4.1. Therapeutic 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).

4.2. Posology and method of administration

Posology

Treatment should be initiated by a healthcare professional experienced in the treatment of narcolepsy or OSA.

Sunosi is not a therapy for the underlying airway obstruction in patients with OSA. Primary OSA therapy should be maintained in these patients.

Blood pressure and heart rate should be assessed before initiating treatment with solriamfetol and should be monitored periodically during treatment, especially after increasing the dose. Pre-existing hypertension should be controlled before initiating treatment with solriamfetol and caution should be exercised in treating patients at higher risk of MACE, particularly patients with pre-existing hypertension, patients with known cardiovascular or cerebrovascular disease and elderly patients.

The need for continued treatment with solriamfetol should be periodically assessed. If a patient experiences increases in blood pressure or heart rate that cannot be managed with dose reduction of solriamfetol or other appropriate medical intervention, discontinuation of solriamfetol should be considered. Caution should be exercised when using other medicinal products that increase blood pressure and heart rate (see section 4.5).

Posology

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.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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 (see section 4.5).

4.4. Special warnings and precautions for use

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 (see section 4.3).

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 (see section 4.6).

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed (see section 5.2).

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 (see section 4.3).

Concomitant use of medicinal products that increase blood pressure and heart rate should be used with caution (see section 4.4).

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.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of solriamfetol in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Sunosi is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Available pharmacological datasuggests excretion of solriamfetol in human 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.

Additionally, solriamfetol has been identified in the breastmilk of postpartum women. There are no data to determine the effects of solriamfetol on breastfed newborn/infants or its effects on milk production [see section 5.2].

Infants exposed to Sunosi should be monitored for signs of any of the adverse reactions as listed in Section 4.8.

Fertility

The effects of solriamfetol in humans are unknown. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Minor influence on the ability to drive is expected in patients receiving stable solriamfetol doses. Dizziness and disturbance in attention may occur following administration of solriamfetol (see section 4.8).

Patients with abnormal levels of sleepiness who take solriamfetol should be advised that their level of wakefulness may not return to normal. Patients with excessive daytime sleepiness, including those taking solriamfetol should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity, especially at the start of the treatment or when the dose is changed.

4.8. Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions were headache (11.1%), nausea (6.6%) and decreased appetite (6.8%).

Tabulated list of adverse reactions

The frequency of adverse reactions is defined using the following MedDRA frequency convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare ( ≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

System Organ Class

Adverse reactions

Frequency

Metabolism and nutrition disorders

Decreased appetite

Common

Psychiatric disorders

Anxiety

Common

Insomnia

Common

Irritability

Common

Bruxism

Common

Agitation

Uncommon

Restlessness

Uncommon

Nervous system disorders

Headache

Very common

Dizziness

Common

Disturbance in attention

Uncommon

Tremor

Uncommon

Cardiac disorders

Palpitations

Common

Tachycardia

Uncommon

Vascular Disorders

Hypertension

Uncommon

Respiratory, thoracic and mediastinal disorders

Cough

Common

Dyspnoea

Uncommon

Gastrointestinal disorders

Nausea

Common

Diarrhoea

Common

Dry mouth

Common

Abdominal pain

Common

Constipation

Common

Vomiting

Common

Skin and subcutaneous tissue disorders

Hyperhidrosis

Common

General disorders and administration site conditions

Feeling jittery

Common

Chest discomfort

Common

Chest pain

Uncommon

Thirst

Uncommon

Investigations

Heart rate increased

Uncommon

Blood pressure increased

Common

Weight decreased

Uncommon

Description of selected adverse reactions

Treatment initiation

The majority of the most frequently reported adverse reactions occurred within the first 2 weeks of initiating treatment and resolved for the majority of patients with a median duration of less than 2 weeks.

Hypersensitivity reactions

In post-marketing experience, there have been reports of hypersensitivity reactions which have occurred with one or more of the following: rash erythematous, rash, urticaria (see section 4.3).

Dose-dependent adverse reactions

In the 12-week clinical trials that compared doses of 37.5 mg, 75 mg and 150 mg/day of solriamfetol to placebo, the following adverse reactions were dose-related: headache, nausea, decreased appetite, anxiety, diarrhoea and dry mouth. The dose relationships were generally similar in OSA and narcolepsy patients. Certain events such as anxiety, insomnia, irritability, and agitation 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 (see section 4.4).

Discontinuation of treatment

In the 12-week placebo-controlled clinical trials, 11 of the 396 patients (3%) who received solriamfetol discontinued due to an adverse reaction compared to 1 of the 226 patients (<1%) who received placebo. The adverse reactions leading to discontinuation that occurred in more than one solriamfetol-treated patients and at a higher rate than placebo were anxiety, palpitations and restlessness, all of which occurred with a frequency less than 1%.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There have been no reports of overdose of solriamfetol in the clinical studies.

In healthy volunteers, there was one adverse reaction of mild tardive dyskinesia and one adverse reaction of moderate akathisia that occurred at a supratherapeutic dose of 900 mg; symptoms resolved after treatment discontinuation.

There is no specific antidote. In the case of inadvertent overdose, symptomatic and supportive medical care should be provided and patients should be carefully monitored, as appropriate.