CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`008975Orig1s008
`
`
`Trade Name:
`
`PURIFIED CORTROPHIN GEL
`
`Generic or Proper
`Name:
`Sponsor:
`
`
`
`(repository corticotropin injection USP)
`
`ANI Pharmaceuticals, Inc.
`
`Approval Date:
`
`October 29, 2021
`
`Indication:
`
`Purified Cortrophin Gel is indicated in the following disorders:
`1. Rheumatic disorders:
`As adjunctive therapy for short-term administration (to tide the
`patient over an acute
`episode or exacerbation) in:
`Psoriatic arthritis.
`Reference ID: 4880561
`Rheumatoid arthritis, including juvenile rheumatoid arthritis
`(selected cases may require
`low-dose maintenance therapy).
`Ankylosing spondylitis.
`Acute gouty arthritis.
`2. Collagen diseases:
`During an exacerbation or as maintenance therapy in selected
`cases of:
`Systemic lupus erythematosus.
`Systemic dermatomyositis (polymyositis).
`3. Dermatologic diseases:
`Severe erythema multiforme (Stevens-Johnson syndrome).
`
`

`

`Severe psoriasis.
`4. Allergic states:
`Atopic dermatitis.
`Serum sickness.
`5. Ophthalmic diseases:
`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:
`Symptomatic sarcoidosis.
`7. Edematous states:
`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:
`Acute exacerbations of multiple sclerosis.
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`008975Orig1s008
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Officer/Employee List
`Multidiscipline Review(s)
`• Summary Review
`• Office Director
`• Cross Discipline Team Leader
`• Clinical
`• Non-Clinical
`• Statistical
`• Clinical Pharmacology
`• Clinical Microbiology/Virology
`Product Quality Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`X
`X
`X
`
`X
`
` X
`X
`
`X
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`008975Orig1s008
`
`
`APPROVAL LETTER
`
`

`

`NDA 008975/S-008
`
`
`
`SUPPLEMENT APPROVAL
`
`
`ANI Pharmaceuticals, Inc.
`Attention: Ellen Connolly
`Vice President, Regulatory Affairs
`210 Main Street West
`Baudette, MN 56623
`
`Dear Ms. Connolly:
`
`Please refer to your supplemental new drug application (sNDA) dated June 29, 2021,
`received June 29, 2021, and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for purified Cortrophin Gel (repository
`corticotrophin injection USP).
`
`This Prior Approval sNDA provides for quality information and supporting data for
`reintroduction of the product in the US market.
`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon
`labeling.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
`the FDA automated drug registration and listing system (eLIST), as described at
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`Prescribing Information and Instructions for Use), with the addition of any labeling
`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
`reportable changes not included in the enclosed labeling.
`
`Information on submitting SPL files using eList may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`Reference ID: 4880561
`
`

`

`NDA 008975/S-008
`Page 2
`
`
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`changes for this NDA, including CBE supplements for which FDA has not yet issued an
`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission, provide a
`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
`Word version. The marked-up copy should provide appropriate annotations, including
`supplement number(s) and annual report date(s).
`
`CARTON AND CONTAINER LABELING
`
`Submit final printed carton and container labeling that are identical to the enclosed
`carton and container labeling (carton labeling submitted on June 29, 2021, and
`container labeling submitted on August 17, 2021), as soon as they are available, but no
`more than 30 days after they are printed. Please submit these labeling electronically
`according to the guidance for industry Providing Regulatory Submissions in Electronic
`Format — Certain Human Pharmaceutical Product Applications and Related
`Submissions Using the eCTD Specifications. For administrative purposes, designate
`this submission “Product Correspondence – Final Printed Carton and Container
`Labeling for approved NDA 008975/S-008.” Approval of this submission by FDA is not
`required before the labeling is used.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information aabout submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format – Promotional Labeling and Advertisign in Materials for Human
`Prescription Drugs.3
`
`You must submit final promotional materials and Prescribing Information, accompanied
`by a Form FDA 2253, at the time of initial dissemination or publication
`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
`Instructions for completing the form can be found at FDA.gov.5
`
`We remind you that you must comply with the requirements for an approved NDA set
`forth under 21 CFR 314.80 and 314.81.
`
`
`
`3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4880561
`
`

`

`NDA 008975/S-008
`Page 3
`
`
`If you have any questions, call Dana Smith, Regulatory Project Manager, at
`240-402-9906.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Naomi Lowy, MD
`Deputy Director
`Division of General Endocrinology
`Office of Cardiology, Hematology,
`Endocrinology, and Nephrology
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURES:
`• Content of Labeling
`o Prescribing Information
`Instructions for Use
`o
`• Carton and Container Labeling
`
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4880561
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`NAOMI N LOWY
`10/29/2021 08:52:24 AM
`
`Reference ID: 4880561
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`008975Orig1s008
`
`OTHER ACTION LETTERS
`
`
`
`
`
`
`
`

