NORDITROPIN 5 MG

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
SOMATROPIN
Available from:
NOVO NORDISK LTD., ISRAEL
ATC code:
H01AC01
Pharmaceutical form:
SOLUTION FOR INJECTION
Composition:
SOMATROPIN 3.3 MG / 1 ML
Administration route:
S.C
Prescription type:
Required
Manufactured by:
NOVO NORDISK A/S, DENMARK
Therapeutic group:
SOMATROPIN
Therapeutic area:
SOMATROPIN
Therapeutic indications:
Children: Short stature due to inadequate or failed secretion of pituitary growth hormone or Turner`s syndrome. Short stature in children with renal insufficiency. Growth disturbance (current height SDS < - 2.5 and parental adjusted height SDS < - 1) in short children born small for gestational age (SGA) with a birth weight and/or length below - 2 SD who failed to show catch-up growth (HV SDS < during the last year) by 4 years of age or later.Children with short stature associated with Noonan syndrome.Adults: Treatment of adults with Hypothalamic-pituitary disease resulting from organic disease or pituitary tumors treated medically surgically or radiotherapy or patients with chilhood onset of G.H. deficiency. תוספת התוויה: 5/6/2019Indication:Children: Short stature due to inadequate or failed secretion of pituitary growth hormone or Turner`s syndrome.Short stature in children with renal insufficiency.Growth disturbance (current height SDS < -2.5 and parental adjusted height SDS < -1) in short childre
Authorization number:
118 75 29922 00
Authorization date:
2020-05-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

28-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

28-01-2021

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE PHARMACISTS'

REGULATIONS (PREPARATIONS) – 1986

This medicine is dispensed with a doctor's prescription only

Norditropin® 15 mg

NordiFlex®

Solution for injection in pre-filled pen

Active ingredient: somatropin15 mg/1.5 ml

Inactive ingredients and allergens in the preparation: see section 6 - Further information

Read all of this leaflet carefully before you start using this medicine. This leaflet

contains concise information about the medicine. If you have any further questions, ask your

doctor or pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them,

even if it seems to you that their medical condition is similar to yours.

This leaflet contains instructions for using your Norditropin® NordiFlex® pen.

1.

What is this medicine intended for?

Norditropin® NordiFlex® contains a biosynthetic human growth hormone called somatropin

which is identical to the growth hormone produced naturally in the body. Children need

growth hormone to help them grow, but adults also need it for their general health.

In children:

growth problems due to inadequate or failed secretion of pituitary growth hormone

growth problems in girls with Turner syndrome

delayed growth in children due to renal insufficiency

growth problems in children with Noonan syndrome

growth disturbance in short children born small for gestational age (SGA) who failed to

show catch-up growth by 4 years of age

In adults:

Treatment of adults with hypothalamic-pituitary disease, resulting from an organic problem or

pituitary tumours, treated medicinally, surgically or by radiotherapy or patients with childhood

onset of growth hormone deficiency.

Therapeutic group: somatropin and somatropin agonists.

2.

Before using the medicine

Do not use this medicine if:

you are sensitive (allergic) to somatropin, to phenol, or to any of the other ingredients

in this medicine (see section 6)

you have had a kidney transplant

you have an active tumour (cancer). Tumours must be inactive and you must have

finished your anti cancer-treatment before you start your treatment with Norditropin®

NordiFlex®

you have an acute critical illness e.g. open heart surgery, abdominal surgery, multiple

accidental trauma, or acute respiratory failure

you have stopped growing (closed epiphyses) and you do not have growth hormone

deficiency

you are pregnant or breastfeeding

Special warnings regarding the use of this medicine:

Before using Norditropin® NordiFlex®, talk to your doctor if:

you have diabetes

you have ever had a cancer or another kind of tumour

you have recurrent headaches, eyesight problems, nausea, or if vomiting occurs

you have abnormal thyroid function

there is an increase in sideways curvature of the spine (scoliosis) which may progress

in any child during rapid growth. During treatment with Norditropin®, your doctor will

check you (or your child) for signs of scoliosis.

you walk with a limp or if you start to limp during your growth hormone treatment

you are over 60 years of age, or have received somatropin treatment as an adult for

more than 5 years, as experience is limited

you suffer from kidney disease; your kidney function should be monitored by your

doctor

you have a replacement therapy with glucocorticoids; consult your doctor regularly,

because you may need adjustment of your glucocorticoid dose

Drug interactions:

If you are taking or if you have recently taken other medicines, including non-

prescription medicines and dietary supplements, tell the doctor or pharmacist. In

particular, inform your doctor if you are taking or have recently taken any of the following

medicines. Your doctor may need to adjust the dose of Norditropin® NordiFlex® or of the

other medicines:

Glucocorticoids – your adult height may be affected if you use Norditropin®

NordiFlex® and glucocorticoids at the same time.

