PURIFIED CORTROPHIN ® GEL (Repository Corticotropin Injection USP) Rx only

Purified Cortrophin Gel is a porcine derived purified corticotropin (ACTH) in a sterile solution of gelatin. It is made up of a complex mixture of ACTH, ACTH related peptides and other porcine pituitary derived peptides.

The drug product is a sterile preparation containing 80 USP units per mL and it contains 0.5% phenol (as preservative), 15.0% gelatin (for prolonged activity), water for injection, and the pH is adjusted with hydrochloric acid and sodium hydroxide.

Purified Cortrophin Gel contains the porcine derived ACTH (1-39) with the following amino acid sequence:

Purified Cortrophin Gel is the anterior pituitary hormone which stimulates the functioning adrenal cortex to produce and secrete adrenocortical hormones.

Following administration of a single intramuscular injection of 80 Units of Cortrophin Gel to healthy volunteers (n=20) in an open label pharmacodynamic study, the median time (range) to reach peak cortisol concentration was 8 (3-12) hours. The baseline corrected geometric mean maximum (CV%) cortisol levels were 34.52 µg/dL (28.2%).

Purified Cortrophin Gel is indicated in the following disorders:

1. Rheumatic disorders:

1. As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:
   Psoriatic arthritis.
   Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy).
   Ankylosing spondylitis.
   Acute gouty arthritis.

2. Collagen diseases:

1. During an exacerbation or as maintenance therapy in selected cases of:
   Systemic lupus erythematosus.
   Systemic dermatomyositis (polymyositis).

3. Dermatologic diseases:

1. Severe erythema multiforme (Stevens-Johnson syndrome).
   Severe psoriasis.

4. Allergic states:

1. Atopic dermatitis
   Serum sickness.

5. Ophthalmic diseases:

1. Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as:
   Allergic conjunctivitis.
   Keratitis.
   Iritis and iridocyclitis.
   Diffuse posterior uveitis and choroiditis.
   Optic neuritis.
   Chorioretinitis.
   Anterior segment inflammation.

6. Respiratory diseases:

1. Symptomatic sarcoidosis.

7. Edematous states:

1. To induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.

8. Nervous system:

1. Acute exacerbations of multiple sclerosis.

Purified Cortrophin Gel is contraindicated for intravenous administration.

Purified Cortrophin Gel is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, hypertension, or sensitivity to proteins derived from porcine sources.

Purified Cortrophin Gel is contraindicated in patients with primary adrenocortical insufficiency or adrenocortical hyperfunction.

Purified Cortrophin Gel is contraindicated in patients with a history of hypersensitivity reaction to corticotropin or any of the inactive ingredients of Purified Cortrophin Gel. Reactions have included anaphylaxis and angioedema.

Chronic administration of corticotropin may lead to adverse effects which are not reversible.

This product should not be administered for treatment until adrenal responsiveness has been verified with the route of administration which will be utilized during treatment, intramuscularly or subcutaneously. A rise in urinary and plasma corticosteroid values provides direct evidence of a stimulatory effect. Although the action of corticotropin is similar to that of exogenous adrenocortical steroids the quantity of adrenocorticoid may be variable. In patients who receive prolonged corticotropin therapy the additional use of rapidly acting corticosteroids before, during and after an unusual stressful situation is indicated.

Masking Symptoms of Other Diseases

Corticotropin may only suppress symptoms and signs of chronic disease without altering the natural course of the disease.

Immunogenicity Potential

Purified Cortrophin Gel is immunogenic. Limited available data suggest that a patient may develop antibodies to Purified Cortrophin Gel after chronic administration and loss of endogenous ACTH and Purified Cortrophin Gel activity. Hypersensitivity reactions including anaphylaxis and angioedema have been reported. Prolonged administration of Purified Cortrophin Gel may increase the risk of hypersensitivity reactions. Sensitivity to porcine protein should be considered before starting therapy and during the course of treatment should symptoms arise.

Ophthalmic Effects

Prolonged use of corticotropin may produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerves.

