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Special warnings and precautions for use The following substances may reduce the patient's insulin
eral is the most frequently occurring undesirable effect. It may
The use of dosages which are inadequate or discontinuation of
occur if the insulin dose is too high in relation to the insulin
Local hypersensitivity reactions (redness, swelling and itching
treatment, especially in insulindependent diabetics, may lead to
Oral hypoglycaemic agents (OHAs), octreotide, monoamine oxi-
requirement. Severe hypoglycaemia may lead to unconsciousness
at the injection site) may occur during treatment with
The individual insulin requirement in adults and children is usually
hyperglycaemia and diabetic ketoacidosis; conditions which are
dase inhibitors (MAOIs), non-selective beta-adrenergic blocking
and/or convulsions and may result in temporary or permanent
insulin. These reactions are usually transitory and normally
between 0.5 and 1.0 U/kg/day. In a meal-related treatment
agents, angiotensin converting enzyme (ACE) inhibitors, salicy-
impairment of brain function or even death. In clinical trials and
they disappear during continued treatment.
50 - 70% of this requirement may be provided by NovoRapid®
Patients, whose blood glucose control is greatly improved, e.g. by
lates, alcohol, anabolic steroids and sulphonamides.
during marketed use the frequency varies with patient popula-
and the remainder by intermediate-acting or long-acting insulin. General disorders and administration site conditions
intensified insulin therapy, may experience a change in their usual
The following substances may increase the patient's insulin
tion and dose regimens, therefore no specific frequency can be
For the use only of registered medical practitioner
warning symptoms of hypoglycaemia, and should be advised
Oedema may occur upon initiation of insulin therapy. These
Colour: PMS 280C
NovoRapid® is administered subcutaneously in the abdominal
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones,
During clinical trials the overall rates of hypoglycaemia did not
symptoms are usually of transitory nature.
wall, the thigh, the deltoid region or the gluteal region. Injection
A consequence of the pharmacodynamics of rapid-acting insulin
differ between patients treated with insulin aspart compared to
sites should be rotated within the same region. When injected
analogues is that if hypoglycaemia occurs, it may occur earlier
Beta-blocking agents may mask the symptoms of hypoglycaemia. Overdose
subcutaneously into the abdominal wall, the onset of action will
after an injection when compared with soluble human insulin.
Alcohol may intensify and prolong the hypoglycaemic effect of
Frequencies of adverse drug reactions from clinical trials, which
A specific overdose for insulin cannot be defined however
occur within 10 – 20 minutes of injection. The maximum effect is
NovoRapid® should be administered in immediate relation to a
by an overall judgement are considered related to insulin aspart
hypoglycaemia may develop over sequential stages if too
Solution for injection in a cartridge for s.c. use.
exerted between 1 and 3 hours after the injection. The duration
meal. The rapid onset of action should therefore be considered in
Pregnancy and lactation
are listed below. The frequencies are defined as: Uncommon
high doses relative to the patient’s requirement are adminis-
Monocomponent, biosynthetic, (r-DNA Origin)
of action is 3 to 5 hours. As with all insulins, the duration of
patients with concomitant diseases or medication where a
NovoRapid® (insulin aspart) can be used in pregnancy. Data from
(>1/1,000, <1/100) and rare (>1/10,000, <1/1,000). Isolated
action will vary according to the dose, injection site, blood flow,
delayed absorption of food might be expected.
two randomised controlled clinical trials (157 and 14 insulin
spontaneous cases are presented as very rare defined as
• Mild hypoglycaemic episodes can be treated by oral
Concomitant illness, especially infections, usually increases the
(<1/10,000), including isolated reports.
administration of glucose or sugary products. It is
Qualitative and quantitative composition
temperature and level of physical activity. As with all insulins,
aspart-exposed pregnancies respectively) do not indicate any
Within each frequency grouping, undesirable effects are pre-
therefore recommended that the diabetic patient
subcutaneous injection in the abdominal wall ensures a faster
adverse effect of insulin aspart on pregnancy or on the health of
When patients are transferred between different types of insulin
sented in order of decreasing seriousness.
