Rasuvo injection

Call your doctor for instructions if you miss an appointment for your methotrexate injection, or if you forget to use the medicine at home.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of methotrexate injection can be fatal.

Do not drink alcohol. Serious side effects can occur when alcohol is combined with methotrexate.

Do not receive a "live" vaccine while using methotrexate, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Methotrexate may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid exposure to sunlight or artificial UV rays (sunlamps, tanning beds, or PUVA treatment), especially if you have psoriasis. Methotrexate injection can make your skin more sensitive to sunlight and your psoriasis may worsen.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• nerve problems--confusion, weakness, coordination problems, drowsiness, feeling irritable, back pain, headache, neck stiffness, seizure (convulsions), vision problems, loss of movement in any part of your body;

• signs of stomach bleeding--diarrhea, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• lung problems--sudden chest pain or tightness, wheezing, trouble breathing, dry cough or hack;

• signs of infection--sudden weakness or ill feeling, fever, chills, sore throat, cough with mucus, vomiting, weight loss, night sweats, swollen glands, mouth sores, red or swollen gums, trouble swallowing;

• kidney problems--swelling, rapid weight gain, little or no urinating; or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• nausea, vomiting, stomach pain or discomfort, diarrhea;

• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;

• mild skin rash;

• headache, dizziness;

• runny or stuffy nose, sore throat, wheezing, trouble breathing;

• abnormal liver function tests;

• easy bruising or bleeding;

• temporary hair loss;

• occasional headache, blurred vision; or

• burning sensation of psoriasis skin lesions.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Aspirin, Nonsteroidal Anti-Inflammatory Drugs, and Steroids

Nonsteroidal anti-inflammatory drugs (NSAIDs) should not be administered prior to or concomitantly with the high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity [see Warnings and Precautions (5.1)].

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including Rasuvo. These drugs have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity.

Despite the potential interactions, studies of methotrexate in patients with rheumatoid arthritis have usually included concurrent use of constant dosage regimens of NSAIDs, without apparent problems. It should be appreciated, however, that the doses used in rheumatoid arthritis (7.5 to 15 mg/week) are somewhat lower than those used in psoriasis and that larger doses could lead to unexpected toxicity. Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored. Steroids may be reduced gradually in patients who respond to methotrexate.

Proton Pump Inhibitors (PPIs) and H2 Blockers

Use caution if high-dose methotrexate is administered to patients receiving proton pump inhibitor (PPI) therapy. Case reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs, such as omeprazole, esomeprazole, and pantoprazole, with methotrexate (primarily at high dose), may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was co-administered with PPIs, but was not observed when methotrexate was co-administered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted.

Oral Antibiotics

Oral antibiotics such as tetracycline, chloramphenicol, and nonabsorbable broad spectrum antibiotics, may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria.

Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with high and low dose methotrexate. Use of Rasuvo with penicillins should be carefully monitored.

Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by decreased tubular secretion and/or an additive antifolate effect.

Hepatotoxins

The potential for increased hepatotoxicity when methotrexate is administered with other hepatotoxic agents has not been evaluated. However, hepatotoxicity has been reported in such cases. Therefore, patients receiving concomitant therapy with Rasuvo and other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) should be closely monitored for possible increased risk of hepatotoxicity.

Theophylline

Methotrexate may decrease the clearance of theophylline; theophylline levels should be monitored when used concurrently with Rasuvo.

Folic Acid and Antifolates

Vitamin preparations containing folic acid or its derivatives may decrease responses to systemically administered methotrexate. Preliminary animal and human studies have shown that small quantities of intravenously administered leucovorin enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentrations following intrathecal administration. However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate. Folate deficiency states may increase methotrexate toxicity.

Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving methotrexate, probably by decreased tubular secretion and/or an additive antifolate effect.

Mercaptopurine

Methotrexate increases the plasma levels of mercaptopurine. The combination of Rasuvo and mercaptopurine may therefore require dose adjustment.

Other Drugs

Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by certain drugs, such as salicylates, phenylbutazone, phenytoin, and sulfonamides.

Renal tubular transport is also diminished by probenecid; use of Rasuvo with this drug should be carefully monitored.

Combined use of methotrexate with gold, penicillamine, hydroxychloroquine, sulfasalazine, or cytotoxic agents, has not been studied and may increase the incidence of adverse effects.

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.

Rasuvo contains methotrexate in a preservative-free sterile solution for a single subcutaneous injection in the following configurations.

Not all pack sizes may be marketed.

Store at controlled room temperature, 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). PROTECT FROM LIGHT.

Handling and Disposal

Handle and dispose of Rasuvo consistent with recommendations for handling and disposal of cytotoxic drugs.1

NDC 59137-530-04
Rx only

20 mg

Rasuvo®
methotrexate
injection

Rasuvo® (methotrexate) injection

20 mg per 0.40 mL

This carton contains 4 pre-assembled 0.40 mL pre-filled Rasuvo auto-injectors.
FOR SUBCUTANEOUS USE ONLY
See full prescribing information for dosage and administration.
Read enclosed patient package insert carefully before using.

Applies to methotrexate: oral tablet

Other dosage forms:

• injectable, powder for solution, solution

Along with its needed effects, methotrexate (the active ingredient contained in Rasuvo) 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 immediately if any of the following side effects occur while taking methotrexate:

• 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
• 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 of methotrexate 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