Infections

Corticotropin may mask some signs of infection, and new infections including those of the eye due to fungi or viruses may appear during its use. There may be decreased resistance and inability to localize infection when corticotropin is used.

Elevated Blood Pressure, Salt and Water Retention, and Hypokalemia

Corticotropin can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. Dietary salt restriction and potassium supplementation may be necessary. Corticotropin increases calcium excretion.

Vaccination

While on corticotropin therapy, patients should not be vaccinated against smallpox. Other immunization procedures should be undertaken with caution in patients who are receiving corticotropin, especially when high doses are administered because of the possible hazards of neurological complications and lack of antibody response.

Fluid and Electrolyte Disturbances
Sodium retention.
Hypokalemic alkalosis.
Fluid retention.
Calcium loss.
Potassium loss.

Musculoskeletal
Muscle weakness.
Loss of muscle mass.
Steroid myopathy.
Osteoporosis.
Vertebral compression fractures.
Aseptic necrosis of femoral and humeral heads.
Pathologic fracture of long bones.

Gastrointestinal
Peptic ulcer with possible perforation and hemorrhage.
Abdominal distention.
Ulcerative esophagitis.
Pancreatitis.

Dermatologic
Injection site reactions.
Impaired wound healing.
Increased sweating.
Thin fragile skin.
Suppression of skin test reactions.
Petechiae and ecchymoses.
Acne.
Hyperpigmentation.
Facial erythema.

Cardiovascular
Hypertension.
Congestive heart failure.
Necrotizing angiitis.

Neurological
Convulsions.
Increased intracranial pressure with papilledema (pseudo-tumor cerebri), usually after treatment.
Headache.
Vertigo.

Endocrine
Menstrual irregularities.
Development of Cushingoid state.
Suppression of growth in children.
Secondary adrenocortical and pituitary insufficiency, particularly in times of stress, as in trauma, surgery or illness.
Decreased carbohydrate tolerance.
Manifestations of latent diabetes mellitus.
Increased requirements for insulin or oral hypoglycemic agents in diabetics.
Hirsutism.

Ophthalmic
Posterior subcapsular cataracts.
Increased intraocular pressure.
Glaucoma with possible damage to optic nerve.
Exophthalmos.

Metabolic
Negative nitrogen balance due to protein catabolism.

Allergic reactions
Allergic reactions manifesting as dizziness, nausea and vomiting, skin reactions, anaphylaxis, including anaphylactic shock, respiratory compromise, angioedema, urticaria, especially in patients with allergic responses to proteins.

Miscellaneous
Weight gain.
Abscess.
Development of antibodies and loss of stimulatory effect.

To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Standard tests for verification of adrenal responsiveness to corticotropin may utilize as much as 80 units as a single injection or one or more injections of a lesser dosage. Verification tests should be performed prior to treatment with corticotropins. The test should utilize the route(s) of administration proposed for treatment. Following verification dosage should be individualized according to the disease under treatment and the general medical condition of each patient. Frequency and dose of the drug should be determined by considering severity of the disease, plasma and urine corticosteroid levels and the initial response of the patient. Only gradual change in dosage schedules should be attempted, after full drug effects have become apparent.

This product may be administered subcutaneously or intramuscularly with the vial and subcutaneously with the prefilled syringe.

In the treatment of acute exacerbations of multiple sclerosis daily subcutaneous or intramuscular doses of 80-120 units for 2-3 weeks.

The chronic administration of more than 40 units daily may be associated with uncontrollable adverse effects.

When reduction in dosage is indicated this should be accomplished gradually by either reducing the amount of each injection, or administering injections at longer intervals, or by a combination of both of the above. During reduction of dosage, careful consideration should be given to the disease being treated, the general medical condition of the patient and the duration over which corticotropin was administered.

