DRUG INTERACTIONS

 

1. Live Vaccinations

  Avoid use of live vaccines in patients treated with SILIQ .

 

2. CYP450 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. 

  Treatment with SILIQ may modulate serum levels of some cytokines.

 

  Therefore, upon initiation or discontinuation of SILIQ 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 

.

BRIEF SUMMARY

 

BRODALUMAB- (Feb 2017)

 

Indn-       To treat  adult patients with moderate-to-severe psoriasis

 

Comp-       Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1,

and 2 followed by 210 mg every 2 weeks

 

ADR-       Most common adverse reactions (incidence .1%) were arthralgia, headache,

fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions,

influenza, neutropenia, and tinea infections. 

 

CI-      Crohnfs disease 

 

 WARNINGS-

 

Infections: 

Serious infections have occurred. Consider the risks and benefits prior to initiating SILIQ in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. 

 

Pat Infm-

 

 

 

=================================================================

 

U.S. FDA APPROVED  DRUGS DURING 2017

 

Sr.No-  4

  

Name of the  Drug-         SILIQ

 

Active Ingredient-           Broadalumab                                                                                                                                                                                                           Pharmacological Classification- 

 

                       To treat  adult patients with moderate-to-severe psoriasis

                       

                                                                                                                           

Date of Approval-          02-15-2017

 

 (Ref- FDA approved List 2017)                                                                                                                                                                                                                     HIGHLIGHTS OF PRESCRIBING INFORMATION

 

These highlights do not include all the information needed to use SILIQ

safely and effectively. See full prescribing information for SILIQ.

SILIQ™ (brodalumab) injection, for subcutaneous use

 

Initial U.S. Approval: 2017

 

WARNING: SUICIDAL IDEATION AND BEHAVIOR

See full prescribing information for complete boxed warning.

 

 Suicidal ideation and behavior, including completed suicides, have

 occurred in patients treated with SILIQ. 

 Prior to prescribing, weigh potential risks and benefits in patients

 with a history of depression and/or suicidal ideation or behavior.

 

 Patients with new or worsening suicidal thoughts and behavior

 should be referred to a mental health professional, as appropriate.

 

 Advise patients and caregivers to seek medical attention for

 manifestations of suicidal ideation or behavior, new onset or

 worsening depression, anxiety, or other mood changes. 

 SILIQ is available only through a restricted program called the

SILIQ REMS Program. 

 

                                                                                                                                                                                   

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               

 

Most common adverse reactions (incidence .1%) were arthralgia, headache,

fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions,

influenza, neutropenia, and tinea infections. 

 ADVERSE REACTIONS 

 

Most common adverse reactions (incidence .1%) were arthralgia, headache,

fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions,

influenza, neutropenia, and tinea infections. 

 

CONTRAINDICATIONS 

 

Crohnfs disease 

 

 WARNINGS AND PRECAUTIONS

 

Infections: 

Serious infections have occurred. Consider the risks and benefits prior 

to initiating SILIQ in patients with a chronic infection or a history of 

recurrent infection. Instruct patients to seek medical advice if signs or 

symptoms of clinically important chronic or acute infection occur. 

 

If a serious infection develops, discontinue SILIQ until the

infection resolves. 

 

Tuberculosis (TB): 

Evaluate patients for TB infection prior to initiating treatment with SILIQ. 

 

 Crohnfs Disease: 

 Crohnfs disease occurred during clinical trials.

 Discontinue SILIQ if patient develops Crohnfs disease while taking SILIQ. 

 

 Immunizations: 

Avoid using live vaccines concurrently with SILIQ.

 

INDICATIONS AND USAGE

 

SILIQ is a human interleukin-17 receptor A (IL-17RA) antagonist indicated

for the treatment of moderate to severe plaque psoriasis in adult patients who

are candidates for systemic therapy or phototherapy and have failed to

respond or have lost response to other systemic therapies. 

 

DOSAGE AND ADMINISTRATION

 

Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1,

and 2 followed by 210 mg every 2 weeks. 

 

 DOSAGE FORMS AND STRENGTHS 

Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. 

 

PATIENT COUNSELING INFORMATION

 

Advise the patient to read the FDA-approved patient labeling 

(Medication Guide and Instructions for Use) before the patient starts using SILIQ, 

and each time the prescription is renewed, as there may be new information 

they need to know.

 

Suicidal Thoughts and Behavior 

Instruct patients and their caregivers to monitor for the emergence of suicidal 

thoughts and behavior and promptly seek medical attention if the patient 

experiences suicidal thoughts, new or worsening depression, anxiety, or other 

mood changes 

 

Instruct patients to carry the wallet card provided and to call the 

National Suicide Prevention Lifeline at 1-800-273-8255 if they experience suicidal 

thoughts.

 

SILIQ REMS Program 

Because of the observed suicidal thoughts and behavior in subjects treated 

with SILIQ, 

SILIQ is available only through a restricted program called the 

SILIQ REMS Program 

 Inform the patient of the following:

 

1.Patients must enroll in the program .

2.Patients will be given a SILIQ Patient Wallet Card that they should carry 

  with them at all times. 

 This card describes symptoms which, if experienced, should prompt the 

 patient to immediately seek medical evaluation. 

 

3.Advise the patient to show the SILIQ Patient Wallet Card to other treating 

 healthcare providers.

 

4. SILIQ is available only from certified pharmacies participating in the program. 

 Therefore, provide patients with the telephone number and website for information

  on how to obtain the product.

 

 Infections

 Inform patients that SILIQ may lower the ability of their immune system to fight

  infections. 

  Instruct patients of the importance of communicating any history of infections 

  to their healthcare providers and to contact their healthcare providers 

  if they develop any signs or symptoms of infection 

 

  Crohns Disease-

   Instruct patients to seek medical advice if they develop signs and symptoms 

   of Crohns disease .

