New Zealand Datasheet
1 PRODUCT NAME
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Neutral insulin 100 IU/ml
3 PHARMACEUTICAL FORM
ACTRAPID is a clear colourless solution containing 100% neutral human insulin. It is
available in 3 ml Penfill
cartridges made of glass, with a plunger (bromobutyl) and a
stopper (bromobutyl/polyisoprene) in a carton, or in 10 ml glass vials closed with a disc
(bromobutyl/polyisoprene rubber) and a protective tamper-proof plastic cap in a carton. One
IU (International Unit) corresponds to 0.035 mg of anhydrous human insulin.
The Penfill cartridges are designed to be used with Novo Nordisk insulin delivery systems.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of diabetes mellitus. Furthermore indicated for the initial stabilisation of diabetes,
during treatment of diabetic ketoacidosis and the hyperosmolar non ketotic syndrome, and
during stress situations such as severe infections and major surgery in diabetic patients.
4.2 Dose and method of administration
ACTRAPID is a-short-acting insulin and is often used in combination with intermediate- or
long acting insulins.
Dosage is individual and determined by the physician in accordance with the needs of the
The individual insulin requirement is usually between 0.5 and 1.0 IU/kg/day. The daily insulin
requirement may be higher in patients with insulin resistance (e.g. during puberty in the
young or due to obesity) and lower in patients with residual, endogenous insulin production.
In patients with diabetes mellitus optimised glycaemic control delays the onset of late
diabetic complications. Close blood glucose monitoring is recommended.
An injection should be followed by a meal or snack containing carbohydrates within 30
Concomitant illness, especially infections and feverish conditions, usually increases the
patient’s insulin requirement. Concomitant diseases in the kidney, liver or affecting the
adrenal, pituitary or thyroid gland can require changes in the insulin dose.
Adjustment of the dosage may also be necessary if patients change physical activity or their
usual diet. Dosage adjustment may be necessary when transferring patients from one
insulin preparation to another (see Warnings and Precautions).
ACTRAPID is usually administered subcutaneously in the abdominal wall. The thigh, the
gluteal region or the deltoid region may also be used. Subcutaneous injection into the
abdominal wall ensures a faster absorption than from other regions of the body. Injection into a
lifted skin fold minimises the risk of intramuscular injection. Keep the needle under the skin for
at least 6 seconds to make sure the entire dose is injected.
Injection sites should always be rotated within the same region in order to reduce the risk of
Intramuscular administrations are possible under guidance by a physician. ACTRAPID may
professionals. The intravenous use of ACTRAPID from any pen or cartridge should be an
exception only in situations where vials are not available. In this case, ACTRAPID should be
drawn into an insulin syringe, provided air is avoided, or infused with an infusion system. This
procedure should only be carried out by healthcare professionals.
Insulin should never be given to patients with hypoglycaemia.
Hypersensitivity to human insulin or any of the excipients.
4.4 Special warnings and precautions for use
Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to
hyperglycaemia. Usually the first symptoms of hyperglycaemia usually set in gradually, over
a period of hours or days. They include thirst, increased frequency of urination, nausea,
vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone
breath. In type 1 diabetes, untreated hyperglycaemic events eventually leads to diabetic
ketoacidosis which is potentially lethal.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement
(see Adverse Effects and Overdosage).
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.
Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy,
my experience a change in their usual warning symptoms of hypoglycaemia and should be
advised accordingly. Usual warning symptoms may disappear in patients with longstanding
Transfer from other insulin products
Transferring a patient to another type or brand of insulin should be done under strict medical
supervision. Changes in strength, brand (manufacturer), type, origin (human insulin, insulin
analogue) and/or method of manufacture may result in the need for a change in dosage. .
Patients transferred to ACTRAPID from another type of insulin may require an increased
number of daily injections or a change in dosage from that used with their usual insulin
products. If an adjustment is needed when switching the patient to Actrapid®, it may occur
with the first dose or during the first few weeks or months.
A few patients who have experienced hypoglycaemic reactions after transfer from animal
source insulin have reported that early warning symptoms of hypoglycaemia were less
pronounced or different from those experienced with their previous insulin.
Injection site reactions
As with any insulin therapy, injection site reactions may occur and include pain, redness,
hives, inflammation, bruising, swelling and itching, Continuous rotation of the injection site
within a given area may help to reduce or prevent these reactions. Reactions usually resolve
in a few days to a few weeks. On rare occasions, injection site reactions may require
discontinuation of ACTRAPID.
Before travelling between different time zones, the patient should be advised to consult the
doctor, since this may mean that the patient has to take insulin and meals at different times.
