Lefanor Overdose

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• Overdose of Lefanor in details
• Lefanor warnings
• Lefanor precautions
• Lefanor reviews

What happens if I overdose Lefanor?

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Lefanor:

Store Lefanor at room temperature at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in bathroom. Keep Lefanor out of the reach of children and away from pets.

Overdose of Lefanor in details

There is no human experience regarding Lefanor overdosage. In mouse and rat acute toxicology studies, the minimally toxic dose for oral Lefanor was 200-500 mg/kg and 100 mg/kg, respectively (approximately >350 times the maximum recommended human dose, respectively). There have been reports of chronic overdosage in patients taking Lefanor at daily dose up to 5 times the recommended daily dose and reports of acute overdose in adults or children. There were no adverse events reported in the majority of case reports of overdosage. Adverse events were consistent with the safety profile for Lefanor. The most frequent adverse events observed were diarrhea, abdominal pain, leukopenia, anemia and elevated liver function tests. In the event of significant overdosage or toxicity, cholestyramine or charcoal administration is recommended to accelerate elimination. Studies with both hemodialysis and CAPD indicate that M1 is not dialyzable.

What should I avoid while taking Lefanor?

Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using Lefanor, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), oral polio, typhoid, chickenpox (varicella), BCG (Bacillus Calmette and Guérin), and nasal flu vaccine.

Lefanor warnings

Embryo-Fetal Toxicity

Lefanor may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-lethality occurred in animal reproduction studies with Lefanor at doses lower than the human exposure level.

Lefanor is contraindicated for use in pregnant women. Exclude pregnancy before starting treatment with Lefanor in females of reproductive potential. Advise females of reproductive potential to use effective contraception during Lefanor treatment and during an accelerated drug elimination procedure after Lefanor treatment. If a woman becomes pregnant while taking Lefanor, stop treatment with Lefanor, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve non-detectable plasma concentrations of teriflunomide, the active metabolite of Lefanor.

Upon discontinuing Lefanor, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving Lefanor treatment who wish to become pregnant must discontinue Lefanor and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of the active metabolite of Lefanor, teriflunomide, are less than 0.02 mg/L (0.02 mcg/mL). Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryo-fetal risk.

Hepatotoxicity

Severe liver injury, including fatal liver failure, has been reported in some patients treated with Lefanor. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) of greater than twice the upper limits of normal (>2×ULN) before initiating treatment, should not be treated with Lefanor. Use caution when Lefanor is given with other potentially hepatotoxic drugs. Monitoring of ALT levels is recommended at least monthly for six months after starting Lefanor, and thereafter every 6–8 weeks. If ALT elevation > 3 fold ULN occurs, interrupt Lefanor therapy and investigate the cause. If likely Lefanor-induced, perform the accelerated drug elimination procedure and monitor liver tests weekly until normalized. If Lefanor-induced liver injury is unlikely because some other cause has been found, resumption of Lefanor therapy may be considered.

If Lefanor and methotrexate are given concomitantly, follow the American College of Rheumatology (ACR) guidelines for monitoring methotrexate liver toxicity with ALT, AST, and serum albumin testing.

Procedure for Accelerated Elimination of Lefanor and its Active Metabolite

The active metabolite of Lefanor, teriflunomide, is eliminated slowly from the plasma.

Use of an accelerated drug elimination procedure will rapidly reduce plasma concentrations of Lefanor and its active metabolite, teriflunomide. Therefore, an accelerated elimination procedure should be considered at any time after discontinuation of Lefanor, and in particular, when a patient has experienced a severe adverse reaction (e.g., hepatotoxicity, serious infection, bone marrow suppression, Stevens-Johnson Syndrome, toxic epidermal necrolysis, peripheral neuropathy, interstitial lung disease), suspected hypersensitivity, or has become pregnant. It is recommended that all women of childbearing potential undergo an accelerated elimination procedure after stopping Lefanor treatment.

Without use of an accelerated drug elimination procedure, it may take up to 2 years to reach plasma teriflunomide concentrations of less than 0.02 mg/L, the plasma concentration not associated with embryo-fetal toxicity in animals.

Elimination can be accelerated by the following procedures:

1)

Administer cholestyramine 8 grams orally 3 times daily for 11 days.