Cyclosporin (immunosuppressive) – as your dose may need to be adjusted.

Insulin – as your dose may need to be adjusted.

Thyroid hormone – as your dose may need to be adjusted.

Gonadotrophin (gonad stimulating hormone) - as your dose may need to be adjusted.

Anticonvulsants – as your dose may need to be adjusted.

Estrogen taken orally or other sex hormones.

Pregnancy, breast-feeding and fertility:

Somatropin containing products are not recommended in women of childbearing potential not

using contraception.

Pregnancy - Stop the treatment and tell your doctor if you become pregnant while you

are using Norditropin® NordiFlex®.

Breast-feeding - Do not use Norditropin® NordiFlex® while you are breast-feeding

because somatropin might pass into your milk.

Driving and using machines:

Norditropin® NordiFlex® does not affect the use of any machines or the ability to drive

safely.

3.

How to use the medicine?

Always use this medicine according to your doctor's instructions. Check with your doctor or

pharmacist if you are not sure about your dose or about how to take this medicine. The

dosage and way of treatment will be determined by your doctor only.

Recommended dose:

The dose for children depends on their body weight and body surface area. Later in life, the

dose depends on your height, weight, gender, and growth hormone sensitivity and will be

adjusted until you are on the right dose.

Children with low production or lack of growth hormone: The usual dose is 0.025

to 0.035 mg per kg body weight per day or 0.7 to 1.0 mg per m

body surface area per

day.

Children with Turner syndrome: The usual dose is 0.045 to 0.067 mg per kg body

weight per day or 1.3 to 2.0 mg per m

body surface area per day.

Children with Noonan syndrome: The usual dose is up to 0.066 mg per kg body

weight per day.

Children with kidney disease: The usual dose is 0.050 mg per kg body weight per

day or 1.4 mg per m² body surface area per day.

Children born small for gestational age (SGA): The usual dose is 0.035 mg per kg

body weight per day or 1.0 mg per m

body surface area per day until final height is

reached (In clinical trials of short children born SGA doses of 0.033 and 0.067 mg per

kg body weight per day have typically been used).

Adults with low production or lack of growth hormone: If your growth hormone

deficiency continues after completion of growth, treatment should be continued.

The usual starting dose is 0.2 to 0.5 mg per day. Dose will be adjusted until you are on

the right dose. If your growth hormone deficiency starts during adult life, the usual

starting dose is 0.1 to 0.3 mg per day. Your doctor will increase this dose each month

until you are getting the dose you need. The usual maximum dose is 1.0 mg per day.

Do not exceed the recommended dosage.

When to use Norditropin® NordiFlex®:

Inject your daily dose into the skin every evening just before bedtime.

How to use Norditropin® NordiFlex®:

Norditropin® NordiFlex® growth hormone solution comes in a multi-dose disposable 1.5 ml

pre-filled pen. Full instructions on how to use the Norditropin® NordiFlex® pen are given at

the end of the leaflet. The instructional key points are as follows:

Check the solution before use by turning the pen upside down once or twice. Do not

use the pen if the solution is cloudy or discoloured.

Norditropin® NordiFlex® is designed to be used with NovoFine® or NovoTwist®

disposable needles up to a length of 8 mm.

Always use a new needle for each injection.

Vary the area you inject so you do not harm your skin.

To make sure you get the proper dose and do not inject air, check the growth hormone

flow before the first injection from a new Norditropin® NordiFlex® pen. Do not use the

pen if a drop of growth hormone solution does not appear at the needle tip.

Do not share your Norditropin® NordiFlex® pen with anyone else.

How long you will need treatment for?

Children with growth failure because of Turner syndrome, kidney disease, children who

were born small for gestation age (SGA), or children with Noonan syndrome: Your

doctor will recommend you continue treatment until you stop growing.

Children or adolescents who lack growth hormone: Your doctor will recommend you

continue treatment into adulthood.

