Adzenys XR ODT

Name: Adzenys XR ODT

Adzenys XR-ODT Overview

Adzenys XR-ODT is a prescription medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in adults and children aged 6 years and older. Adzenys XR-ODT belongs to a group of drugs called amphetamine stimulants. These work to improve focus and decrease hyperactivity by altering the levels of certain natural chemicals in the brain.

This medication is available in an extended-release orally disintegrating tablet. It is typically taken once a day in the morning, with or without food. Allow tablet to fully disintegrate in saliva and then swallow. 

Common side effects of Adzenys XR-ODT include loss of appetite, difficulty falling asleep, and stomach pain. 

Adzenys XR-ODT Drug Class

Adzenys XR-ODT is part of the drug class:

  • Centrally acting sympathomimetics

Adzenys XR-ODT Usage

Take Adzenys XR-ODT exactly as prescribed

  • Adzenys XR-ODT is available in an extended-release orally disintegrating tablet and is typically taken once a day in the morning
  • Adzenys XR-ODT can be taken with or without food.
  • Allow Adzenys XR-ODT to fully disintegrate in saliva then swallow.
  • The Adzenys XR-ODT tablet should remain in the blister pack until you are ready to take it

Taking Adzenys XR-ODT

  • Use dry hands to open the blister; tear along the perforation, bend the blister where indicated and peel back the blister’s labeled backing to take out the tablet; the tablet should not be pushed through the foil
  • As soon as the blister is opened, the tablet should be removed and placed on your tongue
  • The whole tablet should be placed on the tongue and allowed to disintegrate without chewing or crushing. The tablet will disintegrate in saliva so that it can be swallowed.

Proper Use of amphetamine

This section provides information on the proper use of a number of products that contain amphetamine. It may not be specific to Adzenys XR ODT. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming. If you feel that the medicine is not working properly after taking it for several weeks, check with your doctor first and do not increase the dose.

This medicine should come with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Amphetamine is used for different conditions and comes in different forms. Make sure you understand how to take your prescribed brand.

It is best to take this medicine when you wake up in the morning. You may take this medicine with or without food.

Measure the extended-release oral suspension with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid. Shake the bottle before each use.

If you are using the extended-release oral disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Place the tablet in your mouth. It should melt quickly.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (extended-release suspension):
    • For ADHD:
      • Adults and children 6 years of age and older—At first, 2.5 or 5 milligrams (mg) once a day, in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 20 mg per day.
      • Children younger than 6 years of age—Use and dose must be determined by your doctor.
  • For oral dosage form (extended release oral disintegrating tablets):
    • For ADHD:
      • Adults—12.5 milligrams (mg) once a day, in the morning.
      • Children 13 to 17 years of age and older—At first, 6.3 mg once a day, in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 12.5 mg per day.
      • Children 6 to 12 years of age—At first, 6.3 mg once a day, in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 18.8 mg per day.
      • Children younger than 6 years of age—Use and dose must be determined by your doctor.
  • For oral dosage form (tablets):
    • For ADHD:
      • Adults and children 6 years of age and older—At first, 5 milligrams (mg) once or two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg per day.
      • Children 3 to 5 years of age—At first, 2.5 mg once a day. Your doctor may increase your dose as needed.
      • Children younger than 3 years of age—Use is not recommended.
    • For narcolepsy:
      • Adults and children 12 years of age and older—At first, 10 milligrams (mg) once a day, in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg per day.
      • Children 6 to 11 years of age—At first, 5 mg once a day, in the morning. Your doctor may increase your dose as needed.
      • Children younger than 6 years of age—Use and dose must be determined by your doctor.
    • For weight loss:
      • Adults and children 12 years of age and older—5 to 10 milligrams (mg) per day, taken 30 to 60 minutes before each meal. Your doctor may increase your dose as needed. However, the dose is usually not more than 30 mg per day.
      • Children younger than 12 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Uses of Adzenys XR-ODT

  • It is used to treat attention deficit problems with hyperactivity.
  • It may be given to you for other reasons. Talk with the doctor.

How is this medicine (Adzenys XR-ODT) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take Adzenys XR-ODT early in the day to prevent sleep problems.
  • Take with or without food.
  • Do not take this medicine out of the blister pack until you are ready to take it. Take Adzenys XR-ODT right away after opening the blister pack. Do not store the removed drug for future use.
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place on your tongue and let it melt. Water is not needed. Do not swallow it whole. Do not chew, break, or crush it.
  • To gain the most benefit, do not miss doses.
  • Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
  • Talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Dosage and administration

Pre-treatment Screening

Prior to treating patients with Adzenys XR-ODT, assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].

Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically re-evaluate the need for Adzenys XR-ODT use [see Warnings and Precautions (5.1), and Drug Abuse and Dependence (9)].

