant use of medicinal products that increase blood pressure and heart rate should be used with caution
Medicinal products that increase levels of dopamine or that bind directly to dopamine receptors might result in pharmacodynamic interactions with solriamfetol. Concomitant use of such medicinal products should be used with caution.

Alerts

Psychiatric symptoms
Solriamfetol has not been evaluated in patients with a history of or concurrent psychosis or bipolar disorders. Caution should be exercised when treating these patients due to psychiatric adverse reactions that could exacerbate symptoms (e.g. manic episodes) of pre-existing psychiatric disorders.
Patients treated with solriamfetol should be carefully monitored for adverse reactions such as anxiety, insomnia and irritability. These adverse reactions were commonly observed during treatment initiation but tended to resolve with continued treatment. If these symptoms persist or worsen, dose reduction or discontinuation should be considered.
Blood pressure and heart rate
Analyses of data from clinical trials showed that treatment with solriamfetol increases systolic blood pressure, diastolic blood pressure, and heart rate in a dose dependent fashion.
Epidemiological data show that chronic elevations in blood pressure increase the risk of major adverse cardiovascular event (MACE), including stroke, heart attack and cardiovascular death. The magnitude of the increase in absolute risk is dependent on the increase in blood pressure and the underlying risk of MACE in the population being treated. Many patients with narcolepsy and OSA have multiple risk factors for MACE, including hypertension, diabetes, hyperlipidemia and high body mass index (BMI).
Use in patients with unstable cardiovascular disease, serious heart arrhythmias and other serious heart problems is contraindicated
Patients with moderate or severe renal impairment may be at a higher risk of increases in blood pressure and heart rate because of the prolonged half-life of solriamfetol.
Abuse
Sunosi was assessed in a human abuse potential study and demonstrated low abuse potential. Results from this clinical study demonstrated that solriamfetol produced Drug Liking scores higher than placebo, but generally similar or lower than phentermine (a weak stimulant). Caution should be exercised when treating patients with a history of stimulant (e.g. methylphenidate, amphetamine) or alcohol abuse, and these patients should be monitored for signs of misuse or abuse of solriamfetol.
Angle closure glaucoma
Mydriasis may occur in patients taking solriamfetol. Caution is advised in patients with increased ocular pressure or at risk of angle closure glaucoma.
Women of childbearing potential or their partners
Women of childbearing potential or their male partners must use effective method of contraception while taking solriamfetol

Points of recommendation

Do not take SUNOSI if you are taking, or have stopped taking within the past 14 days, a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI).
Before taking SUNOSI, tell your doctor about all of your medical conditions, including if you:
    have heart problems, high blood pressure, kidney problems, diabetes, or high cholesterol.
    have had a heart attack or a stroke.
    have a history of mental health problems (including psychosis and bipolar disorders), or of drug or alcohol abuse or addiction.
    are pregnant or planning to become pregnant. It is not known if SUNOSI will harm your unborn baby.
    are breastfeeding or plan to breastfeed. It is not known if SUNOSI passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take SUNOSI.

Pregnancy level

There are no or limited amount of data from the use of solriamfetol in pregnant women. Animal studies have shown reproductive toxicity . Sunosi is not recommended during pregnancy and in women of childbearing potential not using contraception

Breast feeding warning

It is unknown whether solriamfetol is excreted into human milk. Animal studies have shown excretion of solriamfetol in milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Sunosi therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the women.

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