RASUVO- methotrexate sodium injection, solution
Medac Pharma, Inc
WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY AND DEATH
Rasuvo should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Because of the possibility of serious toxic reactions (which can be fatal), Rasuvo should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy. Deaths have been reported with the use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis. Patients should be closely monitored for bone marrow, liver, lung, skin, and kidney toxicities. Patients should be informed by their physician of the risks involved and be under a physician's care throughout therapy [see Warnings and Precautions (5.1)].
1. Methotrexate has been reported to cause fetal death and/or congenital anomalies.
Therefore, Rasuvo is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks [see Warnings and Precautions (5.2)]. Rasuvo is contraindicated in pregnant women [see Contraindications (4)].
2. Methotrexate elimination is reduced in patients with impaired renal functions, ascites, or pleural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of Rasuvo administration [see Warnings and Precautions (5.6)].
3. Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs) [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].
4. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population [see Warnings and Precautions (5.1)].
5. Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. It is not always fully reversible and fatalities have been reported. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation [see Warnings and Precautions (5.1)].
6. Diarrhea and ulcerative stomatitis require interruption of therapy: otherwise, hemorrhagic enteritis and death from intestinal perforation may occur [see Warnings and Precautions (5.1)].
7. Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue Rasuvo first and, if the lymphoma does not regress, appropriate treatment should be instituted [see Warnings and Precautions (5.8)].
8. Like other cytotoxic drugs, methotrexate may induce "tumor lysis syndrome" in patients with rapidly growing tumors [see Warnings and Precautions (5.9)].
9. Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy [see Warnings and Precautions (5.1)].
10. Potentially fatal opportunistic infections, especially Pneumocystis jiroveci pneumonia, may occur with methotrexate therapy [see Warnings and Precautions (5.1)].
11. Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis [see Warnings and Precautions (5.10)].
1 INDICATIONS AND USAGE
1.1 Rheumatoid Arthritis including Polyarticular Juvenile Idiopathic Arthritis
Rasuvo is indicated in the management of selected adults with severe, active rheumatoid arthritis (RA) (ACR criteria), or children with active polyarticular juvenile idiopathic arthritis (pJIA), who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).
1.2 Psoriasis
Rasuvo is indicated in adults for the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses.
1.3 Limitation of Use
Rasuvo is not indicated for the treatment of neoplastic diseases.
2 DOSAGE AND ADMINISTRATION
2.1 Important Dosing Information
Rasuvo is a single-dose manually-triggered auto-injector for once-weekly subcutaneous use only [see Warnings and Precautions (5.5)]. Administer Rasuvo in the abdomen or the thigh. Rasuvo is only available in doses between 7.5 to 30 mg in 2.5 mg increments. Use another formulation of methotrexate for alternative dosing in patients who require oral, intramuscular, intravenous, intra-arterial, or intrathecal dosing, doses less than 7.5 mg per week, doses more than 30 mg per week, high-dose regimens, or dose adjustments of less than 2.5 mg increments.
2.2 Rheumatoid Arthritis including Polyarticular Juvenile Idiopathic Arthritis
Recommended starting dose of methotrexate:
Adult RA: 7.5 mg as a single oral or subcutaneous dose once weekly.
pJIA: 10 mg/m2 once weekly.
For patients switching from oral methotrexate to Rasuvo, consider any differences in bioavailability between oral and subcutaneously administered methotrexate [see Clinical Pharmacology (12.3)].
Dosages may be adjusted gradually to achieve an optimal response. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. Although there is experience with doses up to 30 mg/m2 /wk in children, there are too few published data to assess how doses over 20 mg/m2 /wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 to 30 mg/m2 /wk (0.65 to 1.0 mg/kg/wk) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered either intramuscularly or subcutaneously.
Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more.
The optimal duration of therapy is unknown. Limited data available from long-term studies in adults indicate that the initial clinical improvement is maintained for at least two years with continued therapy. When methotrexate is discontinued, the arthritis usually worsens within 3 to 6 weeks.
The patient should be fully informed of the risks involved and should be under constant supervision of the physician. Assessment of hematologic, hepatic, renal, and pulmonary function should be made by history, physical examination, and laboratory tests before beginning, periodically during, and before reinstituting Rasuvo therapy [see Warnings and Precautions (5.4)]. Females of childbearing potential should not be started on Rasuvo until pregnancy is excluded [see Contraindications (4) and Warnings and Precautions (5.2)].
All schedules should be continually tailored to the individual patient. An initial test dose may be given prior to the regular dosing schedule to detect any extreme sensitivity to adverse effects.
Maximal myelosuppression usually occurs in seven to ten days.
2.3 Psoriasis
Recommended starting dose of methotrexate:
Psoriasis: 10-25 mg as a single oral, intramuscular, subcutaneous, or intravenous dose once weekly.
For patients switching from oral methotrexate to Rasuvo, consider any differences in bioavailability between oral and subcutaneously administered methotrexate [see Clinical Pharmacology (12.3)].
Dosage may be gradually adjusted to achieve optimal clinical response; 30 mg/week should not ordinarily be exceeded. Once optimal clinical response has been achieved, the dosage should be reduced to the lowest possible amount of drug and to the longest possible rest period. The use of Rasuvo may permit the return to conventional topical therapy, which should be encouraged.
DOSAGE FORMS AND STRENGTHS
Rasuvo is an injection containing methotrexate at a concentration of 50 mg/ml available as a manually-triggered auto-injector that administers a single dose of methotrexate solution in the following dosage strengths:
7.5 mg
10 mg
12.5 mg
15 mg
17.5 mg
20 mg
22.5 mg
25 mg
27.5 mg
30 mg
4 CONTRAINDICATIONS
Rasuvo is contraindicated in the following:
Pregnancy
Rasuvo can cause fetal death or teratogenic effects when administered to a pregnant woman. Rasuvo is contraindicated in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)].
