Otrexup methotrexate 20 mg/.4mL Injection, Solution, 1 syringe — NDC 54436-020-03 (Billing 54436-0020-03)

1 INDICATIONS AND USAGE Otrexup is a folate analog metabolic inhibitor indicated for the: • Management of patients with severe, active rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA), who are intolerant of or had an inadequate response to first-line therapy ( 1.1 ). • Symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy ( 1.2 ). Limitation of Use Otrexup is not indicated for the treatment of neoplastic diseases ( 1.3 ).

1.1Rheumatoid Arthritis including Polyarticular Juvenile Idiopathic Arthritis Otrexup 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).

1.2Psoriasis Otrexup 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.

1.3Limitation of Use Otrexup is not indicated for the treatment of neoplastic diseases.

2 DOSAGE AND ADMINISTRATION Otrexup is for once weekly subcutaneous use only. Administer Otrexup in the abdomen or thigh. ( 2.1 ).

Use another formulation of methotrexate for patients requiring oral, intramuscular, intravenous, intra-arterial, or intrathecal dosing, doses less than 10 mg per week, doses above 25 mg per week, high-dose regimens, or dose adjustments of less than 5 mg increments ( 2.1 ). Starting doses of methotrexate: RA: 7.5 mg once weekly ( 2.2 ). pJIA: 10 mg/m 2 once weekly ( 2.2 ). Psoriasis: 10 to 25 mg once weekly of an oral, intramuscular, subcutaneous, or intravenous formulation ( 2.3 ).

Adjust dose gradually to achieve an optimal response ( 2.2 , 2.3 ).

2.1Important Dosing Information Otrexup is a single-dose auto-injector for once-weekly subcutaneous use only [see Warnings and Precautions ( 5.5 )] . Administer Otrexup in the abdomen or the thigh. Otrexup is available in the following dosage strengths: 10, 12.5, 15, 17.5, 20, 22.5 and 25 mg.

Use another formulation of methotrexate for alternative dosing in patients who require oral, intramuscular, intravenous, intra-arterial, or intrathecal dosing, doses less than 10 mg per week, doses more than 25 mg per week, high-dose regimens, or dose adjustments between the available doses.

2.2Rheumatoid Arthritis including Polyarticular Juvenile Idiopathic Arthritis Recommended starting dose of methotrexate: Adult RA: 7.5 mg once weekly. pJIA : 10 mg/m 2 once weekly. For patients switching from oral methotrexate to Otrexup, 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/m 2 /wk in children, there are too few published data to assess how doses over 20 mg/m 2 /wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 to 30 mg/m 2 /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 Otrexup therapy [see Warnings and Precautions ( 5.4 )] .

Females of childbearing potential should not be started on Otrexup 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.

2.3Psoriasis Recommended starting dose of methotrexate: Psoriasis: single weekly oral, intramuscular, subcutaneous, or intravenous doses of 10-25 mg. For patients switching from oral methotrexate to Otrexup, 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 shoul… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS Otrexup is an injection available as an autoinjector that administers a single 0.4 mL dose of methotrexate solution in the following dosage strengths: 10 mg/0.4 mL methotrexate 12.5 mg/0.4 mL methotrexate 15 mg/0.4 mL methotrexate 17.5 mg/0.4 mL methotrexate 20 mg/0.4 mL methotrexate 22.5 mg/0.4 mL methotrexate 25 mg/0.4 mL methotrexate Injection: Single-dose auto-injector delivering 0.4 mL of methotrexate in the following dosage strengths: 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg and 25 mg ( 3 ).

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling ( Patient Information and Instructions for Use ) Risk of Organ Toxicity Inform patients of the risks of organ toxicity, including gastrointestinal, hematologic, hepatic, infections, neurologic, pulmonary, renal and skin as well as possible signs and symptoms for which they should contact their healthcare provider. Advise patients of the need for close follow-up, including periodic laboratory tests to monitor toxicity [see Warnings and Precautions ( 5.1 and 5.4 )] .

Importance of Proper Dosing and Administration Both the physician and pharmacist should emphasize to the patient that the recommended dose is taken weekly and that mistaken daily use of the recommended dose has led to fatal toxicity [see Dosing and Administration ( 2 )] . Otrexup is intended for use under the guidance and supervision of a physician. Patients should not self-administer until they receive training from a healthcare professional.

The patient’s or caregiver’s ability to administer Otrexup should be assessed. A trainer device is available for training purposes. Patients should be instructed to use administration sites on the abdomen or the thigh.

