Methamphetamine Hydrochloride 5 mg Tablet, 100-count — NDC 68308-115-01 (Billing 68308-0115-01)

WARNINGS Serious Cardiovascular Events Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents : Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults : Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

Hypertension and other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events Pre-existing Psychosis Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Bipolar Illness Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS The following are adverse reactions in decreasing order of severity within each category that have been reported: 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 have been rarely reported at recommended doses.

Dizziness, dysphoria, overstimulation, euphoria, insomnia, tremor, restlessness and headache. Exacerbation of motor and phonic 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.

Miscellaneous: Suppression of growth has been reported with the long-term use of stimulants in children (see WARNINGS ). Skin and Subcutaneous Tissue Disorders: Alopecia. To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch or Mayne Pharma at 1-844-825-8500.

Drug Interactions Insulin requirements in diabetes mellitus may be altered in association with the use of methamphetamine and the concomitant dietary regimen. Methamphetamine may decrease the hypotensive effect of guanethidine . Methamphetamine hydrochloride tablets should not be used concurrently with monoamine oxidase inhibitors (see CONTRAINDICATIONS ).

Concurrent administration of tricyclic antidepressants and indirect-acting sympathomimetic amines such as the amphetamines, should be closely supervised and dosage carefully adjusted. Phenothiazines are reported in the literature to antagonize the CNS stimulant action of the amphetamines.

Drug/Laboratory Test Interactions Literature reports suggest that amphetamines may be associated with significant elevation of plasma corticosteroids. This should be considered if determination of plasma corticosteroid levels is desired in a person receiving amphetamines.

PRECAUTIONS General Methamphetamine hydrochloride tablets should be used with caution in patients with even mild hypertension. Methamphetamine should not be used to combat fatigue or to replace rest in normal persons. Prescribing and dispensing of methamphetamine should be limited to the smallest amount that is feasible at one time in order to minimize the possibility of overdosage.

Information for Patients The patient should be informed that methamphetamine may impair the ability to engage in potentially hazardous activities, such as, operating machinery or driving a motor vehicle. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon] Instruct patients beginning treatment with methamphetamine hydrochloride tablets about the risk of peripheral vasculopathy, including Raynaud's Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.

Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methamphetamine hydrochloride tablets. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

The patient should be cautioned not to increase dosage, except on advice of the physician. Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methamphetamine and should counsel them in its appropriate use. A patient Medication Guide is available for methamphetamine hydrochloride tablets.

The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. Drug Interactions Insulin requirements in diabetes mellitus may be altered in association with the use of methamphetamine and the concomitant dietary regimen.

Methamphetamine may decrease the hypotensive effect of guanethidine . Methamphetamine hydrochloride tablets should not be used concurrently with monoamine oxidase inhibitors (see CONTRAINDICATIONS ). Concurrent administration of tricyclic antidepressants and indirect-acting sympathomimetic amines such as the amphetamines, should be closely supervised and dosage carefully adjusted.

Phenothiazines are reported in the literature to antagonize the CNS stimulant action of the amphetamines. Drug/Laboratory Test Interactions Literature reports suggest that amphetamines may be associated with significant elevation of plasma corticosteroids. This should be considered if determination of plasma corticosteroid levels is desired in a person receiving amphetamines.

Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts).

Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of methamphetamine hydrochloride tablets and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents (e.g., sodium bicarbonate) and urinary alkalinizing agents (e.g., acetazolamide, some thiazides).

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 fr… [Excerpted — this section continues on DailyMed.]

DRUG ABUSE AND DEPENDENCE Controlled Substance Methamphetamine hydrochloride tablets are subject to control under DEA schedule II. Abuse Methamphetamine has been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred.

There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with methamphetamine include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes.

The most severe manifestation of chronic intoxication is psychosis often clinically indistinguishable from schizophrenia. Abuse and/or misuse of methamphetamine have resulted in death. Fatal cardiorespiratory arrest has been reported in the context of abuse and/or misuse of methamphetamine.

Controlled Substance Methamphetamine hydrochloride tablets are subject to control under DEA schedule II.