DESOXYN GRADUMET 15mg

DESCRIPTION

Oral amphetamine-class stimulant agent.
FDA-approved for attention-deficit hyperactivity disorder and for the short-term, adjunctive treatment of exogenous obesity.
Contraindicated for use by patients with a history of drug abuse due to high abuse potential.

COMMON BRAND NAMES

Desoxyn

HOW SUPPLIED

Desoxyn/Methamphetamine Hydrochloride Oral Tab: 5mg

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

For obesity, 5 mg PO before each meal; For ADHD, 20—25 mg/day PO is usually effective.

For obesity, 5 mg PO before each meal; For ADHD, 20—25 mg/day PO is usually effective.

For obesity, 5 mg PO before each meal; For ADHD, 20—25 mg/day PO is usually effective.

6—12 years: For ADHD, 20—25 mg/day PO is usually effective.
< 6 years: Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

A MedGuide is available which informs patients about the cardiac and psychiatric risks associated with use, and should be provided by the authorized dispenser to each patient receiving a prescription.

STORAGE

Desoxyn:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Methamphetamine is contraindicated for use in patients with known hypersensitivity to the sympathomimetic amines or any component of these products. Methamphetamine tablets contain lactose; patients with lactase deficiency should take appropriate precautions with use.

Methamphetamine is contraindicated for use by patients who have a history of substance abuse. Evaluate all patients for a history (or a family history) of abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). Patients may try to obtain methamphetamine for nontherapeutic use or for distribution to others. Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Sparingly prescribe or dispense methamphetamine; appropriate patient selection is imperative, as methamphetamine misuse may cause sudden death and serious cardiovascular adverse events. Manifestations of chronic intoxication or substance abuse with methamphetamine include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes.

Methamphetamine is contraindicated in patients with moderate to severe hypertension, advanced atherosclerosis, and symptomatic cardiovascular disease. Stimulant medications must be used very cautiously in patients with even mild hypertension, tachycardia, or other conditions in which a modest increase in blood pressure or heart rate could be detrimental. Stimulant medications cause a modest increase in average blood pressure (approximately 2 to 4 mmHg) and average heart rate (approximately 3 to 6 beats per minute or bpm); however, some individuals may have larger increases. Periodic blood pressure and heart rate monitoring is recommended in all patients taking methamphetamine. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication.

Methamphetamine is contraindicated for use in patients with advanced arteriosclerosis, symptomatic cardiac disease, or moderate to severe hypertension. The FDA recommends that, in general, stimulant medications not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals; more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million pediatric and young adult patients 2 to 24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient’s pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc more than 0.46 seconds on electrocardiogram (ECG), or heart rate or blood pressure more than 2 standard deviations above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it is reasonable to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

Stroke has occurred in adults receiving stimulants such as methamphetamine at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than pediatric patients of having serious cardiac problems that increase cerebrovascular risk. Adults with such abnormalities should also generally not be treated with stimulant drugs. A patient with cerebrovascular disease should be closely monitored if treatment is considered necessary. Stimulant medications may increase blood pressure or heart rate in some individuals.

Methamphetamine may precipitate motor or phonetic tics in those with Tourette’s syndrome. Evaluate patients and their families for tics and Tourette’s syndrome before methamphetamine initiation. Some patients with Tourette’s syndrome may actually benefit from stimulant therapy; administer under close supervision and at the lowest effective dose.

Methamphetamine should not be administered to patients in an agitated state. In psychotic individuals (e.g., schizophrenia), amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders. Stimulants such as methamphetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder in patients presenting with symptoms of depression; screening should include a detailed psychiatric history including a family history of suicide, bipolar disorder, and depression. Due to its toxic effects in overdose, methamphetamine should only be used in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and post-marketing experience with ADHD medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Methamphetamine is contraindicated for use in patients with hyperthyroidism or thyrotoxicosis. The elevated levels of thyroid hormones in these patients make them extremely sensitive to sympathomimetic drugs. Sympathomimetic stimulation may induce cardiac rhythm disturbances, increased blood pressure, or other side effects.

