Download Questions and answers about using NovoLog®

Questions and answers
about using NovoLog®
What is NovoLog®?
NovoLog® (insulin aspart [rDNA origin] injection) is a fast-acting insulin analog
from Novo Nordisk — a world leader in diabetes care. It is absorbed quickly and
starts working within minutes to lower your blood sugar. This way, you may take
your insulin and eat within 5 to 10 minutes, unlike the 30-minute wait required
with regular human insulin.
What is NovoLog®
FlexPen®?
NovoLog® FlexPen® is a discreet insulin pen that goes with you almost anywhere.*
FlexPen® comes prefilled with NovoLog® and is ready to use in just a few steps.
Please refer to the attached instructions for use. NovoLog® FlexPen® requires low
injection force, making it easy to press.
NovoLog® FlexPen® fits in a pocket or purse, so you’ll have the insulin you need—
right when you need it.†
Does my health
insurance plan cover
NovoLog® FlexPen®?
NovoLog® FlexPen® is available for the same co-pay as vial and syringe on most
health insurance plans.
What type of needles NovoFine® disposable needles† are recommended. NovoFine® needles are very
thin and short.
should I use with
NovoLog® FlexPen®?
How do I save
money on
NovoLog® FlexPen®?
Regardless of your health insurance plan, you can save up to $50 off your first
FlexPen® prescription and up to $25 off your next three prescriptions for a total
savings of up to $125‡ with the Novo Nordisk Savings Card. Learn more about
this offer from your health care provider or by visiting MyFlexPen.com.
How do I get
NovoLog® FlexPen®?
NovoLog® FlexPen® is only available with a prescription. Ask your health care
provider today if NovoLog® FlexPen® is right for you. Find out more about the
benefits of FlexPen® at MyFlexPen.com or call 1-800-727-6500.
Indications and Usage
What is NovoLog® (insulin aspart [rDNA origin] injection)?
•NovoLog® is a man-made insulin used to control high blood sugar in adults and children with diabetes
mellitus.
Important Safety Information
Who should not use NovoLog®?
•Do not use NovoLog® if your blood sugar is too low (hypoglycemia) or you are allergic to any of its
ingredients.
Please see additional Important Safety Information on the next page and accompanying Patient
Information.
*If NovoLog® FlexPen® is kept at room temperature below 86° F for up to 28 days.
Needles are sold separately and may require a prescription in some states. Needles and FlexPen® must not be shared. Refer to the user manual for information on
assembly and injection.
†
Eligible patients only. Discount is not to exceed patient’s out-of-pocket expenses. Please read terms & conditions for eligibility requirements at MyFlexPen.com.
‡
Important Safety Information (continued)
What should I tell my healthcare provider before taking NovoLog® (insulin aspart [rDNA origin]
injection)?
•About all of your medical conditions, including liver or kidney problems.
•If you are pregnant, breastfeeding, or plan to do either.
•About all prescription and nonprescription medicines you take, including supplements, as your dose may
need to change.
How should I take NovoLog®?
•Eat a meal within 5 to 10 minutes after using NovoLog® (insulin aspart [rDNA origin] injection),
a fast-acting insulin, to avoid low blood sugar. Do not inject NovoLog® if you do not plan to eat
right after your injection or bolus pump infusion.
•Do not mix NovoLog® with any other insulin when used in a pump or with any insulin other than NPH
when used with injections by syringe.
•Do not change your dose or type of insulin unless you are told to by your healthcare provider.
•Do not share needles, insulin pens, or syringes.
•Check your blood sugar levels as directed by your healthcare provider.
What should I consider while using NovoLog®?
•Alcohol, including beer and wine, may affect your blood sugar.
•Be careful when driving a car or operating machinery. You may have difficulty concentrating or reacting
if you have low blood sugar. Talk to your healthcare provider if you often have low blood sugar or no
warning signs of low blood sugar.
What are the possible side effects of NovoLog®?
•Low blood sugar, including when too much is taken. Some symptoms include sweating, shakiness,
confusion, and headache. Severe low blood sugar can cause unconsciousness, seizures, and death.
•Serious allergic reactions may occur. Get medical help right away, if you develop a rash over your whole
body, have trouble breathing, a fast heartbeat, or sweating.
•Other side effects include injection site reactions (like redness, swelling, and itching), skin thickening or
pits at the injection site, swelling of your hands and feet, vision changes, low potassium in your blood,
and weight gain.
Please see accompanying Patient Information.
Talk to your doctor about the importance of diet and exercise in your treatment plan.
You can get additional help with your diabetes care at Cornerstones4Care.com.
If you need assistance with prescription drug costs, help may be available.
Visit pparx.org or call 1-888-4PPA-NOW.
You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
FlexPen®, NovoFine®, and NovoLog® are registered trademarks and
Cornerstones4Care™ is a trademark of Novo Nordisk A/S.
© 2012 Novo Nordisk
Printed in the U.S.A.
0912-00011436-1
December 2012
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information
needed to use NovoLog® safely and effectively. See full
prescribing information for NovoLog®.
NovoLog® (insulin aspart [rDNA origin] injection)
solution for subcutaneous use
Initial U.S. Approval: 2000
——— RECENT MAJOR CHANGES ———
•DosageandAdministration(2.3)
7/2009
•WarningsandPrecautions,Administration(5.1) 10/2009
——— INDICATIONS AND USAGE ———
•NovoLog®isaninsulinanalogindicatedtoimproveglycemic
controlinadultsandchildrenwithdiabetesmellitus(1.1).
——— DOSAGE AND ADMINISTRATION ———
•ThedosageofNovoLog®mustbeindividualized.
•Subcutaneous injection:NovoLog®shouldgenerallybegiven
immediately(within5-10minutes)priortothestartofameal
(2.2).
•Use in pumps:ChangetheNovoLog®inthereservoiratleast
every6days,changetheinfusionset,andtheinfusionset
insertionsiteatleastevery3days.NovoLog®shouldnotbe
mixedwithotherinsulinsorwithadiluentwhenitisusedin
thepump(2.3).
•Intravenous use:NovoLog®shouldbeusedatconcentrations
from0.05U/mLto1.0U/mLinsulinaspartininfusionsystems
usingpolypropyleneinfusionbags.NovoLog®hasbeenshown
tobestableininfusionfluidssuchas0.9%sodiumchloride
(2.4).
——— DOSAGE FORMS AND STRENGTHS ———
Eachpresentationcontains100UnitsofinsulinaspartpermL
(U-100)
•10mLvials(3)
•3mLPenFill®cartridgesforthe3mLPenFill®cartridgedevice(3)
•3mLNovoLog®FlexPen®(3)
FULL PRESCRIBING INFORMATION: CONTENTS*
1
INDICATIONS AND USAGE
1.1 TreatmentofDiabetesMellitus
2
DOSAGE AND ADMINISTRATION
2.1 Dosing
2.2 SubcutaneousInjection
2.3 ContinuousSubcutaneousInsulinInfusion(CSII)byExternalPump
2.4 IntravenousUse
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
5.1 Administration
5.2 Hypoglycemia
5.3 Hypokalemia
5.4 RenalImpairment
5.5 HepaticImpairment
5.6 HypersensitivityandAllergicReactions
5.7 AntibodyProduction
5.8 MixingofInsulins
5.9 ContinuousSubcutaneousInsulinInfusionbyExternalPump
6
ADVERSE REACTIONS
7
DRUG INTERACTIONS
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
——— CONTRAINDICATIONS ———
•Donotuseduringepisodesofhypoglycemia(4).
•DonotuseinpatientswithhypersensitivitytoNovoLog®orone
ofitsexcipients.
•Beta-blockers,clonidine,lithiumsalts,andalcoholmayeither
potentiateorweakentheblood-glucose-loweringeffectofinsulin
(7).
•Pentamidinemaycausehypoglycemia,whichmaysometimesbe
followedbyhyperglycemia(7).
•Thesignsofhypoglycemiamaybereducedorabsentinpatients
takingsympatholyticproductssuchasbeta-blockers,clonidine,
guanethidine,andreserpine(7).
——— WARNINGS AND PRECAUTIONS ———
•Hypoglycemiaisthemostcommonadverseeffectofinsulin
therapy.Glucosemonitoringisrecommendedforallpatientswith
diabetes.Anychangeofinsulindoseshouldbemadecautiously
——— USE IN SPECIFIC POPULATIONS ———
andonlyundermedicalsupervision(5.1,5.2).
•Pediatric:Hasnotbeenstudiedinchildrenwithtype2diabetes.
•Insulin,particularlywhengivenintravenouslyorinsettingsof
Hasnotbeenstudiedinchildrenwithtype1diabetes<2yearsof
poorglycemiccontrol,cancausehypokalemia.Usecautionin
age(8.4).
patientspredisposedtohypokalemia(5.3).
•Likeallinsulins,NovoLog®requirementsmaybereducedin
See 17 for PATIENT COUNSELING INFORMATION and
patientswithrenalimpairmentorhepaticimpairment(5.4,5.5).
FDA-approved patient labeling.
•Severe,life-threatening,generalizedallergy,including
Revised: 6/2011
anaphylaxis,mayoccurwithinsulinproducts,including
NovoLog®(5.6).
——— ADVERSE REACTIONS ———
AdversereactionsobservedwithNovoLog®includehypoglycemia,
allergicreactions,localinjectionsitereactions,lipodystrophy,rash
andpruritus(6).
To report SUSPECTED ADVERSE REACTIONS, contact
Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800FDA-1088 or www.fda.gov/medwatch.
——— DRUG INTERACTIONS ———
•Thefollowingmayincreasetheblood-glucose-loweringeffect
andsusceptibilitytohypoglycemia:oralantidiabeticproducts,
pramlintide,ACEinhibitors,disopyramide,fibrates,fluoxetine,
monoamineoxidaseinhibitors,propoxyphene,salicylates,
somatostatinanalogs,sulfonamideantibiotics(7).
•Thefollowingmayreducetheblood-glucose-loweringeffect:
corticosteroids,niacin,danazol,diuretics,sympathomimetic
agents(e.g.,epinephrine,salbutamol,terbutaline),isoniazid,
phenothiazinederivatives,somatropin,thyroidhormones,
estrogens,progestogens(e.g.,inoralcontraceptives),atypical
antipsychotics(7).
8.3 NursingMothers
8.4 PediatricUse
8.5 GeriatricUse
10
OVERDOSAGE
11
DESCRIPTION
12
CLINICAL PHARMACOLOGY
12.1 MechanismofAction
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis,Mutagenesis,ImpairmentofFertility
13.2 AnimalToxicologyand/orPharmacology
14
CLINICAL STUDIES
14.1 SubcutaneousDailyInjections
14.2 ContinuousSubcutaneousInsulinInfusion(CSII)byExternalPump
14.3 IntravenousAdministrationofNovoLog®
16
HOW SUPPLIED/STORAGE AND HANDLING
16.1 HowSupplied
16.2 RecommendedStorage
17
PATIENT COUNSELING INFORMATION
17.1 PhysicianInstructions
17.2 PatientsUsingPumps
17.3 FDA-ApprovedPatientLabeling
*Sectionsorsubsectionsomittedfromthefullprescribinginformationarenotlisted.
