Otrexup

Otrexup™
(oh-TREKS-up)
(methotrexate) Injection, for Subcutaneous Use

What is Otrexup?

Otrexup is a single-dose auto-injector containing a prescription medicine, methotrexate. Methotrexate is used to:

• treat certain adults with severe, active rheumatoid arthritis (RA), and children with active polyarticular juvenile idiopathic arthritis (pJIA), after treatment with other medicines including non-steroidal anti-inflammatory (NSAIDS) have been used and did not work well.
• control the symptoms of severe, resistant, disabling psoriasis in adults when other types of treatment have been used and did not work well.

Otrexup is available in doses of 7.5, 10, 12.5, 15, 17.5, 20, 22.5 and 25 mg. Your doctor will prescribe a different way to take methotrexate if you need to take methotrexate by mouth or in some other way. Your doctor may also change your prescription if your dose does not match the available Otrexup doses, such as doses of less than 7.5 mg, more than 25 mg, or doses in between the available Otrexup doses.

Otrexup should not be used for the treatment of cancer.

Otrexup should not be used for the treatment of children with psoriasis.

What is the most important information I should know about Otrexup? Otrexup can cause serious side effects that can lead to death, including:

1. Organ system toxicity. People who use methotrexate for the treatment of cancer, psoriasis, or rheumatoid arthritis, have an increased risk of death from organ toxicity. Types of organ toxicity can include:

• gastrointestinal
• nerve
• bone marrow
• lung
• liver
• kidneys
• immune system
• skin

Your doctor will do blood tests and other types of tests before you take and while you are taking Otrexup to check for signs and symptoms of organ toxicity. Call your doctor right away if you have any of the following symptoms of organ toxicity:

• vomiting
• diarrhea
• mouth sores
• fever
• confusion
• weakness
• temporary blindness
• seizures
• headache
• back pain
• neck stiffness
• paralysis
• irritability
• sleepiness
• problems with coordination
• dry cough
• trouble breathing
• severe skin rash

2. Women who are pregnant are at increased risk for death of the baby and birth defects. Women who are pregnant or who plan to become pregnant must not take Otrexup. A pregnancy test should be performed before starting Otrexup.

Contraception should be used by both females and males while taking Otrexup. Pregnancy should be avoided if either partner is receiving Otrexup:

• for a minimum of 3 months after treatment with Otrexup for males.
• during and for at least 1 menstrual cycle after treatment with Otrexup for females.

Who should not take Otrexup?

Do not take Otrexup if you:

• are pregnant or planning to become pregnant. See “What is the most important information I should know about Otrexup?”
• are breastfeeding.
• Otrexup can pass into your breast milk and may harm your baby. Do not breastfeed while taking Otrexup. Talk to your doctor about the best way to feed your baby if you take Otrexup.
• have alcohol problems (alcoholism)
• have liver problems
• have problems fighting infection (immunodeficiency syndrome)
• have been told you have (or think you have) a blood disorder such as low levels of white blood cells, red blood cells (anemia), or platelets.
• have had an allergy to methotrexate or any of the ingredients in Otrexup. See the end of this leaflet for a complete list of ingredients in Otrexup.

Talk to your doctor before taking this medicine if you have any of these conditions.

What should I tell my doctor before taking Otrexup?

Before you take Otrexup, tell your doctor if you have any other medical conditions.

Tell your doctor about all of the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements.

Otrexup may affect how other medicines work, and other medicines may affect how Otrexup works causing side effects.

Ask your doctor or pharmacist for a list of medicines if you are not sure.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take Otrexup?

• Read the Instructions for Use that come with Otrexup.
• Take Otrexup exactly as your doctor tells you to take it.
• Inject Otrexup only 1 time each week. Do not take Otrexup every day. Taking Otrexup every day may cause death from toxicity.
• Your doctor will show you or your caregiver how to inject Otrexup. You should not inject Otrexup until you have been trained on the right way to use it.
• Check Otrexup before you inject it. Otrexup should be yellow in color and should not have any lumps or particles in it.
• Otrexup should be injected in the stomach (abdomen) or thigh.
• Do not inject Otrexup within 2 inches of the belly button (navel).
• Do not inject Otrexup in the arms or any other areas of the body.
• Do not inject Otrexup in areas where the skin is tender, bruised, red, scaly, hard, or has scars or stretch marks.
• If you are not sure if Otrexup was injected, or if you have hard time giving the injection, do not inject another dose. Call your pharmacist or doctor right away.
• If you inject too much Otrexup, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking Otrexup?

• Do not drink alcohol while taking Otrexup. Drinking alcohol can increase your chances of getting serious side effects.
• Otrexup can cause dizziness and tiredness. Do not drive a car, operate machinery, or do anything that needs you to be alert until you know how Otrexup affects you.
• Certain vaccinations should be avoided while taking Otrexup. Talk to your doctor before you or members of your household receive any vaccines.

What are the possible side effects of Otrexup?

Otrexup may cause serious side effects, including:

See “What is the most important information I should know about Otrexup?”