2)

Alternatively, administer 50 grams of activated charcoal powder (made into a suspension) orally every 12 hours for 11 days.

Verify plasma teriflunomide concentrations of less than 0.02 mg/L (0.02 µg/mL) by two separate tests at least 14 days apart. If plasma teriflunomide concentrations are higher than 0.02 mg/L, repeat cholestyramine and/or activated charcoal treatment.

The duration of accelerated drug elimination treatment may be modified based on the clinical status and tolerability of the elimination procedure. The procedure may be repeated as needed, based on teriflunomide concentrations and clinical status.

Use of the accelerated drug elimination procedure may potentially result in return of disease activity if the patient had been responding to Lefanor treatment.

Immunosuppression, Bone Marrow Suppression, and Risk of Serious Infections

Lefanor is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. If a serious infection occurs, consider interrupting Lefanor therapy and initiating the accelerated drug elimination procedure. Medications like Lefanor that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. Severe infections including sepsis, which may be fatal, have been reported in patients receiving Lefanor, especially Pneumocystis jiroveci pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid arthritis, may predispose patients to infection.

Cases of tuberculosis were observed in clinical studies with teriflunomide, the metabolite of Lefanor. Prior to initiating Lefanor, all patients should be screened for active and inactive ("latent") tuberculosis infection as per commonly used diagnostic tests. Lefanor has not been studied in patients with a positive tuberculosis screen, and the safety of Lefanor 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 Lefanor and monitored carefully during Lefanor treatment for possible reactivation of the infection.

Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving Lefanor alone. These events have been reported most frequently in patients who received concomitant treatment with methotrexate or other immunosuppressive agents, or who had recently discontinued these therapies; in some cases, patients had a prior history of a significant hematologic abnormality.

Patients taking Lefanor should have platelet, white blood cell count and hemoglobin or hematocrit monitored at baseline and monthly for six months following initiation of therapy and every 6 to 8 weeks thereafter. If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly. If evidence of bone marrow suppression occurs in a patient taking Lefanor, stop treatment with Lefanor, and perform an accelerated drug elimination procedure to reduce the plasma concentration of the Lefanor active metabolite, teriflunomide.

In any situation in which the decision is made to switch from Lefanor to another anti-rheumatic agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds.

Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Drug Reactions with Eosinophilia and Systemic Symptoms

Rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving Lefanor. If a patient taking Lefanor develops any of these conditions, stop Lefanor treatment and perform an accelerated drug elimination procedure.

Malignancy and Lymphoproliferative Disorders

The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppression medications. There is a potential for immunosuppression with Lefanor. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the clinical trials of Lefanor, but larger dosages and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with Lefanor.

Peripheral Neuropathy

Cases of peripheral neuropathy have been reported in patients receiving Lefanor and in clinical studies with teriflunomide, the active metabolite of Lefanor. Most patients recovered after discontinuation of treatment, but some patients had persistent symptoms. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. If a patient taking Lefanor develops a peripheral neuropathy, consider discontinuing Lefanor therapy and performing an accelerated drug elimination procedure.

Interstitial Lung Disease

Interstitial lung disease and worsening of pre-existing interstitial lung disease have been reported during treatment with Lefanor and has been associated with fatal outcomes. The risk of Lefanor-associated interstitial lung disease is increased in patients with a history of interstitial lung disease. Interstitial lung disease is a potentially fatal disorder that may occur acutely at any time during therapy and has a variable clinical presentation. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of Lefanor therapy and for further investigation as appropriate. If discontinuation of Lefanor is necessary, consider performing an accelerated drug elimination procedure.

Vaccinations

No clinical data are available on the efficacy and safety of vaccinations during Lefanor treatment. Vaccination with live vaccines is, however, not recommended. The long half-life of the active metabolite of Lefanor should be considered when contemplating administration of a live vaccine after stopping Lefanor.

Blood Pressure Monitoring

In placebo-controlled studies with the active metabolite of Lefanor, teriflunomide, elevations in blood pressure were observed in some subjects. Blood pressure should be checked before starting treatment with Lefanor and monitored periodically thereafter.

What should I discuss with my healthcare provider before taking Lefanor?

