Warnings for Desoxyn
Included as part of the "PRECAUTIONS" Section
Precautions for Desoxyn
Abuse, Misuse, And Addiction
DESOXYN has a high potential for abuse and misuse. The use of DESOXYN exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. DESOXYN can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse And Dependence ]. Misuse and abuse of CNS stimulants, including DESOXYN, can result in overdose and death [see OVERDOSE ], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing DESOXYN, 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 DESOXYN in a safe place, preferably locked, and instruct patients to not give DESOXYN to anyone else. Throughout DESOXYN treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Risks To Patients With Serious Cardiac Disease
Sudden death has been reported in patients with structural cardiac abnormalities and other serious cardiac disease who were treated with CNS stimulants at recommended ADHD dosage.
Avoid DESOXYN use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems.
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 DESOXYN-treated patients for potential tachycardia and hypertension [see ADVERSE REACTIONS].
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 DESOXYN 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, and 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 DESOXYN.
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 DESOXYN-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.
Peripheral Vasculopathy, Including Raynaud’s Phenomenon
CNS 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. 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 DESOXYN treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for DESOXYN-treated patients who develop signs or symptoms of peripheral vasculopathy.
Seizures
DESOXYN 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, DESOXYN should be discontinued.
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]. The coadministration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to DESOXYN. In these situations, consider an alternative nonserotonergic drug or an alternative drug that does not inhibit CYP2D6 [see DRUG INTERACTIONS].
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 DESOXYN with MAOI drugs is contraindicated [see CONTRAINDICATIONS].
Discontinue treatment with DESOXYN and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of DESOXYN with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate DESOXYN 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.
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].
Before initiating DESOXYN, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor DESOXYN -treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Abuse, Misuse, And Addiction
Educate patients and their families about the risks of abuse, misuse, and addiction of DESOXYN, which can lead to overdose and death, and proper disposal of any unused drug [see WARNINGS AND PRECAUTIONS, Drug Abuse And Dependence, OVERDOSE]. Advise patients to store DESOXYN in a safe place, preferably locked, and instruct patients to not give DESOXYN to anyone else.
Risks To Patients With Serious Cardiac Disease
Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death with DESOXYN use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see WARNINGS AND PRECAUTIONS].
Increased Blood Pressure And Heart Rate
Instruct patients that DESOXYN can cause elevations of their blood pressure and pulse rate and they should be monitored for such effects [see WARNINGS AND PRECAUTIONS].
Psychiatric Adverse Risks
Advise patients that DESOXYN, at recommended doses, may cause psychotic or manic symptoms even in patients without prior history of psychotic symptoms or mania [see WARNINGS AND PRECAUTIONS].
Long-Term Suppression Of Growth In Pediatric Patients
Advise patients, family members, and caregivers that DESOXYN may cause slowing of growth including weight loss [see WARNINGS AND PRECAUTIONS].
Circulation problems In fingers And Roes (Peripheral Vasculopathy, Including Raynaud’s Phenomenon)
Instruct patients beginning treatment with DESOXYN about the risk of peripheral vasculopathy, including Raynaud’s 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 [see WARNINGS AND PRECAUTIONS].
Seizures
Caution patient that DESOXYN may lower the convulsive threshold. Advise patients to contact their healthcare provider immediately and to discontinue DESOXYN if a seizure occurs [see WARNINGS AND PRECAUTIONS].
Serotonin Syndrome
Caution patients about the risk of serotonin syndrome with concomitant use of DESOXYN and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.
Motor And Verbal Tics, And Worsening Of Tourette’s Syndrome
Advise patients that motor and verbal tics and worsening of Tourette’s syndrome may occur during treatment with DESOXYN. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see WARNINGS AND PRECAUTIONS].
Concomitant Medications
Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see DRUG INTERACTIONS].
Pregnancy
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to DESOXYN during pregnancy. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with DESOXYN. Advise patients of the potential fetal effects from the use of DESOXYN during pregnancy [see Use In Specific Populations ].
Lactation
Advise patients not to breastfeed if they are taking DESOXYN [see Use In Specific Populations].
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
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.
Use In Specific Populations
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including DESOXYN, 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/m2 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/m2 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 DESOXYN, 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/m2 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/m2 basis.
Lactation
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 DESOXYN.
Pediatric Use
The safety and effectiveness of DESOXYN for the treatment of ADHD have been established in pediatric patients aged 6 years and older.
The safety and effectiveness of DESOXYN have not been established in pediatric patients younger than 6 years old.
Growth Suppression
Growth should be monitored during treatment with stimulants, including DESOXYN. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].
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.