Drug Interactions between atomoxetine and JayCof-HC

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

The use of opiate agonists is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of opiate agonists may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with opiate agonists should be administered cautiously in patients who might be prone to acute alcohol intake.

Opiate agonists have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop after prolonged use. Abrupt cessation, reduction in dosage, or administration of an opiate antagonist such as naloxone may precipitate withdrawal symptoms. In patients who have developed tolerance to an opiate agonist, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with opiate agonists. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of opiate therapy should be undertaken gradually using a dosage-tapering schedule.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

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.

Opiate agonists have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop after prolonged use. Abrupt cessation, reduction in dosage, or administration of an opiate antagonist such as naloxone may precipitate withdrawal symptoms. In patients who have developed tolerance to an opiate agonist, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with opiate agonists. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of opiate therapy should be undertaken gradually using a dosage-tapering schedule.

Opioid analgesics are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

The use of atomoxetine is contraindicated in patients with narrow angle glaucoma. In clinical trials, atomoxetine use was associated with an increased risk of mydriasis.

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.

The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

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.

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.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

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.

Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

Narcotic (opioid) analgesic agents may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic Escherichia coli, Salmonella, Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. These agents decrease gastrointestinal motility, which may delay the excretion of infective gastroenteric organisms and/or their toxins. Other symptoms and complications such as fever, shedding of organisms, and extraintestinal illness may also be increased or prolonged. Therapy with opioids should be avoided or administered cautiously in patients with infectious diarrhea, particularly that due to pseudomembranous enterocolitis or enterotoxin-producing bacteria or if accompanied by high fever, pus, or blood in the stool.

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

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.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

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 narcotic (opioid) analgesic agents is contraindicated in premature infants. These agents may cross the immature blood-brain barrier to a greater extent than in adults, resulting in disproportionate respiratory depression.

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.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

Patients with Addison's disease may have increased risk of respiratory depression and prolonged CNS depression associated with the use of narcotic (opioid) analgesic agents. Conversely, these agents may cause or potentiate adrenal insufficiency. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with adrenocortical insufficiency. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Opiate agonists have cholinergic activity. Large doses and/or rapid intravenous administration may produce bradycardia and arrhythmias via stimulation of medullary vagal nuclei. Therapy with opiate agonists should be administered cautiously in patients with a history of arrhythmias. Clinical monitoring of cardiovascular status is recommended during therapy.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Opioid agonists may cause spasm of the sphincter of Oddi, which may increase biliary tract pressure. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions and transient elevations in serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be regularly evaluated for worsening symptoms. Therapy with opioids should be administered cautiously in patients with biliary tract disease, gallbladder disease, or acute pancreatitis.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.

Opioid agonists may cause spasm of the sphincter of Oddi, which may increase biliary tract pressure. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions and transient elevations in serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be regularly evaluated for worsening symptoms. Therapy with opioids should be administered cautiously in patients with biliary tract disease, gallbladder disease, or acute pancreatitis.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

The extended-release formulation of pseudoephedrine (Sudafed 24 Hour) 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. Therapy with the extended-release formulation of pseudoephedrine should be administered cautiously in patients with preexisting severe gastrointestinal narrowing or obstruction, whether pathologic or iatrogenic.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

Sympathomimetic agents can induce transient mydriasis via stimulation of alpha-1 adrenergic receptors. In patients with anatomically narrow angles or narrow-angle glaucoma, pupillary dilation can provoke an acute attack. In patients with other forms of glaucoma, mydriasis may occasionally increase intraocular pressure. Therapy with sympathomimetic agents should be administered cautiously in patients with or predisposed to glaucoma, particularly narrow-angle glaucoma.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Narcotic (opioid) analgesic agents are extensively metabolized by the liver, and several of them (e.g., codeine, hydrocodone, meperidine, methadone, morphine, propoxyphene) have active metabolites that are further converted to inactive substances. The serum concentrations of these agents and their metabolites may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with liver disease. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

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.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Opioid agonists may cause spasm of the sphincter of Oddi, which may increase biliary tract pressure. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions and transient elevations in serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be regularly evaluated for worsening symptoms. Therapy with opioids should be administered cautiously in patients with biliary tract disease, gallbladder disease, or acute pancreatitis.

Chewable products frequently may contain aspartame, which is metabolized in the gastrointestinal tract to phenylalanine. Sudafed (brand of pseudoephedrine) chewable 15 mg tablets provide the equivalent of 0.78 mg of phenylalanine per each tablet. The aspartame/phenylalanine content should be considered when this and similar products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Although narcotic (opioid) analgesic agents are generally metabolized by the liver, renal impairment can alter the elimination of these agents and their metabolites (some of which are pharmacologically active), resulting in drug accumulation and increased risk of toxicity. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with significantly impaired renal function. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

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.

Narcotic (opioid) analgesic agents may increase the frequency of seizures in patients with seizure disorders, may increase the risk of seizures occurring in other clinical settings associated with seizures, and, at higher dosages, have been reported to induce seizures in patients without history of seizures. Patients with history of seizure disorders should be regularly evaluated for worsened seizure control during therapy. Prolonged meperidine use may increase the risk of toxicity (e.g., seizures) from the accumulation of the active metabolite (normeperidine).

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.

Narcotic (opioid) analgesic agents may inhibit the urinary voiding reflex and increase the tone of the vesical sphincter in the bladder. Acute urinary retention requiring catheterization may occur, particularly in patients with prostatic hypertrophy or urethral stricture and in older adult patients. These agents may also decrease urine production via direct effects on the kidney and central stimulation of the release of vasopressin. Therapy with opioids should be administered cautiously in patients with or predisposed to urinary retention and/or oliguria. The effects on smooth muscle tone appear to be the most pronounced with morphine.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

There have been reports of urinary retention and urinary hesitation in ADHD patients using atomoxetine. Caution should be used if any urinary symptoms appear, especially in patients with history of urinary disorders.