constantly carry sugar containing products
* produced by recombinant DNA technology in
absorption than other injection sites. However, the faster onset of
the foetus/newborn when compared to insulin human (see Phar-
products, the early warning symptoms of hypoglycaemia may
• Severe hypoglycaemic episodes, where the patient has
action compared to soluble human insulin is maintained regard-
Immune system disorders
change or become less pronounced than those experienced with
become unconscious, can be treated by glucagon (0.5 to
One unit of insulin aspart corresponds to 6 nmol, 0.035 mg
Intensified blood glucose control and monitoring of pregnant
1 mg) given intramuscularly or subcutaneously by a
If necessary, NovoRapid® may also be administered intravenously
women with diabetes (type 1 diabetes, type 2 diabetes or gesta-
which should be carried out by healthcare professionals.
Transferring a patient to a new type or brand of insulin should be
tional diabetes) are recommended throughout pregnancy and
trained person, or glucose given intravenously by a
Symptoms of generalised hypersensitivity may include generalised
NovoRapid® may be used for Continuous Subcutaneous Insulin
done under strict medical supervision. Changes in strength,
when contemplating pregnancy. Insulin requirements usually fall
medical professional. Glucose must also be given
skin rash, itching, sweating, gastrointestinal upset, angioneurotic
Infusion (CSII) in pump systems suitable for insulin infusion. CSII
brand, type, species (animal, human, human insulin analogue)
in the first trimester and increase subsequently during the second
intravenously if the patient does not respond to glucagon
NovoRapid® is a clear, colourless, aqueous, solution.
oedema, difficulties in breathing, palpitation and reduction in
should be administered in the abdominal wall. Infusion sites
and/or method of manufacture may result in a change in dosage.
and third trimesters. After delivery, insulin requirements return
Patients taking NovoRapid® may require an increased number of
blood pressure. Generalised hypersensitivity reactions are poten-
Upon regaining consciousness, administration of oral
When used with an insulin infusion pump NovoRapid® should
daily injections or a change in dosage from that used with their
There are no restrictions on treatment with NovoRapid® during
carbohydrate is recommended for the patient in order to
not be mixed with any other insulin. Patients using CSII should be
usual insulins. If an adjustment is needed, it may occur with the
lactation. Insulin treatment of the nursing mother presents no
Nervous system disorders
Treatment of patients with diabetes mellitus.
comprehensively instructed in the use of the pump system and
first dose or during the first several weeks or months.
risk to the baby. However, the NovoRapid® dosage may need to
Pharmacological properties Posology and method of administration
use the correct reservoir and tubing for the pump. The infusion
As with any insulin, injection site reactions may occur and include
Fast improvement in blood glucose control may be associated
NovoRapid® has a faster onset and a shorter duration of
set (tubing and cannula) should be changed in accordance with
pain, itching, hives, swelling and inflammation. Continuous rota-
with a condition termed acute painful neuropathy, which is usu-
Pharmacodynamic properties Effects on ability to drive and use machines
the instructions in the product information supplied with the
tion of the injection site within a given area may help to reduce
Pharmacotherapeutic group: Insulins and analogues for
The patient’s ability to concentrate and react may be impaired as
Due to the faster onset of action, NovoRapid® should gener-
infusion set. Patients administering NovoRapid® by CSII must
or prevent these reactions. Reactions usually resolve in a few days
injection, fast-acting. ATC code A10A B05.
a result of hypoglycaemia. This may constitute a risk in situations
ally be given immediately before a meal. When necessary,
have alternative insulin available in case of pump system failure.
to a few weeks. On rare occasions, injection site reactions may
The blood glucose lowering effect of insulin occurs when
where these abilities are of special importance (e.g. driving a car
NovoRapid® can be given soon after a meal. Due to the
Renal or hepatic impairment may reduce the patient's insulin
require discontinuation of NovoRapid®.
the molecules facilitate the uptake of glucose by binding to
Refraction anomalies may occur upon initiation of insulin therapy.
shorter duration, NovoRapid® has a lower risk of causing
Omission of a meal or unplanned, strenuous physical exercise
insulin receptors on muscle and fat cells - and simultane-
Patients should be advised to take precautions in order to avoid
These symptoms are usually of transitory nature.
Careful glucose monitoring and dose adjustments of insulin
ously inhibit the output of glucose from the liver.
hypoglycaemia whilst driving, this is particularly important in
aspart are recommended in these patients.
