Interactions between Arava and Cymbalta
1 drug interaction and 27 additional warnings found for the following 2 drugs:
- Arava (leflunomide)
- Cymbalta (duloxetine)
Drug interactions
Major drug interactions
Major:
leflunomide DULoxetine
Applies to: Arava (leflunomide) and Cymbalta (duloxetine)
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)
- EMEA (2001) EMEA public statement on leflunomide (ARAVA) - severe and serious hepatic reactions. Available from URL: http://www.eudra.org/emea.html
- (2025) "Product Information. Arava (leflunomide)." sanofi-aventis
- (2026) "Product Information. Arava (leflunomide)." Sanofi-Aventis Australia Pty Ltd
- (2025) "Product Information. Leflunomide (leflunomide)." Sandoz Ltd
- (2026) "Product Information. Aubagio (teriflunomide)." Genzyme Corporation
- (2026) "Product Information. Teriflunomide (Pharmacor) (teriflunomide)." Pharmacor Pty Ltd
- (2026) "Product Information. Teriflunomide (teriflunomide)." Amarox Ltd
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
leflunomide Food/Lifestyle
Applies to: Arava (leflunomide)
Generally avoid
The consumption of alcohol during therapy with leflunomide may potentiate the risk of liver injury. Leflunomide has been associated with hepatotoxicity, including elevated liver transaminases, hepatitis, jaundice/cholestasis, hepatic failure, and acute hepatic necrosis,
Management
Patients should be advised to avoid excessive alcohol use during leflunomide treatment.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
Moderate:
DULoxetine Food/Lifestyle
Applies to: Cymbalta (duloxetine)
Generally avoid
Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.
Management
Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.
References (1)
- (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
Disease interactions
25 potential interactions Applies to: 20 conditions, including High Blood Pressure, Depression, Bipolar Disorder, Urinary Tract Infection, and Seizures.
Bipolar Disorder
Major:
Cymbalta
The DULoxetine in Cymbalta has a major potential interaction with Bipolar Disorder.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Bipolar Disorder.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Bone Marrow Depression/Low Blood Counts
Major:
Arava
The leflunomide in Arava has a major potential interaction with Bone Marrow Depression/Low Blood Counts.
Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide. Leflunomide is an immunomodulatory agent with antiproliferative activity. The use of leflunomide is not recommended in patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections because of the theoretical potential for immunosuppression. Care should be taken when using this agent in patients with a prior history of a significant hematologic abnormality. It is recommended to monitor blood levels at baseline and regularly during the course of therapy. If evidence of bone marrow suppression occurs, stop treatment and institute appropriate measures according to clinical guidelines.
Dehydration
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Dehydration.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Depression
Major:
Cymbalta
The DULoxetine in Cymbalta has a major potential interaction with Depression.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Diabetes Mellitus
Major:
Arava
The leflunomide in Arava has a major potential interaction with Diabetes Mellitus.
Peripheral neuropathy has been reported during leflunomide therapy. Patients older than 60 years, patients taking concomitant neurotoxic medications, and diabetics may be at an increased risk for peripheral neuropathy. Therapy with leflunomide should be administered cautiously in these patients. Patients should be monitored for symptoms of neuropathy and if confirmed, consider discontinuing therapy and taking measures according to clinical practice.
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Diabetes Mellitus.
In clinical trials, treatment with duloxetine delayed-release worsened the glycemic control in some patients with diabetes. Caution should be used when using duloxetine in diabetic patients and their glycemic levels should be checked regularly.
Glaucoma, Narrow Angle
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Glaucoma, Narrow Angle.
SNRI antidepressants cause pupillary dilation that may trigger an angle closure attack in patients with anatomically narrow angle without iridectomy.
High Blood Pressure
Moderate:
Arava
The leflunomide in Arava has a moderate potential interaction with High Blood Pressure.
Hypertension was reported as an adverse reaction in patients on leflunomide. Blood pressure should be monitored during treatment and periodically thereafter as this agent can increase the blood pressure in these patients.
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with High Blood Pressure.
Selective serotonin and norepinephrine reuptake inhibitor antidepressants (SNRIs) have been associated with sustained increases in blood pressure. Therapy with SNRI antidepressants should be administered cautiously in patients with preexisting hypertension. Blood pressure should be assessed prior to initiating treatment and monitored regularly. The dose should be reduced or discontinued if necessary.
Hyponatremia
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Hyponatremia.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Immunodeficiency
Major:
Arava
The leflunomide in Arava has a major potential interaction with Immunodeficiency.
Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide. Leflunomide is an immunomodulatory agent with antiproliferative activity. The use of leflunomide is not recommended in patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections because of the theoretical potential for immunosuppression. Care should be taken when using this agent in patients with a prior history of a significant hematologic abnormality. It is recommended to monitor blood levels at baseline and regularly during the course of therapy. If evidence of bone marrow suppression occurs, stop treatment and institute appropriate measures according to clinical guidelines.