Methamphetamine is contraindicated for use in patients with glaucoma because of the ability of sympathetic stimulation to block aqueous outflow and raise intraocular pressure. Visual disturbance has been reported and may present as difficulties with accommodation and blurring of vision. If a patient reports ocular discomfort or visual changes, an ophthalmic exam may be necessary to determine the cause.

Use methamphetamine with caution in patients with a history of a seizure disorder because the seizure threshold can be reduced, particularly during excess CNS stimulation (i.e., amphetamine overdosage). The effects of normal therapeutic dosages of amphetamines on the seizure threshold are less clear. Seizure threshold may be reduced in those with electroencephalogram (EEG) abnormalities and very rarely in patients without a seizure history or EEG abnormalities. If seizures occur, methamphetamine discontinuation is recommended.

Amphetamines lower the seizure threshold. Because of a potential increased risk of seizures, amphetamines should not be used during intrathecal radiographic contrast administration. Methamphetamine should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of sympathomimetic stimulants, such as methamphetamine. Patients should consult with their healthcare professional prior to surgical procedures.

Methamphetamine should not be used to combat fatigue or to replace adequate rest. The use of methamphetamine may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.

Patients with diabetes mellitus may have alterations in glycemic control due to the sympathomimetic effect of methamphetamine. Insulin or antidiabetic agent requirements in diabetes mellitus may be altered in association with the use of methamphetamine and the concomitant dietary regimen.

Literature reports suggest that amphetamines may be associated with significant elevation of plasma corticosteroids and potential hypercortisolism. This should be considered if determination of plasma corticosteroid levels is desired in a person receiving amphetamines. The elevation is greatest in the evening. Amphetamines may also interfere with urinary steroid determinations; consider the possible effect of methamphetamine if determination of plasma corticosteroid concentrations is desired.

Stimulant medications are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity of the fingers or toes occurs, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Methamphetamine is FDA-approved for use in weight reduction programs for obese patients in whom alternative therapies, including repeated dietary reduction, exercise, or other medications have been ineffective. Because of the abuse potential of methamphetamine, other amphetamine derivatives are preferred for obesity treatment. Tolerance to the anorectic effect of the amphetamines usually develops within a few weeks. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued. Eating disorders, such as anorexia nervosa or bulimia nervosa, should be ruled out prior to treatment with amphetamines. Patients with eating disorders may have physiologic complications, such as metabolic and electrolyte abnormalities, which increase their susceptibility to the adverse effects of stimulants. In addition, the abuse potential of stimulants in weight loss induction should be considered in patients with an eating disorder.

Methamphetamine is classified as FDA pregnancy risk category C. There are no adequate and well controlled studies of methamphetamine use in pregnant women. Methamphetamine should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential fetal risk. Amphetamines have been shown to have both embryotoxic and teratogenic effects in some animals when administered at high doses. There is one case of a neonate born with a severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia following maternal exposure to dextroamphetamine sulfate and lovastatin during the first trimester of pregnancy. However, most available data indicate that amphetamines are not teratogenic in humans. Among 671 mother-child pairs enrolled in the Collaborative Perinatal Project who had first trimester exposure to amphetamines and 1898 mother-child pairs with amphetamine exposures at any time during pregnancy, there was no evidence suggesting a relationship to large categories of major or minor malformations. Non-teratogenic effects are known to occur in neonates who are born to mothers dependent on amphetamines. These have included increased incidences of premature births, low birth weights and length, lower occipitofrontal circumference, and physical withdrawal symptoms (e.g., abnormal sleep patterns, poor feeding, tremor, agitation, fatigue, and hypertonia). In one prospective comparison study, the infant group exposed to cocaine, methamphetamine, or a combination of cocaine and narcotic in utero had a 35.1% incidence of cranial abnormalities (i.e., intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions) compared to a 5.3% incidence in the normal infant group as assessed by cranial ultrasonography. The authors speculated that the ultrasonographic abnormalities were likely related to the vasoconstrictive properties of the drugs. The effects of methamphetamine during labor and delivery are unknown.