Dosing Considerations for All Patients

Adzenys XR-ODT may be taken with or without food. Individualize the dosage according to the therapeutic needs and response of the patient.

Adzenys XR-ODT should be taken as follows:

  • The tablet should remain in the blister pack until the patient is ready to take it.
  • The patient or caregiver should use dry hands to open the blister.
  • Tear along the perforation, bend the blister where indicated and peel back the blister's labeled backing to take out the tablet. The tablet should not be pushed through the foil.
  • As soon as the blister is opened, the tablet should be removed and placed on the patient's tongue.
  • The whole tablet should be placed on the tongue and allowed to disintegrate without chewing or crushing.
  • The tablet will disintegrate in saliva so that it can be swallowed.

Pediatric Patients

The recommended starting dosage is 6.3 mg once daily in the morning. Increase in increments of 3.1 mg or 6.3 mg at weekly intervals. The maximum recommended dose is 18.8 mg daily for patients 6 to 12 years, and 12.5 mg daily for patients 13 to 17 years [see Use in Specific Populations (8.3), Clinical Studies (14)].

Adults

The recommended dose is Adzenys XR-ODT 12.5 mg daily.

Switching from Other Amphetamine Products

Patients taking ADDERALL XR may be switched to Adzenys XR-ODT at the equivalent dose taken once daily [see Clinical Pharmacology (12.3)]. Refer to Table 1 for equivalent doses of Adzenys XR-ODT and ADDERALL XR. ADDERALL XR (dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate extended-release capsules) is also referred to as mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER).

Table 1: Equivalent Doses of Adzenys XR-ODT and ADDERALL XR (Mixed Salts of a Single-Entity Amphetamine Product) Extended-Release Capsules
Adzenys XR-ODT
Amphetamine extended-release orally disintegrating tablets
3.1 mg 6.3 mg 9.4 mg 12.5 mg 15.7 mg 18.8 mg
ADDERALL XR
Mixed salts of a single-entity amphetamine product extended-release capsules (MAS ER)
5 mg 10 mg 15 mg 20 mg 25 mg 30 mg

If switching from any other amphetamine products, discontinue that treatment, and titrate with Adzenys XR-ODT using the titration schedule [see Dosage and Administration (2.3), (2.4)].

Do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles [see Warnings and Precautions (5.7)].

Dosage Modifications Due to Drug Interactions

Agents that alter urinary pH can impact urinary excretion and alter blood levels of amphetamine. Acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. Adjust Adzenys XR-ODT dosage accordingly [see Drug Interactions (7.1)].

Adverse reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Drug Dependence [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)]
  • Hypersensitivity to amphetamine, or other components of Adzenys XR-ODT [see Contraindications (4)]
  • Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) and Drug Interactions (7.1)]
  • Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
  • Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
  • Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
  • Long-Term Suppression of Growth [see Warnings and Precautions (5.5)]
  • Peripheral Vasculopathy, including Raynaud's phenomenon [see Warnings and Precautions (5.6)]
  • Serotonin Syndrome [see Warnings and Precautions (5.7)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of Adzenys XR-ODT has been established from adequate and well-controlled studies of single-entity amphetamine product extended-release (MAS ER) capsules [see Clinical Studies (14)]. The adverse reactions of MAS ER capsules in these adequate and well-controlled studies are described below.

The premarketing development program for MAS ER included exposures in a total of 1315 participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82 healthy adult subjects). Of these, 635 patients (ages 6 to 12 years) were evaluated in two controlled clinical studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N= 40).

Adverse Reactions Leading to Discontinuation of Treatment

The most frequent adverse reactions leading to discontinuation of MAS ER in controlled and uncontrolled, multiple-dose clinical trials of pediatric patients ages 6 to 12 years (N=595) were anorexia (loss of appetite) (2.9%), insomnia (1.5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%).

In a separate placebo-controlled 4-week study in pediatric patients ages 13 to 17 years with ADHD, five patients (2.1%) discontinued treatment due to adverse events among MAS ER-treated patients (N=233) compared to 0% who received placebo (N=54). The most frequent adverse event leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3).

In one placebo-controlled 4-week study among adults with ADHD with doses 20 mg to 60 mg, 23 patients (12.0% ) discontinued treatment due to adverse events among MAS ER-treated patients (N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse events leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) were insomnia (5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%, n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2).

Adverse Reactions Occurring in Clinical Trials

Adverse reactions reported in a 3-week clinical trial of pediatric patients 6 to 12 years of age and a 4-week clinical trial in pediatric patients 13 to 17 years of age and adults, respectively, treated with MAS ER or placebo are presented in the tables below.

