TENTH SUPPLEMENTAL INDENTURE

The Tenth Supplemental Indenture (this “Tenth Supplemental Indenture”), dated as of October 21, 2013, among Express Scripts Holding Company (formerly Aristotle Holding, Inc.), a corporation duly organized and existing under the laws of the State of Delaware (the “Company”), United BioSource Holdings, Inc., a Delaware corporation, and Express Scripts Pharmacy, Inc. (each an “Additional Guarantor”, and together the “Additional Guarantors”), and Wells Fargo Bank, National Association, as trustee under the indenture referred to below (the “Trustee”).

WHEREAS, the Company, certain Guarantors and the Trustee are parties to the indenture, dated as of November 21, 2011 (the “Base Indenture”), as supplemented by the First Supplemental Indenture thereto, dated as of November 21, 2011 (the “First Supplemental Indenture”), relating to the Company’s 2.750% Notes due 2014 (the “2014 Notes”), the Second Supplemental Indenture thereto, dated as of November 21, 2011 (the “Second Supplemental Indenture”), relating to the Company’s 3.500% Notes due 2016 (the “2016 Notes”), the Third Supplemental Indenture thereto, dated as of November 21, 2011 (the “Third Supplemental Indenture”), relating to the Company’s 4.750% Notes due 2021 (the “2021 Notes”), the Fourth Supplemental Indenture thereto, dated as of November 21, 2011 (the “Fourth Supplemental Indenture”), relating to the Company’s 6.125% Notes due 2041 (the “2041 Notes”), the Fifth Supplemental Indenture thereto, dated as of February 9, 2012 (the “Fifth Supplemental Indenture”), relating to the Company’s 2.100% Notes due 2015 (the “2015 Notes”), the Sixth Supplemental Indenture thereto, dated as of February 9, 2012 (the “Sixth Supplemental Indenture”), relating to the Company’s 2.650% Notes due 2017 (the “2017 Notes”), the Seventh Supplemental Indenture thereto, dated as of February 9, 2012 (the “Seventh Supplemental Indenture”), relating to the Company’s 3.900% Notes due 2022 (together with the 2014 Notes, the 2016 Notes, the 2021 Notes, the 2041 Notes, the 2015 Notes and the 2017 Notes, the “Notes”), the Eighth Supplemental Indenture thereto, dated as of April 2, 2012 (the “Eighth Supplemental Indenture”), to add guarantees, and the Ninth Supplemental Indenture thereto, dated as of May 29, 2012 (together with the First Supplemental Indenture, the Second Supplemental Indenture, the Third Supplemental Indenture, the Fourth Supplemental Indenture, the Fifth Supplemental Indenture, the Sixth Supplemental Indenture, the Seventh Supplemental Indenture and the Eighth Supplemental Indenture, the “Supplemental Indentures” and the Base Indenture as so supplemented, the “Indenture”), to add guarantees;

WHEREAS, each Additional Guarantor desires to provide a full and unconditional guarantee (the “Guarantee”) of the obligations of the Company under the Notes, the Securities (as defined in the Indenture) and the Indenture on the terms and conditions set forth herein;

WHEREAS, the Company has complied with all conditions precedent provided for in the Base Indenture and each Supplemental Indenture relating to this Tenth Supplemental Indenture;

WHEREAS, Section 7.1 of each the First Supplemental Indenture, the Second Supplemental Indenture, the Third Supplemental Indenture, the Fourth Supplemental Indenture, the Fifth Supplemental Indenture, the Sixth Supplemental Indenture and the Seventh Supplemental Indenture provides that without seeking the consent of any Holders, the Company, together with the Trustee, at any time and from time to time, may modify and amend the Base Indenture to add one or more guarantors and to make any amendment that does not adversely affect the interests of the Holders of any Securities in any material respect;

WHEREAS, Section 7.1 of each the First Supplemental Indenture, the Second Supplemental Indenture, the Third Supplemental Indenture, the Fourth Supplemental Indenture, the Fifth Supplemental Indenture, the Sixth Supplemental Indenture and the Seventh Supplemental Indenture provides that no amendment to cure any ambiguity, defect or inconsistency in the Base Indenture or the applicable Supplemental Indenture made solely to conform the Base Indenture or the applicable Supplemental Indenture to any description of the Securities in the offering circular therefor, to the extent that such provision in the offering circular was intended to be a verbatim

recitation of a provision of the Base Indenture or the applicable Supplemental Indenture, shall be deemed to adversely affect the interest of the Holder of any Securities.