Important Administration Instructions

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Purified Cortrophin Gel is a clear, light amber liquid gel at room temperature. Do not use if the solution is discolored or cloudy or the solution contains particulate matter.
• Purified Cortrophin Gel will be a solid gel when refrigerated and needs to be warmed to a liquid gel before administration.
  • oFor Purified Cortrophin Gel vials warm by rolling between your hands for a few minutes.
  • oFor Purified Cortrophin Gel prefilled syringes remove the carton from the refrigerator and leave at room temperature for 45 minutes.
• The recommended injection sites include abdomen, upper thigh, or upper arm. Do not inject within 2 inches of navel.

Information for Patients

Advise patients and/or caregivers to read the FDA-approved patient information (Instructions for Use).

Purified Cortrophin Gel is a clear, light amber liquid gel at room temperature. It is supplied sterile in:

• Multiple-dose vials for intramuscular or subcutaneous use

• Single-dose prefilled syringes for subcutaneous use only

Store Purified Cortrophin Gel vials and prefilled syringes refrigerated at 2° to 8°C (36° to 46°F).

Purified Cortrophin Gel vials and prefilled syringes may be stored at room temperature between 20° to 25°C (68° to 77°F) for up to 24 hours.

After first use discard Purified Cortrophin Gel vials per the table below. Write the revised expiration date in the space provided on the carton labeling.

Discard Purified Cortrophin Gel prefilled syringes immediately after use or by the expiration date stamped on the syringe.

Distributed by:
ANI Pharmaceuticals, Inc.
Baudette, MN 56623
logo

10233 Rev 08/26
10716 Rev 08/26

Purified Cortrophin^® Gel
(Repository Corticotropin Injection USP)
for intramuscular or subcutaneous use

This Instructions for Use contains information on how to inject Purified Cortrophin Gel.

Your healthcare provider should show you how to prepare and inject Purified Cortrophin Gel the right way before you inject it for the first time. Do not try to inject yourself until you have been shown the right way to give your injections by your healthcare provider.

Important information about how to inject Purified Cortrophin Gel

• Purified Cortrophin Gel is given as an injection into the muscle or under the skin as directed by your healthcare provider. Do not inject it into a vein or take by mouth.
• Inject Purified Cortrophin Gel exactly as your healthcare provider tells you. Your healthcare provider will tell you where to give the injection, how much to give, how often and when to give it.
• Do not use Purified Cortrophin Gel until your healthcare provider has taught you how to give the injection.

Before starting, collect all of the supplies that you will need to use for preparing and injecting Purified Cortrophin Gel. You will need the following supplies:

• Vial of Purified Cortrophin Gel
• Syringe
• Needle for withdrawal (20G or as prescribed by your healthcare provider)
• Needle for injection (23G or as prescribed by your healthcare provider)
• 2 alcohol pads
• Cotton balls or gauze pad
• Bandage (if needed)
• Sharps container for throwing away used syringes and needles (see “Disposing of used needles and syringes”)

Preparing Purified Cortrophin Gel

• Wash your hands well and dry with a clean towel.
• Remove the vial from the refrigerator. Check the expiration date on the vial. Do not use if the expiration date has passed.
• Purified Cortrophin Gel will be a solid gel when refrigerated and it needs to be warmed to a liquid gel before injecting. Warm the solid gel in the vial by rolling between your hands for a few minutes. Do not microwave or heat on the stove.
  Warming the vial
• Remove (flip off) the plastic cap from the top of the Purified Cortrophin Gel vial and throw it away in the trash. Do not put the plastic cap back on the vial.
  Removing the vial cap
• Wipe the top of the vial rubber stopper with a new sterile alcohol pad.
  Wipe vial with alcohol wipe
• Use a new sterile 20G needle (or needle prescribed for withdrawal) and syringe to draw up the amount of Purified Cortrophin Gel your healthcare provider has told you to use.
  Draw up into inverted syringe

Injecting Purified Cortrophin Gel

• Prepare the skin where you are going to give the injection by wiping it with a new sterile alcohol pad. Allow to air dry.
• Replace the 20G needle (or needle prescribed for withdrawal) used for drawing the Purified Cortrophin Gel from the vial with the 23G needle (or needle prescribed for injection). Do not use the 20G needle for injecting.
• Give the injection the way your healthcare provider has instructed you.
• There may be a little bleeding at the injection site. You can press a cotton ball or gauze pad over the injection site (do not rub).
• If needed, you may cover the injection site with a bandage.
• Return the vial to the refrigerator as soon as possible.