Infection
Major:
Arava
The leflunomide in Arava has a major potential interaction with Infection.
Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide. Leflunomide is an immunomodulatory agent with antiproliferative activity. The use of leflunomide is not recommended in patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections because of the theoretical potential for immunosuppression. Care should be taken when using this agent in patients with a prior history of a significant hematologic abnormality. It is recommended to monitor blood levels at baseline and regularly during the course of therapy. If evidence of bone marrow suppression occurs, stop treatment and institute appropriate measures according to clinical guidelines.
Liver Disease
Major:
Arava
The leflunomide in Arava has a major potential interaction with Liver Disease.
Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide. Leflunomide is contraindicated in patients with severe hepatic impairment. Leflunomide has been commonly associated with elevations in liver enzymes, primarily ALT and AST. Marked elevations occurred infrequently and reversed with dose reduction or discontinuation of treatment. Leflunomide also must be metabolized by the liver into the active compound which is responsible for the in vivo activity. Therapy with leflunomide is not recommended in patients with preexisting liver disease. Dosage adjustment or discontinuation is recommended for patients experiencing liver enzyme elevations while on leflunomide.
Major:
Cymbalta
The DULoxetine in Cymbalta has a major potential interaction with Liver Disease.
Postmarketing studies have reported that duloxetine and some other SNRIs like milnacipran may aggravate preexisting liver disease. The use of duloxetine delayed-release and milnacipran should be avoided in patients with chronic liver disease or cirrhosis.
Mania
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Mania.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Peripheral Neuropathy
Major:
Arava
The leflunomide in Arava has a major potential interaction with Peripheral Neuropathy.
Peripheral neuropathy has been reported during leflunomide therapy. Patients older than 60 years, patients taking concomitant neurotoxic medications, and diabetics may be at an increased risk for peripheral neuropathy. Therapy with leflunomide should be administered cautiously in these patients. Patients should be monitored for symptoms of neuropathy and if confirmed, consider discontinuing therapy and taking measures according to clinical practice.
Pulmonary Impairment
Major:
Arava
The leflunomide in Arava has a major potential interaction with Pulmonary Impairment.
The use of leflunomide has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), and worsening of preexisting interstitial lung disease have been reported. Caution is recommended when using this agent in patients with a history of ILD or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as cough and dyspnea, with or without associated fever. If ILD is confirmed, consider discontinuing therapy and institute appropriate measures according to clinical guidelines.
Renal Dysfunction
Major:
Arava
The leflunomide in Arava has a major potential interaction with Renal Dysfunction.
The active metabolite of leflunomide is elevated in the plasma of patients with renal impairment. Therapy with leflunomide should be administered cautiously in patients with renal insufficiency.
Major:
Cymbalta
The DULoxetine in Cymbalta has a major potential interaction with Renal Dysfunction.
The use of duloxetine should be avoided in patients with severe renal impairment (GFR <30 mL/min).
Seizures
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Seizures.
SNRI antidepressants may trigger seizures and should be administered with caution in patients with a seizure disorder.
Tuberculosis, Active
Major:
Arava
The leflunomide in Arava has a major potential interaction with Tuberculosis, Active.
Patients should be evaluated for active and latent tuberculosis (TB) infection prior to leflunomide treatment. Leflunomide has not been studied in patients with a positive tuberculosis screen, and the safety of leflunomide in individuals with latent tuberculosis infection is unknown. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with leflunomide and monitored carefully during leflunomide treatment for possible reactivation of the infection.
Tuberculosis, Latent
Major:
Arava
The leflunomide in Arava has a major potential interaction with Tuberculosis, Latent.
Patients should be evaluated for active and latent tuberculosis (TB) infection prior to leflunomide treatment. Leflunomide has not been studied in patients with a positive tuberculosis screen, and the safety of leflunomide in individuals with latent tuberculosis infection is unknown. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with leflunomide and monitored carefully during leflunomide treatment for possible reactivation of the infection.
Urinary Tract Infection
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Urinary Tract Infection.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
Urinary Tract Obstruction
Moderate:
Cymbalta
The DULoxetine in Cymbalta has a moderate potential interaction with Urinary Tract Obstruction.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
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More resources
Arava
A total of 721 drugs are known to interact with Arava.
- Arava is in the following drug classes: antirheumatics, selective immunosuppressants.
- Arava is used to treat Rheumatoid Arthritis.
Cymbalta
A total of 654 drugs are known to interact with Cymbalta.
- Cymbalta is in the drug class serotonin-norepinephrine reuptake inhibitors.
- Cymbalta is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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