STOCKHOLDERS AGREEMENT

Exhibit 10.4

STOCKHOLDERS AGREEMENT

by and among

CHIESI FARMACEUTICI SPA,

CRAIG A. COLLARD,

STEVEN M. LUTZ,

CORNERSTONE BIOPHARMA HOLDINGS, LTD.,

CAROLINA PHARMACEUTICALS, LTD.,

LUTZ FAMILY LIMITED PARTNERSHIP

and

CORNERSTONE THERAPEUTICS INC.

Dated as of May 6, 2009

TABLE OF CONTENTS

STOCKHOLDERS AGREEMENT

     This STOCKHOLDERS AGREEMENT , dated as of May 6, 2009 (this “ Agreement ”), is by and among CHIESI FARMACEUTICI SPA, a corporation organized under the laws of Italy (“ Purchaser ”), CRAIG A. COLLARD, CORNERSTONE BIOPHARMA HOLDINGS, LTD., a limited liability company organized under the laws of Anguilla, CAROLINA PHARMACEUTICALS, LTD., a limited liability company organized under the laws of Bermuda, LUTZ FAMILY LIMITED PARTNERSHIP, North Carolina limited partnership, and STEVEN M. LUTZ (the “ Stockholders ”), and CORNERSTONE THERAPEUTICS INC., a Delaware corporation (the “ Company ”).

RECITALS

      WHEREAS , concurrently with the execution and delivery of this Agreement, (i) Purchaser and certain of the Stockholders are entering into a Stock Purchase Agreement (the “ Initial Stock Purchase Agreement ”), dated the same date as this Agreement, and (ii) the Company and Purchaser are entering into a Stock Purchase Agreement (the “ Company Stock Purchase Agreement ”), also dated the same date as this Agreement;

      WHEREAS , following consummation of the transactions contemplated by the Initial Stock Purchase Agreement and the Company Stock Purchase Agreement, Purchaser will own approximately 13,502,741 shares of the Company’s common stock, par value $0.001 per share (the “ Common Stock ”); and

      WHEREAS , the parties to this Agreement desire to set forth certain agreements regarding future transfers of Common Stock by any of the Stockholders, and regarding an option on the part of Purchaser to purchase certain shares of Common Stock from the Stockholders;

      NOW, THEREFORE , the parties hereto hereby agree as follows:

ARTICLE I

DEFINITIONS

     Section 1.1. Defined Terms . As used in this Agreement, the following terms shall have the respective meanings set forth below:

     “ Beneficially Own ” shall mean, with respect to any security, having the power to direct or control the voting or disposition of such security, and “ Beneficially Owned ” shall have a correlative meaning. For this purpose, securities underlying an immediately exercisable option or conversion or similar right are deemed Beneficially Owned by the holder of the option or other such right.

     “ Beneficial Owner ” shall mean, with respect to any security, a Person who Beneficially Owns such security, and “ Beneficial Ownership ” shall have a correlative meaning.

     “ Blackout Period ” shall mean the period beginning on the Closing and ending at 11:59 p.m. New York City time on the second anniversary of the Closing.

     “ Business Day ” shall mean any day other than a Saturday, Sunday or other day on which commercial banks located in New York City, New York are required or permitted by law to be closed for the conduct of regular banking business.

     “ Call Option Period ” shall mean as to any Stockholder the period beginning at 9:00 a.m. New York City time on the earlier to occur of the (i) the expiration of the Blackout Period and (ii) the date following the date of the Employment Termination Event and ending on the date that is 30 days after such date.

     “ Closing ” shall mean the Closing provided for in the Company Stock Purchase Agreement.

     “ Corporate Affiliate ” shall mean, with respect to any Stockholder, a corporation of which all the capital stock is owned, directly or indirectly, by such Stockholder.

     “ Covered Shares ” shall mean, with respect to each Stockholder, the number of shares of Common Stock set forth opposite the name of such Stockholder on Annex A under “Covered Shares”, ratably and equitably adjusted to take into account any stock split, stock dividend, reverse stock split or similar adjustment to capital stock occurring after the date of this Agreement.

     “ Employment Termination Event ” shall mean (i) as to Craig A. Collard, Cornerstone Biopharma Holdings, Ltd. and Carolina Pharmaceuticals, Ltd. the date of termination of Mr. Collard’s employment with the Company and (ii) as to Steven M. Lutz and Lutz Family Limited Partnership the date of termination of Mr. Lutz’s employment with the Company; provided , that in each such case, a termination that results from a resignation without Good Reason and termination for Cause (as those terms are defined in the applicable employment agreements with the Company) shall not constitute an Employment Termination Event.

     “ Exchange Act ” shall mean the Securities Exchange Act of 1934, as amended.