Due to the risk of precipitation in pump catheters, ACTRAPID should not be used in insulin
pumps for continuous subcutaneous insulin infusion.
Combination of thiazolidinediones and insulin products
Cases of congestive heart failure have been reported when thiazolidinediones were used in
congestive heart failure. This should be kept in mind if treatment with the combination of
thiazolidinediones and insulin medicinal products is considered. If the combination is used,
patients should be observed for signs and symptoms of congestive heart failure, weight gain
and oedema. Thiazolidinediones should be discontinued if any deterioration in cardiac
ACTRAPID contains metacresol, which may cause allergic reactions.
4.5 Interaction with other medicines and other forms of interaction
A number of medicinal products are known to interact with the glucose metabolism.
The following substances may reduce the insulin requirements:
Oral anti-diabetic products, monoamine oxidase inhibitors (MAOI), non-selective beta-
blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic
steroids and sulphonamides..
The following substances may increase the insulin requirements:
sympathomimetics, growth hormone and danazol.
Beta-blocking agents may mask the symptoms of hypoglycaemia and delay recovery from
requirement. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.
4.6 Fertility, pregnancy and lactation
There are no restrictions on the treatment of diabetes with insulin during pregnancy as
insulin does not pass the placental barrier.
diabetes therapy, increase the risk of malformations and death in utero. Intensified blood
throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall
in the first trimester and increase subsequently during the second and third trimesters. After
delivery, insulin requirements normally return rapidly to pre-pregnancy values.
There is no restriction on treatment with ACTRAPID during breast-feeding. Insulin treatment
of the nursing mother involves no risk to the baby. However, the ACTRAPID dosage, diet or
both may need to be adjusted.
Effects on Fertility
4.7 Effects on ability to drive and use machines
The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia.
This may constitute a risk in situations where these abilities are of special importance (e.g.
driving a car or operating machinery).
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is
particularly important in those who have reduced or absent awareness of the warning signs
of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving
should be considered in these circumstances.
4.8 Undesirable effects
a. Summary of the safety profile
The most frequently reported adverse reaction during treatment is hypoglycaemia. In clinical
population, dose regimens and level of glycaemic control, please see section c below.
At the beginning of the insulin treatment, refraction anomalies, oedema and injection site
reactions (pain, redness, hives, inflammation, bruising, swelling and itching at the injection
site) may occur. These reactions are usually of transitory nature. Fast improvement in blood
reversible. Intensification of insulin therapy with abrupt improvement in glycaemic control
associated with temporary worsening of diabetic retinopathy, while long-term
improved glycaemic control decreases the risk of progression of diabetic retinopathy.
b. Tabulated list of adverse reactions
Adverse reactions listed below are based on clinical trial data and classified according to
MedDRA frequency and System Organ Class. Frequency categories are defined according
to the following convention: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known
(cannot be estimated from the available data).
Immune system disorders
Uncommon – Urticaria, rash
Very rare – Anaphylactic reactions*
Metabolism and nutrition
Very common – Hypoglycaemia*
Nervous system disorders
Uncommon – Peripheral neuropathy (painful
Uncommon – Refraction disorders
Very rare – Diabetic retinopathy
Skin and subcutaneous
Uncommon – Lipodystrophy*
General disorders and
Uncommon – Injection site reactions
Uncommon – Oedema
* see section c
c. Description of selected adverse reactions
The occurrence of generalised hypersensitivity reactions (including generalised skin rash,
itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing,
palpitation, reduction in blood pressure and fainting/loss of consciousness) is very rare but
can potentially be life threatening.
The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin
dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to
unconsciousness and/or convulsions and may result in temporary or permanent impairment
of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly.
They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness,
unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive
hunger, vision changes, headache, nausea and palpitation.
Lipodystrophy is reported as uncommon. Lipodystrophy may occur at the injection site.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It
A specific overdose of insulin cannot be defined, however, hypoglycaemia may develop over
sequential stages if too high doses relative to the patient’s requirement are administered:
Mild hypoglycaemic episodes can be treated by oral administration of glucose or
sugary products. It is therefore recommended that the diabetic patient always carries
sugar containing products.
Severe hypoglycaemic episodes, where the patient has become unconscious, can
be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a
trained person or with glucose given intravenously by a healthcare professional.
glucagon within 10 to 15 minutes. Upon regaining consciousness administration of
oral carbohydrate is recommended for the patient in order to prevent a relapse.
