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Interactions between Acuflex and Isoniazid

2 drug interactions and 27 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

acetaminophen isoniazid

Applies to: Acuflex (acetaminophen / phenyltoloxamine) and isoniazid
Monitor

Some reports have suggested that isoniazid may increase the potential hepatotoxicity of acetaminophen. The mechanism may be related to induction of CYP450 2E1 metabolism of acetaminophen to toxic metabolites during concurrent administration, or transient increased metabolism of acetaminophen after discontinuation of isoniazid. Study data have been conflicting and causality is unclear due to the presence of other drugs in some cases. Both isoniazid and acetaminophen have individually been associated with hepatotoxicity.

Management

Until more information is available, concurrent acetaminophen use should be limited. Close attention should be paid to clinical and laboratory evidence of hepatotoxicity. Both drugs should be discontinued if evidence of hepatotoxicity is observed. Aspirin or nonsteroidal inflammatory agents may be safer alternatives.

References (5)
  1. Murphy R, Swartz R, Watkins PB (1990) "Severe acetaminophen toxicity in a patient receiving isoniazid." Ann Intern Med, 113, p. 799-800
  2. Epstein MM, Nelson SD, Slattery JT, Kalhorn TF, Wall RA, Wright JM (1991) "Inhibition of the metabolism of paracetamol by isoniazid." Br J Clin Pharmacol, 31, p. 139-42
  3. Moulding TS, Redeker AG, Kanel GC (1991) "Acetaminophen, isoniazid, and hepatic toxicity." Ann Intern Med, 114, p. 431
  4. Crippin JS (1993) "Acetaminophen hepatotoxicity: potentiation by isoniazid." Am J Gastroenterol, 88, p. 590-2
  5. Nolan CM, Sandblom RE, Thummel KE, Slattery JT, Nelson SD (1994) "Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis." Chest, 105, p. 408-11
Moderate:

isoniazid phenyltoloxamine

Applies to: isoniazid and Acuflex (acetaminophen / phenyltoloxamine)
Generally avoid

Coadministration of monoamine oxidase inhibitors (MAOIs) and antihistamines may result in additive central nervous system depressant effects. In addition, limited data suggest that MAOIs may potentiate and prolong the anticholinergic effects of antihistamines due to inhibition of catecholamine degradation, which may lead to overstimulation of the sympathetic nervous system. In one published report, a woman who had been on phenelzine 30 mg/day for six months developed irritability and visual hallucinations two months following the addition of cyproheptadine 2 mg at bedtime to treat phenelzine-induced anorgasmia. The hallucinations cleared over 48 hours following the discontinuation of her medications. In another published report, a patient developed delirium with symptoms of aggression, paranoia, and vivid auditory as well as visual hallucinations after two days of receiving diphenhydramine 300 mg/day and linezolid 600 mg every 12 hours. The patient also had tachycardia, very warm skin, and possibly blurred vision (as evidenced by constant squinting). Central anticholinergic intoxication and dopaminergic hyperactivity were suspected. Symptoms subsided over four days following the discontinuation of diphenhydramine, while linezolid was continued with no subsequent sequelae. In a third report, a patient developed visual hallucinations associated with confusion and disorientation after nine days of linezolid and antihistamine therapy, including dexchlorpheniramine and cetirizine for the first four days and hydroxyzine for the next five. Physical examination did not reveal any focal neurological signs, myoclonus or ataxia, and cerebral CT scan and EEG were within normal limits. Symptoms resolved two days after linezolid was discontinued.

Management

Prescribing antihistamines in combination with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should generally be avoided. If concomitant treatment is unavoidable, patients should be counseled to avoid hazardous activities requiring 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. It may be appropriate to monitor some patients for increased anticholinergic effects (e.g., constipation, urinary retention, fever, heat intolerance, blurred vision, confusion, hallucinations, dizziness, palpitations, arrhythmias, syncope), since certain populations such as the elderly and those with underlying organic brain disease tend to be more sensitive to these effects and may be susceptible to anticholinergic intoxication. It should be noted that the manufacturers of many of the sedating antihistamines (e.g., chlorpheniramine, dexchlorpheniramine, diphenhydramine, pheniramine, promethazine) consider their use within 14 days of MAOIs to be contraindicated.

References (9)
  1. Kahn DA (1987) "Possible toxic interaction between cyproheptadine and phenelzine." Am J Psychiatry, 144, p. 1242-3
  2. (2002) "Product Information. Periactin (cyproheptadine)." Merck & Co., Inc
  3. (2002) "Product Information. Benadryl (diphenhydramine)." Parke-Davis
  4. (2001) "Product Information. Matulane (procarbazine)." Roche Laboratories
  5. Serio RN (2004) "Acute delirium associated with combined diphenhydramine and linezolid use." Ann Pharmacother, 38, p. 62-5
  6. Ferry T, Ponceau B, Simon M, et al. (2005) "Possibly linezolid-induced peripheral and central neurotoxicity: report of four cases." Infection, 33, p. 151-4
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  9. Cerner Multum, Inc. "Australian Product Information."