1
NovoLog® (insulin aspart [rDNA origin] injection)
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
1.1 Treatment of Diabetes Mellitus
NovoLog®isaninsulinanalogindicatedtoimproveglycemiccontrolinadultsandchildrenwith
diabetesmellitus.
2
DOSAGE AND ADMINISTRATION
2.1 Dosing
NovoLog®isaninsulinanalogwithanearlieronsetofactionthanregularhumaninsulin.The
dosage of NovoLog® must be individualized. NovoLog® given by subcutaneous injection
shouldgenerallybeusedinregimenswithanintermediateorlong-actinginsulin[see Warnings
and Precautions (5), How Supplied/Storage and Handling (16.2)]. The total daily insulin
requirement may vary and is usually between 0.5 to 1.0 units/kg/day. When used in a mealrelatedsubcutaneousinjectiontreatmentregimen,50to70%oftotalinsulinrequirementsmay
beprovidedbyNovoLog®andtheremainderprovidedbyanintermediate-actingorlong-acting
insulin.BecauseofNovoLog®’scomparativelyrapidonsetandshortdurationofglucoselowering
activity,somepatientsmayrequiremorebasalinsulinandmoretotalinsulintopreventpre-meal
hyperglycemiawhenusingNovoLog®thanwhenusinghumanregularinsulin.
DonotuseNovoLog®thatisviscous(thickened)orcloudy;useonlyifitisclearandcolorless.
NovoLog®shouldnotbeusedaftertheprintedexpirationdate.
2.2 Subcutaneous Injection
NovoLog®shouldbeadministeredbysubcutaneousinjectionintheabdominalregion,buttocks,
thigh,orupperarm.BecauseNovoLog®hasamorerapidonsetandashorterdurationofactivity
thanhumanregularinsulin,itshouldbeinjectedimmediately(within5-10minutes)beforeameal.
Injectionsitesshouldberotatedwithinthesameregiontoreducetheriskoflipodystrophy.Aswith
allinsulins,thedurationofactionofNovoLog®willvaryaccordingtothedose,injectionsite,blood
flow,temperature,andlevelofphysicalactivity.
NovoLog® may be diluted with Insulin Diluting Medium for NovoLog® for subcutaneous
injection.DilutingonepartNovoLog®toninepartsdiluentwillyieldaconcentrationone-tenth
thatofNovoLog®(equivalenttoU-10).DilutingonepartNovoLog®toonepartdiluentwillyielda
concentrationone-halfthatofNovoLog®(equivalenttoU-50).
2.3 Continuous Subcutaneous Insulin Infusion (CSII) by External Pump
NovoLog®canalsobeinfusedsubcutaneouslybyanexternalinsulinpump[see Warnings and
Precautions (5.8, 5.9), How Supplied/Storage and Handling (16.2)].Dilutedinsulinshouldnot
beusedinexternalinsulinpumps.BecauseNovoLog®hasamorerapidonsetandashorter
durationofactivitythanhumanregularinsulin,pre-mealbolusesofNovoLog®shouldbeinfused
immediately(within5-10minutes)beforeameal.Infusionsitesshouldberotatedwithinthe
sameregiontoreducetheriskoflipodystrophy.Theinitialprogrammingoftheexternalinsulin
infusionpumpshouldbebasedonthetotaldailyinsulindoseofthepreviousregimen.Although
thereissignificantinterpatientvariability,approximately50%ofthetotaldoseisusuallygivenas
meal-relatedbolusesofNovoLog®andtheremainderisgivenasabasalinfusion.Change the
NovoLog® in the reservoir at least every 6 days, change the infusion sets and the
infusion set insertion site at least every 3 days.
Thefollowinginsulinpumps†havebeenusedinNovoLog®clinicalorin vitrostudiesconducted
byNovoNordisk,themanufacturerofNovoLog®:
•MedtronicParadigm®512and712
•MiniMed508
•Disetronic®D-TRON®andH-TRON®
BeforeusingadifferentinsulinpumpwithNovoLog®,readthepumplabeltomakesurethepump
hasbeenevaluatedwithNovoLog®.
2.4 Intravenous Use
NovoLog®canbeadministeredintravenouslyundermedicalsupervisionforglycemiccontrolwith
closemonitoringofbloodglucoseandpotassiumlevelstoavoidhypoglycemiaandhypokalemia
[see Warnings and Precautions (5), How Supplied/Storage and Handling (16.2)].Forintravenous
use,NovoLog®shouldbeusedatconcentrationsfrom0.05U/mLto1.0U/mLinsulinaspartin
infusionsystemsusingpolypropyleneinfusionbags.NovoLog®hasbeenshowntobestablein
infusionfluidssuchas0.9%sodiumchloride.
InspectNovoLog®forparticulatematteranddiscolorationpriortoparenteraladministration.
3
DOSAGE FORMS AND STRENGTHS
NovoLog®isavailableinthefollowingpackagesizes:eachpresentationcontains100unitsof
insulinaspartpermL(U-100).
•10mLvials
•3mLPenFillcartridgesforthe3mLPenFill®cartridgedeliverydevice(withorwithoutthe
additionofaNovoPen®3PenMate®)withNovoFine®disposableneedles
•3mLNovoLog®FlexPen®
4
CONTRAINDICATIONS
NovoLog®iscontraindicated
•duringepisodesofhypoglycemia
•inpatientswithhypersensitivitytoNovoLog®oroneofitsexcipients.
5
WARNINGS AND PRECAUTIONS
5.1 Administration
NovoLog®hasamorerapidonsetofactionandashorterdurationofactivitythanregularhuman
insulin.AninjectionofNovoLog®shouldimmediatelybefollowedbyamealwithin5-10minutes.
BecauseofNovoLog®’sshortdurationofaction,alongeractinginsulinshouldalsobeusedin
patientswithtype1diabetesandmayalsobeneededinpatientswithtype2diabetes.Glucose
monitoringisrecommendedforallpatientswithdiabetesandisparticularlyimportantforpatients
usingexternalpumpinfusiontherapy.
Any change of insulin dose should be made cautiously and only under medical supervision.
Changingfromoneinsulinproducttoanotherorchangingtheinsulinstrengthmayresultinthe
needforachangeindosage.Aswithallinsulinpreparations,thetimecourseofNovoLog®action
mayvaryindifferentindividualsoratdifferenttimesinthesameindividualandisdependenton
manyconditions,includingthesiteofinjection,localbloodsupply,temperature,andphysical
activity.Patientswhochangetheirlevelofphysicalactivityormealplanmayrequireadjustment
ofinsulindosages.Insulinrequirementsmaybealteredduringillness,emotionaldisturbances,
orotherstresses.
Patients using continuous subcutaneous insulin infusion pump therapy must be trained to
administerinsulinbyinjectionandhavealternateinsulintherapyavailableincaseofpumpfailure.
Needles and NovoLog® FlexPen® must not be shared.
5.2 Hypoglycemia
Hypoglycemiaisthemostcommonadverseeffectofallinsulintherapies,includingNovoLog®.
Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in
temporaryorpermanentimpairmentofbrainfunctionordeath.Severehypoglycemiarequiringthe
assistanceofanotherpersonand/orparenteralglucoseinfusionorglucagonadministrationhas
beenobservedinclinicaltrialswithinsulin,includingtrialswithNovoLog®.
Thetimingofhypoglycemiausuallyreflectsthetime-actionprofileoftheadministeredinsulin
formulations[see Clinical Pharmacology (12)].Otherfactorssuchaschangesinfoodintake(e.g.,
amountoffoodortimingofmeals),injectionsite,exercise,andconcomitantmedicationsmay
alsoaltertheriskofhypoglycemia[see Drug Interactions (7)].Aswithallinsulins,usecautionin
patientswithhypoglycemiaunawarenessandinpatientswhomaybepredisposedtohypoglycemia
(e.g.,patientswhoarefastingorhaveerraticfoodintake).Thepatient’sabilitytoconcentrateand
reactmaybeimpairedasaresultofhypoglycemia.Thismaypresentariskinsituationswherethese
abilitiesareespeciallyimportant,suchasdrivingoroperatingothermachinery.
Rapidchangesinserumglucoselevelsmayinducesymptomsofhypoglycemiainpersonswith
diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be
differentorlesspronouncedundercertainconditions,suchaslongstandingdiabetes,diabetic
nerve disease, use of medications such as beta-blockers, or intensified diabetes control [see
Drug Interactions (7)].Thesesituationsmayresultinseverehypoglycemia(and,possibly,loss
ofconsciousness)priortothepatient’sawarenessofhypoglycemia.Intravenouslyadministered
insulinhasamorerapidonsetofactionthansubcutaneouslyadministeredinsulin,requiringmore
closemonitoringforhypoglycemia.
5.3 Hypokalemia
All insulin products, including NovoLog®, cause a shift in potassium from the extracellular to
intracellularspace,possiblyleadingtohypokalemiathat,ifleftuntreated,maycauserespiratory
paralysis,ventriculararrhythmia,anddeath.Usecautioninpatientswhomaybeatriskforhypokalemia
(e.g.,patientsusingpotassium-loweringmedications,patientstakingmedicationssensitivetoserum
potassiumconcentrations,andpatientsreceivingintravenouslyadministeredinsulin).
5.4 Renal Impairment
Aswithotherinsulins,thedoserequirementsforNovoLog®maybereducedinpatientswithrenal
impairment[see Clinical Pharmacology (12.3)].
5.5 Hepatic Impairment
Aswithotherinsulins,thedoserequirementsforNovoLog®maybereducedinpatientswith
hepaticimpairment[see Clinical Pharmacology (12.3)].
5.6 Hypersensitivity and Allergic Reactions
Local Reactions-Aswithotherinsulintherapy,patientsmayexperienceredness,swelling,or
itchingatthesiteofNovoLog®injection.Thesereactionsusuallyresolveinafewdaystoafew
weeks,butinsomeoccasions,mayrequirediscontinuationofNovoLog®.Insomeinstances,these
reactionsmayberelatedtofactorsotherthaninsulin,suchasirritantsinaskincleansingagent
orpoorinjectiontechnique.Localizedreactionsandgeneralizedmyalgiashavebeenreportedwith
injectedmetacresol,whichisanexcipientinNovoLog®.
Systemic Reactions-Severe,life-threatening,generalizedallergy,includinganaphylaxis,mayoccur
withanyinsulinproduct,includingNovoLog®.AnaphylacticreactionswithNovoLog®havebeen
reportedpost-approval.Generalizedallergytoinsulinmayalsocausewholebodyrash(including
pruritus),dyspnea,wheezing,hypotension,tachycardia,ordiaphoresis.Incontrolledclinicaltrials,
allergicreactionswerereportedin3of735patients(0.4%)treatedwithregularhumaninsulinand
10of1394patients(0.7%)treatedwithNovoLog®.Incontrolledanduncontrolledclinicaltrials,3
of2341(0.1%)NovoLog®-treatedpatientsdiscontinuedduetoallergicreactions.