• fertility problems. Methotrexate, the active ingredient in Otrexup, may affect your ability to have a baby. Males may have a decreased sperm count, and females may have changes to their menstrual cycle. This can happen while taking Otrexup and for a short period of time after you stop.
• certain cancers. Some people who have taken methotrexate have had a certain type of cancer called Non-Hodgkin's lymphoma and other tumors. Your doctor may tell you to stop taking Otrexup if this happens.
• tissue and bone problems. Taking Methotrexate while having radiation therapy may increase the risk of your tissue or bone not receiving enough blood. This may lead to death of the tissue or bone.

Common side effects of Otrexup include:

• nausea
• headache
• stomach pain
• bronchitis
• indigestion (dyspepsia)
• low red, white, and platelet blood cell count
• mouth sores
• rash
• hair loss
• stuffy or runny nose and sore
• dizziness
• sensitivity to light throat
• burning skin lesions
• diarrhea
• lung problems
• abnormal liver function tests
• vomiting

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Otrexup. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I dispose of Otrexup?

• Do not throw away in the household trash. Put used Otrexup in a FDA-cleared sharps disposal container right away after use.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out
  • upright stable during use
  • leak-resistant
  • properly labeled to warn of hazardous waste inside the container
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about the safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
• Safely dispose of Otrexup that is out of date or is no longer needed.

How should I store Otrexup?

Store Otrexup at room temperature between 68°F to 77°F (20°C to 25°C)

• Do not freeze
• Keep Otrexup out of the light.

Keep Otrexup and all medicines out of the reach of children.

General information about the safe and effective use of Otrexup.

Methotrexate is sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use Otrexup for a condition for which it was not prescribed. Do not give Otrexup to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Otrexup. If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about Otrexup that is written for health professionals.

For more information, go to www.Otrexup.com or call 1-855-Otrexup (1-855687-3987).

What are the ingredients in Otrexup?

Active ingredient: methotrexate

Inactive ingredients: hydrochloric acid, sodium chloride, sodium hydroxide and water for injection, USP.

This Patient Information has been approved by the U.S. Food and Drug Administration.

• Celebrex
• Humira
• Imuran

• Kineret
• Orencia
• Sandimmune

© Otrexup Patient Information is supplied by Cerner Multum, Inc. and Otrexup Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Otrexup is a prescription medication used to treat psoriasis, rheumatoid arthritis, and polyarticular juvenile idiopathic arthritis. Otrexup belongs to a group of drugs called dihydrofolic acid reductase inhibitors. These work to treat psoriasis, rheumatoid arthritis, and polyarticular juvenile idiopathic arthritis through a mechanism that is currently not yet fully understood, but is believed to affect immune function.

This medication is available in an injectable form to be given directly under the skin, typically once per week.

Common side effects of Otrexup include nausea, stomach upset, and diarrhea.

Otrexup can also cause dizziness, drowsiness, and/or blurred vision. Do not drive or operate heavy machinery until you know how Otrexup affects you.

Serious side effects have been reported with Otrexup including the following:

• Toxic effects on multiple organ systems. Otrexup has been reported to have toxic effects on the gastrointestinal and immune systems in addition to the blood, blood-forming organs, liver, lungs, kidneys, and skin. Your doctor will order blood tests and other types of tests before you take and while you are using  Otrexup. Call your doctor immediately if you experience any of the following symptoms:
  • vomiting/diarrhea
  • mouth sores
  • fever
  • confusion
  • weakness
  • temporary blindness
  • seizures
  • headache
  • back pain/ neck stiffness
  • paralysis
  • problems with coordination
  • severe skin reaction
  • infection
• Risk of toxicity due to improper dosing. It is very important that you only administer Otrexup once per week. If Otrexup is used more often than once per week, potentially fatal toxicity can develop.
• Harm to your unborn baby. Women who are pregnant are at an increased risk for death of the baby and birth defects. Women who are pregnant or who plan to become pregnant should not take Otrexup. Your doctor will perform a pregnancy test before initiating Otrexup. Women and Men who are of reproductive age should use effective contraception while taking Otrexup. Avoid pregnancy:
  • for a minimum of 3 months after Otrexup treatment for males
  • during and for at least 1 menstrual cycle after treatment with Otrexup for females
• Fertility problems. Otrexup can affect your ability to have a baby. Males may have a decreased sperm count, and females may have changes in their menstrual cycle. This can even occur for a short period after you stop taking Otrexup. 
• Certain cancers. Some people who have taken Otrexup have had a certain type of cancer called Non-Hodgkin's lymphoma and other tumors. If this occurs, you doctor may tell you to stop taking Otrexup. 
• Tissue and bone problems. Taking Otrexup while having radiation therapy may increase the risk of your tissue or bone not receiving enough blood. This may lead to death of the tissue or bone. 

Otrexup can also cause dizziness, drowsiness, and/or blurred vision. Do not drive or operate heavy machinery until you know how Otrexup affects you.