Adjustment of dosage may also be necessary if patients under-
NovoRapid® produces a more rapid onset of action com-
those who have reduced or absent awareness of the warning
Long-term improved glycaemic control decreases the risk of pro-
NovoRapid® can be used in children in preference to soluble
take increased physical activity or change their usual diet. Exercise
pared to soluble human insulin, together with a lower glu-
Dosage of NovoRapid® is individual and determined on the
signs of hypoglycaemia or have frequent episodes of hypogly-
gression of diabetic retinopathy. However, intensification of
human insulin when a rapid onset of action might be beneficial.
taken immediately after a meal may increase the risk of hypogly-
cose concentration, as assessed within the first four hours
basis of the physician’s advice in accordance with the needs
caemia. The advisability of driving should be considered in these
insulin therapy with abrupt improvement in glycaemic control
For example, in the timing of the injections in relation to meals.
after a meal. NovoRapid® has a shorter duration of action
of the patient. It should normally be used in combination
may be associated with worsening of diabetic retinopathy.
compared to soluble human insulin after subcutaneous
with intermediate-acting or long-acting insulin given at least
Contraindications Interaction with other medicinal products and other forms Undesirable effects Skin and subcutaneous tissue disorders
• Hypersensitivity to the active substance or to any of the
Adverse drug reactions observed in patients using NovoRapid®
A number of medicinal products are known to interact with glu-
are mainly dose-dependent and due to the pharmacologic effect
Lipodystrophy may occur at the injection site as a consequence of
of insulin. As for other insulin products, hypoglycaemia, in gen-
failure to rotate injection sites within an area.
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When NovoRapid® is injected subcutaneously, the onset of
ments as well as a significant improvement in post prandial glu-
Renal impairment: A single dose pharmacokinetic study of insulin
Special precautions for disposal and other handling
action will occur within 10-20 minutes of injection. The
cose control in the insulin aspart treated group.
aspart in 18 subjects with renal function ranging from normal to
NovoRapid® Penfill® should only be used in combination with
maximum effect is exerted between 1 and 3 hours after
Insulin aspart is equipotent to soluble human insulin on a molar
severely impaired was performed. No apparent effect of creati-
products that are compatible with them and allow the Penfill® to
injection. The duration of action is 3 to 5 hours.
give an injection are: the front of the waist (abdomen); the but-
Adults. Clinical trials in patients with Type 1 diabetes have
tocks; the front of the thighs or upper arms. The insulin will work
aspart was found. Data were limited in subjects with moderate
NovoRapid® Penfill® is for use by one person only. The cartridge
demonstrated a lower postprandial blood glucose with
more quickly if injected around the waist.
In NovoRapid® substitution of the amino acid proline with aspar-
and severe renal impairment. Subjects with renal failure necessi-
NovoRapid® compared to soluble human insulin. In two
NovoRapid® Penfill® is designed to be used with Novo Nordisk
tic acid at position B28 reduces the tendency to form hexamers
tating dialysis treatment were not investigated.
NovoRapid® Penfill® is designed to be used with the
long-term open label trials in patients with Type 1 diabetes
insulin delivery systems and NovoFine® needles. If you are treated
as observed with soluble human insulin. NovoRapid® is therefore
Novo Nordisk insulin delivery system and NovoFine® needles. Preclinical safety data
comprising 1070 and 884 patients, respectively, NovoRapid®
with NovoRapid® Penfill® and another insulin Penfill® cartridge,
more rapidly absorbed from the subcutaneous layer compared to
NovoRapid® may be used in an infusion pump system (CSII). Tub-
Non-clinical data reveal no special hazard for humans based on
reduced glycosylated haemoglobin by 0.12 [95% C.I. 0.03;
you must use two insulin delivery systems, one for each type of
ings in which the inner surface materials are made of polyethy-
conventional studies of safety pharmacology, repeated dose toxi-
0.22] percentage points and by 0.15 [95% C.I. 0.05; 0.26]
The time to maximum concentration is, on average, half of that
lene or polyolefin have been evaluated and found compatible
city, genotoxicity and toxicity to reproduction.
percentage points compared to human insulin; a difference
Do not refill NovoRapid® Penfill®.
for soluble human insulin. A mean maximum plasma concentra-
In in vitro tests, including binding to insulin and IGF-1 receptor
As a precautionary measure, always carry a spare insulin delivery
tion of 492 ± 256 pmol/l was reached 40 (interquartile range:
For intravenous use, infusion systems with NovoRapid® 100 U/ml
sites and effects on cell growth, insulin aspart behaved in a man-
Elderly. A randomised, double-blind cross-over PK/PD trial
device in case your Penfill® is lost or damaged.
