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PEGINTRON/rIBAVIrIN COMBINATION TreATMeNT FlOW SHeeT FOr ADulTS
INDICATIONS:
PEGINTRON is indicated for use in combination with ribavirin for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease. The following points should be considered when initiating therapy with PEGINTRON in combination with ribavirin: (1) These indications are based on achieving undetectable HCV RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age. The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with ribavirin is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, ribavirin. Combination therapy provides substantially better response rates than monotherapy.
CONTrAINDICATIONS:
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score >6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/ribavirin combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia), and patients with creatinine clearance < 50 mL per min. PATIeNT DATA: Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
o New or worsening ophthalmologic disorders o Pancreatitis and ulcerative or hemorrhagic/ischemic o Serious, acute hypersensitivity reactions and cutaneous eruptions o Ischemic and hemorrhagic cerebrovascular events o Dental/periodontal disorders reported with combination therapy o History of significant or unstable cardiac disease o Severe decreases in neutrophil or platelet counts o Pulmonary infiltrates or pulmonary function impairment o Hypertriglyceridemia may result in pancreatitis (eg, triglycerides o Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes o History of autoimmune disorders mellitus that cannot be effectively treated by medication o Increased creatinine levels in patients with renal insufficiency PATIeNT COuNSelINg: _______________________________________________________________________________________________________________________________________________________________________________________________________
___________________________________________________________________________________________________________________________________________________________________________________________________________________________
Yes o No o N/A o
ONCe WeeKlY STreNgTH OF PEGINTRON (Check appropriate box):
ONCe WeeKlY VOluMe OF PEGINTRON (Check appropriate box):
DAIlY DOSe OF rIBAVIrIN:
o 50 mcg per 0.5 mL o 80 mcg per 0.5 mL o 120 mcg per 0.5 mL o 0.3 mL o 0.35 mL o 0.4 mL o 0.45 mL o 0.5 mL SuggeSTeD lABOrATOrY TeSTS – record lab results/Dates in the Boxes Belowg
HCV Viral LoadHemoglobinaWBC/Neutrophil CountaPlatelet CountaINRLiver Panel (ALT/AST)aBilirubin/AlbuminUric AcidChild-Pugh ScoreTSH/T4Blood GlucoseTriglyceridesSerum Cr/Cr ClearanceOcular ExambDepression a Measure at 2, 4, 8, 12 weeks and 6-week intervals thereafter, or more frequently if abnormalities develop.
b recommended prior to beginning treatment and then periodically thereafter as clinically appropriate.
Before prescribing PegINTrON, please read the accompanying Prescribing Information, including Boxed Warning, about fatal or life-threatening
c Monthly pregnancy tests are recommended during treatment and for 6 months posttherapy for women of child-bearing age.
neuropsychiatric, autoimmune, ischemic, and infectious disorders and ribavirin-associated birth defects and fetal deaths.
Patients with preexisting ophthalmologic disorders should have periodic ophthalmologic exams during interferon alpha treatment. Patients who have preexisting cardiac abnormalities should have electrocardiograms administered before treatment with PEGINTRON/ribavirin.
Please see reverse side for additional Dosing and Selected Safety Information.
DOSe reDuCTION AND/Or DISCONTINuATION MAY Be requIreD
guIDelINeS FOr MODIFICATION Or DISCONTINuATION OF PEGINTRON Or PEGINTRON /rIBAVIrIN
IN THe FOllOWINg SITuATIONS:
AND FOr SCHeDulINg VISITS FOr PATIeNTS WITH DePreSSION
laboratory Values
PegINTrON
ribavirin
Depression
Initial Management (4-8 wks)
Depression Status
Severity (See
DSM-IV for
definitions.)
modification
schedule
Improves
a For patients with a history of stable cardiac disease receiving PEGINTRON in combination with ribavirin, the PEGINTRON dose should be reduced by half and the ribavirin dose by 200 mg/day if a >2 g/dL decrease in hemoglobin is observed during any 4-week period. Both PEGINTRON and ribavirin should be permanently discontinued if patients have hemoglobin levels <12 g/dL after this ribavirin dose reduction.
b 1st dose reduction of ribavirin is by 200 mg/day, except in patients receiving the 1400 mg dose; it is by 400 mg/day; 2nd dose reduction of ribavirin (if needed) is by an additional 200 mg/day.
c For patients on PEGINTRON/ribavirin combination therapy: 1st dose reduction of PEGINTRON is to 1 mcg/kg/week; 2nd dose reduction (if needed) of PEGINTRON is to 0.5 mcg/kg/week. For patients on PEGINTRON monotherapy: decrease PEGINTRON dose to 0.5 mcg/kg/week.
Selected Safety Information
WArNINg: rISK OF SerIOuS DISOrDerS AND
Patients with the following conditions should be closely monitored and may combination therapy and 3 occurred during the follow-up period but had been
rIBAVIrIN-ASSOCIATeD eFFeCTS
require dose reduction or discontinuation of therapy:
on PEGINTRON/ribavirin combination therapy. Alpha interferons, including PegINTrON, may cause or aggravate fatal or
• Hemolytic anemia with ribavirin • Neuropsychiatric events • History of signifi- Additional serious adverse reactions seen in clinical trials at a frequency of ≤1% life-threatening neuropsychiatric, autoimmune, ischemic, and infectious cant or unstable cardiac disease • Hypothyroidism, hyperthyroidism, hyperglycemia, included psychosis, aggressive reaction, relapse of drug addiction/overdose;
disorders. Patients should be monitored closely with periodic clinical and
diabetes mellitus that cannot be effectively treated by medication • New or worsen- nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, reti- laboratory evaluations. Patients with persistently severe or worsening signs
ing ophthalmologic disorders • Ischemic and hemorrhagic cerebrovascular events nal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, or symptoms of these conditions should be withdrawn from therapy. In many,
• Severe decreases in neutrophil or platelet counts • History of autoimmune disorders optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of but not all cases, these disorders resolve after stopping PegINTrON therapy.
