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Interactions between Endolor and Teriflunomide

3 drug interactions and 54 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

acetaminophen teriflunomide

Applies to: Endolor (acetaminophen / butalbital / caffeine) and teriflunomide
Monitor closely

The recent, concomitant, or subsequent use (without the recommended leflunomide or teriflunomide washout period/elimination procedure when indicated) of other agents known to induce hepatotoxicity may potentiate the risk of liver injury associated with leflunomide or teriflunomide. Severe hepatotoxicity, including fatal liver failure, has been reported with both agents. Because teriflunomide is the principal active metabolite of leflunomide and recommended dosages of both result in similar systemic exposure to teriflunomide, a similar risk of liver injury is expected. The risk may be increased by concomitant use of other hepatotoxic drugs and in patients with underlying liver disease.

Management

Caution is advised if leflunomide or teriflunomide must be used in patients who are currently receiving or have recently received treatment with other hepatotoxic agents (e.g., paracetamol; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, nicotinic acid, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice), and vice versa. Liver enzymes and bilirubin should be measured prior to initiation of leflunomide or teriflunomide therapy and monitored thereafter according to product labeling. Patients with preexisting liver disease, active hepatic impairment, or elevated baseline liver enzymes should generally not receive these agents. Patients who develop clinically significant liver injury while receiving leflunomide or teriflunomide should discontinue treatment and undergo accelerated washout/elimination procedures according to product labeling. Cholestyramine or activated charcoal may be used to accelerate elimination of teriflunomide (the active metabolite of leflunomide), which otherwise may remain detectable in plasma for an extended period because of its prolonged half-life. Follow-up monitoring should be conducted until liver function abnormalities resolve, and washout/elimination procedures repeated as clinically indicated. All patients treated with leflunomide or teriflunomide should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.

References (7)
  1. EMEA (2001) EMEA public statement on leflunomide (ARAVA) - severe and serious hepatic reactions. Available from URL: http://www.eudra.org/emea.html
  2. (2025) "Product Information. Arava (leflunomide)." sanofi-aventis
  3. (2026) "Product Information. Arava (leflunomide)." Sanofi-Aventis Australia Pty Ltd
  4. (2025) "Product Information. Leflunomide (leflunomide)." Sandoz Ltd
  5. (2026) "Product Information. Aubagio (teriflunomide)." Genzyme Corporation
  6. (2026) "Product Information. Teriflunomide (Pharmacor) (teriflunomide)." Pharmacor Pty Ltd
  7. (2026) "Product Information. Teriflunomide (teriflunomide)." Amarox Ltd

Moderate drug interactions

Moderate:

acetaminophen butalbital

Applies to: Endolor (acetaminophen / butalbital / caffeine) and Endolor (acetaminophen / butalbital / caffeine)
Monitor

Barbiturates may increase the hepatotoxic potential of acetaminophen and decrease its therapeutic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase in hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

Management

Monitoring for altered efficacy and safety is recommended. Prolonged use or high doses of acetaminophen should be avoided by patients on barbiturate therapy.

References (4)
  1. Pirotte JH (1984) "Apparent potentiation by phenobarbital of hepatotoxicity from small doses of acetaminophen." Ann Intern Med, 101, p. 403
  2. Douidar SM, Ahmed AE (1987) "A novel mechanism for the enhancement of acetaminophen hepatotoxicity by phenobarbital." J Pharmacol Exp Ther, 240, p. 578-83
  3. Wright N, Prescott LF (1973) "Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdose." Scott Med J, 18, p. 56-8
  4. Bock KW, Wiltfang J, Blume R, Ullrich D, Bircher J (1987) "Paracetamol as a test drug to determine glucuronide formation in man: effects of inducers and of smoking." Eur J Clin Pharmacol, 31, p. 677-83
Moderate:

caffeine teriflunomide

Applies to: Endolor (acetaminophen / butalbital / caffeine) and teriflunomide
Monitor

Coadministration with teriflunomide may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 1A2. The proposed mechanism is increased clearance due to teriflunomide-mediated induction of CYP450 1A2. Multiple doses of teriflunomide decreased mean Cmax and AUC of caffeine, a known CYP450 1A2 substrate, by 18% and 55%, respectively.