According to the manufacturer, amphetamines are excreted into breast milk, and women who are taking amphetamines should refrain from nursing. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. Breast milk concentrations in one woman taking 20 mg daily of racemic amphetamine ranged from 55 to 138 ng/mL with milk to plasma ratios of 2.8 to 7.5. The infant was monitored for 24 months and no adverse effects from amphetamine exposure were noted. Similarly, there were no reports of neonatal insomnia or stimulation among 103 nursing infants whose mothers were taking various amounts of amphetamine. In one study of 4 women with attention deficit hyperactivity disorder receiving d-amphetamine (median dose 18 mg/day) while breast-feeding, the mean relative infant dose was 5.7% of the weight-adjusted maternal dose (range: 3.9 to 13.8%). Of the 3 infants in whom blood samples were obtained, plasma d-amphetamine levels were undetectable in one; d-amphetamine levels were approximately 6% and 14% of the corresponding maternal plasma concentrations in the remaining two infants. None of the four infants in the study showed any adverse effects. Methylphenidate may be considered an alternative to amphetamine agents in women who are breast-feeding an infant, although the medical use of stimulant medications has not been evaluated formally. The AAP has previously considered amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. If breast-feeding cannot be avoided during administration of a stimulant, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability. If possible, long-term infant exposure to stimulants through breast milk should be avoided since the consequences of such exposure are unknown. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

Methamphetamine has not been systematically studied in the geriatric patient for the treatment of attention deficit disorder (ADD/ADHD) or obesity. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Most studies exist with methylphenidate, or the amphetamine salts. Medication should be titrated with low doses initially and with a slow increase. Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient. According to the Beers Criteria, stimulants such as amphetamines are considered potentially inappropriate medications (PIMs) for use in geriatric patients with insomnia and should be avoided due to the potential for drug-induced CNS stimulant effects.

Do not use methamphetamine for the treatment of obesity in pediatric patients; safety and efficacy have not been established. Also, the safety and efficacy of methamphetamine for the treatment of attention-deficit hyperactivity disorder (ADHD) have not been established in infants and children less than 6 years of age. All children with ADHD do not require medication, and non-drug measures are often instituted concurrently with drug therapy. Drug treatment should be considered only in light of the complete history and evaluation of the child. The decision to prescribe methamphetamine should depend on the physician’s assessment of the chronicity and severity of the child’s symptoms and their appropriateness for his/her age. Monitoring of the effectiveness of stimulant therapy by the health care prescriber, parents, and teachers is important; periodic reassessment of the need for medication is recommended. Appropriate stimulant therapy should not suppress normal emotions or intellectual ability; the occurrence of certain side effects may indicate a need for dosage reduction. In psychotic children, amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders. New onset psychotic or manic symptoms may develop in children and adolescents receiving therapeutic doses of stimulants. Discontinuation of therapy may be required. Although a direct causal relationship has not been established, aggressive behavior and hostility have been reported during use of some stimulants for ADHD in children. It is recommended to monitor for signs of aggression or worsening of pre-existing aggressive behavior when treatment is initiated. The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. Data obtained on the effects of stimulants on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities or other serious heart problems (e.g., aortic stenosis, cardiomyopathy, congenital heart disease, prosthetic heart valves, valvular heart disease, ventricular dysfunction). Some case reports have involved concomitant medications, such as tricyclic antidepressants. A large retrospective cohort study including over 1.2 million pediatric patients and young adults 2 to 24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in patients with known structural cardiac abnormalities or other serious heart conditions. Exceptions to this warning do exist, but careful screening and monitoring is recommended by the American Heart Association (see separate paragraph detailing cardiac contraindications and precautions).

Abrupt discontinuation of methamphetamine after chronic use is not generally recommended. Discontinuation after the prolonged use of high doses may precipitate withdrawal symptoms and unmask severe mental depression or extreme fatigue; changes are also noted on the sleep electroencephalogram (EEG). Gradual withdrawal of therapy is recommended.

Methamphetamine is contraindicated during or within 14 days following the administration of MAOI therapy because of the possibility of precipitating a hypertensive crisis.