Drug Interactions between apomorphine and chlorpheniramine / guaifenesin / phenylephrine

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.

Alcohol can lower your blood pressure and add to the effects of apomorphine. Drinking alcohol while taking apomorphine may decrease your blood pressure and cause drowsiness. This can cause nausea, extreme drowsiness, slow heartbeat, headaches, and dizziness. If you take apomorphine with alcohol tell your doctor if you have any of these symptoms. 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.

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.

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.

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.

In a study of healthy subjects, the hypotensive effect of apomorphine on systolic and diastolic blood pressure was exacerbated by the concomitant use of alcohol. Patients should avoid alcohol when using apomorphine.

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.

Apomorphine products contain sodium metabisulfite, a sulfite that may cause allergic-type reactions (including anaphylactic symptoms and life-threatening or less severe asthmatic episodes) in certain susceptible patients. While the overall prevalence in the general population is unknown and probably low, sulfite sensitivity is seen more often in patients with asthma than in those without asthma.

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.

Apomorphine has been shown to reduce resting systolic and diastolic blood pressure and may have the potential to exacerbate cardiac and cerebral ischemia in patients with known cardiovascular and cerebrovascular disease. If patients develop signs/symptoms of cardiac or cerebral ischemia, prescribers should reevaluate the continued use of apomorphine.

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.

Apomorphine has been shown to reduce resting systolic and diastolic blood pressure and may have the potential to exacerbate cardiac and cerebral ischemia in patients with known cardiovascular and cerebrovascular disease. If patients develop signs/symptoms of cardiac or cerebral ischemia, prescribers should reevaluate the continued use of apomorphine.

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.

The risks/benefits of apomorphine treatment should be considered before starting this drug in patients with risk factors for prolonged QTc. There is a dose-related prolongation of QTc interval after apomorphine exposure similar to that achieved with therapeutic doses of this drug. For the intermittent injection formulation, doses greater than 6 mg do not provide additional clinical benefit and are not recommended. Drugs that prolong QTc interval have been associated with torsades de pointes and sudden death. The link between QTc prolongation and torsades de pointes is most apparent with larger increases (20 msec and greater), but smaller QTc prolongations may also increase risk, particularly in susceptible patients (e.g., those with hypokalemia, hypomagnesemia, bradycardia, genetic predisposition [such as congenital QT interval prolongation], or concomitant use of other drugs that prolong QTc interval). Although no occurrence of torsades de pointes was reported in association with apomorphine at recommended doses in clinical trials, an increased risk cannot be ruled out due to limited experience.

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.

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.

The risks/benefits of apomorphine treatment should be considered before starting this drug in patients with risk factors for prolonged QTc. There is a dose-related prolongation of QTc interval after apomorphine exposure similar to that achieved with therapeutic doses of this drug. For the intermittent injection formulation, doses greater than 6 mg do not provide additional clinical benefit and are not recommended. Drugs that prolong QTc interval have been associated with torsades de pointes and sudden death. The link between QTc prolongation and torsades de pointes is most apparent with larger increases (20 msec and greater), but smaller QTc prolongations may also increase risk, particularly in susceptible patients (e.g., those with hypokalemia, hypomagnesemia, bradycardia, genetic predisposition [such as congenital QT interval prolongation], or concomitant use of other drugs that prolong QTc interval). Although no occurrence of torsades de pointes was reported in association with apomorphine at recommended doses in clinical trials, an increased risk cannot be ruled out due to limited experience.

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.

Dopamine agonists may impair the systemic regulation of blood pressure, with resultant orthostatic hypotension at any time, but especially during dose escalation. Additionally, patients with Parkinson's disease may have an impaired capacity to respond to an orthostatic challenge. For these reasons, patients with Parkinson's disease (or restless legs syndrome) who are being treated with dopaminergic agonists typically require careful monitoring for signs/symptoms of orthostatic hypotension, especially during dose escalation, and should be advised of this risk.

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.

Apomorphine has not been studied in patients with severe liver dysfunction. Because apomorphine concentration and exposure (AUC and Cmax) is increased, caution should be exercised if apomorphine is administered to patients with mild or moderate liver dysfunction; these patients should be closely monitored.

The risks/benefits of apomorphine treatment should be considered before starting this drug in patients with risk factors for prolonged QTc. There is a dose-related prolongation of QTc interval after apomorphine exposure similar to that achieved with therapeutic doses of this drug. For the intermittent injection formulation, doses greater than 6 mg do not provide additional clinical benefit and are not recommended. Drugs that prolong QTc interval have been associated with torsades de pointes and sudden death. The link between QTc prolongation and torsades de pointes is most apparent with larger increases (20 msec and greater), but smaller QTc prolongations may also increase risk, particularly in susceptible patients (e.g., those with hypokalemia, hypomagnesemia, bradycardia, genetic predisposition [such as congenital QT interval prolongation], or concomitant use of other drugs that prolong QTc interval). Although no occurrence of torsades de pointes was reported in association with apomorphine at recommended doses in clinical trials, an increased risk cannot be ruled out due to limited experience.

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.

Ordinarily, patients with major psychotic disorder should not be treated with dopaminergic antiparkinsonian agents, because of the risk of exacerbating psychosis. Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of these drugs. The use of bromocriptine in patients with severe psychotic disorders is not recommended.

Apomorphine has not been studied in patients with severe renal dysfunction. For patients with mild or moderate renal dysfunction using the intermittent injection formulation, the test dose and starting dose of apomorphine should be reduced to 1 mg. For patients with mild or moderate renal dysfunction using the continuous infusion formulation, the initial extra dose of apomorphine is 0.5 to 1 mg and should not exceed 1 mg; no adjustment is needed for the continuous dose, maximum recommended daily dose, or subsequent extra doses after the initial extra dose.

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.

Somnolence is commonly associated with apomorphine. Patients treated with apomorphine have also reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Falling asleep while engaged in activities of daily living usually occurs in patients with preexisting somnolence, although patients may not give such a history. Before starting treatment with apomorphine, patients should be informed of the risk of drowsiness and asked about factors that could increase the risk with apomorphine, such as the presence of sleep disorders.

Apomorphine may cause dyskinesia or exacerbate preexisting dyskinesia. Patients should be informed that new or worsening dyskinesia may occur.

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.