30-40) minutes after a subcutaneous dose of 0.15 U/kg body-
at concentrations from 0.05 U/ml to 1.0 U/ml insulin aspart in the
ner that closely resembled human insulin. Studies also demon-
comparing insulin aspart with soluble human insulin was
weight in Type 1 diabetic patients. The insulin concentrations
infusion fluids 0.9% sodium chloride, 5% dextrose or 10% dex-
strate that the dissociation of binding to the insulin receptor of
How to inject this insulin
performed in elderly patients with type 2 diabetes (19
returned to baseline about 4 to 6 hours after dose. The absorp-
trose inclusive 40 mmol/l potassium chloride using polypropylene
insulin aspart is equivalent to human insulin.
►Inject the insulin under the skin. Use the injection technique
patients aged 65-83 years, mean age 70 years). The relative
tion rate was somewhat slower in Type 2 diabetic patients, result-
infusion bags are stable at room temperature for 24 hours.
advised by the doctor or nurse and described in the delivery
differences in the pharmacodynamic properties
Although stable over time, a certain amount of insulin will be ini-
max (352 ± 240 pmol/l) and later tmax (60
(GIRmax,AUCGIR, 0-120 min) between insulin aspart and human
(interquartile range: 50-90) minutes). The intra-individual variabil-
List of excipients
tially adsorbed to the material of the infusion bag. Monitoring of
►Keep the needle under the skin for at least 6 seconds to make
insulin in elderly were similar to those seen in healthy sub-
ity in time to maximum concentration is significantly less for
blood glucose is necessary during insulin infusion.
sure that the full dose has been delivered
jects and in younger subjects with diabetes.
NovoRapid® than for soluble human insulin, whereas the intra-
NovoRapid® should not be used if it does not appear clear and
►After each injection be sure to discard the needle. Otherwise,
Children and adolescents. When given to children
the liquid may leak out when the temperature changes.
NovoRapid® showed similar long-term glucose control com-
Children and adolescents. The pharmacokinetic and pharmacody-
Any unused product or waste material should be disposed of in
namic properties of NovoRapid® were investigated in children (6-
For use in an infusion pump system
A clinical trial comparing preprandial soluble human insulin
12 years) and adolescents (13-17 years) with Type 1 diabetes. Instructions to be given to the patient on how to handle
NovoRapid® should never be mixed with any other insulin when
with postprandial insulin aspart was performed in small chil-
Insulin aspart was rapidly absorbed in both age groups, with sim-
dren (26 patients aged 2 to 6 years) and a single dose PK/PD
max as in adults. However, Cmax differed between the age
Follow the instructions and recommendations from the doctor
trial was performed in children (6-12 years) and adolescents
groups, stressing the importance of the individual titration of
Before using NovoRapid®
regarding the use of NovoRapid® in a pump. Before use of
(13-17 years). The pharmacodynamic profile of insulin aspart
►Check the label to make sure it is the right type of insulin
NovoRapid® in the pump system a comprehensive instruction in
in children was similar to that seen in adults. Incompatibilities Elderly: The relative differences in pharmacokinetic properties
►Always check the cartridge, including the rubber plunger
the use and information about any actions to be taken in case of
Clinical trials in patients with Type 1 diabetes have demon-
Substances added to the insulin may cause degradation of the
between insulin aspart and soluble human insulin in elderly sub-
(stopper). Don’t use it if any damage is seen or if there is a gap
illness, too high or too low blood sugar or failure of the pump
strated a reduced risk of nocturnal hypoglycaemia with
insulin, e.g. if the medicinal product contains thiol or sulphites.
jects (65-83 years, mean age 70 years) with type 2 diabetes were
between the rubber plunger and the white label band. See the
insulin aspart compared with soluble human insulin. The risk
similar to those observed in healthy subjects and in younger sub-
Special precautions for storage
delivery system manual for further instructions
• Before inserting the needle, use soap and water to clean the
of daytime hypoglycaemia was not significantly increased.
jects with diabetes. A decreased absorption rate was observed in
Do not use NovoRapid® Penfill® after the expiry date stated on
►Disinfect the rubber membrane with a medicinal swab
hands and the skin where the needle is inserted so as to avoid
Pregnancy. A clinical trial comparing safety and efficacy of
the label/carton. Keep out of the reach and sight of children.
