Drug Interactions between chlorpheniramine / guaifenesin / phenylephrine and ozanimod

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.

Ozanimod may be taken with or without food. While there is no need to strictly avoid most foods and beverages that contain tyramine (usually aged, fermented, cured, smoked, or pickled foods such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut) during treatment with ozanimod, certain foods such as some of the aged cheeses (for example, Boursault, Liederkrantz, Mycella, and Stilton) and pickled herring may contain very high amounts of tyramine and should generally be avoided if possible. Consumption of very high levels of tyramine (greater than 150 mg) while on ozanimod treatment may lead to dangerous increases in your blood pressure, a condition known as hypertensive crisis. Talk to your doctor or pharmacist if you are uncertain about what foods, if any, to avoid. You should seek immediate medical attention if you experience sudden and severe headache, blurred vision, confusion, seizures, chest pain, nausea or vomiting, sudden numbness or weakness (especially on one side of the body), speech difficulties, fever, sweating, lightheadedness, and/or fainting during treatment with ozanimod, as these may be signs and symptoms of a hypertensive crisis. 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.

Ozanimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a presence of Mobitz Type II 2nd degree or 3rd degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a pacemaker, severe untreated sleep apnea or those patients being treated with monoamine oxidase inhibitor drugs.

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.

Ozanimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a presence of Mobitz Type II 2nd degree or 3rd degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a pacemaker, severe untreated sleep apnea or those patients being treated with monoamine oxidase inhibitor drugs.

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.

Ozanimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a presence of Mobitz Type II 2nd degree or 3rd degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a pacemaker, severe untreated sleep apnea or those patients being treated with monoamine oxidase inhibitor drugs.

The use of ozanimod may result in a transient decrease in heart rate and atrioventricular conduction delays upon starting treatment. It is recommended to follow an up-titration scheme to reach the maintenance dosage. Initiation of ozanimod without titration may result in greater decreases in heart rate. If treatment with ozanimod is considered, advice from a cardiologist should be sought for those individuals at risk of cardiovascular effects, particularly conduction delays.

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.

The use of ozanimod may result in a transient decrease in heart rate and atrioventricular conduction delays upon starting treatment. It is recommended to follow an up-titration scheme to reach the maintenance dosage. Initiation of ozanimod without titration may result in greater decreases in heart rate. If treatment with ozanimod is considered, advice from a cardiologist should be sought for those individuals at risk of cardiovascular effects, particularly conduction delays.

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.

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a sphingosine 1-phosphate receptor modulator. It is recommended to promptly schedule a complete physical and neurological examination and should consider an MRI, if a patient develops any unexpected neurological or psychiatric symptoms/signs, any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Exercise care when using this agent in patients with a history of ischemic stroke or cerebral hemorrhage. Treatment should be discontinued if PRES is suspected.

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.

Macular edema has been reported with the use of sphingosine 1-phosphate (S1P) receptor modulators. Care should be exercised when using these drugs in patients with a history of uveitis and patients with diabetes mellitus as these patients are at increased risk for macular edema. Before starting treatment with these agents, an ophthalmic evaluation of the fundus, including the macula, is recommended in all patients and at any time if vision change is reported during treatment. Patients with a history of uveitis and patients with diabetes mellitus should have regular follow-up examinations of the fundus, including the macula during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

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 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.

The use of ozanimod may result in increased blood pressure. Care should be exercised when using this drug in hypertensive patients and those at risk for hypertension. It is recommended to monitor blood pressure during treatment and manage it according to clinical practices.

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.

Ozanimod may increase the risk of infections and some serious infections with opportunistic pathogens including viruses have been reported. Because of reversible sequestration of lymphocytes in lymphoid tissues, this drug causes a mean reduction in peripheral blood lymphocyte count to approximately 45% of baseline values. Prior to treatment, a recent CBC (i.e., within 6 months or after discontinuation of prior therapy), including lymphocyte count must be available. It is recommended to delay treatment initiation in patients with an active infection until complete resolution. Consider withholding or discontinuing treatment if a patient develops a serious infection, and reassess the benefits and risks prior to reinitiating therapy.

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.

The use of ozanimod may result in elevations of aminotransferases. The use of ozanimod in patients with hepatic impairment is not recommended. While on treatment with this drug, if a patient develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine, should have hepatic enzymes checked, and ozanimod should be discontinued if significant liver injury is confirmed.

Macular edema has been reported with the use of sphingosine 1-phosphate (S1P) receptor modulators. Care should be exercised when using these drugs in patients with a history of uveitis and patients with diabetes mellitus as these patients are at increased risk for macular edema. Before starting treatment with these agents, an ophthalmic evaluation of the fundus, including the macula, is recommended in all patients and at any time if vision change is reported during treatment. Patients with a history of uveitis and patients with diabetes mellitus should have regular follow-up examinations of the fundus, including the macula during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Rare cases of severe exacerbation of multiple sclerosis (MS), including disease rebound, have been reported after discontinuation of sphingosine 1-phosphate receptor modulator in MS treated patients. The possibility of severe exacerbation of disease should be considered after stopping treatment with these agents. Patients should be observed for a severe increase in disability upon discontinuation and appropriate treatment should be instituted, as required.

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.

The use of ozanimod may result in a dose-dependent reduction in absolute forced expiratory volume over 1 second (FEV1) and may manifest as early as 3 months after treatment initiation. Care should be exercised when using this drug in patients with respiratory complications. It is recommended to perform spirometric evaluation of respiratory function during therapy if clinically appropriate.

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.

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.

Macular edema has been reported with the use of sphingosine 1-phosphate (S1P) receptor modulators. Care should be exercised when using these drugs in patients with a history of uveitis and patients with diabetes mellitus as these patients are at increased risk for macular edema. Before starting treatment with these agents, an ophthalmic evaluation of the fundus, including the macula, is recommended in all patients and at any time if vision change is reported during treatment. Patients with a history of uveitis and patients with diabetes mellitus should have regular follow-up examinations of the fundus, including the macula during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Vaccinations may be less effective if administered during ozanimod treatment. Patients without a clinical confirmed history of chickenpox or without documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating treatment. It is recommended to obtain a full course of vaccination for antibody-negative patients with varicella vaccine prior to starting treatment with ozanimod and to postpone treatment for 4 weeks to allow the full effect of vaccination. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ozanimod. Avoid the use of live attenuated vaccines during and for 3 months after treatment with ozanimod.