For advice on the management of overdose please contact the National Poisons Centre on
0800 POISON (0800 764766).
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection,
fast-acting, insulin (human). ATC code A10A B01
The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose
following binding of insulin to receptors on muscle and fat cells and to the simultaneous
inhibition of glucose output from the liver.
For ACTRAPID the fast absorption is due to the product being a solution
An average action profile after subcutaneous injection indicates:
within ½ hour
between 1.5 and 3.5 hours
approximately 7-8 hours
5.2 Pharmacokinetic properties
Insulin in the bloodstream has a half-life of a few minutes. Consequently, the time-action
profile of an insulin preparation is determined solely by its absorption characteristics. This pro-
cess is influenced by several factors (e.g. insulin dosage, injection route and site, thickness
of subcutaneous fat, type of diabetes), which is why considerable intra- and inter-patient
variations are seen.
The maximum plasma concentration is reached within 1.5-2.5 hours after subcutaneous
No profound binding to plasma proteins, except circulating insulin antibodies (if present) has
Human insulin is reported to be degraded by insulin protease or insulin-degrading enzymes
and possibly protein disulfide isomerase. A number of cleavage (hydrolysis) sites on the
human insulin molecule have been proposed; none of the metabolites formed following the
cleavage are active.
The terminal half-life is determined by the rate of absorption from the subcutaneous tissue.
The terminal half-life (t
) is therefore a measure of the absorption rather than of the elimination
per se of insulin from plasma (insulin in the blood stream has a t
of a few minutes). Trials
have indicated a t
of about 2-5 hours.
Children and adolescents
The pharmacokinetic profile of ACTRAPID has been studied in a small number (n=18) of
diabetic children (aged 6-12 years) and adolescents (aged 13-17 years). The data are limited
but suggest that the phamacokinetic profile in children and adolescents may be similar to that
importance of individual dose titration.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for injections
In general terms, insulin should only be added to compounds with which it has known
compatibility. Drugs added to the insulin solution may cause degradation of the insulin, e.g.
if the drugs contain thiols or sulphites. Upon mixing ACTRAPID with infusion fluids an
unpredictable amount of insulin will be adsorbed to the infusion material. Monitoring of the
patient's blood glucose during infusion is therefore recommended.
Instructions for use/handling
The carton contains a package leaflet with instructions for use and handling. ACTRAPID
Penfill is accompanied by a package leaflet with detailed instructions for use to be followed.
ACTRAPID vials are for use with insulin syringes with the corresponding unit scale.
ACTRAPID Penfill is for single person use only. The container must not be refilled.
ACTRAPID Penfill is designed to be used with Novo Nordisk insulin delivery systems and
Cartridges and pens should only be used in combination with products that are compatible
with them and allow the cartridge/pen to function safely and effectively.
Needles and ACTRAPID Penfill must not be shared.
In case of emergency in current ACTRAPID Penfill users (hospitalisation or insulin pen
malfunction), ACTRAPID can be withdrawn with an U100 insulin syringe from the cartridge
6.3 Shelf life
The shelf-life is 30 months. The in-use time is 6 weeks.
6.4 Special precautions for storage
Insulin preparations should be stored between 2°C and 8°C (in a refrigerator), not in or near a
freezing compartment. Insulin preparations which have been frozen must not be used.
Insulin preparations should be protected from excessive heat or sunlight. Insulin solutions
should not be used if they do not appear water-clear and colourless. ACTRAPID should not
be used in insulin pumps for continuous subcutaneous insulin infusion.
After first use ACTRAPID vials may be kept at room temperature (below 25°C) for 6 weeks.
ACTRAPID Penfill, can be used or carried as a spare (below 25°C) for 6 weeks.
6.5 Nature and contents of container
ACTRAPID is available as a Penfill of 3 ml in cartons of five, or in glass vials of 10 ml.
6.6 Special precautions for disposal
Penfills must not be shared. The container must not be refilled. The patient should be
advised to discard the needle after each injection.
7 MEDICINE SCHEDULE
Novo Nordisk Pharmaceuticals Ltd
PO Box 51-268
Tel: (09) 916 5590
Fax: (09) 916 5595
9 DATE OF FIRST APPROVAL
ACTRAPID Penfill 15 April 1985
ACTRAPID 10 ml 9 June 1983
10 DATE OF REVISION OF THE TEXT
5 December 2017
CCDS v15.0, 25 September 2017
ACTRAPID, Penfill and NovoFine are trademarks owned by Novo Nordisk A/S, Denmark
SUMMARY TABLE OF CHANGES
Summary of new information
Adverse event reporting requirement added
Poison Centre contact added
Pharmacotherapeutic group updated