 

  Instructions for Injection

  Instruct the patient to perform the first self-injection under the guidance 

  and supervision of a qualified healthcare professional for proper training 

  in subcutaneous injection technique.

 

   Instruct patients who are self-administering to inject the full dose of  SILIQ

 

  Instructions for Use].

  Instruct patients or caregivers in the technique of proper syringe and needle 

   disposal 

 

  Manufactured for:

  Valeant Pharmaceuticals North America LLC

  Bridgewater, NJ 08807 USA

  Manufactured by:

  Valeant Pharmaceuticals Luxembourg S.à.r.l.

  Grand Duchy of Luxembourg, L-1931, Luxembourg U.S.

 

 

 CLINICAL PHARMACOLOGY

 

1. Mechanism of Action

  Brodalumab is a human monoclonal IgG2 antibody that selectively binds 

  to human IL-17RA and inhibits its interactions with cytokines 

   IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer and IL-25. IL-17RA is a protein 

  expressed on the cell surface and is a required component of receptor

  complexes utilized by multiple IL-17 family cytokines. 

    Blocking IL17RA inhibits IL-17 cytokine-induced responses including the 

  release of pro-inflammatory cytokines and chemokines.

 

2. Pharmacodynamics

  Elevated levels of IL-17A, IL-17C and IL-17F are found in psoriatic plaques.

   Serum IL-17A levels, measured at Weeks 12, 24, and 48 of SILIQ 210 mg 

   every 2 weeks of treatment, were higher than the baseline levels in subjects 

  with moderate to severe plaque psoriasis. 

  The relationship between the pharmacodynamic activity and the mechanism(s)

   by which brodalumab exerts its clinical effects is unknown.

 

 

3. Pharmacokinetics

 Absorption

 Following a single subcutaneous dose of 210 mg in subjects with plaque psoriasis, 

  brodalumab reached peak mean (±SD) serum concentration (Cmax) of 

   13.4±7.3 mcg/mL by approximately 3 days post dose. 

  The mean (±SD) area-under-theconcentration-time curve (AUC) of brodalumab 

   was 111±64 mcg•day/mL.

 

 Following multiple subcutaneous doses of 210 mg every 2 weeks, steady-state

  was achieved by Week 4. The mean (±SD) Cmax was 20.6±14.6 mcg/mL and 

  the mean (±SD) AUC over the two week dosing interval was 227±167 mcg•day/mL.

 

Following subcutaneous administration, brodalumab bioavailability was approximately 55%.

 

 Distribution

 Following a single subcutaneous administration of brodalumab 210 mg in subjects 

 with plaque psoriasis, the mean (±SD) apparent volume of distribution 

 (Vz/F) of brodalumab was 8.9±9.4 L.

 

 Elimination

 The metabolic pathway of brodalumab has not been characterized. 

  As a human monoclonal IgG2 antibody, brodalumab is expected to be degraded 

  into small peptides and amino acids via catabolic pathways in a manner similar 

   to endogenous IgG.

 

 Following a single subcutaneous administration of brodalumab 210 mg in subjects 

  with plaque psoriasis, the mean (±SD) apparent total clearance (CL/F) 

  was 3.0±3.5 L/day. 

 

  The clearance of brodalumab increased with decreasing doses due to 

  nonlinear elimination.

 

  Dose Linearity

   Brodalumab exhibited non-linear pharmacokinetics with exposures that 

   increased greater than dose-proportionally over a dose range from 140 mg 

   (approximately 0.67 times the recommended dose) to 350 mg 

   (approximately 1.67 times the recommended dose) following subcutaneous 

   administrations in subjects with plaque psoriasis.

 

 Weight

 Brodalumab trough concentrations were lower in subjects with higher body weight.

 

 Specific Populations

 Hepatic or Renal Impairment

 No trials were conducted to assess the effect of hepatic or renal impairment 

  on the pharmacokinetics of brodalumab.

 

  Age: Geriatric Population

  Population pharmacokinetic analysis indicated that age did not significantly 

  influence the clearance of brodalumab in subjects with plaque psoriasis. 

   Subjects who were 65 years or older had a similar brodalumab clearance 

   as compared to subjects less than 65 years old.

 

  Drug Interaction Studies

  In subjects with plaque psoriasis, one week following a single subcutaneous

   administration of 210 mg brodalumab, the exposure of midazolam (CYP3A4 substrate) 

  was increased by 24% .

 

 USE IN SPECIFIC POPULATIONS

 

1 Pregnancy

 Risk Summary 

 There are no human data on SILIQ use in pregnant women to inform a drug 

  associated risk. Human IgG antibodies are known to cross the placental barrier; 

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

 

 In a combined embryofetal development and pre-and post-natal development study, 

  no adverse developmental effects were observed in infants born to pregnant monkeys 

 after subcutaneous administration of brodalumab during organogenesis 

  through parturition at doses up to 26 times the maximum recommended human dose

  (MRHD)

.

The estimated 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 brodalumab in human milk, the effects on the 

 breastfed infant, or the effects on milk production. Brodalumab was detected in the 

  milk of lactating cynomolgus monkeys. 

 

 The developmental and health benefits of breastfeeding should be considered 

 along with the motherfs clinical need for SILIQ and any potential adverse effects 

 on the breastfed infant from SILIQ or from the underlying maternal condition.

 

3.Pediatric Use

  The safety and effectiveness of SILIQ have not been evaluated in pediatric patients.

 

4. Geriatric Use

  Of the 3066 plaque psoriasis subjects initially randomized to SILIQ in clinical trials, 

 192 (6%) were . 65 years old and no subjects were . 75 years old. 

 

  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 .