Table 2: Adverse Reactions Reported by 2% or More of Pediatric Patients (6-12 years old) Receiving MAS ER with Higher Incidence than on Placebo in a 584-Patient Clinical Study
Body System Adverse Reaction MAS ER
(n=374)
Placebo
(n=210)
General Abdominal Pain (stomachache) 14% 10%
Fever 5% 2%
Infection 4% 2%
Accidental Injury 3% 2%
Asthenia (fatigue) 2% 0%
Digestive System Loss of Appetite 22% 2%
Vomiting 7% 4%
Nausea 5% 3%
Dyspepsia 2% 1%
Nervous System Insomnia 17% 2%
Emotional Lability 9% 2%
Nervousness 6% 2%
Dizziness 2% 0%
Metabolic/Nutritional Weight Loss 4% 0%
Table 3: Adverse Reactions Reported by 5% or More of Pediatric Patients (13-17 Years Old) Weighing ≤ 75kg Receiving MAS ER with Higher Incidence than Placebo in a 287 Patient Clinical Forced Weekly-Dose Titration Study*
Body System Preferred Term MAS ER
(n=233)
Placebo
(n=54)
Note: The following reactions did not meet the criterion for inclusion in Table 3 but were reported by 2% to 4% of adolescent patients receiving MAS ER with a higher incidence than patients receiving placebo in this study: accidental injury, asthenia (fatigue), dry mouth, dyspepsia, emotional lability, nausea, somnolence, and vomiting.
* Included doses up to 40 mg † Dose-related adverse reactions
General Abdominal Pain (stomachache) 11% 2%
Digestive System Loss of Appetite † 36% 2%
Nervous System Insomnia † 12% 4%
Metabolic/Nutritional Weight Loss † 9% 0%
Table 4: Adverse Reactions Reported by 5% or More of Adults Receiving MAS ER with Higher Incidence Than Placebo in a 255 Patient Clinical Forced Weekly-Dose Titration Study*
Body System Preferred Term MAS ER
(n=191)
Placebo
(n=64)
Note: The following reactions did not meet the criterion for inclusion in Table 4 but were reported by 2% to 4% of adult patients receiving MAS ER with a higher incidence than patients receiving placebo in this study: infection, photosensitivity reaction, constipation, tooth disorder (e.g., teeth clenching, tooth infection), emotional lability, libido decreased, somnolence, speech disorder (e.g., stuttering, excessive speech), palpitation, twitching, dyspnea, sweating, dysmenorrhea, and impotence.
* Included doses up to 60 mg.
General Headache 26% 13%
Asthenia 6% 5%
Digestive System Dry Mouth 35% 5%
Loss of Appetite 33% 3%
Nausea 8% 3%
Diarrhea 6% 0%
Nervous System Insomnia 27% 13%
Agitation 8% 5%
Anxiety 8% 5%
Dizziness 7% 0%
Cardiovascular System Tachycardia 6% 3%
Metabolic/Nutritional Weight Loss 10% 0%
Urogenital System Urinary Tract Infection 5% 0%

Adverse Reactions from Clinical Trials and Spontaneous Postmarketing Reports of Other Amphetamine Products

The following adverse reactions are from clinical trials and spontaneous postmarketing reports of other amphetamine products in pediatric patients and adults with ADHD. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Cardiovascular: Palpitations, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, aggression, anger, logorrhea, and paresthesia (including formication).

Eye Disorders: Vision blurred, mydriasis.

Gastrointestinal: Unpleasant taste, constipation, other gastrointestinal disturbances.

Allergic: Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported.

Endocrine: Impotence, change in libido, frequent or prolonged erections.

Skin: Alopecia.

Musculoskeletal, Connective Tissue, and Bone Disorders: rhabdomyolysis.

Psychiatric Disorders: dermatillomania, bruxism.

Vascular Disorders: Raynaud's phenomenon.

PRINCIPAL DISPLAY PANEL - 6.3 mg Tablet Blister Pack Carton

NDC 70165-010-30

Contains:
30 Tablets (5 x 6-count blister cards)
Travel Case

Rx Only

Adzenys XR-ODT™CII
Amphetamine Extended-Release
Orally Disintegrating Tablets

Do not crush or chew tablets

Each tablet contains 6.3 mg of amphetamine
(equivalent to that in a 10 mg strength mixed salts
of a single-entity amphetamine product)

6.3 mg

NEOS™
Therapeutics

PHARMACIST: Dispense the enclosed Medication Guide to each patient.