Nursing Mothers
Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Rasuvo is contraindicated in nursing mothers [see Use in Specific Populations (8.3)].
Alcoholism or Liver Disease
Patients with alcoholism, alcoholic liver disease or other chronic liver disease [see Warnings and Precautions (5.1)].
Immunodeficiency Syndromes
Patients who have overt or laboratory evidence of immunodeficiency syndromes [see Warnings and Precautions (5.1)].
Preexisting Blood Dyscrasias
Patients who have preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia [see Warnings and Precautions (5.1)].
Hypersensitivity
Patients with a known hypersensitivity to methotrexate. Severe hypersensitivity reactions have been observed with methotrexate use
DESCRIPTION
Rasuvo contains methotrexate, a folate analog metabolic inhibitor.
Chemically, methotrexate is [N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-Lglutamic acid.
PATIENT INFORMATION
RASUVO� (ruh-SOO-voh)
(methotrexate)injection, for subcutaneous use
What is Rasuvo?
Rasuvo is a single-dose manually-triggered 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.
Rasuvo is available in doses of 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 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 Rasuvo doses, such as doses of less than 7.5 mg, more than 30 mg, or doses in between the available Rasuvo doses.
Rasuvo should not be used for the treatment of cancer.
Rasuvo should not be used for the treatment of children with psoriasis.
What is the most important information I should know about Rasuvo?
Rasuvo 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
bone marrow
liver
immune system
nerve
lung
kidneys
skin
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
infection
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 Rasuvo. A pregnancy test should be performed before starting Rasuvo.Contraception should be used by both females and males while taking Rasuvo. Pregnancy should be avoided if either partner is receiving Rasuvo:
for a minimum of 3 months after treatment with Rasuvo for males.
during and for at least 1 menstrual cycle after treatment with Rasuvo for females.
Who should not take Rasuvo?
Do not take Rasuvo if you:
are pregnant or planning to become pregnant. See "What is the most important information I should know about Rasuvo?"
are breastfeeding.
Rasuvo can pass into your breast milk and may harm your baby. Do not breastfeed while taking Rasuvo. Talk to your doctor about the best way to feed your baby if you take Rasuvo.
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 Rasuvo. See the end of this leaflet for a complete list of ingredients in Rasuvo.
Talk to your doctor before taking this medicine if you have any of these conditions.
What should I tell my doctor before taking Rasuvo?
Before you take Rasuvo, 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.
Rasuvo may affect how other medicines work, and other medicines may affect how Rasuvo 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 Rasuvo?
Read the Instructions for Use that come with Rasuvo.
Take Rasuvo exactly as your doctor tells you to take it.
Inject Rasuvo only 1 time each week. Do not take Rasuvo every day.
Taking Rasuvo every day may cause death from toxicity.
Your doctor will show you or your caregiver how to inject Rasuvo. You should not inject Rasuvo until you have been trained on the right way to use it.
Check Rasuvo before you inject it. Rasuvo should be yellow to brown in color and should not have any lumps or particles in it.
Rasuvo should be injected under the skin of the abdomen or thigh.
Do not inject Rasuvo within 2 inches of the belly button (navel)
Use a different site each time you inject. This may help to decrease any reactions at the injection site.
Do not inject Rasuvo in the arms or any other areas of the body.
Do not inject Rasuvo in areas where the skin is tender, bruised, red, scaly, hard, or has scars or stretch marks.
If you are not sure if Rasuvo 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 Rasuvo, call your doctor or go to the nearest hospital emergency room right away.
What should I avoid while taking Rasuvo?
Do not drink alcohol while taking Rasuvo. Drinking alcohol can increase your chances of getting serious side effects.
Rasuvo 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 Rasuvo affects you.
Certain vaccinations should be avoided while taking Rasuvo. Talk to your doctor before you or members of your household receive any vaccines.
What are the possible side effects of Rasuvo?
Rasuvo may cause serious side effects, including:
See "What is the most important information I should know about Rasuvo?"
fertility problems. Methotrexate, the active ingredient in Rasuvo, 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 Rasuvo 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 Rasuvo 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 Rasuvo include:
nausea
stomach pain
indigestion (dyspepsia)
mouth sores
rash
stuffy or runny nose and sore throat
diarrhea
abnormal liver function tests
vomiting
headache
bronchitis
low red, white, and platelet blood cell count
hair loss
dizziness
sensitivity to light
burning skin lesions
lung problems
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 Rasuvo. For more information, ask your doctor or pharmacist.
Call you doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I dispose of Rasuvo?
Do not throw away in the household trash. Put used Rasuvo in an FDA-cleared sharps disposal container right away after use.
If you do not have an 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: https://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 Rasuvo that is out of date or is no longer needed.
How should I store Rasuvo?
Store Rasuvo at room temperature between 68�F to 77�F (20�C to 25�C)
Do not freeze
Keep Rasuvo out of the light.
Keep Rasuvo and all medicines out of the reach of children.
General information about the safe and effective use of Rasuvo.
Methotrexate is sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use Rasuvo for a condition for which it was not prescribed. Do not give Rasuvo 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 Rasuvo. If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about Rasuvo that is written for health professionals.
For more information, please contact Medac Pharma, Inc. at our number 1-855-336-3322.
What are the ingredients in Rasuvo?
Active ingredient: methotrexate
Inactive ingredients: sodium chloride, sodium hydroxide and water for injection, USP, and if necessary hydrochloric acid, USP.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured for:
Medac Pharma, Inc.
29 N Wacker Drive, Suite 704
Chicago, IL 60606
