Methamphetamine Hydrochloride 5 mg Tablet, 100-count — NDC 0054-0389-25 (Billing 00054-0389-25)

5 WARNINGS AND PRECAUTIONS • Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. ( 5.2 ) • Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. ( 5.3 ) • Psychiatric Adverse Reactions: Prior to initiating methamphetamine hydrochloride tablets, screen patients for risk factors for developing a manic episode.

If new psychotic or manic symptoms occur, consider discontinuing methamphetamine hydrochloride tablets. ( 5.4 ) • Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted.

( 5.5 ) • Peripheral Vasculopathy, including Raynaud’s Phenomenon: Careful observation for digital changes is necessary during methamphetamine hydrochloride tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. ( 5.6 ) • Seizures: May lower the convulsive threshold.

If a seizure occurs, discontinue methamphetamine hydrochloride tablets. ( 5.7 ) • Serotonin Syndrome: Increased risk when coadministered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue methamphetamine hydrochloride tablets and initiate supportive treatment.

( 5.8 ) • Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating methamphetamine hydrochloride tablets, 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. Discontinue treatment if clinically appropriate.

( 5.9 )

5.1Abuse, Misuse, and Addiction Methamphetamine hydrochloride tablets have a high potential for abuse and misuse. The use of methamphetamine hydrochloride tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Methamphetamine hydrochloride tablets can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 , 9.3 )] .

Misuse and abuse of CNS stimulants, including methamphetamine hydrochloride tablets, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing methamphetamine hydrochloride tablets, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug.

Advise patients to store methamphetamine hydrochloride tablets in a safe place, preferably locked, and instruct patients to not give methamphetamine hydrochloride tablets to anyone else. Throughout methamphetamine treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

5.2Risks 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 dosages. Avoid methamphetamine use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, or other serious heart problems.

5.3Increased 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 methamphetamine hydrochloride tablets-treated patients for potential tachycardia and hypertension [see Adverse Reactions… [Excerpted — this section continues on DailyMed.]

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 )] • Hypersensitivity to amphetamine products or other ingredients of methamphetamine hydrochloride tablets [see Contraindications ( 4 )] • Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] • Risks to Patient with Serious Cardiac Disease [see Warnings and Precautions ( 5.2 )] • Increased Blood Pressure and Heart Rate [see Warnings and Precautions ( 5.3 )] • Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.4 )] • Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5.5 )] • Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions ( 5.6 )] • Seizures [see Warnings and Precautions ( 5.7 )] • Serotonin Syndrome [see Warnings and Precautions ( 5.8 )] • Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.9 )] The following adverse reactions associated with the use of methamphetamine hydrochloride tablets were identified in clinical trials or postmarketing reports.

Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: Elevation of blood pressure, tachycardia and palpitation. Fatal cardiorespiratory arrest has been reported, mostly in the context of abuse/misuse Central Nervous System: Psychotic episodes reported at recommended doses.

Dizziness, dysphoria, overstimulation, euphoria, insomnia, tremor, restlessness and headache. Exacerbation of motor and verbal tics and Tourette’s syndrome Gastrointestinal: Diarrhea, constipation, dryness of mouth, unpleasant taste, intestinal ischemia, and other gastrointestinal disturbances Hypersensitivity: Urticaria Endocrine: Impotence and changes in libido; frequent or prolonged erections Musculoskeletal: Rhabdomyolysis Metabolism and Nutrition Disorders: Suppression of growth has been reported with the long-term use of stimulants in pediatric patients Skin and Subcutaneous Tissue Disorders: Alopecia The following additional adverse reactions have been identified during post approval use of amphetamines: Allergic: Rash, hypersensitivity reactions, including angioedema and anaphylaxis.

Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Cardiovascular: Dyspnea, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use Central Nervous System: dyskinesia, fatigue, aggression, anger, logorrhea, dermatillomania, and paresthesia (including formication) Eye Disorders: Mydriasis Vascular Disorders: Raynaud’s phenomenon Common adverse reactions include: palpitation, dizziness, insomnia, tremor, headache, diarrhea, dryness of mouth.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter GI and urinary pH can alter blood levels of amphetamine. Acidifying agents can decrease amphetamine blood levels, while alkalinizing agents can increase amphetamine blood levels. ( 7.1 )

7.1Drugs Having Clinically Important Interactions with Methamphetamine Hydrochloride Tablets Table 1 presents clinically important drug interactions with methamphetamine hydrochloride tablets. Table 1: Clinically Important Drug Interactions with Methamphetamine Hydrochloride Tablets Monoamine Oxidase Inhibitors (MAOI) Clinical Impact: 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. Intervention: Concomitant use of methamphetamine hydrochloride tablets with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuing MAOI treatment is contraindicated [see Contraindications ( 4 )] . Serotonergic Drugs Clinical Impact: The concomitant use of amphetamines, including methamphetamine, and serotonergic drugs increases the risk of serotonin syndrome.

Intervention: Initiate methamphetamine hydrochloride tablets with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during methamphetamine hydrochloride tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue methamphetamine hydrochloride tablets and the concomitant serotonergic drug(s) [see Warnings and Precautions ( 5.8 )] . Alkalinizing Agents Clinical Impact: Alkalinizing agents may increase exposure to amphetamines and potentiate the action of amphetamine.

Intervention: Avoid co-administration of methamphetamine hydrochloride tablets and gastrointestinal and urinary alkalinizing agents. Acidifying Agents Clinical Impact: Acidifying agents lower blood levels and efficacy of amphetamines. Intervention: Increase dose of methamphetamine hydrochloride tablets based on clinical response.

Tricyclic Antidepressants Clinical Impact: May enhance the activity of tricyclic or sympathomimetic agents causing sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention: Monitor frequently and adjust methamphetamine hydrochloride tablets dose or use alternative therapy based on clinical response. CYP2D6 Inhibitors Clinical Impact: Concomitant use of methamphetamine hydrochloride tablets and CYP2D6 inhibitors may increase the exposure of methamphetamine compared to the use of the drug alone, and increase the risk of serotonin syndrome.

Intervention: Start with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during methamphetamine hydrochloride tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue methamphetamine hydrochloride tablets and the CYP2D6 inhibitor [see Warnings and Precautions ( 5.8 )] . Gastric pH Modulators Clinical Impact: Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone.

Intervention: Monitor patients for changes in clinical effect and use alternative therapy based on clinical response. Guanethidine Clinical Impact: Methamphetamine may decrease the hypotensive effect of guanethidine . Intervention: Monitor patients and adjust therapy based on clinical response.

Insulin requirements in diabetes mellitus may be altered in association with the use of methamphetamine and the concomitant dietary regimen.

7.2Drug/Laboratory Test Interactions Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Methamphetamine hydrochloride tablets contain methamphetamine hydrochloride, a Schedule II controlled substance.

9.2Abuse Methamphetamine hydrochloride tablets have a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions ( 5.1 )] . Methamphetamine hydrochloride tablets can be diverted for non-medical use into illicit channels or distribution. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect.

Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of methamphetamine may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including methamphetamine hydrochloride tablets, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

9.3Dependence Physical Dependence Methamphetamine hydrochloride tablets may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including methamphetamine hydrochloride tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

Tolerance Methamphetamine hydrochloride tablets may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

9.1Controlled Substance Methamphetamine hydrochloride tablets contain methamphetamine hydrochloride, a Schedule II controlled substance.