Reimbursement BILLING GUIDE

Transcription

1 Reimbursement BILLING GUIDE

2 Merck has developed this Reimbursement Billing Guide as a tool to help you navigate the health care insurance environment for KEYTRUDA. IMPORTANT INFORMATION CONTENTS The information available here is compiled from sources believed to be accurate, but Merck makes no representation that it is accurate. This information is subject to change. Payer coding requirements may vary or change over time, so it is important to regularly check with each payer as to payer-specific requirements. The information available here is not intended to be conclusive or exhaustive, and is not intended to replace the guidance of a qualified professional advisor. Merck and its agents make no warranties or guarantees, expressed or implied, concerning the accuracy or appropriateness of this information for your particular use given the frequent changes in public and private payer billing. The use of this information does not guarantee payment or that any payment received will cover your costs. You are solely responsible for determining the appropriate codes and for any action you take in billing. Information about Healthcare Common Procedure Coding System (HCPCS) codes is based on guidance issued by the Centers for Medicare & Medicaid Services (CMS) applicable to Medicare Part B and may not apply to other public or private payers. Consult the relevant manual and/or other guidelines for a description of each code to determine the appropriateness of a particular code and for information on additional codes. Diagnosis codes should be selected only by a health care professional. NDC and Billing and Diagnosis Codes for KEYTRUDA...4 National Drug Code (NDC) and Packaging Information...4 Billing Codes HCPCS Codes...5 Revenue Code For Use in the Hospital Inpatient Setting...5 Current Procedural Terminology (CPT ) Code for Administration...5 Diagnosis Codes...6 Sample Claim Forms Coverage and Reimbursement for KEYTRUDA...14 Commercial and Private Payer Coverage Prior Authorization Checklist Medical Necessity Letter Indications KEYTRUDA is indicated for the treatment of patients with metastatic non small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These indications are approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. PD-L1 = programmed death ligand 1; EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase. Appeals Checklist/Letter Medicare Coverage...16 Medicaid Coverage...16 The Merck Access Program for KEYTRUDA Selected Safety Information...18 References...22 Important Information...22

3 NDC AND BILLING AND DIAGNOSIS CODES FOR KEYTRUDA The following codes may be relevant when billing for KEYTRUDA and its administration. This information is current as of April The information provided here is compiled from sources believed to be accurate, but Merck makes no representation that it is accurate. Information about HCPCS codes is based on guidance issued by the CMS applicable to Medicare Part B and may not apply to other public or private payers. Consult the relevant manual and/or other guidelines for a description of each code to determine the appropriateness of its use and for information on additional codes. Diagnosis codes should be selected only by a health care professional. This information is subject to change. Merck cautions that payer-coding requirements vary and can frequently change, so it is important to regularly check with each payer or, where applicable, the Medicare Administrative Contractor as to payer-specific requirements. You are solely responsible for determining the appropriate codes and for any action you take in billing. The information provided here is not intended to be definitive or exhaustive, and is not intended to replace the guidance of a qualified professional advisor. Diagnosis codes should be selected only by a health care professional. Merck and its agents make no warranties or guarantees, expressed or implied, concerning the accuracy or appropriateness of this information for your particular use given the frequent changes in public and private payer billing. The use of this information does not guarantee payment or that any payment received will cover your costs. Billing Codes Below is a list of possible codes that could be relevant for KEYTRUDA and its administration. Please consult with the applicable payer to understand the payer s specific billing requirements. HCPCS Codes for KEYTRUDA 1 These miscellaneous codes are for use until a unique HCPCS code is assigned to KEYTRUDA. HCPCS CODE J9999 J3590 J3490 C9027 (Effective 01/01/2015, for use only on Medicare hospital outpatient department claims.) Not otherwise classified, antineoplastic drugs Unclassified biologics Unclassified drugs Injection, pembrolizumab, 1 mg 4 5 National Drug Code (NDC) and Packaging Information Revenue Code For Use in the Hospital Inpatient Setting 2 The NDC is typically required when submitting a claim with a miscellaneous HCPCS code. Please consult with the payer to understand specific billing requirements. REVENUE CODE 0636 Drugs requiring detailed coding PRODUCT PACKAGE NDC KEYTRUDA (pembrolizumab) injection 100 mg Carton containing one 100 mg/4 ml (25 mg/ml), single-use vial Current Procedural Terminology (CPT ) a Code for Administration 3 CPT CODE (Some payers may utilize Check with the applicable payer.) Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug a CPT Copyright 2014 American Medical Association. All rights reserved. Please note: The NDC above is the billable NDC that appears on the carton. The NDC on the vial should not be used for billing purposes.