     “ Exempt Transfer ” shall mean any direct or indirect Transfer of Beneficial Ownership of Common Stock made:

     “ Partnership Affiliate ” shall mean, with respect to any Stockholder, a limited partnership, the general partner of which is, or is under the exclusive control of, and the majority of the limited liability partnership interests of which are owned by, such Stockholder.

     “ Per Share Option Price ” shall mean $12.00, ratably and equitably adjusted to take into account any stock split, stock dividend, reverse stock split or similar adjustment to capital stock occurring after the date of this Agreement.

     “ Person ” shall mean any individual, partnership, firm, corporation, association, joint venture, trust or other entity, or any government or political subdivision or agency, department or instrumentality thereof.

     “ Transfer ” shall mean any sale, assignment or other outright transfer of Beneficial Ownership of any shares of Common Stock. “ Transferred ” shall have a correlative meaning.

     “ Trust Affiliate ” shall mean, with respect to any Stockholder, a trust established for the primary benefit of such Stockholder, so long as the only Persons entitled to direct the voting of any Common Stock held by the trust are the transferor, another Stockholder, or a bank or other corporation having trust powers.

     In addition, the following terms are defined elsewhere in the Agreement:

ARTICLE II

REPRESENTATIONS AND WARRANTIES OF THE STOCKHOLDERS

     Each Stockholder represents and warrants, severally but not jointly and solely with respect to such Stockholder and not with respect to the other Stockholder, to Purchaser as follows:

     Section 2.1. Ownership of Shares . As of the date of this Agreement, such Stockholder is the lawful record and beneficial owner of the number of shares of Common Stock set forth next to such Stockholder’s name on Exhibit A free and clear of all liens, charges, security interests, mortgages, pledges, options, preemptive rights, rights of first refusal or first offer, proxies, levies, voting trusts or agreements, or other adverse claims or restrictions on title or transfer of any nature whatsoever (collectively, “ Encumbrances ”), other than restrictions on transfer imposed under applicable securities laws.

     Section 2.2. Authority . Such Stockholder is either (a) an individual with the requisite legal capacity and authority or (b) an entity with the requisite partnership or limited liability company power and authority to execute and deliver this Agreement and to perform the transactions contemplated by this Agreement. This Agreement has been duly and validly executed and delivered by such Stockholder and, assuming the due authorization, execution and delivery of this Agreement by each other party hereto, constitutes legal, valid and binding obligations of such Stockholder, enforceable against such Stockholder in accordance with its terms.

     Section 2.3. Consents and Approvals; No Violations .

     (a) The execution, delivery and performance by such Stockholder of this Agreement and the consummation by such Stockholder of the transactions contemplated hereby do not and will not require any filing or registration with, notification to, or authorization, permit, consent or approval of, or other action

by or in respect of, any U.S. or non-U.S. government, regulatory or administrative authority, agency, instrumentality or commission or any court, tribunal, judicial or arbitral body or other similar authority (a “ Governmental Authority ”) other than where the failure to obtain such consents, approvals, authorizations or permits or to make such filings or notifications would not reasonably be expected to have a Material Adverse Effect (as defined in the Company Stock Purchase Agreement).

     (b) The execution, delivery and performance by such Stockholder of this Agreement and the consummation by such Stockholder of the transactions contemplated hereby do not and will not (i) result in a violation or breach of, or constitute (with or without notice or lapse of time or both) a default under, or give rise to any right of termination, amendment, cancellation, acceleration or loss of benefits or the creation or acceleration of any right or obligation under or result in the creation of any Encumbrance upon any of the properties or assets of such Stockholder under, any of the terms, conditions or provisions of any note, bond, mortgage, indenture, deed of trust, loan, credit agreement, lease, license, permit, concession, franchise, purchase order, sales order, contract, agreement or other instrument, understanding or obligation, whether written or oral (a “ contract ”), to which such Stockholder is a party or by which any of its properties or assets may be bound or (ii) violate any law applicable to such Stockholder or any of his properties or assets, except in each such case as would not reasonably be expected to prevent or delay the consummation of the transactions contemplated hereby.

ARTICLE III

LIQUIDITY AND TRANSFER RESTRICTIONS

     Section 3.1. Ownership of Shares; Legend .

     (a) Each certificate representing any of the shares of Common Stock held by a Stockholder shall bear the following legend in addition to any other legend required under applicable law:

THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO THE TERMS AND CONDITIONS OF A STOCKHOLDERS AGREEMENT BY AND AMONG THE COMPANY AND THE PERSONS SPECIFIED THEREIN, A COPY OF WHICH AGREEMENT IS ON FILE AT THE PRINCIPAL OFFICE OF THE COMPANY. THE SALE, TRANSFER OR OTHER DISPOSITION OF THE SECURITIES IS SUBJ