ADZENYS ER (amphetamine) extended-release oral suspension

ADZENYS ER (amphetamine) extended-release oral suspension

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ADZENYS ER (amphetamine) extended-release oral suspension

ADZENYS ER (amphetamine) extended-release oral suspension contains a 3 to 1 ratio of d- to l amphetamine, a central nervous system stimulant.

The labeled strength reflects the amount of amphetamine in ADZENYS ER whereas the strengths of the mixed salts of a single-entity amphetamine products are in terms of the amount of amphetamine salts. Molecular formula = C9H13N . Molecular weight = 135.21

ADZENYS ER is an extended-release oral suspension containing approximately equal amounts of immediate-release and delayed-release amphetamine.

ADZENYS ER also contains the following inactive ingredients: purified water, sorbitol, propylene glycol, xanthan gum, natural orange flavor, methacrylic acid and methyl methacrylate copolymer, sodium polystyrene sulfonate, vegetable oil, triethyl citrate, methylparaben, citric acid, sucralose, propylparaben, orange color (FD&C Yellow No. 6), and polyethylene glycol.

Indications and usage

ADZENYS ER is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

Mechanism of Action

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known.

Pharmacodynamics

Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Dosage and administration

  • Shake bottle before administering the dose.
  • May be taken with or without food.
  • Do not mix with food or other liquids before consuming.
  • Pediatric patients (ages 6 to 17 years): Starting dose is 6.3 mg (5 mL) once daily in the morning. Maximum dose is 18.8 mg (15 mL) for patients 6 to 12 years, and 12.5 mg (10 mL) once daily for patients 13 to 17 years.
  • Adults: 12.5 mg (10 mL) once daily in the morning.
  • To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine salt compositions and differing pharmacokinetic profiles

Contraindications

  • Known hypersensitivity to amphetamine products or other ingredients in ADZENYS ER.
  • Use of monoamine oxidase inhibitor (MAOI) or within 14 days of the last MAOI dose

Adverse reactions

  • Pediatric patients ages 6 to 12 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever.
  • Pediatric patients ages 13 to 17 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness.
  • Adults: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections.

Warnings and precautions

Potential for Abuse or Dependence: CNS stimulants, including ADZENYS ER, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.

Serious Cardiovascular Reactions: Sudden death, stroke, and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in children and adolescents with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during ADZENYS ER treatment.

Blood Pressure and Heart Rate Increases: CNS stimulants cause an increase in blood pressure (mean increase about 2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor all patients for potential tachycardia and hypertension.

Psychiatric Adverse Events

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 Illness: CNS stimulants may induce a mixed or manic episode in patients with bipolar disorder. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or has a history of depressive symptoms or a family history of suicide, bipolar disorder, and depression).

New Psychotic or Manic Symptoms: CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing ADZENYS ER.

Long-Term Suppression of Growth: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including ADZENYS ER. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted

Peripheral Vasculopathy, including Raynaud’s Phenomenon: Stimulants, including ADZENYS ER, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug.

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.

Potential for Overdose Due to Medication Errors: Medication errors, including substitution and dispensing errors, between ADZENYS ER and other amphetamine products could occur, leading to possible overdosage. To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-permilligram basis because of different amphetamine salt compositions and differing pharmacokinetic profiles.

Potential for Intestinal Necrosis: Cases of intestinal necrosis, including some deaths, have been reported with the concomitant use of sodium polystyrene sulfonate and sorbitol, two of the inactive ingredients in ADZENYS ER. In these cases, patients were administered sodium polystyrene sulfonate to treat hyperkalemia at doses greater than 200 times the amount present in Adzenys ER. However, no absolute safe levels for the interaction of sodium polystyrene sulfonate and sorbitol have been established.

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Drug interactions

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 ADZENYS ER during or within 14 days following the administration of MAOI. Examples; selegiline, isocarboxazid, phenelzine, tranylcypromine

Serotonergic Drugs: The concomitant use of ADZENYS ER and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during ADZENYS ER initiation or dosage increase. If serotonin syndrome occurs, discontinue ADZENYS ER and the concomitant serotonergic drug(s). Examples; selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort

Alkalinizing Agents: Increase blood levels and potentiate the action of amphetamine. Co-administration of ADZENYS ER and gastrointestinal alkalinizing agents should be avoided. Examples; Gastrointestinal alkalinizing agents (e.g., sodium bicarbonate). Urinary alkalinizing agents (e.g., acetazolamide, some thiazides).

Acidifying Agents: Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples; Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid).

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. Examples; desipramine, protriptyline.

CYP2D6 Inhibitors: May increase the exposure of amphetamine. Start with lower doses and monitor frequently and adjust ADZENYS ER dose or use alternative therapy based on clinical response. Examples; paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Gastric pH Modulators: May change the release profile, shape of pharmacokinetic profile and exposure to ADZENYS ER resulting in the potential for dose dumping. Concomitant use of ADZENYS ER with a gastric pH modulator (i.e. H2 blocker or proton pump inhibitor) is not recommended. Examples; omeprazole, esomeprazole, pantoprazole, cimetidine.

Use in specific populations

Pregnancy: The limited available data from published literature and postmarketing reports on the use of prescription amphetamine in pregnant women are insufficient to inform a drug-associated risk for major congenital malformations or miscarriage. Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines

Amphetamines, such as ADZENYS ER, 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: 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 stimulant exposure are unknown. It is possible that large dosages of amphetamine 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, advise patients that breastfeeding is not recommended during treatment with ADZENYS ER.

Pediatric Use: Safety and effectiveness have been established in pediatric patients with ADHD ages 6 to 17 years of age in three adequate and well-controlled clinical trials of up to 4 weeks in duration.

Drug abuse and dependence

Controlled Substance: ADZENYS ER contains amphetamine, a Schedule II controlled substance in the U.S. Controlled Substances Act (CSA).

Abuse

ADZENYS ER, is a CNS stimulant that contains amphetamine which has a high potential for abuse. Abuse is characterized by impaired control of drug use, compulsive use despite harm, and craving.

Signs and symptoms of amphetamine abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been observed. Abusers of amphetamines may use other unapproved routes of administration which can result in overdose and death

To reduce the abuse of ADZENYS ER, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants, monitor for signs of abuse while on therapy, and re-evaluate the need for ADZENYS ER use.

Dependence

Tolerance: Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug’s desired and/or undesired effects over time) may occur during the chronic therapy of CNS stimulants including ADZENYS ER.

Dependence: Physical dependence (which is manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants including ADZENYS ER. Withdrawal symptoms after abrupt cessation following prolonged high dosage administration of CNS stimulants include dysphoric mood; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

Overdosage

Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Other reactions include arrhythmias, hypertension or hypotension, circulatory collapse, nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

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