4 Diagnosis Codes Merck has provided these codes as a reference. When submitting a claim for KEYTRUDA, always verify coding requirements with the relevant payer. Coding requirements may vary by insurer or plan; please refer to the payer-specific policies to understand what codes may be covered. Check with the relevant payers regarding guidance on which diagnoses they will recognize and the applicability of secondary codes to indicate site/organ. Health care professionals are solely responsible for selecting codes that appropriately reflect the patient s diagnosis, the services rendered, and the applicable payer s guidelines. These diagnosis codes may not be applicable to dates of service on or after October 1, 2015, the date that ICD-10-CM codes are set to come into use. Check with the applicable payer for any payer-specific coding requirements relevant to the switch from ICD-9-CM to ICD-10-CM codes. The following information is per the Official ICD-9-CM Guidelines for Coding and Reporting. Please refer to the ICD-9-CM guidelines for additional information. For further coding assistance, contact The Merck Access Program at Possible relevant diagnosis codes for melanoma 172: Malignant Melanoma of Skin 4,5 Includes: melanocarcinoma, melanoma (skin) NOS, melanoma in situ of skin Excludes: skin of genital organs, sites other than skin, vermilion border of lip, anal canal, anus NOS, scrotum ICD-9-CM CODE 154: Malignant Neoplasm of Rectum, Rectosigmoid Junction, and Anus 4,5 Excludes: benign carcinoid tumor of rectum, malignant carcinoid tumor of rectum, malignant melanoma of skin of anus, malignant neoplasm of skin of anus, malignant melanoma of anus: margin, skin, perianal skin, malignant neoplasm of anus: margin, skin, perianal skin Malignant melanoma of skin of lip Malignant melanoma of skin of eyelid, including canthus Malignant melanoma of skin of ear and external auditory canal Malignant melanoma of skin of other and unspecified parts of face Malignant melanoma of skin of scalp and neck Malignant melanoma of skin of trunk except scrotum Malignant melanoma of skin of upper limb, including shoulder Malignant melanoma of skin of lower limb, including hip Malignant melanoma of other specified sites of skin Malignant melanoma of skin, site unspecified ICD-9-CM=International Classification of Diseases, Ninth Revision, Clinical Modification. ICD-10-CM=International Classification of Diseases, Tenth Revision, Clinical Modification. ICD-9-CM CODE Malignant neoplasm of anal canal Malignant neoplasm of anus, unspecified site 184: Malignant Neoplasm of Other and Unspecified Female Genital Organs 4,5 Excludes: carcinoma in situ ICD-9-CM CODE Malignant neoplasm of vagina Malignant neoplasm of labia majora Malignant neoplasm of labia minora Malignant neoplasm of clitoris Malignant neoplasm of vulva, unspecified site Malignant neoplasm of other specified sites of female genital organs Malignant neoplasm of female genital organ, site unspecified 187: Malignant Neoplasm of Penis and Other Male Genital Organs 4,5 ICD-9-CM CODE Malignant neoplasm of prepuce Malignant neoplasm of glans penis Malignant neoplasm of penis, part unspecified Malignant neoplasm of epididymis Malignant neoplasm of spermatic cord Malignant neoplasm of scrotum Malignant neoplasm of other specified sites of male genital organs Malignant neoplasm of male genital organ, site unspecified