5.7 Antibody Production
Increasesinanti-insulinantibodytitersthatreactwithbothhumaninsulinandinsulinasparthave
beenobservedinpatientstreatedwithNovoLog®.Increasesinanti-insulinantibodiesareobserved
morefrequentlywithNovoLog®thanwithregularhumaninsulin.Datafroma12-monthcontrolled
trialinpatientswithtype1diabetessuggestthattheincreaseintheseantibodiesistransient,and
thedifferencesinantibodylevelsbetweentheregularhumaninsulinandinsulinasparttreatment
groupsobservedat3and6monthswerenolongerevidentat12months.Theclinicalsignificance
oftheseantibodiesisnotknown.Theseantibodiesdonotappeartocausedeteriorationinglycemic
controlornecessitateincreasesininsulindose.
5.8 Mixing of Insulins
•MixingNovoLog®withNPHhumaninsulinimmediatelybeforeinjectionattenuatesthepeak
concentrationofNovoLog®,withoutsignificantlyaffectingthetimetopeakconcentrationortotal
bioavailabilityofNovoLog®.IfNovoLog®ismixedwithNPHhumaninsulin,NovoLog®should
bedrawnintothesyringefirst,andthemixtureshouldbeinjectedimmediatelyaftermixing.
•TheefficacyandsafetyofmixingNovoLog®withinsulinpreparationsproducedbyother
manufacturershavenotbeenstudied.
•Insulinmixturesshouldnotbeadministeredintravenously.
5.9 Continuous Subcutaneous Insulin Infusion by External Pump
When used in an external subcutaneous insulin infusion pump, NovoLog® should
not be mixed with any other insulin or diluent.WhenusingNovoLog®inanexternal
insulinpump,theNovoLog®-specificinformationshouldbefollowed(e.g.,in-usetime,frequency
ofchanginginfusionsets)becauseNovoLog®-specificinformationmaydifferfromgeneralpump
manualinstructions.
Pump or infusion set malfunctions or insulin degradation can lead to a rapid onset of
hyperglycemiaandketosisbecauseofthesmallsubcutaneousdepotofinsulin.Thisisespecially
pertinentforrapid-actinginsulinanalogsthataremorerapidlyabsorbedthroughskinandhavea
shorterdurationofaction.Promptidentificationandcorrectionofthecauseofhyperglycemiaor
ketosisisnecessary.Interimtherapywithsubcutaneousinjectionmayberequired[see Dosage and
Administration (2.3), Warnings and Precautions (5.8, 5.9), How Supplied/Storage and Handling
(16.2), and Patient Counseling Information (17.2)].
NovoLog®shouldnotbeexposedtotemperaturesgreaterthan37°C(98.6°F).NovoLog®that
will be used in a pump should not be mixed with other insulin or with a diluent[see
Dosage and Administration (2.3), Warnings and Precautions (5.8, 5.9), How Supplied/Storage and
Handling (16.2), and Patient Counseling Information (17.2)].
6
ADVERSE REACTIONS
Clinical Trial Experience
Becauseclinicaltrialsareconductedunderwidelyvaryingdesigns,theadversereactionrates
reportedinoneclinicaltrialmaynotbeeasilycomparedtothoseratesreportedinanotherclinical
trial,andmaynotreflecttheratesactuallyobservedinclinicalpractice.
2
•Hypoglycemia
Hypoglycemiaisthemostcommonlyobservedadversereactioninpatientsusinginsulin,
includingNovoLog®[see Warnings and Precautions (5)].
•Insulin initiation and glucose control intensification
Intensificationorrapidimprovementinglucosecontrolhasbeenassociatedwithatransitory,
reversibleophthalmologicrefractiondisorder,worseningofdiabeticretinopathy,andacute
painfulperipheralneuropathy.However,long-termglycemiccontroldecreasestheriskof
diabeticretinopathyandneuropathy.
•Lipodystrophy
Long-termuseofinsulin,includingNovoLog®,cancauselipodystrophyatthesiteofrepeated
insulininjectionsorinfusion.Lipodystrophyincludeslipohypertrophy(thickeningofadipose
tissue)andlipoatrophy(thinningofadiposetissue),andmayaffectinsulinabsorption.Rotate
insulininjectionorinfusionsiteswithinthesameregiontoreducetheriskoflipodystrophy.
•Weight gain
Weightgaincanoccurwithsomeinsulintherapies,includingNovoLog®,andhasbeen
attributedtotheanaboliceffectsofinsulinandthedecreaseinglucosuria.
•Peripheral Edema
Insulinmaycausesodiumretentionandedema,particularlyifpreviouslypoormetabolic
controlisimprovedbyintensifiedinsulintherapy.
•Frequencies of adverse drug reactions
ThefrequenciesofadversedrugreactionsduringNovoLog®clinicaltrialsinpatientswithtype
1diabetesmellitusandtype2diabetesmellitusarelistedinthetablesbelow.
Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes
Mellitus (Adverse events with frequency ≥ 5% and occurring more frequently with
NovoLog® compared to human regular insulin are listed)
NovoLog® + NPH
Human Regular Insulin + NPH
N= 596
N= 286
Preferred Term
N
(%)
N
(%)
Hypoglycemia*
448
75%
205
72%
Headache
70
12%
28
10%
Injuryaccidental
65
11%
29
10%
Nausea
43
7%
13
5%
Diarrhea
28
5%
9
3%
*Hypoglycemiaisdefinedasanepisodeofbloodglucoseconcentration<45mg/dL,withorwithout
symptoms.SeeSection14fortheincidenceofserioushypoglycemiaintheindividualclinicaltrials.
Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes
Mellitus (except for hypoglycemia, adverse events with frequency ≥ 5% and
occurring more frequently with NovoLog® compared to human regular insulin are
listed)
NovoLog® + NPH Human Regular Insulin + NPH
N= 91
N= 91
N
(%)
N
(%)
Hypoglycemia*
25
27%
33
36%
Hyporeflexia
10
11%
6
7%
Onychomycosis
9
10%
5
5%
Sensorydisturbance
8
9%
6
7%
Urinarytractinfection
7
8%
6
7%
Chestpain
5
5%
3
3%
Headache
5
5%
3
3%
Skindisorder
5
5%
2
2%
Abdominalpain
5
5%
1
1%
Sinusitis
5
5%
1
1%
*Hypoglycemiaisdefinedasanepisodeofbloodglucoseconcentration<45mg/dL,withorwithout
symptoms.SeeSection14fortheincidenceofserioushypoglycemiaintheindividualclinicaltrials.
Postmarketing Data
The following additional adverse reactions have been identified during postapproval use of
NovoLog®.Becausetheseadversereactionsarereportedvoluntarilyfromapopulationofuncertain
size,itisgenerallynotpossibletoreliablyestimatetheirfrequency.Medicationerrorsinwhich
other insulins have been accidentally substituted for NovoLog® have been identified during
postapprovaluse[see Patient Counseling Information (17)].
7
DRUG INTERACTIONS
Anumberofsubstancesaffectglucosemetabolismandmayrequireinsulindoseadjustmentand
particularlyclosemonitoring.
•Thefollowingareexamplesofsubstancesthatmayincreasetheblood-glucose-loweringeffect
andsusceptibilitytohypoglycemia:oralantidiabeticproducts,pramlintide,ACEinhibitors,
disopyramide,fibrates,fluoxetine,monoamineoxidase(MAO)inhibitors,propoxyphene,
salicylates,somatostatinanalog(e.g.,octreotide),sulfonamideantibiotics.
•Thefollowingareexamplesofsubstancesthatmayreducetheblood-glucose-lowering
effect:corticosteroids,niacin,danazol,diuretics,sympathomimeticagents(e.g.,epinephrine,
salbutamol,terbutaline),isoniazid,phenothiazinederivatives,somatropin,thyroidhormones,
estrogens,progestogens(e.g.,inoralcontraceptives),atypicalantipsychotics.
•Beta-blockers,clonidine,lithiumsalts,andalcoholmayeitherpotentiateorweakenthebloodglucose-loweringeffectofinsulin.
•Pentamidinemaycausehypoglycemia,whichmaysometimesbefollowedbyhyperglycemia.
•Thesignsofhypoglycemiamaybereducedorabsentinpatientstakingsympatholytic
productssuchasbeta-blockers,clonidine,guanethidine,andreserpine.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
PregnancyCategoryB.Allpregnancieshaveabackgroundriskofbirthdefects,loss,orother
adverseoutcomeregardlessofdrugexposure.Thisbackgroundriskisincreasedinpregnancies
complicatedbyhyperglycemiaandmaybedecreasedwithgoodmetaboliccontrol.Itisessentialfor
patientswithdiabetesorhistoryofgestationaldiabetestomaintaingoodmetaboliccontrolbefore
NovoLog® (insulin aspart [rDNA origin] injection)
Serum glucose (mg/dL)
300
250
200
150
100
50
0
0
1
2
3
4
5
6
Time (h)
Figure 2. Serial mean serum glucose collected up to 6 hours following a single
pre-meal dose of NovoLog® (solid curve) or regular human insulin (hatched curve)
injected immediately before a meal in 22 patients with type 1 diabetes.
A double-blind, randomized, two-way cross-over study in 16 patients with type 1 diabetes
demonstrated that intravenous infusion of NovoLog® resulted in a blood glucose profile that
wassimilartothatafterintravenousinfusionwithregularhumaninsulin.NovoLog®orhuman
insulinwasinfuseduntilthepatient’sbloodglucosedecreasedto36mg/dL,oruntilthepatient
demonstratedsignsofhypoglycemia(riseinheartrateandonsetofsweating),definedasthetime
ofautonomicreaction(R)(seeFigure3).
Mean Blood Glucose (mg/dL)
180
162
144
126
108
90
72
54
36
18
0
0
10
R–20
R–10
R
R+10
R+20
R+30
R+40
R+50
R+60
Time (min)
Note: The slashes on the mean profile indicate a jump on the time axis
Figure 3. Mean blood glucose profiles following intravenous infusion of NovoLog®
(hatched curve) and regular human insulin (solid curve) in 16 patients with type 1
diabetes. R represents the time of autonomic reaction.
12.3 Pharmacokinetics
ThesinglesubstitutionoftheaminoacidprolinewithasparticacidatpositionB28inNovoLog®
reduces the molecule’s tendency to form hexamers as observed with regular human insulin.
NovoLog®is,therefore,morerapidlyabsorbedaftersubcutaneousinjectioncomparedtoregular
humaninsulin.
Inarandomized,double-blind,crossoverstudy17healthyCaucasianmalesubjectsbetween18
and40yearsofagereceivedanintravenousinfusionofeitherNovoLog®orregularhumaninsulin
at1.5mU/kg/minfor120minutes.Themeaninsulinclearancewassimilarforthetwogroups
withmeanvaluesof1.2l/h/kgfortheNovoLog®groupand1.2l/h/kgfortheregularhuman
insulingroup.
