Methylin Disease Interactions

Some CNS stimulants are contraindicated in patients with marked agitation and/or anxiety since these symptoms may be aggravated. CNS stimulants may also exacerbate symptoms of behavior disturbance and thought disorder in psychotic patients, particularly children. Therapy with CNS stimulants should be administered cautiously in patients with a history of psychosis or a predisposition to agitated states.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

The use of most CNS stimulants is contraindicated in patients with glaucoma, as these agents exhibit sympathomimetic activity and may induce mydriasis provoking an increase in intraocular pressure.

CNS stimulants increase blood pressure and heart rate; the use of some agents may be contraindicated in patients with severe/uncontrolled hypertension. Caution should be used when administering to patients with preexisting high blood pressure (even mild hypertension) and other cardiovascular conditions. All patients under treatment should be regularly monitored for potential tachycardia and hypertension.

The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.

CNS stimulants (especially amphetamines) have a high potential for abuse and misuse, which can lead to development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants can result in overdose and death; this risk is increased with higher doses or unapproved methods of administration (e.g., snorting, injection). Before prescribing a CNS stimulant, each patient's risk for abuse, misuse, and addiction should be assessed. Throughout therapy, it is recommended to reassess each patient's risk and frequently monitor for signs/symptoms of abuse, misuse, and addiction. Therapy with CNS stimulants should be administered cautiously, if at all, in patients with a history of alcohol or substance abuse. The use of some agents is contraindicated in patients with a history of drug abuse.

CNS stimulants have been reported to worsen Tourette's syndrome and exacerbate motor and verbal tics. Before initiating therapy, it is recommended to assess family history and clinically evaluate patients for tics or Tourette's syndrome. Therapy with CNS stimulants, if necessary, should be administered cautiously in patients with tic disorders or family history of Tourette's syndrome. The manufacturers of the CNS stimulants, methylphenidate (racemic) and dexmethylphenidate (the more pharmacologically active d-enantiomer), consider their use to be contraindicated in such patients.

Methylphenidate (racemic) and dexmethylphenidate (the more pharmacologically active d-enantiomer) exhibit sympathomimetic activity and may elevate blood pressure and pulse rate. Therapy with these agents should be administered cautiously in patients with hypertension. Blood pressure should be monitored periodically during therapy.

There is some clinical evidence that methylphenidate may lower the seizure threshold, occasionally even in patients without a history of seizures or prior EEG abnormalities. Therapy with methylphenidate (racemic) or dexmethylphenidate (the more pharmacologically active d-enantiomer) should be administered cautiously in patients with or predisposed to seizures. The medication should be discontinued if seizures occur during its use.

In general, CNS stimulants are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with CNS stimulants should be administered cautiously in patients with moderate to severe liver disease, and the dosage should be adjusted accordingly in certain agents. Additionally, postmarketing reports have shown that atomoxetine can cause severe liver injury; laboratory testing should be done at the first sign/symptom of liver dysfunction (jaundice, dark urine, upper quadrant tenderness) and treatment should be discontinued in patients with evidence of liver injury.

Overall CNS stimulants should be administered with caution in patients with significantly impaired renal function as the reduction in the rate of elimination may alter the therapeutic response. The dosage should be adjusted accordingly in certain agents.

Due to general central nervous system stimulation, therapy with CNS stimulant drugs may cause seizures. These drugs may lower the convulsive threshold in patients with history of seizures, with prior electroencephalogram (EEG) abnormalities without seizures, and very rarely, without history of seizures and no prior EEG evidence of seizures. Therapy with CNS stimulants should be used with caution in patients with or predisposed to seizures. If seizures occur, therapy should be discontinued.

Hematologic toxicity, including thrombocytopenia, easy bruisability, epistaxis, leukopenia, anemia and eosinophilia, has been reported rarely during use of methylphenidate. However, a causal relationship has not been established. Therapy with methylphenidate (racemic) or dexmethylphenidate (the more pharmacologically active d-enantiomer) should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Periodic hematologic monitoring may be appropriate in all patients during prolonged therapy.

The extended-release formulation of methylphenidate (Concerta) contains a non-deformable material. There have been rare reports of obstructive symptoms in patients with known strictures following the ingestion of similar sustained-release products. The extended-release formulation of methylphenidate should ordinarily not be administered in patients with preexisting severe gastrointestinal narrowing or obstruction, whether pathologic or iatrogenic (e.g., small bowel inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, or Meckel's diverticulum). The medication should only be used in patients who are able to swallow the tablet whole.