5 190: Malignant Neoplasm of Eye 4,5 Excludes: carcinoma in situ, dark area on retina and choroid, cartilage, malignant melanoma of eyelid (skin), malignant neoplasm of eyelid (skin), optic nerve, orbital bone, retinal freckle ICD-9-CM CODE Malignant neoplasm of eyeball, except conjunctiva, cornea, retina, and choroid Malignant neoplasm of orbit Malignant neoplasm of lacrimal gland Malignant neoplasm of conjunctiva Malignant neoplasm of cornea Malignant neoplasm of retina Malignant neoplasm of choroid Malignant neoplasm of lacrimal duct Malignant neoplasm of other specified sites of eye Malignant neoplasm of eye, part unspecified Other Codes 4,5 The following diagnosis codes may be used by providers who administer KEYTRUDA. ICD-9-CM CODE It is expected that ICD-10-CM codes will apply to services provided on or after October 1, Check with the applicable payer for any payer-specific coding requirements relevant to the switch from ICD-9-CM to ICD-10-CM codes. Possible relevant diagnosis codes for melanoma C43: Malignant Melanoma of Skin 6 The C43 series: Excludes: melanoma in situ, malignant melanoma of skin of genital organs, Merkel cell carcinoma, malignant neoplasm of vermilion border of lip ICD-10-CM CODE C43.0 Malignant melanoma of lip C43.10 Malignant melanoma of unspecified eyelid, including canthus C43.11 Malignant melanoma of right eyelid, including canthus C43.12 Malignant melanoma of left eyelid, including canthus C43.20 Malignant melanoma of unspecified ear and external auricular canal C43.21 Malignant melanoma of right ear and external auricular canal C43.22 Malignant melanoma of left ear and external auricular canal C43.30 Malignant melanoma of unspecified part of face C43.31 Malignant melanoma of nose C43.39 Malignant melanoma of other part of face 8 V58.12 Encounter for antineoplastic immunotherapy C43.4 Malignant melanoma of scalp and neck C43.51 Malignant melanoma of anal skin 9 V10.82 Personal history of malignant melanoma of skin C43.52 Malignant melanoma of skin of breast C43.59 Malignant melanoma of other part of trunk C43.60 Malignant melanoma of unspecified upper limb, including shoulder Possible relevant diagnosis codes for NSCLC C43.61 Malignant melanoma of right upper limb, including shoulder 162: Malignant Neoplasm of Trachea, Bronchus, and Lung 5 C43.62 Malignant melanoma of left upper limb, including shoulder Excludes: benign carcinoid tumor of bronchus, malignant carcinoid tumor of bronchus C43.70 Malignant melanoma of unspecified lower limb, including hip ICD-9-CM CODE C43.71 Malignant melanoma of right lower limb, including hip Trachea C43.72 Malignant melanoma of left lower limb, including hip Main bronchus C43.8 Malignant melanoma of overlapping sites of skin Upper lobe, bronchus or lung C43.9 Malignant melanoma of skin, unspecified Middle lobe, bronchus or lung Lower lobe, bronchus or lung Other parts of bronchus or lung Bronchus and lung, unspecified