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

acetaminophen Food/Lifestyle

Applies to: Acuflex (acetaminophen / phenyltoloxamine)
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.

References (1)
  1. (2022) "Product Information. Acetaminophen (acetaminophen)." Camber Pharmaceuticals, Inc

Moderate food/lifestyle interactions

Moderate:

isoniazid Food/Lifestyle

Applies to: isoniazid
Generally avoid

Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.

Generally avoid

Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).

Adjust dosing interval

Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.

Management

The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 30 minutes before or 2 hours after meals). Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.

References (17)
  1. Smith CK, Durack DT (1978) "Isoniazid and reaction to cheese." Ann Intern Med, 88, p. 520-1
  2. Dimartini A (1995) "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol, 10, p. 197-8
  3. Uragoda CG, Kottegoda SR (1977) "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle, 58, p. 83-9
  4. Self TH, Chrisman CR, Baciewicz AM, Bronze MS (1999) "Isoniazid drug and food interactions." Am J Med Sci, 317, p. 304-11
  5. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  6. (2023) "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC.
  7. (2023) "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd
  8. (2023) "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB
  9. Saukkonen JJ, Cohn DL, Jasmer RM, et al. (2006) "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med, 174, p. 935-52
  10. Bouazzi OE, Hammi S, Bourkadi JE, et al. (2024) First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/
  11. Wang P, Pradhan K, Zhong XB, Ma X (2016) "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B, 6, p. 384-92
  12. Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. (2016) "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother, 71, p. 703-10
  13. Hahn JA, Ngabirano C, Fatch R, et al. (2023) "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS, 37, p. 1535-43
  14. Huang YS, Chern HD, Su WJ, et al. (2003) "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology, 37, p. 924-30
  15. Sousou JM, Griffith EM, Marsalisi C, Reddy P (2024) Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/
  16. Miki M, Ishikawa T, Okayama H (2005) "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med, 44, p. 1133-6
  17. (2021) "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc.
Moderate:

phenyltoloxamine Food/Lifestyle

Applies to: Acuflex (acetaminophen / phenyltoloxamine)
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.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Disease interactions

24 potential interactions Applies to: 18 conditions, including Asthma, COPD, Peripheral Neuropathy, Hypotension, and HIV-1 Infection.

Alcoholism

Major:

Acuflex

The acetaminophen in Acuflex has a major potential interaction with Alcoholism.

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.

Major:

isoniazid

Isoniazid has a major potential interaction with Alcoholism.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Major:

isoniazid

Isoniazid has a major potential interaction with Alcoholism.

The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.

Asthma

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Asthma.

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.

Cardiovascular Conditions and Disorders

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Cardiovascular Conditions and Disorders.

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.

COPD

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with COPD.

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.

Dehydration

Major:

Acuflex

The acetaminophen in Acuflex has a major potential interaction with Dehydration.

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.

Diabetes Mellitus

Major:

isoniazid

Isoniazid has a major potential interaction with Diabetes Mellitus.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Gastrointestinal Obstruction

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Gastrointestinal Obstruction.

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.

Glaucoma/Intraocular Hypertension

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

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.

Hemodialysis

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with Hemodialysis.

Isoniazid is substantially removed by hemodialysis and should be administered after dialysis.

HIV-1 Infection

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with HIV-1 Infection.

Caution and close monitoring is advised when using isoniazid in patients with HIV seropositive patients. Patients with pulmonary tuberculosis and HIV infection may have problems with malabsorption. Screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of multi-drug resistant tuberculosis.

Hyperthyroidism

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with 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.

Hypotension

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Hypotension.

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.

Liver Disease

Major:

Acuflex

The acetaminophen in Acuflex has a major potential interaction with Liver Disease.

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.

Major:

isoniazid

Isoniazid has a major potential interaction with Liver Disease.

The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Liver Disease.

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.

Malnourishment

Major:

Acuflex

The acetaminophen in Acuflex has a major potential interaction with Malnourishment.

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.

Major:

isoniazid

Isoniazid has a major potential interaction with Malnourishment.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Peripheral Neuropathy

Major:

isoniazid

Isoniazid has a major potential interaction with Peripheral Neuropathy.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Phenylketonuria

Moderate:

Acuflex

The acetaminophen in Acuflex has a moderate potential interaction with Phenylketonuria.

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).

Renal Dysfunction

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Renal Dysfunction.

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.

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with Renal Dysfunction.

Isoniazid may cause cerebellar syndrome in patients with chronic kidney disease. Patients with end-stage renal disease have been reported to have an increased risk of developing tuberculosis. Careful monitoring is recommended if this drug is used in patients with severe renal dysfunction. Dosage adjustments in renal impairment are generally not necessary except in slow acetylators with a creatinine clearance below 10 mL/min. Approximately 50% of Blacks and Caucasians are slow acetylators, and most Eskimos and Asians are rapid acetylators.

Urinary Retention

Moderate:

Acuflex

The phenyltoloxamine in Acuflex has a moderate potential interaction with Urinary Retention.

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.

More resources

Acuflex

A total of 760 drugs are known to interact with Acuflex.

isoniazid

A total of 742 drugs are known to interact with isoniazid.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.