`

`¢ FN U.S. FOOD & DRUG
`
`ADMINISTRATION
`
`“aa :
`
`NDA 008975/S-008
`
`ANI Pharmaceuticals, Inc.
`Attention: Kassidy Good
`Director Corticotropin Regulatory Affairs
`210 Main Street West
`Baudette, MN 56623
`
`Dear Ms. Good:
`
`REFUSALTO FILE
`
`Pleaserefer to your supplemental new drug application (NDA), received March 23,
`2020, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA), for purified Cortrophin Gel (repository corticotrophin injection USP).
`
`After a preliminary review, we find your application is not sufficiently complete to permit
`a substantive review. Therefore, we are refusingto file this application under 21 CFR
`314.101(d) for the following reasons:
`
`Chemistry, Manufacturing and Controls
`
`1. Immunogenicity
`
`In our General Advice Letter, dated May 18, 2018, and our responseto questionsin
`your meeting package, dated March 15, 2018, you were advised that your proposed
`product may havedifferences
`comparedto the
`previously marketed product that may affect safety of your product — notably
`immunogenicity. In your response youstated, hemost important addition made By
`© from the last approved product |Is
`You further suggested in your response
`that your proposed product and the approved product weresimilar “with no added
`concern that would increase immunogenicity beyond whatis currently on the label.” We
`do not consider your response as adequate to address the potential concern for
`immunogenicity.
`
`Conduct a risk assessmentto address patient or product specific factors that can affect
`immunogenicity particularly with the multiple indications as proposed in your package
`insert.
`
`2. Virus clearance/validation
`You provided study reports for virus clearance/validation from the contract laboratory
`® butit is not possible to review those reports becausedetails onthe
`preparation of samplesforviral clearance are not disclosed.
`
`Reference ID: 4598727
`
`

`

`NDA 008975/S-008
`Page 2
`
`
`
`
`
`
`.
`oubmita
`the above suggestions into consideration.
`
`virus clearance/validation study report
`
`taking
`
`Wealso encourage you to considerredesigningafit-for-purpose virus
`clearance/validation study appropriate to your manufacturing process with a well-
`developed scaled-down model.
`In addition to modelviruses studied, you might consider
`including a modelretrovirus in the virus clearance study (to serve as a modelfor porcine
`endogenousretroviruses, which have been shownto beinfectious, unlike endogenous
`retroviruses from other species2.*).
`
`You may also consider possible improvements to your manufacturing process
`to improvethe potentialfor vira
`
`clearance.
`
`3. Drug Substance Manufacturing
`
`2 Infection of humancells by an endogenousretrovirus of pigs, C. Patience et al., Nature Medicine, 3,
`282-286 (1997).
`
`3 The porcine virome and xenotransplantation, J. Denner, Virology Journal, 14, 171-177 (2017).
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4598727
`
`

`

`NDA 008975/S-008
`Page 3
`
`
`
`4. Microbiology
`
`Your supplemental NDAlacks essential microbiological information that precludes a
`review to assessthesterility assurance for your product.
`
`e
`
`Thefollowing validation reports were not provided: container closure integrity
`CCIT
`validation, vial depyrogenation process,
`
`test
`
`e The description of the proposed manufacturing area and thefacility floor
`plan/layouts were notprovided.
`
`e The Water For Injection monitoring and environmental monitoring program were
`not described.
`
`Th
`
`bioburden specicationili
`were not provided.
`
`e The actions to be takenin eventof a |e failure were not described.
`
`e
`
`tis noted that Antimicrobial Effectiveness Test (AET) will be conducte
`for one submission batch.
`It is further noted
`drug product packageinsert doesnot indicate an after opening expiry
`the
`at
`and that the vial will be warmed up prior to use and returned to 2-8°C conditions
`after each use. A risk assessment summarizing studies that demonstrate
`preservative efficacy under the specified in-use storage conditions(i.e., store at
`2-8°C and warm upprior to each use) wasnot provided.
`
`For moreinformation please refer to the Agency’s
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4598727
`
`