6 C20: Malignant Neoplasm of Rectum 6 The C20 series: Excludes: malignant carcinoid tumor of the rectum C21: Malignant Neoplasm of Anus and Anal Canal 6 The C21 series: Excludes: malignant carcinoid tumors of the colon, malignant melanoma of anal margin, malignant melanoma of anal skin, malignant melanoma of perianal skin, other and unspecified malignant neoplasm of anal margin, other and unspecified malignant neoplasm of anal skin, other and unspecified malignant neoplasm of perianal skin ICD-10-CM CODE C21.0 Malignant neoplasm of anus, unspecified C21.1 Malignant neoplasm of anal canal C21.2 Malignant neoplasm of cloacogenic zone C21.8 Malignant neoplasm of overlapping sites of rectum, anus, and anal canal C51: Malignant Neoplasm of Vulva 6 The C51 series: Excludes: carcinoma in situ of vulva C52: Malignant Neoplasm of Vagina 6 The C52 series: Excludes: carcinoma in situ of vagina C57: Malignant Neoplasm of Other and Unspecified Female Genital Organs 6 ICD-10-CM CODE C57.7 Malignant neoplasm of other specified female genital organs C57.8 Malignant neoplasm of overlapping sites of female genital organs C57.9 Malignant neoplasm of female genital organ, site unspecified C60: Malignant Neoplasm of Penis 6 ICD-10-CM CODE C60.0 Malignant neoplasm of prepuce C60.1 Malignant neoplasm of glans penis C60.2 Malignant neoplasm of body of penis C60.8 Malignant neoplasm of overlapping sites of penis C60.9 Malignant neoplasm of penis, unspecified ICD-10-CM CODE C63: Malignant Neoplasm of Other and Unspecified Male Genital Organs 6 10 C51.0 Malignant neoplasm of labium majus 11 C51.1 Malignant neoplasm of labium minus ICD-10-CM CODE C51.2 Malignant neoplasm of clitoris C63.00 Malignant neoplasm of unspecified epididymis C51.8 Malignant neoplasm of overlapping sites of vulva C63.01 Malignant neoplasm of right epididymis C51.9 Malignant neoplasm of vulva, unspecified C63.02 Malignant neoplasm of left epididymis C63.10 Malignant neoplasm of unspecified spermatic cord C63.11 Malignant neoplasm of right spermatic cord C63.12 Malignant neoplasm of left spermatic cord C63.2 Malignant neoplasm of scrotum C63.7 Malignant neoplasm of other specified male genital organs C63.8 Malignant neoplasm of overlapping sites of male genital organs C63.9 Malignant neoplasm of male genital organ, unspecified

7 C69: Malignant Neoplasm of Eye and Adnexa6 The C69 series: Excludes: malignant neoplasm of connective tissue of eyelid, malignant neoplasm of eyelid (skin), malignant neoplasm of optic nerve, dark area on retina, neoplasm of unspecified behavior of retina and choroid, retinal freckle, malignant neoplasm of orbital bone ICD-10-CM CODE 12 Possible relevant diagnosis codes for NSCLC C33: Malignant Neoplasm of Trachea6 C34: Malignant Neoplasm of Bronchus and Lung6 The C34 series: Excludes: Kaposi s sarcoma of lung, malignant carcinoid tumor of the bronchus and lung ICD-10-CM CODE C69.00 Malignant neoplasm of unspecified conjunctiva C69.01 Malignant neoplasm of right conjunctiva C34.00 Malignant neoplasm of unspecified main bronchus C69.02 Malignant neoplasm of left conjunctiva C34.01 Malignant neoplasm of right main bronchus C69.10 Malignant neoplasm of unspecified cornea C34.02 Malignant neoplasm of left main bronchus C69.11 Malignant neoplasm of right cornea C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung C69.12 Malignant neoplasm of left cornea C34.11 Malignant neoplasm of upper lobe, right bronchus or lung C69.20 Malignant neoplasm of unspecified retina C34.12 Malignant neoplasm of upper lobe, left bronchus or lung C69.21 Malignant neoplasm of right retina C34.2 Malignant neoplasm of middle lobe, bronchus or lung C69.22 Malignant neoplasm of left retina C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung C69.30 Malignant neoplasm of unspecified choroid C34.31 Malignant neoplasm of lower lobe, right bronchus or lung C69.31 Malignant neoplasm of right choroid C34.32 Malignant neoplasm of lower lobe, left bronchus or lung C69.32 Malignant neoplasm of left choroid C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung C69.40 Malignant neoplasm of unspecified ciliary body C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung C69.41 Malignant neoplasm of right ciliary body C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung C69.42 Malignant neoplasm of left ciliary body C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung C69.50 Malignant neoplasm of unspecified lacrimal gland and duct C34.91 Malignant neoplasm of unspecified part of right bronchus or lung C69.51 Malignant neoplasm of right lacrimal gland and duct C34.92 Malignant neoplasm of unspecified part of left bronchus or lung C69.52 Malignant neoplasm of left lacrimal gland and duct C69.60 Malignant neoplasm of unspecified orbit C69.61 Malignant neoplasm of right orbit C69.62 Malignant neoplasm of left orbit C69.80 Malignant neoplasm of overlapping sites of unspecified eye and adnexa C69.81 Malignant neoplasm of overlapping sites of right eye and adnexa C69.82 Malignant neoplasm of overlapping sites of left eye and adnexa C69.90 Malignant neoplasm of unspecified sites of unspecified eye C69.91 Malignant neoplasm of unspecified site of right eye C69.92 Malignant neoplasm of unspecified site of left eye ICD-10-CM CODE Z Personal history of malignant melanoma Sample Claim Forms This is a sample UB-04 (CMS-1450) paper claim for hospital outpatient billing for a patient receiving KEYTRUDA, corresponding to CPT code This is a sample CMS-1500 paper claim for office billing for a patient receiving KEYTRUDA, corresponding to CPT code