Bioavailability and Absorption-NovoLog®hasafasterabsorption,afasteronsetofaction,anda
shorterdurationofactionthanregularhumaninsulinaftersubcutaneousinjection(seeFigure2and
Figure4).TherelativebioavailabilityofNovoLog®comparedtoregularhumaninsulinindicates
thatthetwoinsulinsareabsorbedtoasimilarextent.
80
Free serum insulin (mU/L)
conceptionandthroughoutpregnancy.Insulinrequirementsmaydecreaseduringthefirsttrimester,
generallyincreaseduringthesecondandthirdtrimesters,andrapidlydeclineafterdelivery.Careful
monitoringofglucosecontrolisessentialinthesepatients.Therefore,femalepatientsshouldbe
advisedtotelltheirphysicianiftheyintendtobecome,oriftheybecomepregnantwhiletaking
NovoLog®.
Anopen-label,randomizedstudycomparedthesafetyandefficacyofNovoLog®(n=157)versus
regularhumaninsulin(n=165)in322pregnantwomenwithtype1diabetes.Two-thirdsofthe
enrolledpatientswerealreadypregnantwhentheyenteredthestudy.Becauseonlyone-thirdof
thepatientsenrolledbeforeconception,thestudywasnotlargeenoughtoevaluatetheriskof
congenitalmalformations.BothgroupsachievedameanHbA1cof~6%duringpregnancy,and
therewasnosignificantdifferenceintheincidenceofmaternalhypoglycemia.
Subcutaneous reproduction and teratology studies have been performed with NovoLog® and
regularhumaninsulininratsandrabbits.Inthesestudies,NovoLog®wasgiventofemalerats
beforemating,duringmating,andthroughoutpregnancy,andtorabbitsduringorganogenesis.
TheeffectsofNovoLog®didnotdifferfromthoseobservedwithsubcutaneousregularhuman
insulin.NovoLog®,likehumaninsulin,causedpre-andpost-implantationlossesandvisceral/
skeletal abnormalities in rats at a dose of 200 U/kg/day (approximately 32 times the human
subcutaneousdoseof1.0U/kg/day,basedonU/bodysurfacearea)andinrabbitsatadoseof10
U/kg/day(approximatelythreetimesthehumansubcutaneousdoseof1.0U/kg/day,basedonU/
bodysurfacearea).Theeffectsareprobablysecondarytomaternalhypoglycemiaathighdoses.
Nosignificanteffectswereobservedinratsatadoseof50U/kg/dayandinrabbitsatadoseof
3U/kg/day.Thesedosesareapproximately8timesthehumansubcutaneousdoseof1.0U/kg/
dayforratsandequaltothehumansubcutaneousdoseof1.0U/kg/dayforrabbits,basedonU/
bodysurfacearea.
8.3 Nursing Mothers
Itisunknownwhetherinsulinaspartisexcretedinhumanmilk.UseofNovoLog®iscompatible
withbreastfeeding,butwomenwithdiabeteswhoarelactatingmayrequireadjustmentsoftheir
insulindoses.
8.4 Pediatric Use
NovoLog®isapprovedforuseinchildrenforsubcutaneousdailyinjectionsandforsubcutaneous
continuousinfusionbyexternalinsulinpump.NovoLog®hasnotbeenstudiedinpediatricpatients
youngerthan2yearsofage.NovoLog®hasnotbeenstudiedinpediatricpatientswithtype2
diabetes.PleaseseeSection 14 CLINICAL STUDIESforsummariesofclinicalstudies.
8.5 Geriatric Use
Ofthetotalnumberofpatients(n=1,375)treatedwithNovoLog®in3controlledclinicalstudies,
2.6%(n=36)were65yearsofageorover.One-halfofthesepatientshadtype1diabetes(18/1285)
andtheotherhalfhadtype2diabetes(18/90).TheHbA1cresponsetoNovoLog®,ascompared
tohumaninsulin,didnotdifferbyage,particularlyinpatientswithtype2diabetes.Additional
studiesinlargerpopulationsofpatients65yearsofageoroverareneededtopermitconclusions
regarding the safety of NovoLog® in elderly compared to younger patients. Pharmacokinetic/
pharmacodynamicstudiestoassesstheeffectofageontheonsetofNovoLog®actionhavenot
beenperformed.
10
OVERDOSAGE
Excessinsulinadministrationmaycausehypoglycemiaand,particularlywhengivenintravenously,
hypokalemia.Mildepisodesofhypoglycemiausuallycanbetreatedwithoralglucose.Adjustments
indrugdosage,mealpatterns,orexercise,maybeneeded.Moresevereepisodeswithcoma,
seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon
or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be
necessarybecausehypoglycemiamayrecurafterapparentclinicalrecovery.Hypokalemiamust
becorrectedappropriately.
11
DESCRIPTION
NovoLog®(insulinaspart[rDNAorigin]injection)isarapid-actinghumaninsulinanalogusedto
lowerbloodglucose.NovoLog®ishomologouswithregularhumaninsulinwiththeexceptionofa
singlesubstitutionoftheaminoacidprolinebyasparticacidinpositionB28,andisproducedby
recombinantDNAtechnologyutilizingSaccharomyces cerevisiae(baker’syeast).Insulinasparthas
theempiricalformulaC256H381N65079S6andamolecularweightof5825.8.
60
40
20
0
0
1
2
3
4
5
6
Time (h)
Figure 1. Structural formula of insulin aspart.
NovoLog®isasterile,aqueous,clear,andcolorlesssolution,thatcontainsinsulinaspart100
Units/mL,glycerin16mg/mL,phenol1.50mg/mL,metacresol1.72mg/mL,zinc19.6mcg/mL,
disodiumhydrogenphosphatedihydrate1.25mg/mL,sodiumchloride0.58mg/mLandwaterfor
injection.NovoLog®hasapHof7.2-7.6.Hydrochloricacid10%and/orsodiumhydroxide10%
maybeaddedtoadjustpH.
12
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
TheprimaryactivityofNovoLog®istheregulationofglucosemetabolism.Insulins,including
NovoLog®,bindtotheinsulinreceptorsonmuscleandfatcellsandlowerbloodglucoseby
facilitatingthecellularuptakeofglucoseandsimultaneouslyinhibitingtheoutputofglucosefrom
theliver.
12.2 Pharmacodynamics
Studies in normal volunteers and patients with diabetes demonstrated that subcutaneous
administrationofNovoLog®hasamorerapidonsetofactionthanregularhumaninsulin.
In a study in patients with type 1 diabetes (n=22), the maximum glucose-lowering effect
of NovoLog® occurred between 1 and 3 hours after subcutaneous injection (see Figure 2).
ThedurationofactionforNovoLog®is3to5hours.Thetimecourseofactionofinsulinand
insulinanalogssuchasNovoLog®mayvaryconsiderablyindifferentindividualsorwithinthe
sameindividual.TheparametersofNovoLog®activity(timeofonset,peaktimeandduration)
asdesignatedinFigure2shouldbeconsideredonlyasgeneralguidelines.Therateofinsulin
absorptionandonsetofactivityisaffectedbythesiteofinjection,exercise,andothervariables[see
Warnings and Precautions (5.1)].
Figure 4. Serial mean serum free insulin concentration collected up to 6 hours
following a single pre-meal dose of NovoLog® (solid curve) or regular human
insulin (hatched curve) injected immediately before a meal in 22 patients with
type 1 diabetes.
In studies in healthy volunteers (total n=107) and patients with type 1 diabetes (total n=40),
NovoLog®consistentlyreachedpeakserumconcentrationsapproximatelytwiceasfastasregular
humaninsulin.Themediantimetomaximumconcentrationinthesetrialswas40to50minutes
forNovoLog®versus80to120minutesforregularhumaninsulin.Inaclinicaltrialinpatientswith
type1diabetes,NovoLog®andregularhumaninsulin,bothadministeredsubcutaneouslyatadose
of0.15U/kgbodyweight,reachedmeanmaximumconcentrationsof82and36mU/L,respectively.
Pharmacokinetic/pharmacodynamiccharacteristicsofinsulinasparthavenotbeenestablishedin
patientswithtype2diabetes.
Theintra-individualvariabilityintimetomaximumseruminsulinconcentrationforhealthymale
volunteers was significantly less for NovoLog® than for regular human insulin. The clinical
significanceofthisobservationhasnotbeenestablished.
In a clinical study in healthy non-obese subjects, the pharmacokinetic differences between
NovoLog®andregularhumaninsulindescribedabove,wereobservedindependentofthesiteof
injection(abdomen,thigh,orupperarm).
Distribution and Elimination-NovoLog®haslowbindingtoplasmaproteins(<10%),similarto
thatseenwithregularhumaninsulin.Aftersubcutaneousadministrationinnormalmalevolunteers
(n=24), NovoLog® was more rapidly eliminated than regular human insulin with an average
apparenthalf-lifeof81minutescomparedto141minutesforregularhumaninsulin.
Specific Populations
Children and Adolescents-ThepharmacokineticandpharmacodynamicpropertiesofNovoLog®
andregularhumaninsulinwereevaluatedinasingledosestudyin18children(6-12years,n=9)
andadolescents(13-17years[Tannergrade≥2],n=9)withtype1diabetes.Therelativedifferences
in pharmacokinetics and pharmacodynamics in children and adolescents with type 1 diabetes
3
betweenNovoLog®andregularhumaninsulinweresimilartothoseinhealthyadultsubjectsand
adultswithtype1diabetes.
Gender-Inhealthyvolunteers,nodifferenceininsulinaspartlevelswasseenbetweenmenand
womenwhenbodyweightdifferencesweretakenintoaccount.Therewasnosignificantdifference
inefficacynoted(asassessedbyHbA1c)betweengendersinatrialinpatientswithtype1diabetes.
Obesity-Asinglesubcutaneousdoseof0.1U/kgNovoLog®wasadministeredinastudyof
23patientswithtype1diabetesandawiderangeofbodymassindex(BMI,22-39kg/m2).The
pharmacokineticparameters,AUCandCmax,ofNovoLog®weregenerallyunaffectedbyBMIinthe
differentgroups–BMI19-23kg/m2(N=4);BMI23-27kg/m2(N=7);BMI27-32kg/m2(N=6)and
BMI>32kg/m2(N=6).ClearanceofNovoLog®wasreducedby28%inpatientswithBMI>32kg/
m2comparedtopatientswithBMI<23kg/m2.
Renal Impairment-Somestudieswithhumaninsulinhaveshownincreasedcirculatinglevels
ofinsulininpatientswithrenalfailure.Asinglesubcutaneousdoseof0.08U/kgNovoLog®was
administeredinastudytosubjectswitheithernormal(N=6)creatinineclearance(CLcr)(>80ml/
min)ormild(N=7;CLcr=50-80ml/min),moderate(N=3;CLcr=30-50ml/min)orsevere(butnot
requiringhemodialysis)(N=2;CLcr=<30ml/min)renalimpairment.Inthissmallstudy,therewas
noapparenteffectofcreatinineclearancevaluesonAUCandCmaxofNovoLog®.Carefulglucose
monitoringanddoseadjustmentsofinsulin,includingNovoLog®,maybenecessaryinpatients
withrenaldysfunction[see Warnings and Precautions (5.4)].