Management

Caution is advised if teriflunomide is used concomitantly with drugs that are substrates of CYP450 1A2. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever teriflunomide is added to or withdrawn from therapy with these drugs.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2012) "Product Information. Aubagio (teriflunomide)." Genzyme Corporation

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

acetaminophen Food/Lifestyle

Applies to: Endolor (acetaminophen / butalbital / caffeine)
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
Major:

butalbital Alcohol (Ethanol)

Applies to: Endolor (acetaminophen / butalbital / caffeine)
Generally avoid

Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

Management

The combination of ethanol and barbiturates should be avoided.

References (5)
  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102

Minor food/lifestyle interactions

Minor:

caffeine Food/Lifestyle

Applies to: Endolor (acetaminophen / butalbital / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References (2)
  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

Disease interactions

51 potential interactions Applies to: 40 conditions, including High Blood Pressure, Depression, GERD, Vitamin D Deficiency, and Heart Attack.

Acute Alcohol Intoxication

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Acute Alcohol Intoxication.

The use of barbiturates is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of barbiturates may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with barbiturates should be administered cautiously in patients who might be prone to acute alcohol intake.

Adrenal Insufficiency

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Adrenal Insufficiency.

Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.

Alcoholism

Major:

Endolor

The acetaminophen in Endolor 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:

Endolor

The butalbital in Endolor has a major potential interaction with Alcoholism.

Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of barbiturates should be undertaken gradually using a dosage-tapering schedule.

Angina

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Angina.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Asphyxia

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Asphyxia.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

Bone Marrow Depression/Low Blood Counts

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Hematologic toxicity, including agranulocytosis, thrombocytopenic purpura and megaloblastic anemia, has been reported rarely during use of barbiturates. Therapy with barbiturates should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Blood counts are recommended prior to and periodically during long-term therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, easy bruising, petechiae, bleeding, pallor, dizziness, or jaundice. Barbiturate therapy should be discontinued if blood dyscrasias occur.

Dehydration

Major:

Endolor

The acetaminophen in Endolor 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.

Depression

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Depression.

The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Depression.

Barbiturates depress the central nervous system and may cause or exacerbate mental depression. Therapy with barbiturates should be administered cautiously in patients with a history of depression or suicidal tendencies. It may be prudent to refrain from dispensing large quantities of medication to these patients.

Dermatitis, Drug-Induced

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Dermatitis, Drug-Induced.

Skin eruptions may precede rare but potentially fatal barbiturate-induced reactions such as systemic lupus erythematosus and exfoliative dermatitis, the latter of which may be accompanied by hepatitis and jaundice. Therapy with barbiturates should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to barbiturates. Barbiturate therapy should be withdrawn promptly at the first sign of a dermatologic adverse effect. However, cutaneous reactions may proceed to an irreversible stage even after cessation of medication due to the slow rate of metabolism and excretion of barbiturates. Patients should be advised to promptly report signs that may indicate impending development of barbiturate-related cutaneous lesions, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Rashes may be more likely to occur with phenobarbital and mephobarbital.

Diabetes Mellitus

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Diabetes Mellitus.

Peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), has been reported with the use of teriflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. Care should be taken when prescribing this agent to patients at risk and if a patient develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing teriflunomide therapy and performing an accelerated elimination procedure.

Drug Dependence

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Drug Dependence.

Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of barbiturates should be undertaken gradually using a dosage-tapering schedule.

GERD

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with GERD.

Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

Heart Attack

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Heart Attack.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Heart Disease

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Heart Disease.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

High Blood Pressure

Major:

Endolor

The caffeine in Endolor has a major potential interaction with High Blood Pressure.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

Major:

Endolor

The caffeine in Endolor has a major potential interaction with High Blood Pressure.

