Drug Interactions between chlorpheniramine / guaifenesin / phenylephrine and haloperidol

Alcohol can increase the nervous system side effects of haloperidol such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with haloperidol. Do not use more than the recommended dose of haloperidol, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

Alcohol can increase the nervous system side effects of chlorpheniramine such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with chlorpheniramine. Do not use more than the recommended dose of chlorpheniramine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

Both phenylephrine and caffeine can increase blood pressure and heart rate, and combining them may enhance these effects. Talk to your doctor before using these medications, especially if you have a history of high blood pressure or heart disease. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

As you stop smoking during treatment with nicotine, your dosage requirement of haloperidol may need to be changed. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The use of most miscellaneous antipsychotics is contraindicated in patients with severe central nervous system depression or comatose states from any cause (e.g., lesion, disease, drug or alcohol induced).

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

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

The use of most miscellaneous antipsychotics is contraindicated in patients with severe central nervous system depression or comatose states from any cause (e.g., lesion, disease, drug or alcohol induced).

The use of neuroleptic agents is contraindicated in comatose patients and patients with severe central nervous system depression. Neuroleptic agents may potentiate the CNS and respiratory depression in these patients.

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.

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.

Neuroleptic agents may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include hypertension, edema, arrhythmias, thrombophlebitis, myocarditis, angina, myocardial infarction, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with neuroleptic agents should be administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since neuroleptic agents can reverse its vasopressor effects and cause a further lowering of blood pressure.

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

Antipsychotic drugs are not approved for the treatment of patients with dementia-related psychosis. Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo.

Elderly patients with dementia- related psychosis treated with antipsychotic drugs are at increased risk of death. Most of these drugs are not approved for the treatment of patients with dementia- related psychosis.

Neuroleptic agents may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include hypertension, edema, arrhythmias, thrombophlebitis, myocarditis, angina, myocardial infarction, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with neuroleptic agents should be administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since neuroleptic agents can reverse its vasopressor effects and cause a further lowering of blood pressure.

Neuroleptic agents may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include hypertension, edema, arrhythmias, thrombophlebitis, myocarditis, angina, myocardial infarction, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with neuroleptic agents should be administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since neuroleptic agents can reverse its vasopressor effects and cause a further lowering of blood pressure.

Neuroleptic agents may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include hypertension, edema, arrhythmias, thrombophlebitis, myocarditis, angina, myocardial infarction, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with neuroleptic agents should be administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since neuroleptic agents can reverse its vasopressor effects and cause a further lowering of blood pressure.

The use of neuroleptic agents in the presence of thyrotoxicosis has been associated with severe neurotoxicity that includes rigidity and inability to walk or talk. Therapy with haloperidol should be administered cautiously in patients with thyrotoxicosis or hyperthyroidism.

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.

Neuroleptic agents may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include hypertension, edema, arrhythmias, thrombophlebitis, myocarditis, angina, myocardial infarction, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with neuroleptic agents should be administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since neuroleptic agents can reverse its vasopressor effects and cause a further lowering of blood pressure.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with the use of antipsychotic drugs. The diagnostic evaluation is complicated and the management requires immediate discontinuation of the antipsychotic therapy and intensive symptomatic treatment and medical monitoring. If a patient that has recovered from NMS requires antipsychotic drug treatment again, the reintroduction of therapy should be carefully considered as NMS recurrences have been reported.

The central dopaminergic blocking effects of neuroleptic agents may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). NMS is observed most frequently when high-potency agents like haloperidol are administered intramuscularly, but may occur with any neuroleptic agent given for any length of time. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria, and acute renal failure. Neuroleptic agents should not be given to patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of neuroleptic agents should be carefully considered, since NMS may recur.

The use of neuroleptic agents is associated with pseudo- parkinsonian symptoms such as akinesia, bradykinesia, tremors, pill- rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually 1 to 2 weeks following initiation of therapy or an increase in dosage. Older neuroleptic agents such as haloperidol are more likely to induce these effects. The manufacturers of haloperidol consider its use to be contraindicated in patients with Parkinson's disease.

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.

The use of neuroleptic agents is contraindicated in comatose patients and patients with severe central nervous system depression. Neuroleptic agents may potentiate the CNS and respiratory depression in these patients.

The use of alcohol with haloperidol should be avoided due to possible additive effects and hypotension.

Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.

Haloperidol should be administered cautiously to patients with severe cardiovascular disorders because of the possibility of transient hypotension and/or precipitation of anginal pain. In the presence of severe hypotension requiring vasopressor therapy, the preferred drugs may be norepinephrine, phenylephrine, or metaraminol, as usual doses of epinephrine may be ineffective since haloperidol inhibits its vasopressor effect.

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.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.

Haloperidol should be administered cautiously to patients with severe cardiovascular disorders because of the possibility of transient hypotension and/or precipitation of anginal pain. In the presence of severe hypotension requiring vasopressor therapy, the preferred drugs may be norepinephrine, phenylephrine, or metaraminol, as usual doses of epinephrine may be ineffective since haloperidol inhibits its vasopressor effect.

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.

Neuroleptic agents may cause hypotension (including orthostatic hypotension) and associated reflex tachycardia, syncope or dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few months. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Therapy with neuroleptic agents should be administered cautiously in patients with conditions that would predispose them to hypotension, such as hypovolemia or dehydration (e.g., due to severe diarrhea or vomiting). In addition, neuroleptic agents can interfere with the body's ability to regulate core body temperature, occasionally producing hyperthermia during strenuous exercise, exposure to hot weather, and concomitant treatment with anticholinergic medications. Patients who are dehydrated may be particularly susceptible.