Do not take Otrexup if you:

• are allergic to Otrexup or to any of its ingredients 
• have bone marrow hypoplasia, leukopenia, thrombocytopenia, or anemia
• have any immunodeficiency syndromes
• have liver disease
• are pregnant, plan to become pregnant, or suspect you might be pregnant
• are breastfeeding or plan to breastfeed

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your age
• your height

The recommended dose range of Otrexup for the treatment of psoriasis is 10 mg - 25 mg injected under the skin (subcutaneously), typically once per week.

The recommended dose range of Otrexup for the treatment of rheumatoid arthritis is 7.5 mg - 20 mg injected under the skin (subcutaneously), typically once per week.

The recommended dose range of Otrexup for the treatment of polyarticular juvenile idiopathic arthritis is 10 mg - 20 mg per square meter of body surface area injected under the skin (subcutaneously), typically once per week.

• Store Otrexup at room temperature between 68°F to 77°F (20°C to 25°C)
• Keep Otrexup out of the light
• Do not freeze
• Always keep your Otrexup out of the reach of children

Methotrexate injection is used alone or together with other medicines to treat several types of cancer, such as breast, head and neck, lung, blood, bone, lymph node, and uterus cancers.

Methotrexate is also used to treat adults with severe rheumatoid arthritis and children with polyarticular juvenile idiopathic arthritis who had other treatments that did not work well. It is also used to control symptoms of severe psoriasis in adults who have not been helped by other treatments.

Methotrexate belongs to the group of medicines known as antineoplastics (cancer medicines). It blocks an enzyme that is needed by cells to live. This interferes with the growth of cancer cells, which are eventually destroyed by the body. For patients with arthritis or psoriasis, methotrexate may work by improving the immune system.

This medicine is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Black, tarry stools
• blood in the urine or stools
• bloody vomit
• diarrhea
• joint pain
• reddening of the skin
• sores in the mouth or lips
• stomach pain
• swelling of the feet or lower legs

• Back pain
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, or warmth at the injection site
• blurred vision
• confusion
• convulsions (seizures)
• cough or hoarseness
• dark urine
• dizziness
• drowsiness
• fever or chills
• headache
• lower back or side pain
• painful or difficult urination
• pinpoint red spots on the skin
• shortness of breath
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Hair loss, temporary
• loss of appetite
• nausea or vomiting

• Acne
• boils on skin
• pale skin
• skin rash or itching

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Otrexup. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Talk with your doctor before getting any vaccines. Use with Otrexup may either raise the chance of an infection or make the vaccine not work as well.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Avoid drinking alcohol while taking this medicine.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun. Keep protecting yourself from sunburn for as long as you were told by your doctor.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, loose stools (diarrhea), not hungry, or more thirst.
• Patients with cancer who take Otrexup (methotrexate injection (subcutaneous)) may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. Talk with the doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 3 months after care ends. Use birth control that you can trust.
• A pregnancy test will be done to show that you are NOT pregnant before starting Otrexup. If you get pregnant while taking this medicine, call your doctor right away.
• Use birth control that you can trust to prevent pregnancy during care and for some time after care ends. Talk with your doctor to see how long to use birth control after you stop Otrexup.
• If you are a woman and you miss a period, have unprotected sex, or think that your birth control has not worked, call your doctor right away.

Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate. Leucovorin administration should begin as promptly as possible. As the time interval between methotrexate administration and leucovorin initiation increases, the effectiveness of leucovorin in counteracting toxicity decreases. Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin.

In cases of massive overdosage, hydration and urinary alkalinization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules. Generally speaking, neither hemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. However, effective clearance of methotrexate has been reported with acute, intermittent hemodialysis using a high-flux dialyzer (Wall, SM et al: Am J Kidney Dis 28 (6): 846-854, 1996).

Accidental intrathecal overdosage may require intensive systemic support, high-dose systemic leucovorin, alkaline diuresis and rapid CSF drainage and ventriculolumbar perfusion.

In postmarketing experience, overdose with methotrexate has generally occurred with oral and intrathecal administration, although intravenous and intramuscular overdose have also been reported.

Reports of oral overdose often indicate accidental daily administration instead of weekly (single or divided doses). Symptoms commonly reported following oral overdose include those symptoms and signs reported at pharmacologic doses, particularly hematologic and gastrointestinal reaction. For example, leukopenia, thrombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, gastrointestinal bleeding. In some cases, no symptoms were reported.

There have been reports of death following overdose. In these cases, events such as sepsis or septic shock, renal failure, and aplastic anemia were also reported.

Symptoms of intrathecal overdose are generally central nervous system (CNS) symptoms, including headache, nausea and vomiting, seizure or convulsion, and acute toxic encephalopathy. In some cases, no symptoms were reported. There have been reports of death following intrathecal overdose. In these cases, cerebellar herniation associated with increased intracranial pressure, and acute toxic encephalopathy have also been reported.

There are published case reports of intravenous and intrathecal carboxypeptidase G2 treatment to hasten clearance of methotrexate in cases of overdose.