Hepatic Impairment -Somestudieswithhumaninsulinhaveshownincreasedcirculatinglevels
ofinsulininpatientswithliverfailure.Asinglesubcutaneousdoseof0.06U/kgNovoLog®was
administeredinanopen-label,single-dosestudyof24subjects(N=6/group)withdifferentdegree
ofhepaticimpairment(mild,moderateandsevere)havingChild-PughScoresrangingfrom0
(healthyvolunteers)to12(severehepaticimpairment).Inthissmallstudy,therewasnocorrelation
between the degree of hepatic failure and any NovoLog® pharmacokinetic parameter. Careful
glucosemonitoringanddoseadjustmentsofinsulin,includingNovoLog®,maybenecessaryin
patientswithhepaticdysfunction[see Warnings and Precautions (5.5)].
The effect of age, ethnic origin, pregnancy and smoking on the pharmacokinetics and
pharmacodynamicsofNovoLog®hasnotbeenstudied.
13
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the
carcinogenic potential of NovoLog®. In 52-week studies, Sprague-Dawley rats were dosed
subcutaneouslywithNovoLog®at10,50,and200U/kg/day(approximately2,8,and32times
thehumansubcutaneousdoseof1.0U/kg/day,basedonU/bodysurfacearea,respectively).Ata
doseof200U/kg/day,NovoLog®increasedtheincidenceofmammaryglandtumorsinfemales
whencomparedtountreatedcontrols.TheincidenceofmammarytumorsforNovoLog®wasnot
significantlydifferentthanforregularhumaninsulin.Therelevanceofthesefindingstohumansis
notknown.NovoLog®wasnotgenotoxicinthefollowingtests:Amestest,mouselymphomacell
forwardgenemutationtest,humanperipheralbloodlymphocytechromosomeaberrationtest,in
vivomicronucleustestinmice,andinex vivoUDStestinratliverhepatocytes.Infertilitystudies
inmaleandfemalerats,atsubcutaneousdosesupto200U/kg/day(approximately32timesthe
humansubcutaneousdose,basedonU/bodysurfacearea),nodirectadverseeffectsonmaleand
femalefertility,orgeneralreproductiveperformanceofanimalswasobserved.
13.2 Animal Toxicology and/or Pharmacology
Instandardbiologicalassaysinmiceandrabbits,oneunitofNovoLog®hasthesameglucoseloweringeffectasoneunitofregularhumaninsulin.Inhumans,theeffectofNovoLog®ismore
rapid in onset and of shorter duration, compared to regular human insulin, due to its faster
absorptionaftersubcutaneousinjection(seeSection 12 CLINICAL PHARMACOLOGYFigure2
andFigure4).
14
CLINICAL STUDIES
14.1 Subcutaneous Daily Injections
Twosix-month,open-label,active-controlledstudieswereconductedtocomparethesafetyand
efficacyofNovoLog®toNovolin®Rinadultpatientswithtype1diabetes.Becausethetwostudy
designsandresultsweresimilar,dataareshownforonlyonestudy(seeTable3).NovoLog®was
administeredbysubcutaneousinjectionimmediatelypriortomealsandregularhumaninsulinwas
administeredbysubcutaneousinjection30minutesbeforemeals.NPHinsulinwasadministered
asthebasalinsulinineithersingleordivideddailydoses.ChangesinHbA1candtheincidence
ratesofseverehypoglycemia(asdeterminedfromthenumberofeventsrequiringinterventionfrom
athirdparty)werecomparableforthetwotreatmentregimensinthisstudy(Table3)aswellasin
theotherclinicalstudiesthatarecitedinthissection.Diabeticketoacidosiswasnotreportedinany
oftheadultstudiesineithertreatmentgroup.
Table 3. Subcutaneous NovoLog® Administration in Type 1 Diabetes(24weeks;
n=882)
NovoLog® + NPH Novolin® R + NPH
N
596
286
7.9±1.1
8.0±1.2
BaselineHbA1c(%)*
-0.1±0.8
0.0±0.8
ChangefromBaselineHbA1c(%)
TreatmentDifferenceinHbA1c,Mean
-0.2(-0.3,-0.1)
(95%confidenceinterval)
Baselineinsulindose(IU/kg/24hours)*
0.7±0.2
0.7±0.2
End-of-Studyinsulindose(IU/kg/24hours)*
0.7±0.2
0.7±0.2
Patientswithseverehypoglycemia(n,%)**
104(17%)
54(19%)
Baselinebodyweight(kg)*
75.3±14.5
75.9±13.1
WeightChangefrombaseline(kg)*
0.5±3.3
0.9±2.9
*ValuesareMean±SD
**Severehypoglycemiareferstohypoglycemiaassociatedwithcentralnervoussystemsymptomsand
requiringtheinterventionofanotherpersonorhospitalization.
A24-week,parallel-groupstudyofchildrenandadolescentswithtype1diabetes(n=283)aged6
to18yearscomparedtwosubcutaneousmultiple-dosetreatmentregimens:NovoLog®(n=187)
orNovolin®R(n=96).NPHinsulinwasadministeredasthebasalinsulin.NovoLog®achieved
glycemiccontrolcomparabletoNovolin®R,asmeasuredbychangeinHbA1c(Table4)andboth
treatmentgroupshadacomparableincidenceofhypoglycemia.Subcutaneousadministrationof
NovoLog®andregularhumaninsulinhavealsobeencomparedinchildrenwithtype1diabetes
(n=26)aged2to6yearswithsimilareffectsonHbA1candhypoglycemia.
NovoLog® (insulin aspart [rDNA origin] injection)
Table 4. Pediatric Subcutaneous Administration of NovoLog® in Type 1 Diabetes
(24weeks;n=283)
NovoLog® + NPH Novolin® R + NPH
N
187
96
8.3±1.2
8.3±1.3
BaselineHbA1c(%)*
0.1±1.0
0.1±1.1
ChangefromBaselineHbA1c(%)
TreatmentDifferenceinHbA1c,Mean
0.1(-0.5,0.1)
(95%confidenceinterval)
Baselineinsulindose(IU/kg/24hours)*
0.4±0.2
0.6±0.2
End-of-Studyinsulindose(IU/kg/24hours)*
0.4±0.2
0.7±0.2
Patientswithseverehypoglycemia(n,%)**
11(6%)
9(9%)
Diabeticketoacidosis(n,%)
10(5%)
2(2%)
Baselinebodyweight(kg)*
50.6±19.6
48.7±15.8
WeightChangefrombaseline(kg)*
2.7±3.5
2.4±2.6
*ValuesareMean±SD
**Severehypoglycemiareferstohypoglycemiaassociatedwithcentralnervoussystemsymptomsand
requiringtheinterventionofanotherpersonorhospitalization.
An open-label, 16-week parallel design trial compared pre-prandial NovoLog® injection in
conjunctionwithNPHinjectionstoNovoLog®administeredbycontinuoussubcutaneousinfusion
in127adultswithtype2diabetes.ThetwotreatmentgroupshadsimilarreductionsinHbA1cand
ratesofseverehypoglycemia(Table8)[see Indications and Usage (1), Dosage and Administration
(2), Warnings and Precautions (5) and How Supplied/Storage and Handling (16.2)].
Table 8. Pump Therapy in Type 2 Diabetes (16weeks;n=127)
NovoLog® pump NovoLog® + NPH
N
66
61
8.2±1.4
8.0±1.1
BaselineHbA1c(%)*
-0.6±1.1
-0.5±0.9
ChangefromBaselineHbA1c(%)
TreatmentDifferenceinHbA1c,Mean
0.1(0.4,0.3)
(95%confidenceinterval)
*ValuesareMean±SD
Baselineinsulindose(IU/kg/24hours)*
0.7±0.3
0.8±0.5
**Severehypoglycemiareferstohypoglycemiaassociatedwithcentralnervoussystemsymptomsand
requiringtheinterventionofanotherpersonorhospitalization.
End-of-Studyinsulindose(IU/kg/24hours)*
0.9±0.4
0.9±0.5
One six-month, open-label, active-controlled study was conducted to compare the safety and
Baselinebodyweight(kg)*
96.4±17.0
96.9±17.9
efficacyofNovoLog®toNovolin®Rinpatientswithtype2diabetes(Table5).NovoLog®was
1.7±3.7
0.7±4.1
administeredbysubcutaneousinjectionimmediatelypriortomealsandregularhumaninsulinwas WeightChangefrombaseline(kg)*
administeredbysubcutaneousinjection30minutesbeforemeals.NPHinsulinwasadministeredas *ValuesareMean±SD
thebasalinsulinineithersingleordivideddailydoses.ChangesinHbA1candtheratesofsevere 14.3 Intravenous Administration of NovoLog®
hypoglycemia(asdeterminedfromthenumberofeventsrequiringinterventionfromathirdparty)
See Section 12.2 CLINICAL PHARMACOLOGY/Pharmacodynamics.
werecomparableforthetwotreatmentregimens.
®
16
HOW SUPPLIED/STORAGE AND HANDLING
Table 5. Subcutaneous NovoLog Administration in Type 2 Diabetes (6months;
n=176)
16.1 How Supplied
NovoLog® + NPH Novolin® R + NPH NovoLog®isavailableinthefollowingpackagesizes:eachpresentationcontaining100Unitsof
insulinaspartpermL(U-100).
N
90
86
10mLvials
NDC0169-7501-11
8.1±1.2
7.8±1.1
BaselineHbA1c(%)*
3mLPenFill®cartridges*
NDC0169-3303-12
-0.3±1.0
-0.1±0.8
ChangefromBaselineHbA1c(%)
®FlexPen®
3mLNovoLog
NDC0169-6339-10
TreatmentDifferenceinHbA1c,Mean
-0.1(-0.4,-0.1)
(95%confidenceinterval)
*NovoLog®PenFill®cartridgesaredesignedforusewithNovoNordisk3mLPenFill®cartridge
compatibleinsulindeliverydevices(withorwithouttheadditionofaNovoPen®3PenMate®)with
Baselineinsulindose(IU/kg/24hours)*
0.6±0.3
0.6±0.3
NovoFine®disposableneedles.
End-of-Studyinsulindose(IU/kg/24hours)*
0.7±0.3
0.7±0.3
16.2 Recommended Storage
Patientswithseverehypoglycemia(n,%)**
9(10%)
5(8%)
Unused NovoLog® should be stored in a refrigerator between 2° and 8°C (36° to 46°F). Do
Baselinebodyweight(kg)*
88.4±13.3
85.8±14.8
notstoreinthefreezerordirectlyadjacenttotherefrigeratorcoolingelement.Do not freeze
WeightChangefrombaseline(kg)*
1.2±3.0
0.4±3.1
NovoLog® and do not use NovoLog® if it has been frozen.NovoLog®shouldnotbedrawn
*ValuesareMean±SD
intoasyringeandstoredforlateruse.