►Always use a new needle for each injection to prevent
insulin aspart vs. insulin human in the treatment of pregnant
Store in a refrigerator in original package at (2°C – 8°C) not in or
• When filling a new reservoir, be certain not to leave large air
women with type 1 diabetes (322 exposed pregnancies
younger subjects with type 2 diabetes and slightly lower than in
too near the freezer section or cooling element. Do not freeze. NovoRapid® must not be used
bubbles in either the syringe or the tubing
(insulin aspart: 157; insulin human: 165)) did not indicate
Keep the cartridge in the outer carton in order to protect from light.
►If the cartridge or the device containing the cartridge is
• Changing of the infusion set (tubing and needle) must be
any adverse effect of insulin aspart on pregnancy or on the
Hepatic impairment: A single dose pharmacokinetic study of
NovoRapid® Penfill® in use or carried as a spare can be kept at
dropped, damaged or crushed, there is a risk of leakage of
done according to the instructions in the product information
insulin aspart was performed in 24 subjects with hepatic function
ambient temperature (not above 30°C) for up to 4 weeks, but
In addition the data from a clinical trial including 27 women
Novo Nordisk Producao Farmaceutica do Brasil Ltda.
ranging from normal to severely impaired. In subjects with hep-
any remainder must be discarded. Do not refrigerate.
►If it has not been stored correctly or if it has been frozen
with gestational diabetes randomised to treatment with
To get the benefit of insulin infusion, and to detect possible mal-
atic impairment absorption rate was decreased and more vari-
►If the insulin does not appear clear and colourless.
Montes Claros, Minas Gerais, Brazil 39404004.
insulin aspart vs. insulin human (insulin aspart: 14; insulin
Nature and contents of container
function of the insulin pump, it is recommended to measure the
able, resulting in delayed tmax from about 50 min in subjects with
NovoRapid® is for injection under the skin (subcutaneously) or for
human: 13) showed similar safety profiles between treat-
A glass (Type 1) cartridge which contains a piston (bromobutyl
normal hepatic function to about 85 min in subjects with moder-
NovoRapid®, Penfill® and NovoFine® are trademarks
rubber) and is closed with a disc (bromobutyl/polyisoprene rub-
continuous infusion in a pump system. NovoRapid® may also be
ate and severe hepatic impairment. AUC, C
owned by Novo Nordisk A/S, Denmark
ber) containing 3 ml of solution. Cartons of 5 X 3ml cartridges.
given intravenously by health care professionals under close
What to do in case of pump system failure
similar in subjects with reduced hepatic function compared with
Always have alternative insulin available for injection under the
subjects with normal hepatic function.
Always vary the sites to inject, to avoid lumps. The best places to
skin in case of pump system failure.
 UNNI 4-19-12.DOC (DO NOT DELETE) 9/10/2012 3:01 PM Indian Patent Law and TRIPS: Redrawing the Flexibility Framework in the Context of Public Policy and Health Presented in March 2011 at the University of the Pacific, McGeorge School of Law Symposium on The Global Impact and Implementation of Human Rights Norms. IV. THE PATENTS (AMENDMENT) ACT, 2002 . 333 V. THE PATENTS (AMENDMENT)
SISTEMA NACIONAL DE VIGILANCIA EN SALUD PÚBLICA DATOS BÁSICOS 1. INFORMACIÓN GENERAL REG-R02.003.0000-001 V:02 AÑO 2012 1.1 Código de la UPGD Razón social de la unidad primaria generadora del dato 1.2 Nombre del evento Código del evento 1.3 Fecha de Notificación (dd/mm/aaaa) 2. IDENTIFICACIÓN DEL PACIENTE 2.1 Tipo de Documento 2.2 Número de Identificac