Drug Interactions between chlorpheniramine / guaifenesin / phenylephrine and sertraline

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: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be 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 sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

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.

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.

Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Families and caregivers should be advised of the need for close observation and communication with the treating physician. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to 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.

Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Families and caregivers should be advised of the need for close observation and communication with the treating physician. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.

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.

Selective serotonin reuptake inhibitors (SSRIs), like other antidepressants, may occasionally cause or activate mania or hypomania. The reported incidence ranged from 0.1% to 2% in premarketing testing of several SSRIs. Patients with bipolar disorder are generally more likely to experience mania from antidepressants. Therapy with SSRIs should be administered cautiously in patients with a history of mania or bipolar disorder. Prior to initiating treatment, it is recommended to adequately screen patients for bipolar disorder, including a family history of suicide, bipolar disorder, and depression.

The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with altered platelet function. Petechiae, purpura, ecchymosis, increased bleeding times, epistaxis and gastrointestinal hemorrhage have been reported. Therapy with SSRIs should be administered cautiously in patients with severe active bleeding or a hemorrhagic diathesis.

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.

The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with altered platelet function. Petechiae, purpura, ecchymosis, increased bleeding times, epistaxis and gastrointestinal hemorrhage have been reported. Therapy with SSRIs should be administered cautiously in patients with severe active bleeding or a hemorrhagic diathesis.

The use of selective serotonin reuptake inhibitors (SSRIs) has rarely been associated with hyponatremia, sometimes secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). These events have generally been reversible following discontinuation of SSRI therapy and/or medical intervention. SSRI-related hyponatremia may be more common in elderly female patients and those who are volume-depleted or receiving concomitant diuretic therapy. Caution may be warranted when SSRI therapy is administered in these patients and patients with preexisting hyponatremia or SIADH. Serum electrolytes, especially sodium as well as BUN and plasma creatinine, should be monitored regularly.

Selective serotonin reuptake inhibitors (SSRIs), like other antidepressants, may occasionally cause or activate mania or hypomania. The reported incidence ranged from 0.1% to 2% in premarketing testing of several SSRIs. Patients with bipolar disorder are generally more likely to experience mania from antidepressants. Therapy with SSRIs should be administered cautiously in patients with a history of mania or bipolar disorder. Prior to initiating treatment, it is recommended to adequately screen patients for bipolar disorder, including a family history of suicide, bipolar disorder, and depression.

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.

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.

Some SSRI antidepressants such as fluoxetine, paroxetine and sertraline may have an effect on pupil size causing dilation. This effect can potentially narrow the eye angle resulting in increased intraocular pressure and angle closure glaucoma, especially in predisposed patients. These drugs should be used with caution in patients with angle-closure glaucoma or history of 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.

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

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

The use of selective serotonin reuptake inhibitors (SSRIs) has rarely been associated with hyponatremia, sometimes secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). These events have generally been reversible following discontinuation of SSRI therapy and/or medical intervention. SSRI-related hyponatremia may be more common in elderly female patients and those who are volume-depleted or receiving concomitant diuretic therapy. Caution may be warranted when SSRI therapy is administered in these patients and patients with preexisting hyponatremia or SIADH. Serum electrolytes, especially sodium as well as BUN and plasma creatinine, should be monitored regularly.

Treatment with SSRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.

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.

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.

Selective serotonin reuptake inhibitors (SSRIs) are primarily metabolized by the liver. The plasma concentrations of SSRIs and their metabolites may be increased and the half-lives prolonged in patients with impaired hepatic function. Dosage adjustments may be necessary in accordance with the individual product package labeling.

Selective serotonin reuptake inhibitors (SSRIs), like other antidepressants, may occasionally cause or activate mania or hypomania. The reported incidence ranged from 0.1% to 2% in premarketing testing of several SSRIs. Patients with bipolar disorder are generally more likely to experience mania from antidepressants. Therapy with SSRIs should be administered cautiously in patients with a history of mania or bipolar disorder. Prior to initiating treatment, it is recommended to adequately screen patients for bipolar disorder, including a family history of suicide, bipolar disorder, and depression.

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.

Selective serotonin reuptake inhibitors (SSRIs) may trigger seizures in approximately 0.2% of patients, and some of them are not recommended in patients with unstable epilepsy. Therapy with SSRIs should be administered cautiously in patients with seizure disorders.

The use of selective serotonin reuptake inhibitors (SSRIs) has rarely been associated with hyponatremia, sometimes secondary to development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). These events have generally been reversible following discontinuation of SSRI therapy and/or medical intervention. SSRI-related hyponatremia may be more common in elderly female patients and those who are volume-depleted or receiving concomitant diuretic therapy. Caution may be warranted when SSRI therapy is administered in these patients and patients with preexisting hyponatremia or SIADH. Serum electrolytes, especially sodium as well as BUN and plasma creatinine, should be monitored regularly.

The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with altered platelet function. Petechiae, purpura, ecchymosis, increased bleeding times, epistaxis and gastrointestinal hemorrhage have been reported. Therapy with SSRIs should be administered cautiously in patients with severe active bleeding or a hemorrhagic diathesis.

The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with altered platelet function. Petechiae, purpura, ecchymosis, increased bleeding times, epistaxis and gastrointestinal hemorrhage have been reported. Therapy with SSRIs should be administered cautiously in patients with severe active bleeding or a hemorrhagic diathesis.

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

The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with altered platelet function. Petechiae, purpura, ecchymosis, increased bleeding times, epistaxis and gastrointestinal hemorrhage have been reported. Therapy with SSRIs should be administered cautiously in patients with severe active bleeding or a hemorrhagic diathesis.

The use of selective serotonin reuptake inhibitors (SSRIs) may occasionally cause significant weight loss, which may be undesirable in patients suffering from anorexia, malnutrition or excessive weight loss. Anorexia may occur in approximately 5% to 10% of patients. Weight change should be monitored during therapy if an SSRI is used in these patients.

The use of selective serotonin reuptake inhibitors (SSRIs) may occasionally cause significant weight loss, which may be undesirable in patients suffering from anorexia, malnutrition or excessive weight loss. Anorexia may occur in approximately 5% to 10% of patients. Weight change should be monitored during therapy if an SSRI is used in these patients.

Sertraline is primarily metabolized by the liver. Although renal excretion of unchanged drug appears to be a minor route of elimination, some metabolites are excreted in the urine to some extent. The clinical significance of possible metabolite accumulation is unknown. Caution may be warranted when sertraline therapy is administered in patients with severe renal dysfunction.

The use of selective serotonin reuptake inhibitors (SSRIs) may occasionally cause significant weight loss, which may be undesirable in patients suffering from anorexia, malnutrition or excessive weight loss. Anorexia may occur in approximately 5% to 10% of patients. Weight change should be monitored during therapy if an SSRI is used in these patients.