8 COVERAGE AND REIMBURSEMENT FOR KEYTRUDA Commercial and Private Payer Coverage Medical Necessity Letter Insurers may require a medical necessity letter as part of the prior authorization process (see sample letter). Each patient may have a unique billing situation for coverage, coding, and reimbursement that is dependent on the patient s health plan and associated benefits. Insurers may require a prior authorization, including submission of a letter of medical necessity. It is important to review the insurer s guidelines for obtaining a prior authorization, as these can differ depending on the insurer, the medication being prescribed, and other factors. Please ensure the accurate completion of reimbursement- or coverage-related documentation for therapies according to the specific requirements of the patient s plan. Prior Authorization Checklist The items listed below may be necessary to obtain a prior authorization decision from an insurer: Completed prior authorization request form (if required by patient s insurer) Note: Some payers may require specific forms to be completed for certain medications or therapeutic areas. Always verify that the correct form is completed. Letter of medical necessity B e sure to note the proposed treatment plan and include the Provider ID number in the letter 14 Documentation that supports the treatment decision, such as: P reviously given treatments/therapies P atient clinical notes detailing the relevant diagnosis R elevant laboratory results Product package insert Appeals Checklist/Letter As a first step in the appeal process, ensure that the claim was completed and submitted correctly. Prior to initiating the appeal process, it is important to identify the reason for denial, which can often be found in the explanation of benefits (EOB), as well as the specific insurer s instructions and processes regarding the appeal process (eg, forms, information, timelines). Below is a list of forms and documents that might be helpful when filing an appeal: Additional relevant documentation (if available) regarding the treatment decision Letter of medical necessity It might be necessary to provide the following information when making a request for prior authorization: Be sure to note the proposed treatment plan and include the Provider ID number in the letter. Patient information, including name, insurance policy number, and date of birth Physician information, including name and tax ID number Facility information, including name and tax ID number Date of service Formal letter appealing the denial Patient diagnosis Relevant procedure and HCPCS codes for services/products to be performed/provided Product NDC Setting of care Patient clinical notes detailing the relevant diagnosis The EOB that details the reason for the denial Relevant documentation regarding treatment decisions, such as: Previously tried treatments/therapies Patient clinical notes detailing the relevant diagnosis Relevant laboratory results Product package insert Additional relevant documentation (if available) regarding the treatment decision 15

9 The Merck Access Program for KEYTRUDA Medicare Coverage The Merck Access Program has been designed to provide information that can help answer questions specific to access and support for KEYTRUDA. The Merck Access Program may answer questions about: Insurance coverage for patients Medicare coverage for KEYTRUDA (pembrolizumab) injection, for intravenous infusion is expected to follow the CMS guidance in the Medicare Benefit Policy Manual, Chapter 15. Medicare covers FDA-approved indications, when administered incident to a physician visit and when deemed reasonable or necessary for the patient.7 Billing and coding information Co-pay assistance for eligible patients Benefits investigations, prior authorization, and appeals Referrals to the Patient Assistance Program Product distribution You can also request to be contacted by a Reimbursement Associate. Medicaid Coverage 16 Each state may apply its own rules on how drug utilization is managed. This could include requirements for prior authorization, and additional documents are commonly required. Keep in mind that Medicaid-eligible persons may be covered by either a Medicaid fee-for-service plan or a Medicaid managed care plan. In some situations coverage for a product can differ, as between Medicaid fee-for-service and Medicaid managed care plans. Therefore, a Medicaid patient s benefits should be confirmed to identify any additional needs. Note: For questions on billing if a portion of the package is wasted, consult the applicable payer s policy regarding wastage. The Merck Access Program is available online (merckaccessprogram-keytruda.com) and via a toll-free telephone number ( ) between 8:00 am and 8:00 pm ET, Monday through Friday. 17

