DRUG INTERACTIONS-(summary)

­ • Live Vaccines: Live vaccines should not be given with COSENTYX.

DRUG INTERACTIONS-(details)-

Drug interaction trials have not been conducted with COSENTYX.

1. Live Vaccines Patients treated with COSENTYX may not receive live vaccinations 

2. Non-Live Vaccines Patients treated with COSENTYX may receive non-live vaccinations.

Healthy individuals who received a single 150 mg dose of COSENTYX 2 weeks prior to vaccination with a non-U.S. approved group C meningococcal polysaccharide conjugate vaccine and a non-U.S. approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination.

The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX

3. CYP450 Substrates A role for IL-17A in the regulation of CYP450 enzymes has not been reported.

The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFa, IFN) during chronic inflammation. Thus, COSENTYX, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes.

Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate.

BRIEF SUMMARY

SECKINUMAB- (Jan 2015)

Indn-       indicated for the treatment of moderate to severe plaque

Comp-      ­ • Injection: 150 mg/mL solution in a single-use Sensoready® pen                     • Injection: 150 mg/mL solution in a single-use prefilled syringe                                         • For Injection: 150 mg, lyophilized powder in a single-use vial for reconstitution for healthcare professional use only                                                                                           • Recommended dose is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3 and 4 followed by 300 mg every 4 weeks. For some patients, a dose of 150 mg may be acceptable

ADR-      ­ Most common adverse reactions (> 1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

CI-      Serious hypersensitivity reaction to secukinumab or to any of the excipients.

WARNINGS-

­ • Infections: Serious infections have occurred. Caution should be exercised when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. If a serious infection develops, discontinue until the infection resolves.

Pat Infm-                                                                                                                       Patient Counseling-                                                                                                        Instruct patients to read the Medication Guide before startintherapy and to reread the Medication Guide each time the prescription is renewed.

Advise patients of the potential benefits and risks of the drug

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Novel Drug Approvals for 2015

1.Name       - COSENTYX

2. Active Ingredient-     Secukinumab

3. Indication-      indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Date of Approval  Jan 2015

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use COSENTYX safely and effectively. See full prescribing information for COSENTYX.

COSENTYXTM (secukinumab) injection, for subcutaneous use COSENTYXTM (secukinumab) for injection, for subcutaneous use

Initial U.S. Approval: 2015

INDICATIONS AND USAGE-

­ COSENTYX is a human interleukin-IL-17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

ADVERSE REACTIONS-

­ Most common adverse reactions (> 1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

CONTRAINDICATIONS-

­ Serious hypersensitivity reaction to secukinumab or to any of the excipients.

WARNINGS AND PRECAUTIONS-

­ • Infections: Serious infections have occurred. Caution should be exercised when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. If a serious infection develops, discontinue COSENTYX until the infection resolves.

 • Tuberculosis (TB): Prior to initiating treatment with COSENTYX, evaluate for TB.

 • Crohn’s Disease: Exacerbations observed in clinical trials. Caution should be exercised when prescribing COSENTYX to patients with active Crohn’s disease.

 • Hypersensitivity Reactions: If an anaphylactic reaction or other serious allergic reaction occurs, discontinue COSENTYX immediately and initiate appropriate therapy. 

DOSAGE AND ADMINISTRATION-

­ • Recommended dose is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3 and 4 followed by 300 mg every 4 weeks. For some patients, a dose of 150 mg may be acceptable.

 • See Full Prescribing Information for preparation of the Sensoready® pen and prefilled syringe.

 • Reconstitute COSENTYX lyophilized powder in a vial with Sterile Water for Injection. Reconstitution should be performed by a healthcare provider.-

DOSAGE FORMS AND STRENGTHS-

­ • Injection: 150 mg/mL solution in a single-use Sensoready® pen                                         • Injection: 150 mg/mL solution in a single-use prefilled syringe                                       • For Injection: 150 mg, lyophilized powder in a single-use vial for reconstitution for healthcare professional use only 

PATIENT COUNSELING INFORMATION

Advise the patient to read FDA-approved patient labeling [Medication Guide and Instructions for Use].

Patient Counseling-                                                                                                        Instruct patients to read the Medication Guide before starting COSENTYX therapy and to reread the Medication Guide each time the prescription is renewed.

Advise patients of the potential benefits and risks of COSENTYX.

Infections Inform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection

 Hypersensitivity-                                                                                                             Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions

 Instruction on Injection Technique-                                                                              Perform the first self-injection under the supervision of a qualified healthcare professional.

If a patient or caregiver is to administer COSENTYX, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX

 Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items.

Instruct patients to inject the full amount of COSENTYX (1 or 2 subcutaneous injections of 150 mg) according to the directions provided in the Medication Guide and Instructions for Use.

Dispose of needles, syringes and pens in a puncture-resistant container.

Manufactured by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 US License No. 1244 © Novartis T201X-XX Month Yea

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.

2. Pharmacodynamics-                                                                                                  Elevated levels of IL-17A are found in psoriatic plaques. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques.

3. Pharmacokinetics-                                                                                              Absorption-                                                                                                              Following a single subcutaneous dose of either 150 mg (one-half the recommended dose) or 300 mg in plaque psoriasis patients, secukinumab reached peak mean (+ SD) serum concentrations (Cmax) of 13.7 ± 4.8 mcg/mL and 27.3 ± 9.5 mcg/mL, respectively, by approximately 6 days post dose.

Distribution -                                                                                                                  The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in plaque psoriasis patients. Intravenous use is not recommended 

Elimination-                                                                                                                   The metabolic pathway of secukinumab has not been characterized. As a human IgG1? monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Specific Populations-

Hepatic or Renal Impairment: No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.

Age: Geriatric Population: Population pharmacokinetic analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with plaque psoriasis.

Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.

USE IN SPECIFIC POPULATIONS

1. Pregnancy-                                                                                                         Pregnancy Category B There are no adequate and well controlled trials of COSENTYX in pregnant women.

3. Nursing Mothers-                                                                                                          It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, caution should be exercised when COSENTYX is administered to a nursing woman.

.4. Pediatric Use-                                                                                                              Safety and effectiveness of COSENTYX in pediatric patients have not been evaluated.

5. Geriatric Use-                                                                                                               Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, a total of 230 were 65 years or older, and 32 subjects were 75 years or older.

Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects.

 OVERDOSAGE-

Doses up to 30 mg/kg intravenously (i.e., approximately 2000 to 3000 mg) have been administered in clinical trials without dose-limiting toxicity. In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of