**Severehypoglycemiareferstohypoglycemiaassociatedwithcentralnervoussystemsymptomsand
Vials:Afterinitialuseavialmaybekeptattemperaturesbelow30°C(86°F)forupto28days,but
requiringtheinterventionofanotherpersonorhospitalization.
shouldnotbeexposedtoexcessiveheatorsunlight.Openedvialsmayberefrigerated.
14.2 Continuous Subcutaneous Insulin Infusion (CSII) by External Pump
Unpuncturedvialscanbeuseduntiltheexpirationdateprintedonthelabeliftheyarestoredin
Two open-label, parallel design studies (6 weeks [n=29] and 16 weeks [n=118]) compared arefrigerator.Keepunusedvialsinthecartonsotheywillstaycleanandprotectedfromlight.
®
NovoLog tobufferedregularhumaninsulin(Velosulin)inadultswithtype1diabetesreceivinga PenFill® cartridges or NovoLog® FlexPen®:
subcutaneousinfusionwithanexternalinsulinpump.Thetwotreatmentregimenshadcomparable
OnceacartridgeoraNovoLog®FlexPen®ispunctured,itshouldbekeptattemperaturesbelow
changesinHbA1candratesofseverehypoglycemia.
30°C (86°F) for up to 28 days, but should not be exposed to excessive heat or sunlight. A
Table 6. Adult Insulin Pump Study in Type 1 Diabetes(16weeks;n=118)
NovoLog®FlexPen®orcartridgeinusemustNOTbestoredintherefrigerator.KeeptheNovoLog®
NovoLog® Buffered human insulin FlexPen®andallPenFill®cartridgesawayfromdirectheatandsunlight.UnpuncturedNovoLog®
FlexPen®andPenFill®cartridgescanbeuseduntiltheexpirationdateprintedonthelabelifthey
N
59
59
arestoredinarefrigerator.KeepunusedNovoLog®FlexPen®andPenFill®cartridgesinthecarton
7.3±0.7
7.5±0.8
BaselineHbA1c(%)*
sotheywillstaycleanandprotectedfromlight.
0.0±0.5
0.2±0.6
ChangefromBaselineHbA1c(%)
Always remove the needle after each injection and store the 3 mL PenFill® cartridge
delivery device or NovoLog® FlexPen® without a needle attached. This prevents
TreatmentDifferenceinHbA1c,Mean
0.3(-0.1,0.4)
contamination and/or infection, or leakage of insulin, and will ensure accurate
(95%confidenceinterval)
dosing. Always use a new needle for each injection to prevent contamination.
Baselineinsulindose(IU/kg/24hours)*
0.7±0.8
0.6±0.2
Pump:
End-of-Studyinsulindose(IU/kg/24hours)* 0.7±0.7
0.6±0.2
NovoLog®inthepumpreservoirshouldbediscardedafteratleastevery6daysofuseorafter
Patientswithseverehypoglycemia(n,%)**
1(2%)
2(3%)
exposuretotemperaturesthatexceed37°C(98.6°F).Theinfusionsetandtheinfusionsetinsertion
Baselinebodyweight(kg)*
77.4±16.1
74.8±13.8
siteshouldbechangedatleastevery3days.
WeightChangefrombaseline(kg)*
0.1±3.5
-0.0±1.7
Summary of Storage Conditions:
*ValuesareMean±SD
Thestorageconditionsaresummarizedinthefollowingtable:
**Severehypoglycemiareferstohypoglycemiaassociatedwithcentralnervoussystemsymptomsand
Table 9. Storage conditions for vial, PenFill® cartridges and NovoLog® FlexPen®
requiringtheinterventionofanotherpersonorhospitalization.
Not in-use (unopened) Not in-use
In-use (opened)
Arandomized,16-week,open-label,paralleldesignstudyofchildrenandadolescentswithtype1 NovoLog®
RoomTemperature
(unopened)
RoomTemperature
diabetes(n=298)aged4-18yearscomparedtwosubcutaneousinfusionregimensadministered presentation
®
(below30°C)
Refrigerated
(below30°C)
viaanexternalinsulinpump:NovoLog (n=198)orinsulinlispro(n=100).Thesetwotreatments
resultedincomparablechangesfrombaselineinHbA1candcomparableratesofhypoglycemiaafter
10mLvial
28days
Until
28days
16weeksoftreatment(seeTable7).
expirationdate (refrigerated/room
Table 7. Pediatric Insulin Pump Study in Type 1 Diabetes(16weeks;n=298)
temperature)
NovoLog®
Lispro
Until
28days
3mLPenFill® 28days
N
198
100
cartridges
expirationdate (Donotrefrigerate)
8.0±0.9
8.2±0.8
BaselineHbA1c(%)*
3mLNovoLog® 28days
Until
28days
-0.1±0.8
-0.1±0.7
ChangefromBaselineHbA1c(%)
FlexPen®
expirationdate (Donotrefrigerate)
TreatmentDifferenceinHbA1c,Mean
-0.1(-0.3,0.1)
(95%confidenceinterval)
Baselineinsulindose(IU/kg/24hours)*
0.9±0.3
0.9±0.3
Storage of Diluted NovoLog®
NovoLog®dilutedwithInsulinDilutingMediumforNovoLog®toaconcentrationequivalentto
End-of-Studyinsulindose(IU/kg/24hours)*
0.9±0.2
0.9±0.2
U-10orequivalenttoU-50mayremaininpatientuseattemperaturesbelow30°C(86°F)for
Patientswithseverehypoglycemia(n,%)**
19(10%)
8(8%)
28days.
Diabeticketoacidosis(n,%)
1(0.5%)
0(0)
Storage of NovoLog® in Infusion Fluids
Baselinebodyweight(kg)*
54.1±19.7
55.5±19.0
Infusion bags prepared as indicated under Dosage and Administration (2) are stable at room
WeightChangefrombaseline(kg)*
1.8±2.1
1.6±2.1
temperaturefor24hours.Someinsulinwillbeinitiallyadsorbedtothematerialoftheinfusionbag.
4
17
PATIENT COUNSELING INFORMATION
[See FDA-Approved Patient Labeling (17.3)]
17.1 Physician Instructions
Maintenanceofnormalornear-normalglucosecontrolisatreatmentgoalindiabetesmellitus
andhasbeenassociatedwithareductionindiabeticcomplications.Patientsshouldbeinformed
aboutpotentialrisksandbenefitsofNovoLog®therapyincludingthepossibleadversereactions.
Patientsshouldalsobeofferedcontinuededucationandadviceoninsulintherapies,injection
technique,life-stylemanagement,regularglucosemonitoring,periodicglycosylatedhemoglobin
testing,recognitionandmanagementofhypo-andhyperglycemia,adherencetomealplanning,
complicationsofinsulintherapy,timingofdose,instructionintheuseofinjectionorsubcutaneous
infusiondevices,andproperstorageofinsulin.Patientsshouldbeinformedthatfrequent,patientperformedbloodglucosemeasurementsareneededtoachieveoptimalglycemiccontrolandavoid
bothhyper-andhypoglycemia.
Thepatient’sabilitytoconcentrateandreactmaybeimpairedasaresultofhypoglycemia.This
maypresentariskinsituationswheretheseabilitiesareespeciallyimportant,suchasdrivingor
operatingothermachinery.Patientswhohavefrequenthypoglycemiaorreducedorabsentwarning
signsofhypoglycemiashouldbeadvisedtousecautionwhendrivingoroperatingmachinery.
Accidental substitutions between NovoLog® and other insulin products have been reported.
Patientsshouldbeinstructedtoalwayscarefullycheckthattheyareadministeringtheappropriate
insulin to avoid medication errors between NovoLog® and any other insulin. The written
prescription for NovoLog® should be written clearly, to avoid confusion with other
insulin products, for example, NovoLog® Mix 70/30.
17.2 Patients Using Pumps
Patientsusingexternalpumpinfusiontherapyshouldbetrainedinintensiveinsulintherapywith
multipleinjectionsandinthefunctionoftheirpumpandpumpaccessories.
Thefollowinginsulinpumps†havebeenusedinNovoLog®clinicalorin vitrostudiesconductedby
NovoNordisk,themanufacturerofNovoLog®:
•MedtronicParadigm®512and712
•MiniMed508
•Disetronic®D-TRON®andH-TRON®
BeforeusinganotherinsulinpumpwithNovoLog®,readthepumplabeltomakesurethepump
hasbeenevaluatedwithNovoLog®.
NovoLog®isrecommendedforuseinanyreservoirandinfusionsetsthatarecompatiblewith
insulinandthespecificpump.Pleaseseerecommendedreservoirandinfusionsetsinthepump
manual.
To avoid insulin degradation, infusion set occlusion, and loss of the preservative
(metacresol), insulin in the reservoir should be replaced at least every 6 days;
infusion sets and infusion set insertion sites should be changed at least every 3
days.
Insulin exposed to temperatures higher than 37°C (98.6°F) should be discarded.
Thetemperatureoftheinsulinmayexceedambienttemperaturewhenthepumphousing,cover,
tubing,orsportcaseisexposedtosunlightorradiantheat.Infusionsitesthatareerythematous,
pruritic,orthickenedshouldbereportedtomedicalpersonnel,andanewsiteselectedbecause
continuedinfusionmayincreasetheskinreactionand/oraltertheabsorptionofNovoLog®.Pump
orinfusionsetmalfunctionsorinsulindegradationcanleadtohyperglycemiaandketosisina
shorttimebecauseofthesmallsubcutaneousdepotofinsulin.Thisisespeciallypertinentfor
rapid-actinginsulinanalogsthataremorerapidlyabsorbedthroughskinandhaveshorterduration
of action. These differences are particularly relevant when patients are switched from multiple
injectiontherapy.Promptidentificationandcorrectionofthecauseofhyperglycemiaorketosisis
necessary.Problemsincludepumpmalfunction,infusionsetocclusion,leakage,disconnectionor
kinking,anddegradedinsulin.Lesscommonly,hypoglycemiafrompumpmalfunctionmayoccur.
Iftheseproblemscannotbepromptlycorrected,patientsshouldresumetherapywithsubcutaneous
insulininjectionandcontacttheirphysician[see Dosage and Administration (2), Warnings and
Precautions (5) and How Supplied/Storage and Handling (16.2)].
17.3 FDA Approved Patient Labeling
Seeseparateleaflet.
Rx only
DateofIssue:June2011
Version:19
Novo Nordisk®, NovoLog®, NovoPen® 3, PenFill®, Novolin®, FlexPen®, PenMate® and
NovoFine® are registered trademarks of Novo Nordisk A/S.
NovoLog®iscoveredbyUSPatentNos.5,618,913;5,866,538,andotherpatentspending.
FlexPen®iscoveredbyUSPatentNos.6,582,404;6,004,297;6,235,004,andotherpatents
pending.PenFill®iscoveredbyUSPatentNo.5,693,027.
†Thebrandslistedaretheregisteredtrademarksoftheirrespectiveownersandarenottrademarks
ofNovoNordiskA/S.
Manufacturedby:
NovoNordiskA/S
DK-2880Bagsvaerd,Denmark
ForinformationaboutNovoLog®contact:
NovoNordiskInc.