Do not stop using Norditropin® NordiFlex® without discussing it with your doctor first.

If you accidently took a higher dose:

Long-term overdosing can cause abnormal growth and coarsening of facial features. If you

have taken an overdose, or if a child has accidentally injected himself with some medicine,

immediately see a doctor or go to a hospital emergency room and bring the medicine

package with you.

If you forget to use the medicine:

If you forget to take the medicine at the scheduled time, take the next dose as usual, at the

normal time and consult your doctor. Do not take a double dose to make up for a forgotten

dose.

Adhere to the treatment as recommended by the doctor. Even if your health improves, do not

stop taking this medicine without consulting your doctor.

If you stop using the medicine:

Do not stop using Norditropin® NordiFlex® without discussing it with your doctor first.

Do not take medicines in the dark! Check the label and the dose each time you take

medicine. Wear glasses if you need them. If you have any further questions about

using this medicine, ask your doctor or pharmacist.

4.

Side effects

As with any medicine, the use of this medicine may cause side effects in some users. Do not

be alarmed when reading the list of side effects. You may not suffer from any of them.

Side effects seen in children and adults (unknown frequency):

Rash; wheezing; swollen eyelids, face or lips; complete collapse. Any of these

may be signs of allergic reactions.

Headache, eyesight problems, feeling sick (nausea), and being sick (vomiting).

These may be signs of raised pressure in the brain.

Serum thyroxin levels may decrease.

Hyperglycaemia (elevated levels of blood sugar).

If you get any of these effects, see a doctor as soon as possible. Stop using Norditropin®

NordiFlex® until your doctor says you can continue treatment.

Formation of antibodies directed against somatropin has been rarely observed during

Norditropin® therapy. Increased levels of liver enzymes have been reported.

Cases of leukaemia and relapse of brain tumours have also been reported in patients treated

with somatropin (the active ingredient in Norditropin® NordiFlex®), although there is no

evidence that somatropin was responsible.

If you think you are suffering from any of these diseases, speak to your doctor.

Additional side effects in children:

Uncommon (may affect up to 1 in 100 children):

Headache

Redness, itching, and pain in the area of injection.

Rare (may affect up to 1 in 1,000 children):

Rash

Muscle and joint pain

Swollen hands and feet due to fluid retention.

In rare cases, children using Norditropin® NordiFlex® have experienced hip and knee pain or

have started limping. These symptoms may be caused by a disease affecting the top of the

thigh bone (Legg-Calvé disease) or because the end of the bone has slipped from the

cartilage (slipped capital femoral epiphysis) and may not be due to Norditropin® NordiFlex®.

In children with Turner syndrome, a few cases of increased growth of hands and feet

compared to height have been observed in clinical trials.

A clinical trial in children with Turner syndrome has shown that high doses of Norditropin®

can possibly increase the risk of getting ear infections.

Additional side effects in adults:

Very common (may affect more than 1 in 10 adults):

Swollen hands and feet due to fluid retention.

Common (may affect up to 1 in 10 adults):

Headache

Feeling of skin crawling (formication) and numbness or pain mainly in fingers

Joint pain and stiffness; muscle pain.

Uncommon (may affect up to 1 in 100 adults):

Type 2 diabetes

Carpal tunnel syndrome - tingling and pain in fingers and hands

Itching (can be intense) and pain in the area of injection

Muscle stiffness.

If you experience any side effect, if any side effect gets worse or if you experience a

side effect not listed in this leaflet, consult your doctor or pharmacist, as your dose

may need to be reduced.

Reporting of side effects

Reporting side effects to the ministry of health is possible by clicking the link “Report side

effects of drug treatment”, listed at the MoH website (www.health.gov.il

), which refers to a

form for this matter or via the following link:

https://sideeffects.health.gov.il

5.

How to store the medicine?

Avoid poisoning! This medicine, and any other medicine, must be kept in a safe place out

of the sight and reach of children and/or infants in order to avoid poisoning. Do not induce

vomiting unless explicitly instructed to do so by a doctor.

Do not use this medicine after the expiry date (Exp. Date) which is stated on the

package. The expiry date refers to the last day of that month.

Store unused Norditropin® NordiFlex® pens in a refrigerator (2°C – 8°C) in the outer

carton, in order to protect them from light. Do not freeze or expose to heat. Do not store

close to any cooling elements.