CNS stimulants increase blood pressure and heart rate; the use of some agents may be contraindicated in patients with severe/uncontrolled hypertension. Caution should be used when administering to patients with preexisting high blood pressure (even mild hypertension) and other cardiovascular conditions. All patients under treatment should be regularly monitored for potential tachycardia and hypertension.

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with High Blood Pressure.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with High Blood Pressure.

Teriflunomide may increase the blood pressure. Caution should be taken when using this agent in hypertensive patients. It is recommended to check blood pressure before the start of teriflunomide treatment and periodically thereafter and elevated blood pressure should be appropriately managed during treatment with teriflunomide.

Hyperkinetic Syndrome of Childhood

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.

Paradoxical reactions characterized by excitability and restlessness may occur in pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with barbiturates.

Hyperthyroidism

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Hyperthyroidism.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Hyperthyroidism.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Immunodeficiency

Major:

teriflunomide

Teriflunomide has a major potential interaction with Immunodeficiency.

Immunosuppressive agents may increase the risk of progressive multifocal leukoencephalopathy (PML). Certain agents are contraindicated in patients who have or have had PML. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with these agents. Health care professionals should monitor patients for any new sign or symptom suggestive of PML. Therapy dosing should be withheld immediately and an appropriate diagnostic evaluation should be performed at the first sign or symptom suggestive of PML.

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Immunodeficiency.

Cases of decrease in white blood cell count and in platelet count have been observed with the use teriflunomide. Care should be taken when using this agent in immunosuppressed patients. It is recommended to obtain a complete blood cell count within 6 months before the initiation of treatment and further monitoring should be based on signs and symptoms suggestive of bone marrow suppression.

Infection

Major:

teriflunomide

Teriflunomide has a major potential interaction with Infection.

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents. Patients receiving immunosuppressants are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections including opportunistic infections. Caution should be exercised when considering their use in patients with severe or chronic infections. It is recommended to interrupt therapy in patients who develop a new infection while undergoing treatment and to monitor these patients closely for any sign or symptom indicative of infection.

Interstitial Lung Disease

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Interstitial Lung Disease.

Interstitial lung disease and worsening of preexisting interstitial lung disease, including acute interstitial pneumonitis, have been reported during treatment with teriflunomide. Caution should be exercised when prescribing this agent to patients with pulmonary complication. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and if discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

Liver Disease

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Liver Disease.

Barbiturates are extensively metabolized by the liver. The plasma clearance of barbiturates may be decreased and the half-lives prolonged in patients with impaired hepatic function. Therapy with barbiturates should be administered cautiously and initiated at reduced dosages in patients with liver disease. Barbiturates are not recommended for use in patients with cirrhosis, hepatic failure, hepatic coma, or other severe hepatic impairment.

Major:

Endolor

The acetaminophen in Endolor 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:

teriflunomide

Teriflunomide has a major potential interaction with Liver Disease.

Teriflunomide is contraindicated in patients with severe hepatic impairment. No dosage adjustment is necessary for patients with mild and moderate hepatic impairment. Severe liver injury including fatal liver failure have been reported in patients treated with leflunomide. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of teriflunomide with other potentially hepatotoxic drugs may increase the risk of severe liver injury. If drug-induced liver injury is suspected, discontinue therapy with teriflunomide and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with preexisting liver disease may be at increased risk of developing elevated serum transaminases while on therapy with teriflunomide. It is recommended to obtain transaminase and bilirubin levels within 6 months before initiation of therapy. Monitor ALT levels at least monthly for six months after starting therapy.

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Liver Disease.

In general, CNS stimulants are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with CNS stimulants should be administered cautiously in patients with moderate to severe liver disease, and the dosage should be adjusted accordingly in certain agents. Additionally, postmarketing reports have shown that atomoxetine can cause severe liver injury; laboratory testing should be done at the first sign/symptom of liver dysfunction (jaundice, dark urine, upper quadrant tenderness) and treatment should be discontinued in patients with evidence of liver injury.

Malnourishment

Major:

Endolor

The acetaminophen in Endolor 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.

Panhypopituitarism

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Panhypopituitarism.

Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.

Peptic Ulcer

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Peptic Ulcer.

Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

Peripheral Arterial Disease

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Peripheral Arterial Disease.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

Peripheral Neuropathy

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Peripheral Neuropathy.

Peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), has been reported with the use of teriflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. Care should be taken when prescribing this agent to patients at risk and if a patient develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing teriflunomide therapy and performing an accelerated elimination procedure.

Phenylketonuria

Moderate:

Endolor

The acetaminophen in Endolor 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).

Pheochromocytoma

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Pheochromocytoma.

Many CNS stimulants are contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

Porphyria

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Porphyria.

The use of barbiturates is contraindicated in patients with a history of porphyria. Barbiturates may exacerbate acute intermittent porphyria or porphyria variegata by inducing the enzymes responsible for porphyrin synthesis.

Post MI Syndrome

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Post MI Syndrome.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Psychosis

Major:

Endolor

The caffeine in Endolor has a major potential interaction with Psychosis.

The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.

Pulmonary Impairment

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Pulmonary Impairment.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Pulmonary Impairment.

Interstitial lung disease and worsening of preexisting interstitial lung disease, including acute interstitial pneumonitis, have been reported during treatment with teriflunomide. Caution should be exercised when prescribing this agent to patients with pulmonary complication. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and if discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

Renal Dysfunction

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Renal Dysfunction.

Overall CNS stimulants should be administered with caution in patients with significantly impaired renal function as the reduction in the rate of elimination may alter the therapeutic response. The dosage should be adjusted accordingly in certain agents.

Respiratory Arrest

Major:

Endolor

The butalbital in Endolor has a major potential interaction with Respiratory Arrest.

Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with barbiturates should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.

Seizures

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Seizures.

Due to general central nervous system stimulation, therapy with CNS stimulant drugs may cause seizures. These drugs may lower the convulsive threshold in patients with history of seizures, with prior electroencephalogram (EEG) abnormalities without seizures, and very rarely, without history of seizures and no prior EEG evidence of seizures. Therapy with CNS stimulants should be used with caution in patients with or predisposed to seizures. If seizures occur, therapy should be discontinued.

Tachyarrhythmia

Moderate:

Endolor

The caffeine in Endolor has a moderate potential interaction with Tachyarrhythmia.

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

Tuberculosis, Active

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Tuberculosis, Active.

Cases of tuberculosis have been observed with the use of teriflunomide. It is recommended to screen patients for latent tuberculosis infection before initiating therapy with teriflunomide. The safety of teriflunomide in patients with a positive tuberculosis screen, and in individuals with latent tuberculosis infection is unknown. Care should be exercised and in those patients testing positive, standard medical practice treatment should be given prior to teriflunomide therapy initiation.

Tuberculosis, Latent

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Tuberculosis, Latent.

Cases of tuberculosis have been observed with the use of teriflunomide. It is recommended to screen patients for latent tuberculosis infection before initiating therapy with teriflunomide. The safety of teriflunomide in patients with a positive tuberculosis screen, and in individuals with latent tuberculosis infection is unknown. Care should be exercised and in those patients testing positive, standard medical practice treatment should be given prior to teriflunomide therapy initiation.

Vaccination

Moderate:

teriflunomide

Teriflunomide has a moderate potential interaction with Vaccination.

Vaccination with live vaccines is not recommended in patients treated with teriflunomide. No clinical data are available on the efficacy and safety of live vaccinations in patients taking teriflunomide. The long half-life of teriflunomide should be considered when contemplating administration of a live vaccine after stopping treatment.

Vitamin D Deficiency

Moderate:

Endolor

The butalbital in Endolor has a moderate potential interaction with Vitamin D Deficiency.

Rickets and osteomalacia have rarely been reported following prolonged use of barbiturates, possibly due to increased metabolism of vitamin D as a result of enzyme induction by barbiturates. Long-term therapy with barbiturates should be administered cautiously in patients with vitamin D deficiency.

More resources

Endolor

A total of 1014 drugs are known to interact with Endolor.

teriflunomide

A total of 783 drugs are known to interact with teriflunomide.

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.