You should not use this medication if you are allergic to Lefanor, if you have liver disease, or if you are pregnant or may become pregnant.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take this medication:

• a history of liver disease or hepatitis;

• kidney disease;

• any type of infection;

• a history of tuberculosis;

• a blood cell disorder (such as anemia, easy bruising or bleeding);

• a weak immune system or bone marrow disorder; or

• if you are using any drugs that weaken your immune system (such as cancer medicine or steroids).

FDA pregnancy category X. This medication can cause birth defects. Do not use Lefanor if you are pregnant. Your doctor may want you to have a pregnancy test to make sure you are not pregnant before you start taking Lefanor.

Stop taking Lefanor if you miss a period, and tell your doctor right away if you become pregnant during treatment. If you become pregnant while taking Lefanor, you will need to receive medications to help your body eliminate the drug quickly. This will reduce the risk of harm to your unborn baby. You will also need to go through this drug elimination procedure if you plan to become pregnant after you stop taking Lefanor.

Use effective birth control while you are taking Lefanor. After your treatment ends, continue using birth control until you have received the drug elimination medications.

If a man fathers a child during or after Lefanor treatment, the baby may have birth defects. Use a condom to prevent pregnancy while you are taking Lefanor. After your treatment ends, continue using condoms until you have received the medications to help your body eliminate Lefanor.

It is not known whether Lefanor passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Lefanor precautions

Embryo-Fetal Toxicity

Lefanor may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-lethality occurred in animal reproduction studies with Lefanor at doses lower than the human exposure level.

Lefanor is contraindicated for use in pregnant women. Exclude pregnancy before starting treatment with Lefanor in females of reproductive potential. Advise females of reproductive potential to use effective contraception during Lefanor treatment and during an accelerated drug elimination procedure after Lefanor treatment. If a woman becomes pregnant while taking Lefanor, stop treatment with Lefanor, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve non-detectable plasma concentrations of teriflunomide, the active metabolite of Lefanor.

Upon discontinuing Lefanor, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving Lefanor treatment who wish to become pregnant must discontinue Lefanor and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of the active metabolite of Lefanor, teriflunomide, are less than 0.02 mg/L (0.02 mcg/mL). Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryo-fetal risk.

Hepatotoxicity

Severe liver injury, including fatal liver failure, has been reported in some patients treated with Lefanor. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) of greater than twice the upper limits of normal (>2×ULN) before initiating treatment, should not be treated with Lefanor. Use caution when Lefanor is given with other potentially hepatotoxic drugs. Monitoring of ALT levels is recommended at least monthly for six months after starting Lefanor, and thereafter every 6–8 weeks. If ALT elevation > 3 fold ULN occurs, interrupt Lefanor therapy and investigate the cause. If likely Lefanor-induced, perform the accelerated drug elimination procedure and monitor liver tests weekly until normalized. If Lefanor-induced liver injury is unlikely because some other cause has been found, resumption of Lefanor therapy may be considered.

If Lefanor and methotrexate are given concomitantly, follow the American College of Rheumatology (ACR) guidelines for monitoring methotrexate liver toxicity with ALT, AST, and serum albumin testing.

Procedure for Accelerated Elimination of Lefanor and its Active Metabolite

The active metabolite of Lefanor, teriflunomide, is eliminated slowly from the plasma.

Use of an accelerated drug elimination procedure will rapidly reduce plasma concentrations of Lefanor and its active metabolite, teriflunomide. Therefore, an accelerated elimination procedure should be considered at any time after discontinuation of Lefanor, and in particular, when a patient has experienced a severe adverse reaction (e.g., hepatotoxicity, serious infection, bone marrow suppression, Stevens-Johnson Syndrome, toxic epidermal necrolysis, peripheral neuropathy, interstitial lung disease), suspected hypersensitivity, or has become pregnant. It is recommended that all women of childbearing potential undergo an accelerated elimination procedure after stopping Lefanor treatment.

Without use of an accelerated drug elimination procedure, it may take up to 2 years to reach plasma teriflunomide concentrations of less than 0.02 mg/L, the plasma concentration not associated with embryo-fetal toxicity in animals.

Elimination can be accelerated by the following procedures:

1)

Administer cholestyramine 8 grams orally 3 times daily for 11 days.

2)

Alternatively, administer 50 grams of activated charcoal powder (made into a suspension) orally every 12 hours for 11 days.

