Drug Interaction Report

Using chlorpheniramine together with dextromethorphan may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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.

Osilodrostat may increase the blood levels and effects of dextromethorphan. 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.

Ask your doctor before using acetaminophen together with ethanol (alcohol). This can cause serious side effects that affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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 increase the nervous system side effects of dextromethorphan 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 dextromethorphan. Do not use more than the recommended dose of dextromethorphan, 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.

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

Chronic alcohol abusers may be at increased risk of hepatotoxicity during treatment with acetaminophen (APAP). Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously, if at all, in patients who consume three or more alcoholic drinks a day. In general, patients should avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure. They should also be advised to seek medical attention if they experience signs and symptoms of liver injury such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.

Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.

Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.

Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease. Patients with hepatic impairment may be at increased risk of toxicity. Severe liver injury, including cases of acute liver failure and death, have been reported in patients using this drug. Clinical monitoring of hepatic function is recommended. Caution is advised if using acetaminophen in patients with chronic malnutrition or severe hypovolemia. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.

Osilodrostat lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency. Patients should be evaluated for precipitating causes of hypocortisolism. Serum/plasma cortisol, 24-hour urine free cortisol, and patient's signs/symptoms should be monitored periodically during treatment. Osilodrostat should be decreased or temporarily discontinued if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report hypocortisolism symptoms. Therapy should be stopped and exogenous glucocorticoid replacement therapy should be administered if serum/plasma cortisol levels are below the target range and patients have symptoms of adrenal insufficiency. Osilodrostat should be restarted at a lower dose when urine free cortisol and serum/plasma cortisol levels are within the target range, and/or patient symptoms have resolved.

The use of osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

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.

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 osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

The use of osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

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.

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 osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

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.

Dosage adjustment of osilodrostat is required for patients with moderate to severe liver dysfunction. The recommended starting dose for patients with moderate liver dysfunction is 1 mg orally twice a day, and for patients with severe liver dysfunction is 1 mg orally once a day in the evening. No dose adjustment is required in patients with mild liver dysfunction. More frequent monitoring of adrenal function may be needed during dose titration in all patients with liver dysfunction.

The use of osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

Several oral acetaminophen and acetaminophen-combination products, particularly flavored chewable tablets, contain the artificial sweetener, aspartame (NutraSweet). Aspartame is converted to phenylalanine in the gastrointestinal tract following ingestion. Chewable and effervescent formulations of acetaminophen products may also contain phenylalanine. The aspartame/phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

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.

No dosage adjustment of osilodrostat is required for patients with impaired renal function. However, in patients with moderate to severe renal dysfunction, urinary free cortisol (UFC) levels should be interpreted with caution due to reduced UFC excretion.

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.