Desoxyn® (methamphetamine hydrochloride tablets, USP)

Desoxyn® (methamphetamine hydrochloride tablets, USP)

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Desoxyn® (methamphetamine hydrochloride tablets, USP)

DESOXYN® (methamphetamine hydrochloride tablets, USP), chemically known as (S)-N,α-dimethylbenzeneethanamine hydrochloride, is a member of the amphetamine group of sympathomimetic amines.

DESOXYN tablets contain 5 mg of methamphetamine hydrochloride for oral administration.

Inactive Ingredients: Corn starch, lactose, sodium paraminobenzoate, stearic acid and talc.

Clinical pharmacology

Methamphetamine is a sympathomimetic amine with CNS stimulant activity. Peripheral actions include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. Other central nervous system actions, or metabolic effects, may be involved, for example.

The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

In humans, methamphetamine is rapidly absorbed from the gastrointestinal tract. 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 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.

Indications and usage

Attention Deficit Disorder with Hyperactivity: DESOXYN tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children over 6 years of age with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

Contraindications

In patients known to be hypersensitive to amphetamine, or other components of DESOXYN. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products.

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. 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.

Warnings

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.

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.

Aggression: Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD.

Long-Term Suppression of Growth: Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.

Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, including Raynaud’s phenomenon: Stimulants, including DESOXYN, 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.

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

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).

Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

Precautions

DESOXYN 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.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]

  • Instruct patients beginning treatment with DESOXYN about the risk of peripheral vasculopathy, including Raynaud’s
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    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 DESOXYN.
  • Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

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.

DESOXYN should not be used concurrently with monoamine oxidase inhibitors.

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.

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 DESOXYN 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 frequently and adjust or use alternative therapy based on clinical response. Examples of tricyclic antidepressants include desipramine, Protriptyline.

CYP2D6 Inhibitors: The concomitant use of DESOXYN and CYP2D6 inhibitors may increase the exposure of DESOXYN compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during DESOXYN initiation and after a dosage increase. If serotonin syndrome occurs, discontinue DESOXYN and the CYP2D6 inhibitor. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs: The concomitant use of DESOXYN and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during DESOXYN initiation or dosage increase. If serotonin syndrome occurs, discontinue DESOXYN and the concomitant serotonergic drug(s). Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort.

MAO Inhibitors: Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer DESOXYN concomitantly or within 14 days after discontinuing MAOI. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue.

Proton Pump Inhibitors: Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Data are not available on long-term potential for carcinogenicity, mutagenicity, or impairment of fertility.

Use in specific populations

Pregnancy: Pregnancy Category C. Methamphetamine has been shown to have teratogenic and embryocidal effects in mammals given high multiples of the human dose. There are no adequate and well-controlled studies in pregnant women. DESOXYN tablets should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Nonteratogenic effects: Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation and significant lassitude.

Usage in Nursing Mothers: Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use: Long-term effects of methamphetamine in children have not been established

Geriatric Use: Clinical Studies of DESOXYN did not include sufficient numbers of subjects age 65 years and over to determine whether elderly subjects respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy observed in this population.

Adverse reactions

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 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. Skin and Subcutaneous Tissue Disorders: Alopecia.

Drug abuse and dependence

Controlled Substance: DESOXYN 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.

Overdosage

Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Serotonin syndrome has also been reported. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

Dosage and administration

DESOXYN tablets are given orally.

Methamphetamine should be administered at the lowest effective dosage, and dosage should be individually adjusted. Late evening medication should be avoided because of the resulting insomnia.

Attention Deficit Disorder with Hyperactivity: For treatment of children 6 years or older with a behavioral syndrome characterized by moderate to severe distractibility, short attention span, hyperactivity, emotional lability and impulsivity: an initial dose of 5 mg DESOXYN once or twice a day is recommended. Daily dosage may be raised in increments of 5 mg at weekly intervals until an optimum clinical response is achieved. The usual effective dose is 20 to 25 mg daily. The total daily dose may be given in two divided doses daily.

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