Drug Interactions between chlorpheniramine / guaifenesin / phenylephrine and theophylline

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

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.

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

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.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

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 theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

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 theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

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.

Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

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 metabolites of theophylline, which are generally undetectable in patients with normal renal function, may accumulate in patients with renal impairment and contribute to the toxicity of theophylline. In addition, the plasma protein binding of theophylline may be significantly decreased in renal impairment, resulting in elevated free drug concentrations and further increasing the risk of toxicity. Therapy with theophyllines should be administered cautiously in patients with impaired renal function. Dosage adjustments and more intensive monitoring of serum theophylline concentrations may be required.

The use of theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

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.

Theophylline is removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

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.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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.