Princeton,NewJersey08540
1-800-727-6500
www.novonordisk-us.com
©2002-2011NovoNordiskA/S
143208-R17/11
NovoLog® (insulin aspart [rDNA origin] injection)
Patient Information
NovoLog® (NŌ-vō-log)
(insulin aspart [rDNA origin] Injection)
Important:
Know your insulin.Donotchangethetypeofinsulinyouuse
unlesstoldtodosobyyourhealthcareprovider.Theamountof
insulinyoutakeaswellasthebesttimeforyoutotakeyourinsulin
mayneedtochangeifyoutakeadifferenttypeofinsulin.
Makesureyouknowthetypeandstrengthofinsulinprescribedforyou.
ReadthePatientInformationthatcomeswithNovoLog®before
youstarttakingitandeachtimeyougetarefill.Theremaybenew
information.Thisleafletdoesnottaketheplaceoftalkingwithyour
healthcareprovideraboutyourdiabetesoryourtreatment.Make
sureyouknowhowtomanageyourdiabetes.Askyourhealthcare
providerifyouhaveanyquestionsaboutmanagingyourdiabetes.
What is NovoLog®?
NovoLog®isaman-madeinsulinthatisusedtocontrolhighblood
sugarinadultsandchildrenwithdiabetesmellitus.
•Inject NovoLog® into the skin of your stomach area,
upper arms, buttocks or upper legs.NovoLog®mayaffect
yourbloodsugarlevelssoonerifyouinjectitintotheskinof
yourstomacharea.Never inject NovoLog® into a vein or
into a muscle.
•Change (rotate) your injection site within the chosen
area (for example, stomach or upper arm) with each
dose. Do not inject into the exact same spot for each
injection.
•If you take too much NovoLog®, your blood sugar may
fall low (hypoglycemia).Youcantreatmildlowblood
sugar(hypoglycemia)bydrinkingoreatingsomethingsugary
rightaway(fruitjuice,sugarcandies,orglucosetablets).Itis
importanttotreatlowbloodsugar(hypoglycemia)rightaway
becauseitcouldgetworseandyoucouldpassout(become
unconscious).Ifyoupassoutyouwillneedhelpfromanother
personoremergencymedicalservicesrightaway,andwillneed
treatmentwithaglucagoninjectionortreatmentatahospital.
See“WhatarethepossiblesideeffectsofNovoLog®?”formore
informationonlowbloodsugar(hypoglycemia).
•If you forget to take your dose of NovoLog®, your
blood sugar may go too high (hyperglycemia).Ifhigh
bloodsugar(hyperglycemia)isnottreateditcanleadtoserious
problems,likelossofconsciousness(passingout),comaor
evendeath.Followyourhealthcareprovider’sinstructionsfor
treatinghighbloodsugar.Knowyoursymptomsofhighblood
sugarwhichmayinclude:
•increasedthirst
•fruitysmellonthebreath
•frequenturination
•drowsiness
•lossofappetite
•ahardtimebreathing
•highamountsofsugarandketonesinyoururine
•nausea,vomiting(throwingup)orstomachpain
•Check your blood sugar levels.Askyourhealthcare
providerwhatyourbloodsugarsshouldbeandwhenyoushould
checkyourbloodsugarlevels.
Your insulin dosage may need to change because of:
•illness
•changeindiet
•stress
•othermedicinesyoutake
•changeinphysicalactivityorexercise
Who should not use NovoLog®?
Do not take NovoLog® if:
•Yourbloodsugaristoolow(hypoglycemia).
•YouareallergictoanythinginNovoLog®.Seetheendofthis
leafletforacompletelistofingredientsinNovoLog®.Checkwith
yourhealthcareproviderifyouarenotsure.
Tell your healthcare provider:
•about all of your medical conditions.Medicalconditions
canaffectyourinsulinneedsandyourdoseofNovoLog®.
•if you are pregnant or breastfeeding.Youandyour
healthcareprovidershouldtalkaboutthebestwaytomanage
yourdiabeteswhileyouarepregnantorbreastfeeding.
NovoLog®hasnotbeenstudiedinnursingwomen.
•about all medicines you take,includingprescriptionsand
non-prescriptionmedicines,vitaminsandherbalsupplements.
YourNovoLog®dosemaychangeifyoutakeothermedicines.
Know the medicines you take.Keepalistofyourmedicines
withyoutoshowyourhealthcareproviderswhenyougetanew
medicine.
What should I avoid while using NovoLog®?
•Alcohol.Alcohol,includingbeerandwine,mayaffectyour
How should I take NovoLog®?
bloodsugarwhenyoutakeNovoLog®.
OnlyuseNovoLog®ifitappearsclearandcolorless.Theremaybe
airbubbles.Thisisnormal.Ifitlookscloudy,thickened,orcolored, •Driving and operating machinery.Youmayhave
difficultyconcentratingorreactingifyouhavelowbloodsugar
orifitcontainssolidparticlesdonotuseitandcallNovoNordisk
(hypoglycemia).Becarefulwhenyoudriveacaroroperate
at1-800-727-6500.
machinery.Askyourhealthcareproviderifitisalrighttodriveif
NovoLog®comesin:
youoftenhave:
•10mLvials(smallbottles)forusewithsyringe
•lowbloodsugar
®
•3mLPenFill cartridgesforusewiththeNovoNordisk3mL
•decreasedornowarningsignsoflowbloodsugar
®
PenFill cartridgecompatibleinsulindeliverydevicesand
®
What
are the possible side effects of NovoLog®?
NovoFine disposableneedles.Thecartridgedeliverydevicecan
beusedwithaNovoPen®3PenMate®
•Low blood sugar (hypoglycemia).Symptomsoflowblood
sugarmayinclude:
•3mLNovoLog®FlexPen®
•sweating
• blurredvision
Read the instructions for use that come with your
•troubleconcentratingorconfusion
NovoLog® product.Talktoyourhealthcareproviderifyouhave
•dizzinessorlightheadedness• hunger
anyquestions.Yourhealthcareprovidershouldshowyouhowto
injectNovoLog®beforeyoustarttakingit.
•shakiness
• slurredspeech
•fastheartbeat
• tinglingoflipsandtongue
•Take NovoLog® exactly as prescribed.Youshouldeata
•anxiety,irritabilityormoodchanges
mealwithin5to10minutesafterusingNovoLog®toavoidlow
bloodsugar.
•headache
•NovoLog® is a fast-acting insulin.TheeffectsofNovoLog® Severelowbloodsugarcancauseunconsciousness(passing
startworking10to20minutesafterinjectionorboluspump
out),seizures,anddeath.Knowyoursymptomsoflowblood
infusion.
sugar.Followyourhealthcareprovider’sinstructionsfortreating
lowbloodsugar.Talktoyourhealthcareprovideriflowblood
•Do not inject NovoLog® if you do not plan to eat right
sugarisaproblemforyou.
after your injection or bolus pump infusion.
•Serious allergic reaction (whole body reaction).Get
•Thegreatestbloodsugarloweringeffectisbetween1and3
medical help right away, if you developarashoveryour
hoursaftertheinjectionorinfusion.Thisbloodsugarlowering
wholebody,havetroublebreathing,afastheartbeat,orsweating.
lastsfor3to5hours.
•Reactions at the injection site (local allergic reaction).
•While using NovoLog® you may have to changeyour
Youmaygetredness,swelling,anditchingattheinjectionsite.
totaldoseofinsulin,yourdoseoflonger-actinginsulin,orthe
Ifyoukeephavingskinreactionsortheyareserioustalktoyour
numberofinjectionsoflonger-actinginsulinyouuse.Pump
healthcareprovider.YoumayneedtostopusingNovoLog®and
usersgivenNovoLog®mayneedtochangetheamountoftotal
useadifferentinsulin.Donotinjectinsulinintoskinthatisred,
insulingivenasabasalinfusion.
swollen,oritchy.
•Do not mix NovoLog®:
•Skin thickens or pits at the injection site
•withanyotherinsulinswhenusedinapump
(lipodystrophy).Change(rotate)whereyouinjectyourinsulin
•withanyinsulinsotherthanNPHwhenusedwithinjections
tohelptopreventtheseskinchangesfromhappening.Donot
bysyringe
injectinsulinintothistypeofskin.
IfyourhealthcareproviderrecommendsdilutingNovoLog®,follow
•Swelling
of your hands and feet
yourhealthcareprovider’sinstructionsexactlysothatyouknow:
•Visionchanges
•HowtomakeNovoLog®moredilute(thatis,asmallernumberof
•Lowpotassiuminyourblood(hypokalemia)
unitsofNovoLog®foragivenamountofliquid)and
•Weightgain
•HowtousethismorediluteformofNovoLog®.Do not use
ThesearenotallofthepossiblesideeffectsfromNovoLog®.
dilute insulin in a pump.
5
Askyourhealthcareproviderorpharmacistformoreinformation.
Callyourhealthcareproviderformedicaladviceaboutsideeffects.
YoumayreportsideeffectstoFDAat1-800-FDA-1088.
How should I store NovoLog®?
All Unopened NovoLog®:
•Keep all unopened NovoLog® in the refrigerator
between 36° to 46°F (2° to 8°C).
•Donotfreeze.DonotuseNovoLog®ifithasbeenfrozen.
•KeepunopenedNovoLog®inthecartontoprotectfromlight.
NovoLog® in use:
•Vials
•Keepintherefrigeratororatroomtemperaturebelow86°F
(30°C)forupto28days.
•Keepvialsawayfromdirectheatorlight.
•Throwawayanopenedvialafter28daysofuse,evenifthere
isinsulinleftinthevial.
•DonotdrawupNovoLog®intoasyringeandstorefor
lateruse.
•Unopenedvialscanbeuseduntiltheexpirationdateon
theNovoLog®label,ifthemedicinehasbeenstoredina
refrigerator.
•PenFill® Cartridges or NovoLog® FlexPen®
•Keepatroomtemperaturebelow86°F(30°C)forupto
28days.
•DonotstoreaPenFill®cartridgeorNovoLog®FlexPen®that
youareusingintherefrigerator.
•KeepPenFill®cartridgesandNovoLog®FlexPen®awayfrom
directheatorlight.
•ThrowawayausedPenFill®cartridgeorNovoLog®
FlexPen®after28days,evenifthereisinsulinleftinthe
cartridgeorsyringe.
•NovoLog® in the pump reservoir and the complete
external pump infusion set
•Theinfusionsetandtheinfusionsiteshouldbechangedat
least every 3 days.Theinsulininthereservoirshould
bechangedat least every 6 daysevenifyouhavenot
usedalloftheinsulin.Changetheinfusionsetandthe
infusionsitemoreoftenthanevery3daysifyouhavehigh
bloodsugar(hyperglycemia),thepumpalarmsounds,orthe
insulinflowisblocked(occlusion).
General advice about NovoLog®
Medicinesaresometimesprescribedforconditionsthatare
notmentionedinthepatientleaflet.DonotuseNovoLog®fora
conditionforwhichitwasnotprescribed.DonotgiveNovoLog®
tootherpeople,eveniftheyhavethesamesymptomsyouhave.
Itmayharmthem.
