Lisdexa S.K. 10 MG/ML Oral Solution

/ K.S.KIM INTERNATIONAL (SK- PHARMA) LTD., ISRAEL

ADHD: The recommended starting dosage in adults and pediatric patients 6 years and older is 30 mg (equivalent to 3 ml) once daily in the morning. Dosage may be adjusted in increments of 10 mg (equivalent to 1 ml) or 20 mg (equivalent to 2 ml) at approximately weekly intervals up to maximum recommended dosage of 70 mg (equivalent to 7 ml) once daily.
Moderate to Severe BED in Adults: The recommended starting dosage in adults is 30 mg (equivalent to 3 ml) once daily to be titrated in increments of 20 mg (equivalent to 2 ml) at approximately weekly intervals to Page 3 of 36 achieve the recommended target dose of 50 to 70 mg (equivalent to 5 ml to 7 ml) once daily. The maximum recommended dosage is 70 mg/once daily (equivalent to 7 ml/once daily).
Patients with Renal Impairment: In patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73 m2), the maximum dosage should not exceed 50 mg (equivalent to 5 ml) once daily. In patients with end stage renal disease (ESRD, GFR < 15 mL/min/1.73 m2), the maximum recommended dosage is 30 mg (equivalent to 3 ml) once daily.
See prescribing information for full details.

A central nervous system (CNS) stimulant indicated for:
• the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients ages 6 years and above.
• the treatment of Moderate to Severe Binge Eating Disorder (BED) for patients over 18 years.
Limitation of Use:
This medicinal product is not indicated or recommended for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The safety and effectiveness for the treatment of obesity have not been established.

* Hypersensitivity to the active substance or to any of the excipients.
* Known hypersensitivity to amphetamine products Anaphylactic reactions, Stevens Johnson Syndrome, angioedema, and urticaria have been observed in post-marketing reports.
* Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis.

Abuse, Misuse and Addiction: This medicinal product has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Lisdexamfetamine can be diverted for non-medical use into illicit channels or distribution. Misuse and abuse of CNS stimulants can result in overdose and death, and this risk is increase with higher doses or unapproved methods of administration, such as snorting or injection.
Driving and using machines: This medicinal product can cause dizziness, drowsiness and visual disturbances including difficulties with accommodation and blurred vision. These could have a moderate influence on the ability to drive and use machines. Patients should be warned of these possible effects and advised that if affected, they should avoid potentially hazardous activities
such as driving or operating machinery.
Risks to Patients with Serious Cardiac Disease: Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage.
Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
Increased Blood Pressure and Heart Rate: CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases. Monitor all patients for potential tachycardia and hypertension.
Psychiatric Adverse Reactions:
Exacerbation of Pre-existing Psychosis: CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
Induction of a Manic Episode in Patients with Bipolar Disorder: CNS stimulants may induce a /manic or mixed episode. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, and depression).
New Psychotic or Manic Symptoms: CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms, (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing treatment.
Long-Term Suppression of Growth in Pediatric Patients: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in Lisdexamfetamine-treated pediatric patients. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. This medicinal product is not approved for use in pediatric patients below 6 years of age.
Peripheral Vasculopathy, including Raynaud’s Phenomenon: CNS stimulants, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Lisdexamfetamine-treated patients who develop signs or symptoms of peripheral vasculopathy.
Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort. The co- administration with CYP2D6 inhibitors may also increase the risk with increased exposure to the active metabolite of dextroamphetamine. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Concomitant use of Lisdexamfetamine with MAOI drugs is contraindicated.
Discontinue treatment with Lisdexamfetamine and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur and initiate supportive symptomatic treatment. If concomitant use of Lisdexamfetamine with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Lisdexamfetamine with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Before initiating Lisdexamfetamine, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.
See prescribing information for full details.

The most frequently reported adverse reactions in clinical trials (2% or more and twice rate of placebo) in pediatric patients ages 6 to 17 years, and/or adults were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting.
See prescribing information for full details.

MAO Inhibitors (MAOI): MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Do not administer Lisdexamfetamine during or within 14 days following the administration of MAOI.
Serotonergic Drugs: Concomitant use with serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Lisdexamfetamine initiation or dosage increase. If serotonin syndrome occurs, discontinue treatment.
CYP2D6 Inhibitors: Concomitant use with CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of Lisdexamfetamine compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during treatment initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Lisdexamfetamine and the CYP2D6 inhibitor.
Alkalinizing Agents: Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Co-administration of Lisdexamfetamine and urinary alkalinizing agents should be avoided.
Acidifying Agents: Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Increase dose based on clinical response.
Tricyclic Antidepressants: May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response.
See prescribing information for full details.

Pregnancy: The limited available data from published literature and postmarketing reports on use of Lisdexamfetamine in pregnant women are not sufficient to inform a drug associated risk for major birth defects and miscarriage. Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as Lisdexamfetamine, cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. Infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight. Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.
Lactation: Lisdexamfetamine is a pro-drug of dextroamphetamine. Based on limited case reports in published literature, amphetamine (d-or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breastfeeding is not recommended during treatment.      
See prescribing information for full details.       

Clinical Effects of Overdose: Overdose of CNS stimulants is characterized by the following sympathomimetic effects:
• Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.
• CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.
• Life-threatening hyperthermia (temperatures greater than 40o C) and rhabdomyolysis may develop.
Overdose Management: Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of this medicinal product should be considered when treating patients with overdose. Lisdexamfetamine and d-amphetamine are not dialyzable. Consider contacting a medical toxicologist for additional overdose management recommendations.

Do not store above 30°C.