Drug Interactions between Chemists Own Paracetamol Capseals and daclizumab

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

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.

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.

Depression-related events, including suicidal ideation or suicide attempt, have been reported with the use of daclizumab. If severe depression and/or suicidal ideation is present, consider discontinuation of therapy. Caution is recommended when using this agent in patients with previous depressive disorders.

Infections of the upper respiratory tract, urinary tract, and viral infections, sometimes serious, have been reported with the use of daclizumab. It is recommended to avoid daclizumab in patients with a severe active infection. Monitor for signs and symptoms of an infection and consider withholding treatment until the infection resolves.

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.

Daclizumab use can cause life-threatening severe liver injury, including liver failure and autoimmune hepatitis. The use of daclizumab is contraindicated in patients with a history of autoimmune hepatitis or other autoimmune condition involving the liver, and in patients with preexisting liver disease of hepatic impairment, including ALT or AST at least two times the upper limit of normal. Prior to starting therapy with daclizumab, it is recommended to obtain serum transaminases (ALT and AST) and total bilirubin levels in all patients. Continue to monitor levels of transaminase levels and total bilirubin monthly, before each next dose, and follow transaminase levels and total bilirubin monthly for 6 months after the last dose of daclizumab. Treatment modifications are recommended based on serum transaminase and total bilirubin values. If patients develop clinical signs or symptoms suggestive of hepatic dysfunction, immediately discontinue treatment and promptly measure serum transaminases and total bilirubin. Discontinue treatment if autoimmune hepatitis is suspected.

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.

Tuberculosis has been reported with the use of daclizumab in countries where tuberculosis is endemic. Prior to initiating treatment, it is recommended to evaluate high-risk patients for tuberculosis infection. Patients testing positive for tuberculosis should be treated according to standard medical practice before initiating treatment with daclizumab.

Tuberculosis has been reported with the use of daclizumab in countries where tuberculosis is endemic. Prior to initiating treatment, it is recommended to evaluate high-risk patients for tuberculosis infection. Patients testing positive for tuberculosis should be treated according to standard medical practice before initiating treatment with daclizumab.

Serious skin reaction, including photosensitivity reactions, have occurred in patients treated with daclizumab. It is recommended to use daclizumab with caution in patients with a history of skin conditions, including eczema or psoriasis, as the use of this agent may exacerbate those conditions. If a patient develops a serious diffuse or inflammatory rash, it is recommended to evaluate the patient before the next dose and to discontinue treatment as appropriate.

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).

Serious skin reaction, including photosensitivity reactions, have occurred in patients treated with daclizumab. It is recommended to use daclizumab with caution in patients with a history of skin conditions, including eczema or psoriasis, as the use of this agent may exacerbate those conditions. If a patient develops a serious diffuse or inflammatory rash, it is recommended to evaluate the patient before the next dose and to discontinue treatment as appropriate.