Administration should not be made within 2 inches of the navel. Instruct patients not to administer Otrexup to the arms or any other areas of the body, as delineated in the Otrexup Instructions for Use [see Instructions for Use ] . Embryo-Fetal Toxicity Advise females of reproductive potential that Otrexup can cause fetal harm and is contraindicated in pregnancy.

Advise women of childbearing potential that Otrexup should not be started until pregnancy is excluded. Women should be fully counseled on the serious risk to the fetus should they become pregnant while undergoing treatment. Inform patients to contact their physician if they suspect that they are pregnant [see Boxed Warning , Contraindications ( 4 ), Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 )] .

Advise females of reproductive potential to use effective contraception during Otrexup therapy and for 6 months after the final dose [see Use in Specific Populations ( 8.3 )] . Advise males of reproductive potential to use effective contraception during Otrexup therapy and for 3 months after the final dose [see Use in Specific Populations ( 8.3 )] . Infertility Advise patients of reproductive potential that Otrexup may cause impairment of fertility, oligospermia, and menstrual dysfunction [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.3 )] .

Lactation Advise females not to breastfeed during treatment with Otrexup and for one week after the final dose [see Use in Specific Populations ( 8.3 )] . Ability to Drive or Operate Machinery Inform patients that adverse reactions such as dizziness and fatigue may affect their ability to drive or operate machinery. Proper Storage and Disposal Advise patients to store Otrexup at room temperature (68 to 77°F or 20 to 25°C).

Inform patients and caregivers of the need for proper disposal after use, including the use of a sharps disposal container. Address Medical Inquiries to: Antares Pharma, Inc. Medical Communications 100 Princeton South, Suite 300 Ewing, NJ 08628 1-855-Otrexup (1-855-687-3987) Manufactured for: Antares Pharma, Inc.

100 Princeton South, Suite 300 Ewing, NJ 08628 USA Otrexup™ is the subject of US Patent Nos. 8,021,335, 6,746,429, 8,480,631, 8,562,564, 8,579,865, and 8,945,063. ©2019 Antares Pharma, Inc., Ewing, NJ 08628 Antares Pharma Logo

Instructions for Use Read this Instructions for Use before using Otrexup™ (oh-TREKS-up) (methotrexate) injection, for subcutaneous use Prepare to Use Otrexup Do not remove cap (marked 1) or safety clip (marked 2) until you are ready to inject Otrexup. Wash your hands well with soap and warm water. Check the expiration date on the label.

Do not use if expired. Check the seal. Do not use Otrexup if the seal is broken ( See Figure B ).

In addition to Otrexup, you will need the following items: 1 alcohol swab and 1 cotton ball or gauze. Check the Liquid Look at the viewing window ( See Figure C ). The liquid should be yellow in color and should not have any lumps or particles in it.

You may see an air bubble. This is normal. Choose an Injection Site Otrexup should be injected into the stomach (abdomen) or thigh.

Do not inject Otrexup within 2 inches of the belly button (navel) ( See Figure D ). 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.

Wipe the area with an alcohol swab. Allow the skin to dry and do not touch this area again before giving Otrexup. Do not fan or blow on the clean area.

Give your Injection Step 1: Remove Cap (marked 1) Twist cap marked 1 to remove ( See Figure E ). This will break the seal. You may notice 1 or 2 drops of medicine.

This is normal. Do not touch the needle end with your hands or fingers. This could inject the medicine into your hand.

Do not replace the cap after it has been removed. After the cap is removed Otrexup must be used or disposed of safely (See step 5). STEP 2: Remove the Safety Clip (marked 2) Flip the Safety Clip marked 2 ( See Figure F ).

STEP 3: Inject Otrexup Place needle end of Otrexup flat against thigh or stomach (abdomen) at a 90° and firmly push device against the injection site until fully depressed. You will hear a click, hold for 3 seconds (slowly count 1,2,3) ( See Figure G ). After counting to 3, remove Otrexup from the injection site.

You may notice a small amount of blood or liquid at the administration site, which is normal. Press a cotton ball or gauze on the area for 10 seconds. Do not rub the area.

Step 4: Check the Viewing Window Check the viewing window ( See Figure H ). The viewing window will be half blocked with a red flag to show that the full dose was delivered. ( See Figure H ).

Dispose of Otrexup in a puncture-proof disposable container (See Step 5) . If the viewing window is not half blocked with a red flag , call your doctor or pharmacist, or call 1-855-Otrexup (1-855-687-3987) for help. Do not use another Otrexup without talking to your doctor.

Step 5: 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 and 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 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 fre… [Excerpted — this section continues on DailyMed.]