`

`NDA 008975/S-008
`Page 4
`
`Please note that this filing review represents a preliminary review of the application and
`is not indicative of deficiencies that would be identified if we performed a complete
`review.
`
`Within 30 days of the date of this letter, you may request in writing a Type A meeting
`about our refusal to file the application. A meeting package should be submitted with
`this Type A meeting request. To file this application over FDA's protest, you must avail
`yourself of this meeting.
`
`If, after the meeting, you still do not agree with our conclusions, you may request that
`the application be filed over protest. In that case, the filing date will be 60 days after the
`date you requested the meeting. The application will be considered a new original
`application for user fee purposes, and you must remit the appropriate fee. If you choose
`to file over protest, FDA will generally not review any amendments to the application
`and will generally not issue information requests during the review cycle. Resubmission
`goals will not apply to any resubmission of this application.
`
`PROPOSED PROPRIETARY NAME
`
`If you intend to have a proprietary name for the above-referenced product, submit a new
`request for review of a proposed proprietary name when you resubmit the application.
`For questions regarding proprietary name review requests, please contact the OSE
`Project Management Staff via telephone at 301-796-3414 or via email at
`OSECONSULTS@cder.fda.gov.
`
`If you have any questions, call Dana Smith, Regulatory Project Manager, at 1-240-402-
`9906.
`
`Sincerely yours,
`
`{See appended electronic signature page}
`
`Theresa E. Kehoe, MD
`Division Director (Acting)
`Division of General Endocrinology
`Office of Cardiology, Hematology, Endocrinology,
`and Nephrology
`Center for Drug Evaluation and Research
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4598727
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`THERESA E KEHOE
`04/27/2020 03:53:30 PM
`
`Reference ID: 4598727
`
`

`

`
` CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`008975Orig1s008
`
`
`LABELING
`
`

`

`PURIFIED CORTROPHIN® GEL
`(Repository Corticotropin Injection USP)
`
`Rx only
`
`DESCRIPTION
`
`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:
`
`Ser-
`1
`
`Lys-
`11
`
`Lys-
`21
`
`Leu-
`31
`
`Tyr-
`2
`
`Pro-
`12
`
`Val-
`22
`
`Ala-
`32
`
`Ser-
`3
`
`Val-
`13
`
`Tyr-
`23
`
`Glu-
`33
`
`Met-
`4
`
`Gly-
`14
`
`Pro-
`24
`
`Ala-
`34
`
`Glu-
`5
`
`Lys-
`15
`
`Asn-
`25
`
`Phe-
`35
`
`His-
`6
`
`Lys-
`16
`
`Gly-
`26
`
`Pro-
`36
`
`Phe-
`7
`
`Arg-
`17
`
`Ala-
`27
`
`Leu-
`37
`
`Arg-
`8
`
`Arg-
`18
`
`Glu-
`28
`
`Glu-
`38
`
`Trp-
`9
`
`Pro-
`19
`
`Asp-
`29
`
`Phe-
`39
`
`Gly-
`10
`
`Val-
`20
`
`Glu-
`30
`
`OH
`
`CLINICAL PHARMACOLOGY
`
`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%).
`
`INDICATIONS AND USAGE
`
`Purified Cortrophin Gel is indicated in the following disorders:
`
`1. Rheumatic disorders:
`As adjunctive therapy for short-term administration (to tide the patient over an acute
`episode or exacerbation) in:
`Psoriatic arthritis.
`
`Reference ID: 4880561
`
`

`

`Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require
`low-dose maintenance therapy).
`Ankylosing spondylitis.
`Acute gouty arthritis.
`2. Collagen diseases:
`During an exacerbation or as maintenance therapy in selected cases of:
`Systemic lupus erythematosus.
`Systemic dermatomyositis (polymyositis).
`3. Dermatologic diseases:
`Severe erythema multiforme (Stevens-Johnson syndrome).
`Severe psoriasis.
`4. Allergic states:
`Atopic dermatitis.
`Serum sickness.
`5. Ophthalmic diseases:
`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:
`Symptomatic sarcoidosis.
`7. Edematous states:
`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:
`Acute exacerbations of multiple sclerosis.
`
`
`CONTRAINDICATIONS
`
`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.
`
`WARNINGS
`
`Reference ID: 4880561
`
`

`

`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. 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.
`
`Reference ID: 4880561
`
`