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.

Neuroleptic agents may cause hypotension (including orthostatic hypotension) and associated reflex tachycardia, syncope or dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few months. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Therapy with neuroleptic agents should be administered cautiously in patients with conditions that would predispose them to hypotension, such as hypovolemia or dehydration (e.g., due to severe diarrhea or vomiting). In addition, neuroleptic agents can interfere with the body's ability to regulate core body temperature, occasionally producing hyperthermia during strenuous exercise, exposure to hot weather, and concomitant treatment with anticholinergic medications. Patients who are dehydrated may be particularly susceptible.

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 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.

Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.

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.

Cases of sudden death, QT interval prolongation and ventricular arrhythmias including Torsade de Pointes have been reported in patients using haloperidol. Although cases have been reported even in the absence of predisposing factors, special caution is advised in treating patients with other QT- prolonging conditions (including electrolyte imbalance such as hypokalemia and hypomagnesemia), using QT- prolonging drugs, with underlying cardiac abnormalities, hypothyroidism and familial long QT syndrome. Consider periodic EKG assessment on these patients. Treatment should be discontinued and a cardiac evaluation should be considered if a patient develops signs or symptoms of ventricular arrhythmia.

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.

Cases of sudden death, QT interval prolongation and ventricular arrhythmias including Torsade de Pointes have been reported in patients using haloperidol. Although cases have been reported even in the absence of predisposing factors, special caution is advised in treating patients with other QT- prolonging conditions (including electrolyte imbalance such as hypokalemia and hypomagnesemia), using QT- prolonging drugs, with underlying cardiac abnormalities, hypothyroidism and familial long QT syndrome. Consider periodic EKG assessment on these patients. Treatment should be discontinued and a cardiac evaluation should be considered if a patient develops signs or symptoms of ventricular arrhythmia.

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.

Haloperidol appears to be primarily converted in the liver to several metabolites, one of which is believed to be pharmacologically active. The metabolites and approximately 1% of the parent drug are excreted in the urine. Patients with impaired renal and/or hepatic function may be at greater risk for adverse effects due to drug and metabolite accumulation. Therapy with haloperidol should be administered cautiously in such patients. Lower initial dosages and slower titration may be appropriate.

Cases of sudden death, QT interval prolongation and ventricular arrhythmias including Torsade de Pointes have been reported in patients using haloperidol. Although cases have been reported even in the absence of predisposing factors, special caution is advised in treating patients with other QT- prolonging conditions (including electrolyte imbalance such as hypokalemia and hypomagnesemia), using QT- prolonging drugs, with underlying cardiac abnormalities, hypothyroidism and familial long QT syndrome. Consider periodic EKG assessment on these patients. Treatment should be discontinued and a cardiac evaluation should be considered if a patient develops signs or symptoms of ventricular arrhythmia.

The use of antipsychotics has been associated with events of leukopenia, neutropenia and agranulocytosis. Possible risk factors include preexisting low white blood cell count, and history of drug induced leukopenia/neutropenia. Patients with these risk factors should have complete blood count monitored frequently during the first few months of therapy. Patients should also be monitored for any signs or symptoms of infection. Treatment should be discontinued in any patient who develops a sore throat, fever, stomatitis, or other signs of infection along with a low WBC count or severe neutropenia (ANC < 1000/mm3).

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.

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.

Haloperidol appears to be primarily converted in the liver to several metabolites, one of which is believed to be pharmacologically active. The metabolites and approximately 1% of the parent drug are excreted in the urine. Patients with impaired renal and/or hepatic function may be at greater risk for adverse effects due to drug and metabolite accumulation. Therapy with haloperidol should be administered cautiously in such patients. Lower initial dosages and slower titration may be appropriate.

Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.

Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs; the syndrome consists of potentially irreversible, involuntary, dyskinetic movements. The risk appears highest in older patients (particularly older women) but it is not possible to predict which patients are likely to develop TD; whether antipsychotic drugs differ in their potential to cause TD is unknown. The risk of TD and the likelihood that it will become irreversible increase with the duration of therapy and the total cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low dosages; it may also occur after discontinuation of therapy. TD may remit (partially or completely) upon discontinuation of antipsychotic therapy, although antipsychotic therapy itself may suppress (or partially suppress) signs/symptoms of TD, possibly masking the underlying process; the effect of symptomatic suppression on the long-term course of TD is unknown. In patients with preexisting drug-induced TD, initiating or increasing the dosage of antipsychotic therapy may temporarily mask the symptoms of TD but could eventually worsen the condition. In patients requiring chronic therapy, the lowest dose and shortest duration of therapy producing a satisfactory clinical response are recommended; the need for continued therapy should be reassessed periodically. If signs/symptoms of TD occur during antipsychotic therapy, discontinuation of the offending agent should be considered; however, some patients may require treatment despite the presence of TD.

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.

Neuroleptic agents may cause hypotension (including orthostatic hypotension) and associated reflex tachycardia, syncope or dizziness, particularly during initiation of therapy or rapid escalation of dosage. Tolerance to the hypotensive effects often develops after a few doses to a few months. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Therapy with neuroleptic agents should be administered cautiously in patients with conditions that would predispose them to hypotension, such as hypovolemia or dehydration (e.g., due to severe diarrhea or vomiting). In addition, neuroleptic agents can interfere with the body's ability to regulate core body temperature, occasionally producing hyperthermia during strenuous exercise, exposure to hot weather, and concomitant treatment with anticholinergic medications. Patients who are dehydrated may be particularly susceptible.