Disposing of your used needles and syringe

• Put your used needles and syringe in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) your used needles and syringe in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • omade of a heavy-duty plastic,
  • ocan be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • oupright and stable during use,
  • oleak-resistant, and
  • oproperly 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 safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: 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.

Storing Purified Cortrophin Gel

• Store vials of Purified Cortrophin Gel in the refrigerator between 36°F to 46°F (2°C to 8°C).
• 1 mL vials: Throw away (discard) any 1 mL vials 6 months after first use or by the expiration date printed on the label, whichever occurs first.
• 5 mL vials: Throw away (discard) any 5 mL vials 28 days after first use or by the expiration date printed on the label, whichever occurs first.
• Write the revised discard by date in the space provided on the carton labeling.

Keep Purified Cortrophin Gel and all medicines out of the reach of children.

Distributed by: ANI Pharmaceuticals, Inc., Baudette, MN 56623

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: October 2023

PURIFIED CORTROPHIN GEL
(Repository Corticotropin Injection USP)

40 USP units/0.5 mL and 80 USP units/mL
Single-dose prefilled syringe

For Subcutaneous Use Only

This Instructions for Use contains information on how to prepare and inject Purified Cortrophin Gel prefilled syringe.
Your healthcare provider should show you how to prepare and inject Purified Cortrophin Gel the right way before you inject it for the first time. Do not try to inject yourself until you have been shown the right way to give your injections by your healthcare provider.
Purified Cortrophin Gel prefilled syringe (see Figure A).	Figure_A.jpg Figure A
Important information you need to know before injecting Purified Cortrophin Gel
Read all of this Instructions for Use carefully before using the Purified Cortrophin Gel prefilled syringe. Purified Cortrophin Gel is given as an injection directly under the skin as directed by your healthcare provider. oDo not inject it into a vein or take by mouth. Inject Purified Cortrophin Gel exactly as your healthcare provider tells you. Your healthcare provider will tell you where to give the injection, how much to give, how often, and when to give it. oYou may need more than 1 injection based on your prescribed dose. Do not use Purified Cortrophin Gel until your healthcare provider has shown you how to give the injection. Do not use if the tamper evident seal is torn, loose, or not present. Do not use the Purified Cortrophin Gel prefilled syringe if it has been dropped on a hard surface or damaged.
1.Collect your supplies
Use a clean, flat surface, such as a table. You will need (see Figure B): o1 Purified Cortrophin Gel prefilled syringe (see Figure A) o1 alcohol pad o1 cotton ball or gauze pad o1 bandage (if needed) oSharps container for throwing away used syringes and needles (see “Disposing of your used prefilled syringes and needles”)	Figure_B.jpg Figure B
2.Preparing the prefilled syringe
Remove the carton from the refrigerator and place on a clean surface for 45 minutes to let the prefilled syringe warm up to room temperature 68°F to 77°F (20°C to 25°C) (see Figure C). oPurified Cortrophin Gel will be a solid gel when refrigerated and it needs to be warmed to a liquid gel before injecting. oRemove the prefilled syringe by the syringe body only. Do not remove the prefilled syringe by the plunger rod or needle cover. oDo not remove the needle cover while allowing the prefilled syringe to reach room temperature. oDo not warm the prefilled syringe in any other way. For example, do not microwave or heat on the stove. oDo not use the prefilled syringe if the gel in the syringe still appears to be solid.	Figure_C.jpg Figure C
3.Check your medicine
