DRUG INTERACTIONS

 

1. Live Vaccinations

Avoid use of live vaccines in patients treated with TALTZ .

 

2. Cytochrome P450 Substrates

 The formation of CYP450 enzymes can be altered by increased levels

  of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFá, IFN) during chronic 

  inflammation. Thus, TALTZ, an antagonist of IL-17A, could normalize 

  the formation of CYP450 enzymes.

 

 Therefore, upon initiation or discontinuation of TALTZ in patients who 

 are receiving concomitant drugs which are CYP450 substrates, 

 particularly those with a narrow therapeutic index, consider monitoring

 for effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) 

 and consider dosage modification of the CYP450 substrate.

DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016

 

No    Drug Name   Active Ingredient   Approval Date   FDA-Approved use 

                                                                                           on Approval date

 

4.      Taltz              Ixekizumab            3/22/2016         To treat adults with moderate-to-

                                                                                         severe plaque psoriasis                                                                                                                                                                                                                                                        Press Release                                                                                                                    Drug trials Snapshot                                                                                             

Approved by FDA  on 3/22/2016  (Ref- FDA approved List- 2016) 

 

 

HIGHLIGHTS OF PRESCRIBING INFORMATION 

 

These highlights do not include all the information needed to use

TALTZ safely and effectively. See full prescribing information for TALTZ.

 

TALTZ (ixekizumab) injection, for subcutaneous use 

Initial U.S. Approval: 2016

 

 

INDICATIONS AND USAGE

 

TALTZ ™ is a humanized interleukin-17A antagonist indicated for the                           treatment of adults with moderate-to-severe plaque psoriasis who are                        candidates for systemic therapy or phototherapy.

 

ADVERSE REACTIONS

 

Most common (.1%) adverse reactions associated with TALTZ treatment 

are injection site reactions, upper respiratory tract infections, nausea, 

and tinea infections.

CONTRAINDICATIONS

 

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

 

WARNINGS AND PRECAUTIONS

.

Infections: Serious infections have occurred. Instruct patients to seek medical 

advice if signs or symptoms of clinically important chronic or acute infection occur.

 If a serious infection develops, discontinue TALTZ until the infection resolves. 

.

Tuberculosis (TB): Evaluate for TB prior to initiating treatment.

 

.

Hypersensitivity: If a serious allergic reaction occurs, discontinue TALTZ

 immediately and initiate appropriate therapy. 

.

Inflammatory Bowel Disease: Crohnfs disease and ulcerative colitis, 

including exacerbations, occurred during clinical trials. 

Patients who are treated with TALTZ and have inflammatory bowel 

disease should be monitored closely. 

 

 

INDICATIONS AND USAGE

 

TALTZ ™ is a humanized interleukin-17A antagonist indicated for the                           treatment of adults with moderate-to-severe plaque psoriasis who are                        candidates for systemic therapy or phototherapy.

 

DOSAGE AND ADMINISTRATION

 

Administer by subcutaneous injection. 

Recommended dose is 160 mg (two 80 mg injections) at Week 0,

 followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12,

then 80 mg every 4 weeks. 

 

DOSAGE FORMS AND STRENGTHS

Autoinjector  Injection: 80 mg/mL solution in a single-dose prefilled autoinjector.

 Prefilled Syringe

 

 Injection: 80 mg/mL solution in a single-dose prefilled syringe. 

 

 

 PATIENT COUNSELING INFORMATION

 

 Advise the patient and/or caregiver to read the FDA-approved patient labeling 

 before the patient starts using TALTZ, and each time the prescription is renewed,

 as there may be new information they need to know.

 

Instructions on Self-Administration: Provide guidance to patients and caregivers

 on proper subcutaneous injection technique, including aseptic technique, 

and how to use the autoinjector or prefilled syringe correctly 

Use].

 

Infection: Inform patients that TALTZ may lower the ability of their immune system 

to fight infections. Instruct patients of the importance of communicating 

any history of infections to the healthcare provider, and contacting their

healthcare provider if they develop any symptoms of infection .

