Methamphetamine Hydrochloride

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 ) 5.1 Abuse, 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. 5.2 Risks 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. 5.3 Increased 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 ( 6 )] . 5.4 Psychiatric Adverse Reactions 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 methamphetamine hydrochloride tablets 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, or 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. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in 0.1% of CNS stimulant-treated patients compared to 0% in placebo-treated patients. If such symptoms occur, consider discontinuing methamphetamine hydrochloride tablets. 5.5 Long-Term Suppression of Growth in Pediatric Patients CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in methamphetamine-treated pediatric patients treated with CNS stimulants. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. 5.6 Peripheral Vasculopathy, including Raynaud’s Phenomenon CNS stimulants, including methamphetamine hydrochloride tablets, 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 post-marketing 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 CNS stimulant. Careful observation for digital changes is necessary during methamphetamine treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for methamphetamine-treated patients who develop signs or symptoms of peripheral vasculopathy. 5.7 Seizures Methamphetamine hydrochloride tablets may lower the convulsive threshold in patients with prior history of seizure, in patients with prior EEG abnormalities in the absence of seizures, and in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, methamphetamine hydrochloride tablets should be discontinued. 5.8 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 [see Drug Interactions ( 7.1 )] . The coadministration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to methamphetamine hydrochloride tablets. In these situations, consider an alternative nonserotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions ( 7.1 )] . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Concomitant use of methamphetamine hydrochloride tablets with MAOI drugs is contraindicated [see Contraindications ( 4 )] . Discontinue treatment with methamphetamine hydrochloride tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of methamphetamine hydrochloride tablets with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate methamphetamine hydrochloride tablets with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome. 5.9 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported [see Adverse Reactions ( 6 )] . Before initiating methamphetamine hydrochloride tablets, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor methamphetamine hydrochloride tablets-treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.