While using Norditropin® NordiFlex® 15 mg/1.5 ml pen, you can either:

Keep it for up to 4 weeks in a refrigerator (2°C – 8°C), or

Keep it for up to 3 weeks at room temperature (below 25°C).

Do not use Norditropin® NordiFlex® pens if they have been frozen or exposed to

excessive temperatures.

Do not use Norditropin® NordiFlex® pens if the growth hormone solution is cloudy or

discoloured.

Always store Norditropin® NordiFlex® without a needle attached.

Always keep the pen cap fully closed on the Norditropin® NordiFlex® pen when you

are not using it.

Always use a new needle for each injection.

Do not throw away any medicines via wastewater or household waste. Ask your

pharmacist how to throw away medicines you no longer use. These measures will help

protect the environment.

6.

Further information

In addition to the active ingredient, the medicine contains also:

Mannitol; poloxamer 188; phenol (3.0 mg); histidine; water for injection; hydrochloric acid and

sodium hydroxide.

What the medicine looks like and contents of the pack:

Norditropin® NordiFlex® is a clear and colourless solution for injection in a multi-dose

disposable 1.5 ml pre-filled pen.

1 ml of Norditropin® NordiFlex® solution contains 10 mg somatropin.

1 mg of somatropin is equivalent to 3 IU of somatropin.

Norditropin® NordiFlex® is marketed in two strengths:

10 mg/1.5 ml and 15 mg/1.5 ml (equivalent to 6.7 mg/ml and 10 mg/ml, respectively). Not all

strengths may be marketed.

License holder name and address:

Novo Nordisk Ltd.,

1 Atir Yeda street

Kfar Saba,

464301

Manufacturer name and address:

Novo Nordisk A/S,

Novo Allé, DK-2880 Bagsværd, Denmark

This leaflet was revised in July 2020.

Registration number of the medicine in the National Drug Registry of Ministry of

Health:

Norditropin® 15 mg: 118-73-29920-00

NORDITROPIN NOR 15 IL PIL JUL20-NOTIFICATION

Norditropin® NordiFlex®

15 mg/1.5 ml

Instructions for using the

Norditropin® NordiFlex® pen

Read these instructions

carefully before using

Norditropin® NordiFlex®

Norditropin® NordiFlex®

15 mg/1.5 ml is a multi-

dose injection pen pre-

filled with human growth

hormone solution.

You can use the dosage

selector to select any

dose from 0.075 to 4.50

mg, in increments of

0.075 mg. Your doctor will

decide the correct dose

for you.

Norditropin® NordiFlex®

is designed to be used

with NovoFine® or

NovoTwist® disposable

needles up to a length of

8 mm.

Start by checking the

name, strength, and

colour of the label of your

Norditropin® NordiFlex®

pen to make sure that it

contains the growth

hormone strength you

need.

Only use the pen if the

solution inside the

cartridge is clear and

colourless.

Always use a new needle

for each injection.

Always check the flow

before the first injection

from a new pen, see step

3 – ‘Check the flow’.

Never share your pen or

your needles with anyone

else. It might lead to

cross-infection.

Always keep your pen

and needles out of sight

and reach of children.

Caregivers must be very

careful when handling

used needles - to reduce

the risk of needle sticks

and cross-infection.

1. Check the pen

Check the name,

strength and coloured

label of your

Norditropin®

NordiFlex® pen to make

sure that it contains the

growth hormone

strength you need.

Pull off the pen cap (A).

Check that the solution

inside the cartridge is

clear and colourless by

tipping the pen upside

down once or twice.

Do not use the pen if the

solution inside the

cartridge is unclear or

cloudy.

A

2. Attach the needle

Always use a new

needle for each

injection. This reduces

the risk of contamination,

infection, leakage of

solution, blocked needles,

and inaccurate dosing.

Never bend or damage

the needle.

Remove the protective

paper tab from the

needle.

Screw the needle straight

onto the pen (B). Make

sure the needle is on

tight.

The needle has two caps. You

need to remove them both:

Pull off the outer needle

cap and keep it to

correctly remove the

needle from the pen after

the injection. Remove the

inner needle cap by

pulling on the central tip

and throw it away.

3. Check the flow:

Before your first

injection with each new

pen, you need to check

the flow to make sure

you get the proper dose

and do not inject any air:

Select 0.075 mg (C) - This

is one ‘click’ after 0.0 on

the dose selector at the

end of the pen.