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); use with ribavirin: ribavirin may cause birth defects and death of the unborn
• Pulmonary infiltrates or pulmonary function impairment • Child-Pugh score >6 emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, child. extreme care must be taken to avoid pregnancy in female patients
(Class B and C) • Increased creatinine levels in patients with renal insufficiency gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombo- and in female partners of male patients. ribavirin causes hemolytic anemia.
• Serious, acute hypersensitivity reactions and cutaneous eruptions • Dental/ cytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus- The anemia associated with ribavirin therapy may result in a worsening
periodontal disorders reported with combination therapy • Hypertriglyceridemia may like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, of cardiac disease. ribavirin is genotoxic and mutagenic and should be
result in pancreatitis (eg, triglycerides >1000 mg/dL) • Weight loss and growth vasculitis, and phototoxicity. considered a potential carcinogen.
inhibition reported with combination therapy in pediatric patients.
Greater than 96% of all subjects in clinical trials experienced one or more adverse events. Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal Contraindications
Most common adverse reactions (>40%) in adult patients receiving either PEGINTRON ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, PEGINTRON is contraindicated in patients with known hypersensitivity reactions or PEGINTRON/ribavirin are injection site inflammation/reaction, fatigue/asthenia, sometimes directed towards others, have occurred in patients with and without a such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability. previous psychiatric disorder during PEGINTRON treatment and follow-up. syndrome and toxic epidermal necrolysis to interferon alpha or any other component The adverse reaction profile was similar between weight-based and flat-dose of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh Adverse events
PEGINTRON/ribavirin therapies. Weight-based PEGINTRON/ribavirin dosing resulted score >6 [class B and C]) in cirrhotic CHC patients before or during treatment. Serious adverse reactions have occurred in approximately 12% of subjects in in increased rates of anemia. Most common adverse reactions with PEGINTRON/ PEGINTRON/ribavirin combination therapy is additionally contraindicated in women clinical trials. The most common serious events occurring in subjects treated with ribavirin (weight-based) therapy were psychiatric, which occurred among 68-69% who are pregnant or may become pregnant, men whose female partners are PEGINTRON and ribavirin were depression and suicidal ideation, each occurring at a of patients and included depression, irritability, and insomnia, each reported by pregnant, patients with hemoglobinopathies (eg, thalassemia major, sickle-cell frequency of less than 1%. The most common fatal events occurring in subjects treated approximately 30-40% of subjects in all treatment groups. Suicidal behavior anemia), and patients with creatinine clearance < 50 mL per min.
with PEGINTRON and ribavirin were cardiac arrest, suicidal ideation, and suicide attempt, (ideation, attempts, and suicides) occurred in 2% of all patients during all occurring in less than 1% of subjects.
Pregnancy
treatment or during follow-up after treatment cessation. Other common reactions ribavirin therapy should not be started until a report of a negative pregnancy test The incidence of serious adverse reactions was comparable between PEGINTRON included injection site reactions, fatigue/asthenia, headache, rigors, fever, nausea,
has been obtained immediately prior to planned initiation of therapy. Patients monotherapy (~12%) and PEGINTRON/ribavirin combination therapy weight-based myalgia, anxiety/emotional lability/irritability. The severity of some of these
should use at least two effective forms of contraception and have monthly (12%) or flat-dose (17%). In many but not all cases, adverse reactions resolved systemic symptoms tends to decrease as treatment continues.
pregnancy tests during therapy and for 6 months after completion of therapy. after dose reduction or discontinuation of therapy. Some patients experienced
Subjects receiving PEGINTRON/ribavirin as re-treatment after failing a If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should ongoing or new serious adverse reactions during the 6-month follow-up period. In a study previous interferon combination regimen reported adverse reactions similar to previous be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been with PEGINTRON/ribavirin (weight-based) combination therapy in adult patients, anemia treatment-naïve patients receiving this regimen. established to monitor maternal-fetal outcomes of pregnancies in female patients and with weight-based dosing occurred at an increased rate (29% vs. 19%); however, the In general, the adverse reaction profile in the pediatric population was similar to that female partners of male patients exposed to ribavirin during treatment, and for 6 months majority of these cases were mild and responded to dose reductions. The incidence observed in adults. Most common adverse reactions (>25%) in pediatric patients following cessation of treatment. Physicians and patients are encouraged to report such of serious adverse reactions reported for the weight-based ribavirin group was 12%. receiving PEGINTRON/ribavirin are pyrexia, headache, neutropenia, fatigue, anorexia, There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/ribavirin injection site erythema, abdominal pain, and vomiting. Before prescribing PegINTrON, please read the accompanying Prescribing Information, including Boxed Warning, about fatal or life-threatening
neuropsychiatric, autoimmune, ischemic, and infectious disorders and ribavirin-associated birth defects and fetal deaths.
Copyright 2011 Schering Corp., a subsidiary of Merck & Co., Inc. All rights reserved. INFC-1007725-0000 8/11

Source: http://www.merck-cares.com/merck-cares/hcp/pdf/Pegintron_Treatment_FlowSheet.pdf