Thisleafletsummarizesthemostimportantinformationabout
NovoLog®.IfyouwouldlikemoreinformationaboutNovoLog®
ordiabetes,talkwithyourhealthcareprovider.Youcanaskyour
healthcareproviderorpharmacistforinformationaboutNovoLog®
thatiswrittenforhealthcareprofessionals.Call1-800-727-6500or
visitwww.novonordisk-us.comformoreinformation.
Helpfulinformationforpeoplewithdiabetesispublishedby
theAmericanDiabetesAssociation,1701NBeauregardStreet,
Alexandria,VA22311andonwww.diabetes.org.
NovoLog® ingredients include:
•insulinaspart
•zinc
•glycerin
•phenol
•metacresol
•sodiumchloride
•disodiumhydrogenphosphatedihydrate
•waterforinjection
AllNovoLog®vials,PenFill®cartridgesandNovoLog®FlexPen®
arelatexfree.
DateofIssue:June2011
Version:11
Novo Nordisk®, NovoLog®, PenFill®, FlexPen®, NovoPen®, NovoFine®, and
PenMate® are registered trademarks of Novo Nordisk A/S.
NovoLog®iscoveredbyUSPatentNos.5,618,913,5,866,538,andother
patentspending.
FlexPen®iscoveredbyUSPatentNos.6,582,404,6,004,297,6,235,004,
andotherpatentspending.
PenFill®iscoveredbyUSPatentNo.5,693,027.
Manufacturedby:
NovoNordiskA/S
DK-2880Bagsvaerd,Denmark
ForinformationaboutNovoLog®contact:
NovoNordiskInc.
100CollegeRoadWest
Princeton,NewJersey08540
©2002-2011NovoNordiskA/S
143208-R17/11
NovoLog® (insulin aspart [rDNA origin] injection)
NovoLog® FlexPen®
Introduction
PleasereadthefollowinginstructionscarefullybeforeusingyourNovoLog®FlexPen®.
NovoLog®FlexPen®isadisposabledial-a-doseinsulinpen.Youcanselectdosesfrom1to60units
inincrementsof1unit.NovoLog®FlexPen®isdesignedtobeusedwithNovoFine®needles.
NovoLog®FlexPen®shouldnotbeusedbypeoplewhoareblindorhaveseverevisualproblems
withoutthehelpofapersonwhohasgoodeyesightandwhoistrainedtousetheNovoLog®
FlexPen®therightway.
NovoLog® FlexPen®
NovoFine® needle
Pen cap
Big outer Inner needle
Protective
Getting ready
needle cap
cap Needle tab
Makesureyouhavethe
followingitems:
• NovoLog®FlexPen®
• NewNovoFine®needle
• Alcoholswab
Rubber
stopper
Cartridge
Cartridge scale
Preparing Your
NovoLog® FlexPen®
Washyourhandswithsoap
andwater.Beforeyoustarttoprepareyour
injection,checkthelabeltomakesurethatyouaretakingtheright
typeofinsulin.Thisisespeciallyimportantifyoutakemorethan1type
ofinsulin.NovoLog®shouldlookclear.
A.Pulloffthepencap(seediagramA).
Wipetherubberstopperwithanalcoholswab.
B. Attaching the needle
Removetheprotectivetabfromadisposableneedle.
ScrewtheneedletightlyontoyourFlexPen®.Itisimportantthatthe
needleisputonstraight(seediagramB).
NeverplaceadisposableneedleonyourNovoLog®FlexPen®until
youarereadytotakeyourinjection.
Pointer
PushDose button
selector
A
B
D
Toreducetheriskofunexpectedneedlesticks,neverputtheinner
needlecapbackontheneedle.
E
E.Turnthedoseselectortoselect2units(seediagramE).
G.Keeptheneedlepointingupwards,pressthepush-buttonalltheway
in(seediagramG).Thedoseselectorreturnsto0.
Adropofinsulinshouldappearattheneedletip.Ifnot,changethe
needleandrepeattheprocedurenomorethan6times.
Ifyoudonotseeadropofinsulinafter6times,donotusethe
NovoLog®FlexPen®andcontactNovoNordiskat1-800-727-6500.
Asmallairbubblemayremainattheneedletip,butitwillnotbe
injected.
Donotusethecartridgescaleprintedonthecartridgetomeasure
yourdoseofinsulin.
Giving the injection
Dotheinjectionexactlyasshowntoyoubyyourhealthcareprovider.
Yourhealthcareprovidershouldtellyouifyouneedtopinchtheskin
beforeinjecting.
After the injection
Do not recap the needle.Recappingcanleadtoaneedlestickinjury.Removetheneedlefromthe
NovoLog®FlexPen®aftereachinjection.Thishelpstopreventinfection,leakageofinsulin,andwill
helptomakesureyouinjecttherightdoseofinsulin.
PuttheneedleandanyemptyNovoLog®FlexPen®oranyusedNovoLog®FlexPen®still
containinginsulininasharpscontainerorsometypeofhardplasticormetalcontainerwitha
screwtopsuchasadetergentbottleoremptycoffeecan.Thesecontainersshouldbesealed
andthrownawaytherightway.Checkwithyourhealthcareproviderabouttherightwaytothrow
awayusedsyringesandneedles.Theremaybelocalorstatelawsabouthowtothrowaway
usedneedlesandsyringes.Donotthrowawayusedneedlesandsyringesinhouseholdtrashor
recyclingbins.
TheNovoLog®FlexPen®preventsthecartridgefrombeingcompletelyemptied.Itisdesignedto
deliver300units.
K
K.PutthepencapontheNovoLog®FlexPen®andstorethe
NovoLog®FlexPen®withouttheneedleattached(seediagramK).
Maintenance
YourFlexPen®isdesignedtoworkaccuratelyandsafely.Itmustbehandledwithcare.Avoiddropping
yourFlexPen®asitmaydamageit.IfyouareconcernedthatyourFlexPen®isdamaged,useanew
one.YoucancleantheoutsideofyourFlexPen®bywipingitwithadampcloth.Donotsoakorwash
yourFlexPen®asitmaydamageit.DonotrefillyourFlexPen®.
RemovetheneedlefromtheNovoLog®FlexPen®aftereachinjection.Thishelpstoensure
sterility,preventleakageofinsulin,andwillhelptomakesureyouinjecttherightdoseofinsulin
forfutureinjections.
Becarefulwhenhandlingusedneedlestoavoidneedlesticksandtransferofinfectiousdiseases.
KeepyourNovoLog®FlexPen®andneedlesoutofthereachofchildren.
UseNovoLog®FlexPen®asdirectedtotreatyourdiabetes.
NeedlesandNovoLog®FlexPen®mustnotbeshared.Alwaysuseanewneedleforeachinjection.
NovoNordiskisnotresponsibleforharmduetousingthisinsulinpenwithproductsnot
recommendedbyNovoNordisk.
Asaprecautionarymeasure,alwayscarryaspareinsulindeliverydeviceincaseyourNovoLog®
FlexPen®islostordamaged.
RemembertokeepthedisposableNovoLog®FlexPen®withyou.Donotleaveitinacarorother
locationwhereitcangettoohotortoocold.
2 units
selected
F
G
Selecting your dose
Checkandmakesurethatthedoseselectorissetat0.
H.Turnthedoseselectortothenumberofunitsyouneedtoinject.
Thepointershouldlineupwithyourdose.
Thedosecanbecorrectedeitherupordownbyturningthedose
selectorineitherdirectionuntilthecorrectdoselinesupwiththe
pointer(seediagramH).Whenturningthedoseselector,becarefulnot
topressthepush-buttonasinsulinwillcomeout.
Youcannotselectadoselargerthanthenumberofunitsleftinthe
cartridge.
Youwillhearaclickforeverysingleunitdialed.Donotsetthedose
bycountingthenumberofclicksyouhear.
J
L
•ScrewonanewNovoFine®needle.
•Removethebigouterneedlecapandtheinnerneedlecap.
•Doanairshotasdescribedin“Givingtheairshotbeforeeach
20
injection”.
•Putthebigouterneedlecapontotheneedle.Donotputonthe
innerneedlecap.
•Turnthedoseselectorsothedoseindicatorwindowshows20units.
•HoldtheNovoLog®FlexPen®sotheneedleispointingdown.
•Pressthepush-buttonallthewayin.
Theinsulinshouldfillthelowerpartofthebigouterneedlecap(seediagramL).Ifthe
NovoLog®FlexPen®hasreleasedtoomuchortoolittleinsulin,dothefunctioncheckagain.
Ifthesameproblemhappensagain,donotuseyourNovoLog®FlexPen®andcontact
NovoNordiskat1-800-727-6500.
C
Becarefulnottobendordamagetheneedlebeforeuse.
F. HoldyourNovoLog®FlexPen®withtheneedlepointingup.
Tapthecartridgegentlywithyourfingerafewtimestomakeanyair
bubblescollectatthetopofthecartridge(seediagramF).
0
L.IfyourNovoLog®FlexPen®isnotworkingtherightway,followthe
stepsbelow:
D.Pullofftheinnerneedlecapanddisposeofit(seediagramD).
Giving the airshot before each injection
Beforeeachinjectionsmallamountsofairmaycollectinthecartridge
duringnormaluse.Toavoidinjectingairandtoensureproperdosing:
J. Keeptheneedleintheskinforatleast6seconds,andkeepthepushbuttonpressedallthewayinuntiltheneedlehasbeenpulledoutfrom
theskin(seediagramJ).Thiswillmakesurethatthefulldosehas
beengiven.
YoumayseeadropofNovoLog®attheneedletip.Thisisnormaland
hasnoeffectonthedoseyoujustreceived.Ifbloodappearsafteryou
taketheneedleoutofyourskin,presstheinjectionsitelightlywitha
finger.Do not rub the area.
I
Function Check
C.Pulloffthebigouterneedlecap(seediagramC).
Alwaysuseanewneedleforeachinjectiontohelpensuresterility
andpreventblockedneedles.
I. Inserttheneedleintoyourskin.
Injectthedosebypressingthepush-buttonallthewayinuntilthe0
linesupwiththepointer(seediagramI).Becarefulonlytopushthe
buttonwheninjecting.
Turningthedoseselectorwillnotinjectinsulin.
4
6
Patient Instructions for Use
6
H
5 units
selected
4
6
24 units
selected
24
Novo Nordisk®, NovoLog®, PenFill®, FlexPen®, NovoPen®, NovoFine®, and PenMate® are registered trademarks of
Novo Nordisk A/S.
NovoLog®iscoveredbyUSPatentNos.5,618,913,5,866,538,andotherpatentspending.FlexPen®iscoveredby
USPatentNos.6,582,404,6,004,297,6,235,004,andotherpatentspending.PenFill®iscoveredbyUSPatentNo.
5,693,027.
Manufacturedby:
NovoNordiskA/S
DK-2880Bagsvaerd,Denmark
ForinformationaboutNovoLog®contact:
NovoNordiskInc.
100CollegeRoadWest
Princeton,NewJersey08540
©2002-2011NovoNordiskA/S
143208-R17/11