Hold the pen with the

needle pointing upwards

and tap the top of the pen

gently with your finger a

few times to let any air

bubbles rise to the top

(D).

B

D

Holding the pen with the

needle upwards, press

the push-button at the

bottom of the pen all the

way in (E). A drop of

solution will appear at the

needle tip.

If no drop appears, repeat

steps (C) to (E) up to 6

times until a drop

appears. If there is still no

drop, change the needle

and repeat steps (C) to

(E) once more.

Do not use the pen if a

drop does not appear.

Use a new pen.

Always check the flow

before the first injection

from a new pen.

Check the flow again if

your pen has been

dropped or knocked

against a hard surface, or

if you suspect something

is wrong with it.

4. Select the dose

Check that the dosage

selector is set at 0.0.

Select the number of mg

your doctor has

prescribed for you (F).

The dose can be

increased or decreased

by turning the dosage

selector in either direction.

When turning the dosage

selector backwards, be

careful not to press the

push-button because the

solution will come out.

You cannot set a dose

larger than the number of

mg left in the pen.

E

F

5. Inject the dose

Use the injection method

shown to you by your

doctor or nurse.

Vary the area you inject

so you do not harm your

skin.

Insert the needle into your

skin. Deliver the dose by

pressing the push-button

all the way in. Be careful

to press the push-button

only when injecting (G).

Keep the push-button

fully depressed and let

the needle remain under

the skin for at least 6

seconds. This ensures

that you get the full dose.

6. Remove the needle

Carefully put the outer

needle cap back on the

needle without touching

the needle. Unscrew the

needle and throw it away

carefully as instructed by

your doctor or nurse (H).

Never put the inner

needle cap back on once

you have removed it from

the needle. You may

accidentally stick yourself

with the needle.

Put the pen cap back on

after every use.

Always remove and

dispose of the needle

after each injection and

store the pen without

the needle attached.

This reduces the risk of

infection, contamination,

leakage of solution,

blocked needles, and

inaccurate dosing.

When the pen is empty,

throw it away without the

needle attached, as

advised by your doctor or

nurse and local

authorities.

Caregivers must be very

careful when handling

used needles to reduce

the risk of needle sticks

and cross-infection.

G

7. Maintenance

Your Norditropin®

NordiFlex® pen must be

handled with care.

Do not drop your pen or

knock it against hard

surfaces. If you drop it or

suspect that something is

wrong with it, always screw

on a new needle and check

the flow before you inject.

Do not try to refill your pen –

it is pre-filled.

Do not try to repair your pen

or pull it apart.

Protect your pen from dust,

dirt, frost, and direct sunlight.

Do not try to wash, soak, or

lubricate your pen. If

necessary clean it with a

mild detergent on a

moistened cloth.

Do not freeze your pen and

do not store it close to any

cooling elements, for

example in the fridge.

For information about storing

your pen, please see section

5 of the patient leaflet ‘How

to store this medicine’.

NOR NOR API JUL20V1

1.

NAME OF THE MEDICINAL PRODUCT

Norditropin

®

10 mg

-

NordiFlex

®

, solution for injection in pre-filled pen

Norditropin

®

15 mg -

NordiFlex

®

, solution for injection in pre-filled pen

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Norditropin

NordiFlex

: 10 mg/1.5 ml

One ml of solution contains 6.7 mg somatropin

Norditropin

NordiFlex

: 15 mg/1.5 ml

One ml of solution contains 10 mg somatropin

Somatropin (recombinant DNA origin produced in E-coli)

1 mg of somatropin corresponds to 3 IU (International Unit) of somatropin

For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Solution for injection in pre-filled pen

Clear, colourless solution

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Children:

Short stature due to inadequate or failed secretion of pituitary growth hormone or

Turner`s

syndrome.

Short stature in children with renal insufficiency.

Growth disturbance (current height SDS < -2.5 and parental adjusted height SDS < -1)

in short children born small for gestational age (SGA) with a birth weight and/or length

below -2 SD who failed to show catch-up growth (HV SDS < 0 during the last year) by

4 years of age or later.

Children with short stature associated with Noonan syndrome.

Adults:

NOR NOR API JUL20 V1

Treatment of adults with Hypothalamic-pituitary disease resulting from organic disease or

pituitary tumors treated medically surgically or radiotherapy or patients with childhood onset

of G.H. deficiency.