 

Allergic Reactions: Advise patients to seek immediate medical attention 

if they experience any symptoms of serious hypersensitivity reactions .

 

Eli Lilly and Company, Indianapolis, IN 46285, USA

US License Number 1891

Product of Ireland

Copyright © yyyy, Eli Lilly and Company. All rights reserved.

 

 CLINICAL PHARMACOLOGY

 

1. Mechanism of Action

 Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds 

 with 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. Ixekizumab inhibits the release 

 of proinflammatory cytokines and chemokines.

 

2.Pharmacokinetics

 Absorption

 Following a single subcutaneous dose of 160 mg in subjects with plaque

 psoriasis, ixekizumab reached peak mean (±SD) serum concentrations 

(C max ) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.

 

 Steady-state concentrations were achieved approximately 10 weeks 

 after switching from the 80 mg every 2 weeks dosing regimen to

the 80 mg every 4 weeks dosing regimen at Week 12. 

The mean ±SD steady-state trough concentration was 3.5 ±2.5 mcg/mL.

 

In studies of subjects with plaque psoriasis, ixekizumab bioavailability 

ranged from 60% to 81% following subcutaneous injection. 

Administration of ixekizumab via injection in the thigh achieved a higher

 bioavailability relative to that achieved using other injection sites

 including the arm and abdomen.

 

Distribution

The mean (geometric CV%) volume of distribution at steady-state was

 7.11 L (29%) in subjects with plaque psoriasis.

 

Elimination

The metabolic pathway of ixekizumab has not been characterized. 

As a humanized IgG4 monoclonal antibody ixekizumab is expected 

to be degraded into small peptides and amino acids via catabolic

pathways in the same manner as endogenous IgG.

 

The mean systemic clearance was 0.39 L/day (37%)and the mean

 (geometric CV%) half-life was 13 days (40%) in subjects with plaque psoriasis. 

 USE IN SPECIFIC POPULATIONS

 

1. Pregnancy

 Risk Summary

 There are no available data on TALTZ use in pregnant women to inform 

 any drug associated risks. Human IgG is known to cross the placental barrier; 

 therefore, TALTZ may be transmitted from the mother to the developing fetus.

 

 An embryofetal development study conducted in pregnant monkeys at doses

 up to 19 times the maximum recommended human dose (MRHD) revealed 

 no evidence of harm to the developing fetus. When dosing was continued 

 until parturition, neonatal deaths were observed at 1.9 times the MRHD.

 

 The clinical significance of these nonclinical findings is  unknown.

The background risk of major birth defects and miscarriage for the indicated 

 population is unknown. 

 

In the U.S.general population, the estimated background risk of major birth

 defects and miscarriage in clinically recognized pregnancies is 2 to 4% 

 and 15 to 20%, respectively.

 

 2. Lactation

 Risk Summary

 There are no data on the presence of ixekizumab in human milk, the effects 

 on the breastfed infant, or the effects on milk production. Ixekizumab was 

 detected in the milk of lactating cynomolgus monkeys. 

 

The developmental and health benefits of breastfeeding should be 

 considered along with the mother’s clinical need for TALTZ and any

 potential adverse effects on the breastfed infant from TALTZ or from 

the underlying maternal condition.

 

4. Pediatric Use

The safety and effectiveness of TALTZ in pediatric patients (<18 years of age) 

have not been evaluated.

 

5. Geriatric Use

 Of the 4204 psoriasis subjects exposed to TALTZ, a total of 301 were 65

 years or older, and 36 subjects were 75 years or older. Although no 

 differences in safety or efficacy were observed between older and younger

 subjects, 6 number of subjects aged 65 and over is not sufficient to 

 determine whether they respond differently from younger subjects

 

6. OVERDOSAGE

 In the event of overdosage, monitor the patient for any signs or symptoms 

 of adverse reactions and institute appropriate symptomatic treatment immediately.