10 Selected Safety Information Melanoma Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis. Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis. Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA. Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids. Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia. Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis. Other clinically important immune-mediated adverse reactions can occur. The following clinically significant immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction. Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA. KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients. Adverse reactions, reported in at least two patients, that led to discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients. The most frequent serious adverse reactions, reported in 2% or more of patients, were renal failure, dyspnea, pneumonia, and cellulitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%). No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients. Before prescribing KEYTRUDA, please read the accompanying Prescribing Information.

11 Selected Safety Information NSCLC Pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis. Colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis. Hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA. Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or Grade 4 hypophysitis. Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%). Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 hyperthyroidism Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia. Nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following steroid taper. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction. The following clinically significant, immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum sickness, myasthenia gravis, bullous pemphigoid, and Guillain-Barré syndrome. Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA. KEYTRUDA was discontinued due to adverse reactions in 14% of patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), decreased appetite (25%), dyspnea (23%), and cough (29%). No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients. Before prescribing KEYTRUDA, please read the accompanying Prescribing Information.

12 REFERENCES 1. CMS 2015 Alpha-Numeric HCPCS File. Alpha-Numeric-HCPCS.html. Accessed April 23, CMS. Medicare Claims Processing Manual, Chapter Guidance/Guidance/Manuals/Downloads/clm104c17.pdf. Accessed April 23, American Medical Association. CPT code/relative value search. CPTRelativeValueSearch.do?submitbutton=accept. Accessed April 28, OptumInsight, Inc. ICD-9-CM Expert for Hospitals Volumes 1, 2 & CMS. ICD-9-CM Diagnosis and Procedure Codes: Abbreviated and Full Code Titles. cms.gov/medicare/coding/icd9providerdiagnosticcodes/codes.html. Accessed April 23, CMS. ICD-10-CM Tabular List of Diseases and Injuries. ftp://ftp.cdc.gov/pub/health_statistics/nchs/ Publications/ICD10CM/2015/ICD10CM_FY2015_Full_PDF.zip. Accessed April 23, CMS. Medicare Benefit Policy Manual, Chapter Guidance/Guidance/Manuals/Downloads/bp102c15.pdf. Accessed April 23, IMPORTANT INFORMATION The information available here is compiled from sources believed to be accurate, but Merck makes no representation that it is accurate. This information is current as of April This information is subject to change. Payer coding requirements may vary or change over time, so it is important to regularly check with each payer as to payer-specific requirements. The information available here is not intended to be conclusive or exhaustive, and is not intended to replace the guidance of a qualified professional advisor. Merck and its agents make no warranties or guarantees, expressed or implied, concerning the accuracy or appropriateness of this information for your particular use given the frequent changes in public and private payer billing. The use of this information does not guarantee payment or that any payment received will cover your costs. You are solely responsible for determining the appropriate codes and for any action you take in billing. Information about HCPCS codes is based on guidance issued by the CMS applicable to Medicare Part B and may not apply to other public or private payers. Consult the relevant manual and/or other guidelines for a description of each code to determine the appropriateness of a particular code and for information on additional codes. Diagnosis codes should be selected only by a health care professional. The Medication Guide also is available. For additional copies of the Prescribing Information, please call , visit keytruda.com, or contact your Merck representative. Copyright 2015 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. ONCO /15 keytruda.com