Check the expiration date on the syringe label (see Figure D). Do not use if expiration date has passed. Make sure that you have the right dose as prescribed to you by your healthcare provider. Your dose may require more than 1 injection. Check that the liquid gel in the syringe is light amber (yellow) in color. Do not use if the gel appears cloudy or has particles in it. Throw it away (discard) and get a new syringe. It is ready to be used when the medicine is a liquid gel and not a solid gel.	Figure_D.jpg Figure D
4.Selecting an injection site
Wash your hands well and dry with a clean towel. Choose an injection site on the stomach (abdomen) area or upper thigh (see Figure E). oDo not inject within 2 inches of the belly button (navel). Do not inject in areas where the skin is red, swollen, irritated, inflamed tender, bruised, scaly, hard, or has scars or stretch marks.	Figure_E.jpg Figure E
If someone else is giving you the injection, it can also be injected in the side and back of the upper arm (see Figure F).	Figure_F.jpg Figure F
5.Injecting Purified Cortrophin Gel
Clean the injection site with an alcohol pad (see Figure G). Allow to air dry.	Figure_G.jpg Figure G
Hold the syringe by the body with one hand. oDo not move or pull back on the plunger. Remove the needle cover with the other hand and throw it away (discard) (see Figure H). oDo not touch the needle. oDo not recap the needle. oYou may see a drop of liquid at the end of the needle. This is normal.	Figure_H.jpg Figure H
With one hand, gently pinch the area of the cleaned skin and hold it firmly (see Figure I). Insert the needle into the pinched skin at a 45-degree angle (see Figure I). Release the pinched skin and slowly push down the plunger until all the medicine has been injected. Pull the needle out of the skin while keeping the syringe at the same angle.	Figure_I.jpg Figure I
There may be a small amount of blood at the injection site. You can press a cotton ball or gauze pad over the injection site. Do not rub the injection site. If needed, you may cover the injection site with a bandage (see Figure J).	Figure_J.jpg Figure J
6.Disposing of your used prefilled syringes and needles
Throw away (discard) the prefilled syringe into an FDA cleared sharps container right away after use (see Figure K). Do not throw away (dispose of) your used needles and syringe in your household trash.	Figure_K.jpg Figure K
If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: omade of a heavy-duty plastic, ocan be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, oupright and stable during use, oleak-resistant, and oproperly 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 safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: 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.
Storing Purified Cortrophin Gel prefilled syringes
Store Purified Cortrophin Gel prefilled syringes in the carton provided in the refrigerator between 36°F to 46°F (2°C to 8°C). Purified Cortrophin Gel prefilled syringes may be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 24 hours. Keep Purified Cortrophin Gel prefilled syringes in the carton until ready to use. Throw away (discard) Purified Cortrophin Gel prefilled syringes right away after use or by the expiration date stamped on the syringe. Keep Purified Cortrophin Gel and all medicines out of the reach of children.
Distributed by: ANI Pharmaceuticals, Inc., Baudette, MN 56623 This Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: February 2025

NDC 62559-860-15
Purified Cortrophin^® Gel (repository corticotropin injection USP)
400 USP units/5 mL (80 USP units/mL)
For intramuscular or subcutaneous use.
5 mL, multiple-dose vial
Rx only
5mL_carton

NDC 62559-860-11
Purified Cortrophin^® Gel (repository corticotropin injection USP)
80 USP units/mL
For intramuscular or subcutaneous use.
1 mL, multiple-dose vial
Rx only
1mL_carton

Rx only
NDC 62559-861-35
Purified Cortrophin^® Gel (repository corticotropin injection USP)
40 USP units/0.5 mL
For subcutaneous use only.
Single-dose Prefilled Syringe
Remove the Purified Cortrophin Gel carton from the refrigerator 45 minutes prior to injecting.
half_mL_PFS

Rx only
NDC 62559-861-11
Purified Cortrophin^® Gel (repository corticotropin injection USP)
80 USP units/mL
For subcutaneous use only.
Single-dose Prefilled Syringe
Remove the Purified Cortrophin Gel carton from the refrigerator 45 minutes prior to injecting.
1mL_PFS