`

`PRECAUTIONS
`
`General
`
`Patients with latent tuberculosis or tuberculin reactivity who receive corticotropin should be
`closely observed as reactivation of the disease may occur. During prolonged corticotropin
`therapy, these patients should receive chemoprophylaxis.
`
`Skin testing should be performed prior to treatment of all patients with suspected sensitivity to
`porcine protein. Immediately following intramuscular or subcutaneous administration of
`corticotropin all patients should be observed carefully for sensitivity reactions.
`
`Relative adrenocortical insufficiency induced by prolonged corticotropin therapy may be
`minimized by gradual reduction of corticotropin dosage. This type of insufficiency may persist
`for months after discontinuation of therapy; therefore, in any situation of stress during that
`period, hormone therapy should be reinstituted.
`
`There is an enhanced effect of corticotropin in patients with hypothyroidism and in those with
`cirrhosis.
`
`The lowest possible dosage of corticotropin should be used to control the condition under
`treatment, and when reduction in dosage is possible the reduction should be gradual.
`
`Corticotropin should be administered for treatment only when the disease is intractable to more
`conventional therapy. Corticotropin should be adjunctive and not the sole therapy in the
`treatment of a disease.
`
`Since maximal corticotropin stimulation of the adrenals may be limited during the first few days
`of treatment, other drugs should be administered when an immediate therapeutic effect is
`desirable.
`
`When infection is present appropriate anti-infective therapy should be administered during
`corticotropin and following discontinuation of corticotropin therapy.
`
`Treatment of acute gouty arthritis should be limited to a few days. Since rebound attacks may
`occur when corticotropin is discontinued, conventional concomitant therapy should be
`administered during corticotropin treatment, and for several days after it is stopped.
`
`Psychic derangements may appear when corticotropin is used, ranging from euphoria, insomnia,
`mood swings, personality changes, and depression, to frank psychotic manifestations. Also,
`existing emotional instability or psychotic tendencies may be aggravated by corticotropin.
`
`Corticotropin should be used with caution in patients with diabetes, abscess, pyogenic infections,
`diverticulitis, renal insufficiency, and myasthenia gravis.
`
`Growth and development of infants and children on prolonged corticotropin therapy should be
`carefully observed.
`
`Reference ID: 4880561
`
`

`

`Although controlled clinical trials have shown ACTH to be effective in speeding the resolution
`of acute exacerbations of multiple sclerosis, they do not show that it affects the ultimate outcome
`or natural history of the disease.
`
`Since complications of treatment with ACTH are dependent on the size of the dose and the
`duration of treatment, a risk/benefit decision must be made in each individual case as to dose and
`duration of treatment.
`
`Drug Interactions
`
`Aspirin should be used cautiously in conjunction with corticotropin in hypoprothrombinemia.
`
`Pregnancy
`
`Since fetal abnormalities have been observed in experimental animals, use of this drug in
`pregnancy, nursing mothers, or women of childbearing potential requires that the potential
`benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus.
`Infants born of mothers who have received substantial doses of corticotropin during pregnancy
`should be carefully observed for signs of hypoadrenalism.
`
`ADVERSE REACTIONS
`
`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
`Impaired wound healing.
`Increased sweating.
`Thin fragile skin.
`
`Reference ID: 4880561
`
`

`

`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, shock, skin reactions,
`especially in patients with allergic responses to proteins.
`
`Miscellaneous
`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.
`
`Reference ID: 4880561
`
`

`

`DOSAGE AND ADMINISTRATION
`
`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.
`
`In the treatment of acute exacerbations of multiple sclerosis daily 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.
`
`This product may be administered subcutaneously or intramuscularly.
`
`Parenteral drug products should be inspected visually for particulate matter and discoloration
`prior to administration whenever solution and container permit.
`
`HOW SUPPLIED/STORAGE AND HANDLING
`
`Purified Cortrophin Gel is supplied sterile in 5 mL multiple-dose vials (NDC 62559-860-15)
`containing 80 USP units/mL.
`
`Store Purified Cortrophin Gel refrigerated at 2° to 8°C (36° to 46°F).
`
`Distributed by:
`ANI Pharmaceuticals, Inc.
`Baudette, MN 56623
`
`
`
`
`10233 Rev 10/21
`
`
`
`
`
`Reference ID: 4880561
`
`

`

`INSTRUCTIONS FOR USE
`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)
`• Several alcohol pads
`• Cotton balls or gauze pad
`• Bandage (if needed)
`• Sharps container for throwing away used syringes and needles.
`
`
`Preparing Purified Cortrophin Gel
`• Wash your hands thoroughly 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; it
`needs to be warmed to a liquid gel before injecting. Warm the
`contents of the vial by rolling between your hands for a few
`minutes. Do not microwave or heat on the stove.
`
`
`
`
`
`
`Reference ID: 4880561
`
`

`

`• Remove (flip off) the plastic cap from the top of the Purified
`Cortrophin Gel vial and throw away this plastic cap in the trash.
`Do not put the plastic cap back on the vial.
`
`• Wipe the top of the vial rubber stopper with a new sterile
`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.
`
`
`
`
`
`
`
`
`Injecting Purified Cortrophin Gel
`• Prepare the skin where you are going to give the injection by wiping it with a new sterile
`alcohol wipe. 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.
`• 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 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:
`o made of a heavy-duty plastic,
`o can be closed with a tight-fitting, puncture-resistant lid, without sharps being able
`to come out,
`o upright and stable during use,
`leak-resistant, and
`o
`o 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 safe sharps disposal, and for specific information
`
`•
`
`Reference ID: 4880561
`
`

`

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