WHEREAS, pursuant to Section 7.1 of each of the First Supplemental Indenture, the Second Supplemental Indenture, the Third Supplemental Indenture, the Fourth Supplemental Indenture, the Fifth Supplemental Indenture, the Sixth Supplemental Indenture and the Seventh Supplemental Indenture, the Company, the Trustee and the Additional Guarantors are authorized to execute and deliver this Tenth Supplemental Indenture.

NOW, THEREFORE, for good and valuable consideration, the receipt of which is acknowledged, the parties hereby agree as follows:

1.Capitalized Terms. Capitalized terms used herein without definition shall have the meanings assigned to them in the Indenture.

2.Guarantee, Etc. Each Additional Guarantor hereby agrees that from and after the date hereof it shall be a Guarantor under the Indenture and be bound by the terms thereof applicable to Guarantors and shall be entitled to all of the rights and subject to all of the obligations of a Guarantor thereunder.

3.Cross-Default. Section 5.1(3) of the Base Indenture is hereby amended and restated in its entirety as follows:

“default under any mortgage, indenture or instrument under which there may be issued or by which there may be secured or evidenced any Indebtedness for money borrowed by the Company or any Restricted Subsidiary (or the payment of which is guaranteed by any Restricted Subsidiary), if that default is caused by a failure to pay principal at its stated maturity after giving effect to any applicable grace period, or results in the acceleration of such Indebtedness prior to its stated maturity and, in each case, the principal amount of any such Indebtedness, together with the principal amount of any other Indebtedness under which there has been a payment default after stated maturity or the maturity of which has been so accelerated, aggregates $100 million or more;”

4.Ratification of Indenture; Supplemental Indenture Part of Indenture. The Indenture is in all respects ratified and confirmed, and all terms, conditions and provisions thereof shall remain in full force and effect, except to the extent that such terms, conditions or provisions may have been amended hereby. This Tenth Supplemental Indenture shall form a part of the Indenture for all purposes, and every Holder of Securities heretofore or hereafter authenticated and delivered shall be bound hereby.

5.Representations and Warranties. Each Additional Guarantor hereby represents that (a) it is duly organized, validly existing and in good standing under the laws of the jurisdiction of its organization, (b) it has full power, authority and legal rights to execute and deliver this Tenth Supplemental Indenture and to perform its obligations hereunder and under the Indenture, (c) the execution, delivery and performance by it of this Tenth Supplemental Indenture has been duly authorized by all necessary corporate action, and no other proceedings or actions on the part of such Additional Guarantor are necessary therefor and (d) this Tenth Supplemental Indenture has been duly and validly executed and delivered by such Additional Guarantor and constitutes a legal, valid and binding obligation of such Additional Guarantor, enforceable against such Additional Guarantor in accordance with its terms (subject to applicable bankruptcy, insolvency, receivership, reorganization, moratorium and other similar laws of general applicability relating to or affecting creditors’ rights and to general equity principles).

6.No Personal Liability of Directors, Officers, Employees or Stockholders. No director, officer, employee, member or stockholder of any Additional Guarantor, as such, will have any liability for any obligations of the Company, or any other Guarantor under the Securities, the Indenture or the Guarantees, or for any claim based on, in respect of, or by reason of, such obligations or their creation. Each Holder of Securities, by accepting a Security, waives and releases the Company, each Guarantor and each Additional Guarantor from all such liability. The waiver and release are part of the consideration for issuance of the Guarantee by the Additional Guarantors.

8.Counterparts. This Tenth Supplemental Indenture may be executed in any number of counterparts, each of which shall be deemed an original; but all such counterparts shall together constitute but one and the same instrument.

9.Effect of Headings. The Section headings herein are for convenience only and shall not affect the construction hereof.

10.Trustee. The Trustee shall not be responsible in any manner whatsoever for or in respect of the validity or sufficiency of this Tenth Supplemental Indenture or for or in respect of the recitals contained herein, all of which recitals are made solely by the Additional Guarantors and the Company.

By:    /s/ Keith J. Ebling        
Name: Keith J. Ebling
Title: Executive Vice President and General Counsel

By:     /s/ Keith J. Ebling        
    Name:    Keith J. Ebling
    Title:    President

By:     /s/ Martin P. Akins        
    Name:    Martin P. Akins
    Title:    Secretary