Actrapid Innolet

Main information

  • Trade name:
  • Actrapid Innolet 100 IU/mL Solution for injection
  • Dosage:
  • 100 IU/mL
  • Pharmaceutical form:
  • Solution for injection
  • Units in package:
  • Syringe, 3mL glass cartridge, 5 dose units
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Novo Nordisk A/S

Documents

Localization

  • Available in:
  • Actrapid Innolet 100 IU/mL Solution for injection
    New Zealand
  • Language:
  • English

Therapeutic information

  • 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.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 10682
  • Authorization date:
  • 26-02-2002
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

New Zealand Datasheet

1 PRODUCT NAME

ACTRAPID

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Insulin

human,

rDNA

(produced

recombinant

technology

Saccharomyces

cerevisiae).

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

patient.

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

minutes.

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

lipodystrophy.

Intramuscular administrations are possible under guidance by a physician. ACTRAPID may

also

administered

intravenously,

which

should

only

carried

healthcare

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.

4.3 Contraindications

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

Hyperglycaemia

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

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

diabetes.

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

combination

with

insulin,

especially

patients

with

risk

factors

development

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

symptoms occurs.

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:

Oral

contraceptives,

thiazides,

glucocorticoids,

thyroid

hormones,

beta-

sympathomimetics, growth hormone and danazol.

Beta-blocking agents may mask the symptoms of hypoglycaemia and delay recovery from

hypoglycaemia.

Octreotide/lanreotide

either

increase

decrease

insulin

requirement. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no restrictions on the treatment of diabetes with insulin during pregnancy as

insulin does not pass the placental barrier.

Both

hypoglycaemia

hyperglycaemia,

which

occur

inadequately

controlled

diabetes therapy, increase the risk of malformations and death in utero. Intensified blood

glucose

control

monitoring

pregnant

women

with

diabetes

recommended

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.

Breast-feeding

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

Not applicable.

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

trials

during

marketed

use,

frequencies

hypoglycaemia

vary

with

patient

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

glucose

control

associated

with

acute

painful

neuropathy,

which

usually

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

disorders

Very common – Hypoglycaemia*

Nervous system disorders

Uncommon – Peripheral neuropathy (painful

neuropathy)

Eye disorders

Uncommon – Refraction disorders

Very rare – Diabetic retinopathy

Skin and subcutaneous

tissue disorders

Uncommon – Lipodystrophy*

General disorders and

administration site

conditions

Uncommon – Injection site reactions

Uncommon – Oedema

* see section c

c. Description of selected adverse reactions

Anaphylactic 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.

Hypoglycaemia

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

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

allows

continued

monitoring

benefit/risk

balance

medicine.

Healthcare

professionals

asked

report

suspected

adverse

reactions

https://nzphvc.otago.ac.nz/reporting

4.9 Overdose

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.

Glucose

must

also

given

intravenously

patient

does

respond

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:

Onset:

within ½ hour

Maximum effect:

between 1.5 and 3.5 hours

Duration:

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.

Absorption

The maximum plasma concentration is reached within 1.5-2.5 hours after subcutaneous

administration.

Distribution

No profound binding to plasma proteins, except circulating insulin antibodies (if present) has

been observed.

Metabolism

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.

Elimination

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

adults.

However,

there

were

differences

between

groups

stressing

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

pharmacology,

repeated

dose

toxicity,

genotoxicity,

carcinogenic

potential,

toxicity

reproduction.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycerol

Metacresol

Zinc chloride

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Water for injections

6.2 Incompatibilities

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

NovoFine

needles.

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

Prescription Medicine

8 SPONSOR

Novo Nordisk Pharmaceuticals Ltd

PO Box 51-268

Pakuranga

Auckland

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

Section changed

Summary of new information

Adverse event reporting requirement added

Poison Centre contact added

Pharmacotherapeutic group updated

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