Patient Handout

Print without Office InfoPrint with Office Info

Amphetamine Levels and Effects while Breastfeeding

Summary of Use during Lactation

In dosages prescribed for medical indications, some evidence indicates that amphetamine does not affect nursing infants adversely. The effect of amphetamine in milk on the neurological development of the infant has not been well studied. Large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Breastfeeding is generally discouraged in mothers who are actively abusing amphetamines.[1][2][3]

Drug Levels

Maternal Levels. A nursing woman was taking racemic amphetamine 5 mg orally 4 times daily at 10 am, noon, 2 pm and 4 pm for narcolepsy. Trough milk levels of 55 and 68 mcg/L were found before the 10 am dose on days 10 and 42 postpartum, respectively. Milk levels were 118 and 138 mcg/L before the 2 pm doses on days 10 and 42, respectively.[4]

A woman took 35 mg of amphetamine daily for narcolepsy and exclusively breastfed her infant for 6 months. Breastmilk samples were taken just before her morning dose at 2, 5 and 9 weeks postpartum. Breastmilk levels of amphetamine were 74, 82 and 82 mcg/L, respectively. These values represent a weight-adjusted dosage of 1.9% to 2.1% of the maternal dosage and an absolute infant dosage of 11.1 to 12.4 mcg/kg daily.[5]

Infant Levels. Amphetamine was measured in a 12-hour urine collection in a breastfed infant whose mother was taking racemic amphetamine 5 mg 4 times daily. The infant's urinary excretion of amphetamine ranged from 0.1 to 0.3% of the mother's urinary excretion.[4]

The infant of a mother who was taking amphetamine 35 mg daily for narcolepsy during pregnancy and postpartum was exclusively breastfed for 6 months. Infant blood samples were taken just before the mother's morning amphetamine dose at 2, 5 and 9 weeks postpartum. Infant serum concentrations at these times were 3.1, 2 and 1.4 mcg/L, respectively. These values represented 15%, 7% and 5% of simultaneous maternal serum concentrations.[5]

Effects in Breastfed Infants

One infant whose mother was being treated for narcolepsy with racemic amphetamine 5 mg 4 times daily was exposed to the drug in milk for the (unspecified) duration of breastfeeding. There were no signs of abnormal development during the first 2 years of life.[4]

The infant of a mother who was taking amphetamine 35 mg daily for narcolepsy during pregnancy and postpartum was exclusively breastfed for 6 months. The infant experienced no adverse reactions and grew normally.[5]

Effects on Lactation and Breastmilk

In 2 papers by the same authors, 20 women with normal physiologic hyperprolactinemia were studied on days 2 or 3 postpartum. Eight received dextroamphetamine 7.5 mg intravenously, 6 received 15 mg intravenously and 6 who served as controls received intravenous saline. The 7.5 mg dose reduced serum prolactin by 25 to 32% compared to control, but the difference was not statistically significant. The 15 mg dose significantly decreased serum prolactin by 30 to 37% at times after the infusion. No assessment of milk production was presented.[6][7] The authors also quoted data from another study showing that a 20 mg oral dose of dextroamphetamine produced a sustained suppression of serum prolactin by 40% in postpartum women. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

In a retrospective Australian study, mothers who used intravenous amphetamines during pregnancy were less likely to be breastfeeding their newborn infants at discharge than mothers who abused other drugs (27% vs 42%). The cause of this difference was not determined.[8]

A mother took amphetamine 35 mg daily for narcolepsy during pregnancy and postpartum. She exclusively breastfed her infant for 6 months with no evidence of an adverse effect on milk production.[5]

Alternate Drugs to Consider

(Therapeutic use) Dextroamphetamine, Lisdexamfetamine, Methylphenidate

References

1. Oei JL, Kingsbury A, Dhawan A et al. Amphetamines, the pregnant woman and her children: A review. J Perinatol. 2012;32:737-47. PMID: 22652562

2. AAP Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012;129:e827-41. PMID: 22371471

3. Wong S, Ordean A, Kahan M. SOGC clinical practice guidelines: Substance use in pregnancy: No. 256, April 2011. Int J Gynaecol Obstet. 2011;114:190-202. PMID: 21870360

4. Steiner E, Villen T, Hallberg M et al. Amphetamine secretion in breast milk. Eur J Clin Pharmacol. 1984;27(1):123-4. PMID: 6489423

5. Ohman I, Wikner BN, Beck O, Sarman I. Narcolepsy treated with racemic amphetamine during pregnancy and breastfeeding. J Hum Lact. 2015;31:374-6. PMID: 25948577

6. DeLeo V, Cella SG, Camanni F et al. Prolactin lowering effect of amphetamine in normoprolactinemic subjects and in physiological and pathological hyperprolactinemia. Horm Metab Res. 1983;15:439-43. PMID: 6642414

7. Petraglia F, De Leo V, Sardelli S et al. Prolactin changes after administration of agonist and antagonist dopaminergic drugs in puerperal women. Gynecol Obstet Invest. 1987;23:103-9. PMID: 3583091

8. Oei JL, Abdel-Latif ME, Clark R et al. Short-term outcomes of mothers and infants exposed to antenatal amphetamines. Arch Dis Child Fetal Neonatal Ed. 2010;95:F36-F41. PMID: 19679891

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