ADZENYS ER SIDE EFFECTS
- Generic Name: amphetamine extended-release oral suspension
- Brand Name: Adzenys ER
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Drug Dependence.
- Hypersensitivity to amphetamine, or other components of ADZENYS ER.
- Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors.
- Serious Cardiovascular Reactions.
- Blood Pressure and Heart Rate Increases.
- Psychiatric Adverse Reactions.
- Long-Term Suppression of Growth.
- Peripheral Vasculopathy, including Raynaud’s phenomenon.
- Serotonin Syndrome.
- Potential for Intestinal Necrosis.
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 ER has been established from adequate and well-controlled studies of single-entity amphetamine product extended-release (MAS ER) capsules. 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) 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 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 none 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 Controlled Trials
Adverse reactions reported in a 3-week clinical trial of pediatric patients 6 to 12 years and a 4week 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 1: Adverse Reactions Reported by 2% or More of Children (6-12 years old) Receiving MAS ER with Higher Incidence than on Placebo in a 584-Patient Clinical Study
| Body System | Preferred Term | 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%a | |
| Metabolic/Nutritional | Weight Loss | 10% | 0% |
Table 2: Adverse Reactions Reported by 5% or More of Adolescents (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) |
| General | Abdominal Pain (stomachache) | 11% | 2% |
| Digestive System | Loss of Appetite b | 36% | 2% |
| Nervous System | Insomnia b | 12% | 4% |
| Metabolic/Nutritional | Weight Loss b | 9% | 0% |
| * Included doses up to 40 mg b Dose-related adverse reactions Note: The following reactions did not meet the criterion for inclusion in Table 2 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. |
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Table 3: 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) |
| 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% |
| * Included doses up to 60 mg. | |||
| Note: The following reactions did not meet the criterion for inclusion in Table 3 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. | |||
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
SRC: NLM .