METHAMPHETAMINE Drug Interactions: What You Need to Know

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 )

7.1 Drugs Having Clinically Important Interactions with methamphetamine hydrochloride tablets, USP Table 1 presents clinically important drug interactions with methamphetamine hydrochloride tablets, USP .

Table

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

Intervention

Avoid co-administration of methamphetamine hydrochloride tablets, USP 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, USP 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, USP dose or use alternative therapy based on clinical response. CYP2D6 Inhibitors Clinical Impact: Concomitant use of methamphetamine hydrochloride tablets, USP and CYP2D6 inhibitors may increase the exposure of methamphetamine hydrochloride tablets, USP 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, USP initiation and after a dosage increase. If serotonin syndrome occurs, discontinue methamphetamine hydrochloride tablets, USP and the CYP2D6 inhibitor [see Warnings and Precautions 5.8]. Gastric pH Modulators Clinical Impact: Time to maximum concentration (Tmax) 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 ofguanethidine.

Intervention

Monitor patients and adjust therapy based on clinicalresponse. Insulin requirements in diabetes mellitus may be altered in association with the use of methamphetamine and the concomitant dietary regimen.

7.2 Drug/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.

CONTRAINDICATIONS In patients known to be hypersensitive to amphetamine, or other components of methamphetamine hydrochloride tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products (see ADVERSE REACTIONS ). Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis (see WARNINGS and DRUG INTERACTIONS ). It is also contraindicated in patients with glaucoma, advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism or known hypersensitivity or idiosyncrasy to sympathomimetic amines. Methamphetamine should not be given to patients who are in an agitated state or who have a history of drug abuse.

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 <span class="opacity-50 text-xs">[see Drug Abuse and Dependence ( 9.2 , 9.3 )]</span> . Misuse and abuse of CNS stimulants, including methamphetamine hydrochloride tablets, can result in overdose and death <span class="opacity-50 text-xs">[see Overdosage ( 10 )]</span> , 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> .

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 <span class="opacity-50 text-xs">[see Drug Interactions ( 7.1 )]</span> . 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 <span class="opacity-50 text-xs">[see Drug Interactions ( 7.1 )]</span> . 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 <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> . 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.