Cadence PharmaceuticalsOfirmev (acetaminophen) Injection, 10mg/mL

NDA 022450 COMPLETE RESPONSE

Cadence Pharmaceuticals 21481 High Bluff Drive, Suite 200 San Diego, CA 92130

Attention: Tracy Ross-Teichert Director, Regulatory Affairs

Dear Ms. Ross:

Please refer to your new drug application (NDA) dated May 12, 2009, received May 13,2009, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Ofirmev (acetaminophen) Injection, 10mg/mL.

We acknowledge receipt of your amendments dated May 19, 22, and 27, June 4, 23(2), 26, and 29, July 28, August 11, 12, 14, and 28, September 10, 14(2), 18, and 27, October 21 and 23(2) November 2, 4, 7, 9, and 23, and December 4(2), 10, and 14, 2009, and January 13(2), 2010.

We have completed the review of your application, and have determined that we cannot approve this application in its present form. We have described below our reasons for this action and, where possible, our recommendations to address these issues.

FACILITY INSPECTIONS

During a recent inspection of the Baxter Healthcare manufacturing facility in Cleveland, MS for this application, our investigator conveyed deficiencies to the representative of the facility. Satisfactory compliance with Current Good Manufacturing Practices for Drugs is required for all manufacturing and testing facilities listed in the NDA before this application may be approved.

LABELING

We reserve comment on the proposed labeling until the application is otherwise adequate. If you revise labeling, your response must include updated content of labeling [21 CFR 314.50()(1)()] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.

NDA 022450 Page 2

SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at

21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.

1. Describe in detail any significant changes or findings in the safety profile.

2. When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data as follows:

e Present new safety data from the studies/clinical trials for the proposed indication using the same format as the original NDA submission.

e Present tabulations of the new safety data combined with the original NDA data.

e Include tables that compare frequencies of adverse events in the original NDA with the retabulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.

3. Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.

4. Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.

5. Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original NDA data.

6. Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).

7. Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.

8. Provide English translations of current approved foreign labeling not previously submitted.

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OTHER

Within one year after the date of this letter, you are required to resubmit or take one of the other actions available under 21 CFR 314.110. If you do not take one of these actions, we will consider your lack of response a request to withdraw the application under 21 CFR 314.65. A resubmission must fully address all the deficiencies listed. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

Under 21 CFR 314.102(d), you may request a meeting or telephone conference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the FDA’s Guidance for Industry - Formal Meetings Between the FDA and Sponsors or Applicants, May 2009 at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM153222.pdf.

The drug product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, call Ramani Sista, Regulatory Project Manager, at (301) 796-1236. Sincerely, {See appended electronic signature page}

Sharon Hertz, M.D.

Deputy Director

Division of Anesthesia, Analgesia and Rheumatology Products

Office of Drug Evaluation II

Center for Drug Evaluation and Research

Application Submission

Type/Number Type/Number Submitter Name Product Name

NDA-22450 ORIG-1 CADENCE Ofirmev (acetaminophen for PHARMACEUTICA injection) LS INC

This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.

SHARON H HERTZ 02/10/2010