Verify plasma teriflunomide concentrations of less than 0.02 mg/L (0.02 µg/mL) by two separate tests at least 14 days apart. If plasma teriflunomide concentrations are higher than 0.02 mg/L, repeat cholestyramine and/or activated charcoal treatment.

The duration of accelerated drug elimination treatment may be modified based on the clinical status and tolerability of the elimination procedure. The procedure may be repeated as needed, based on teriflunomide concentrations and clinical status.

Use of the accelerated drug elimination procedure may potentially result in return of disease activity if the patient had been responding to Lefanor treatment.

Immunosuppression, Bone Marrow Suppression, and Risk of Serious Infections

Lefanor is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. If a serious infection occurs, consider interrupting Lefanor therapy and initiating the accelerated drug elimination procedure. Medications like Lefanor that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. Severe infections including sepsis, which may be fatal, have been reported in patients receiving Lefanor, especially Pneumocystis jiroveci pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid arthritis, may predispose patients to infection.

Cases of tuberculosis were observed in clinical studies with teriflunomide, the metabolite of Lefanor. Prior to initiating Lefanor, all patients should be screened for active and inactive ("latent") tuberculosis infection as per commonly used diagnostic tests. Lefanor has not been studied in patients with a positive tuberculosis screen, and the safety of Lefanor 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 Lefanor and monitored carefully during Lefanor treatment for possible reactivation of the infection.

Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving Lefanor alone. These events have been reported most frequently in patients who received concomitant treatment with methotrexate or other immunosuppressive agents, or who had recently discontinued these therapies; in some cases, patients had a prior history of a significant hematologic abnormality.

Patients taking Lefanor should have platelet, white blood cell count and hemoglobin or hematocrit monitored at baseline and monthly for six months following initiation of therapy and every 6 to 8 weeks thereafter. If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly. If evidence of bone marrow suppression occurs in a patient taking Lefanor, stop treatment with Lefanor, and perform an accelerated drug elimination procedure to reduce the plasma concentration of the Lefanor active metabolite, teriflunomide.

In any situation in which the decision is made to switch from Lefanor to another anti-rheumatic agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds.

Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Drug Reactions with Eosinophilia and Systemic Symptoms

Rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving Lefanor. If a patient taking Lefanor develops any of these conditions, stop Lefanor treatment and perform an accelerated drug elimination procedure.

Malignancy and Lymphoproliferative Disorders

The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppression medications. There is a potential for immunosuppression with Lefanor. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the clinical trials of Lefanor, but larger dosages and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with Lefanor.

Peripheral Neuropathy

Cases of peripheral neuropathy have been reported in patients receiving Lefanor and in clinical studies with teriflunomide, the active metabolite of Lefanor. Most patients recovered after discontinuation of treatment, but some patients had persistent symptoms. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. If a patient taking Lefanor develops a peripheral neuropathy, consider discontinuing Lefanor therapy and performing an accelerated drug elimination procedure.

Interstitial Lung Disease

Interstitial lung disease and worsening of pre-existing interstitial lung disease have been reported during treatment with Lefanor and has been associated with fatal outcomes. The risk of Lefanor-associated interstitial lung disease is increased in patients with a history of interstitial lung disease. Interstitial lung disease is a potentially fatal disorder that may occur acutely at any time during therapy and has a variable clinical presentation. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of Lefanor therapy and for further investigation as appropriate. If discontinuation of Lefanor is necessary, consider performing an accelerated drug elimination procedure.

Vaccinations

No clinical data are available on the efficacy and safety of vaccinations during Lefanor treatment. Vaccination with live vaccines is, however, not recommended. The long half-life of the active metabolite of Lefanor should be considered when contemplating administration of a live vaccine after stopping Lefanor.

Blood Pressure Monitoring

In placebo-controlled studies with the active metabolite of Lefanor, teriflunomide, elevations in blood pressure were observed in some subjects. Blood pressure should be checked before starting treatment with Lefanor and monitored periodically thereafter.

What happens if I miss a dose of Lefanor?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

References

1. DailyMed. "LEFLUNOMIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. DrugBank. "leflunomide". http://www.drugbank.ca/drugs/DB01097 (accessed September 17, 2018).
3. MeSH. "Immunosuppressive Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).

Reviews

Consumer reviews

Information checked by Dr. Sachin Kumar, MD Pharmacology