Get your patient on Methamphetamine Hydrochloride - Methamphetamine Hydrochloride tablet (Methamphetamine Hydrochloride)

Prior to treating patients with methamphetamine hydrochloride tablets, assess:

• for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical examination) [see Warnings and Precautions (5.2 )] .
• the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating methamphetamine hydrochloride tablets [see Warnings and Precautions (5.9 )] .

Administer methamphetamine hydrochloride tablets orally once daily or in two divided doses daily. Avoid taking methamphetamine hydrochloride tablets late in the evening due to the risk of insomnia.

For pediatric patients 6 years of age and older, the recommended starting dosage is 5 mg methamphetamine hydrochloride tablets once or twice daily. The daily dosage may be increased in increments of 5 mg at weekly intervals based on clinical response of the patient. The recommended dosage range is 20 mg to 25 mg daily.

Agents that alter urinary pH can impact excretion and alter blood levels of amphetamine. Acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. Adjust methamphetamine hydrochloride tablets dosage based on clinical response [see Drug Interactions (7.1 )] .

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including methamphetamine hydrochloride tablets, during pregnancy. Healthcare providers are encouraged to advise patients to register by contacting the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting online at www.womensmentalhealth.org/research/pregnancyregistry/adhd-medications/.

Risk Summary

Available data from epidemiologic studies and postmarketing reports on use of methamphetamine and amphetamine in pregnant women over decades of use have not identified a drug-associated risk of major birth defects or miscarriage. Neonates exposed to amphetamines in utero are at risk for withdrawal symptoms following delivery. Adverse pregnancy outcomes including premature delivery and low birth weight have been seen in infants born to mothers taking amphetamines during pregnancy (see Clinical Considerations) .

In animals, administration of methamphetamine during organogenesis resulted in developmental toxicity, including neonatal death and fetal malformations, at doses equivalent to the maximum recommended human dose (MRHD) on a mg/m ² basis. Oral administration of methamphetamine to rats during pregnancy, pregnancy and lactation, or lactation resulted in developmental toxicity in the offspring, including, neonatal mortality and delayed development, at a maternal dose similar to the MRHD on a mg/m ² basis.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Amphetamines, such as methamphetamine, cause vasoconstriction and thereby decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. Infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight.

Monitor infants born to mothers taking methamphetamine for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.

Data

Animal Data

Based on published data, methamphetamine administration during the period of organogenesis caused malformations and pup mortality in mammals at doses equivalent to the maximum recommended human dose (MRHD) on a mg/m ² basis. Oral administration of methamphetamine (0, or 3.75 mg/kg) to pregnant rats during gestation, throughout gestation and lactation, or only during lactation resulted in an increase in neonatal pup mortality. Delayed somatic development (pinna unfolding and eye opening) and impairments in neurobehavioral development (righting reflex, incline plane test, and forelimb grip strength) were observed in the pups. The dose with adverse effects was equivalent to the MRHD of 25 mg on a mg/m ² basis.

Risk Summary

Based on limited case reports in the published literature, methamphetamine and its active metabolite, amphetamine, are present in human milk. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large doses of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with methamphetamine hydrochloride tablets.

The safety and effectiveness of methamphetamine hydrochloride tablets for the treatment of ADHD have been established in pediatric patients aged 6 years and older.

The safety and effectiveness of methamphetamine hydrochloride tablets have not been established in pediatric patients younger than 6 years old.

Growth Suppression

Growth should be monitored during treatment with stimulants, including methamphetamine hydrochloride tablets. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions (5.5 ), Adverse Reactions (6 )] .

Clinical studies of methamphetamine hydrochloride tablets did not include sufficient numbers of subjects age 65 years and over to determine whether elderly subjects respond differently from younger subjects.

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.

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.

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 )] .

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.

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.

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.

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.

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.

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.

Table 1 presents clinically important drug interactions with methamphetamine hydrochloride tablets.

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

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The exact mode of therapeutic action in the treatment of ADHD is not known.

Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Absorption

Methamphetamine is absorbed from the gastrointestinal tract.

Elimination

Metabolism

The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine. The biological half-life has been reported in the range of 4 to 5 hours.

Excretion

Excretion occurs primarily in the urine and is dependent on urine pH. Alkaline urine will significantly increase the drug half-life. Approximately 62% of an oral dose is eliminated in the urine within the first 24 hours with about one-third as intact drug and the remainder as metabolites.

Carcinogenicity and Mutagenesis

Carcinogenicity, mutagenic, or genotoxic potential of methamphetamine has not been fully characterized.

Impairment of Fertility

There have been no adequate studies performed in animals at current standards to evaluate the effect of methamphetamine treatment on fertility. However, published studies in mice and rats exposed to repeated daily dosing of methamphetamine report irregular estrous cycling and decreased ovarian reserve in females, and decreased sperm density, motility, and percent of sperm with normal morphology in males. The clinical significance of these findings is not clear.