4.2

Posology and method of administration

Norditropin

should only be prescribed by doctors with special knowledge of the therapeutic

indication of use.

Posology

The dosage is individual and must always be adjusted in accordance with the individual's

clinical and biochemical response to therapy.

Generally recommended dosages:

Paediatric population:

Growth hormone insufficiency

0.025-0.035 mg/kg/day or 0.7-1.0 mg/m

/day

When GHD persists after growth completion, growth hormone treatment should be continued

to achieve full somatic adult development including lean body mass and bone mineral

accrual (for guidance on dosing, see Replacement therapy in adults).

Turner syndrome

0.045-0.067 mg/kg/day or 1.3-2.0 mg/m

/day

Pediatric patients with short stature associated with Noonan syndrom

A dosage of up to 0.066 mg/kg/day is recommended.

Chronic renal disease

0.050 mg/kg/day or 1.4 mg/m

/day (see section 4.4)

Small for Gestational Age

0.035 mg/kg/day or 1.0 mg/m

/day

A dose of 0.035 mg/kg/day is usually recommended until final height is reached (see section

5.1).

Treatment should be discontinued after the first year of treatment, if the height velocity SDS

is below +1.

Treatment should be discontinued if height velocity is < 2 cm/year and, if confirmation is

required, bone age is > 14 years (girls) or > 16 years (boys), corresponding to closure of the

epiphyseal growth plates.

Adult population:

Replacement therapy in adults

The dosage must be adjusted to the need of the individual patient.

In patients with childhood onset GHD, the recommended dose to restart is 0.2-0.5 mg/day

with subsequent dose adjustment on the basis of IGF-1 concentration determination.

In patients with adult onset GHD, it is recommended to start treatment with a low dose: 0.1-

0.3 mg/day. It is recommended to increase the dosage gradually at monthly intervals based

on the clinical response and the patient’s experience of adverse events. Serum IGF-1 can be

used as guidance for the dose titration. Women may require higher doses than men, with

men showing an increasing IGF-1 sensitivity over time. This means that there is a risk that

women, especially those on oral oestrogen replacement are undertreated while men are

overtreated.

Dose requirements decline with age. Maintenance dosages vary considerably from person to

person, but seldom exceed 1.0 mg/day.

NOR NOR API JUL20 V1

Method of administration

Generally, daily subcutaneous administration in the evening is recommended. The injection

site should be varied to prevent lipoatrophy.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Somatropin must not be used when there is any evidence of activity of a tumour. Intracranial

tumours must be inactive and antitumour therapy must be completed prior to starting growth

hormone (GH) therapy. Treatment should be discontinued if there is evidence of tumour

growth.

Somatropin should not be used for longitudinal growth promotion in children with closed

epiphyses.

Patients with acute critical illness suffering complications following open heart surgery,

abdominal surgery, multiple accidental trauma, acute respiratory failure, or similar conditions

should not be treated with somatropin (see section 4.4).

children with chronic renal disease, treatment with Norditropin

NordiFlex

should be

discontinued at renal transplantation.

4.4

Special warnings and precautions for use

Children treated with somatropin should be regularly assessed by a specialist in child growth.

Somatropin treatment should always be instigated by a physician with special knowledge of

growth hormone insufficiency and its treatment. This is true also for the management of

Turner syndrome, chronic renal disease, SGA, and Noonan syndrome. Data of final adult

height following the use of Norditropin

are limited for children with Noonan Syndrome and

are not available for children with chronic renal disease.

The maximum recommended daily dose should not be exceeded (see section 4.2).

The stimulation of longitudinal growth in children can only be expected until epiphyseal

closure.

Children

Treatment of growth hormone deficiency in patients with Prader-Willi syndrome

There have been reports of sudden death after initiating somatropin therapy in patients with

Prader-Willi syndrome, who had one or more of the following risk factors: severe obesity,

history of upper airway obstruction or sleep apnoea, or unidentified respiratory infection.

Small for Gestational Age

In short children born SGA other medical reasons or treatments that could explain growth

disturbance should be ruled out before starting treatment.

Experience in initiating treatment in SGA patients near onset of puberty is limited. It is

therefore not recommended to initiate treatment near onset of puberty.

Experience with patients with Silver-Russell syndrome is limited.

Turner syndrome

Monitoring of growth of hands and feet in Turner syndrome patients treated with somatropin

is recommended, and a dose reduction to the lower part of the dose range should be

considered if increased growth is observed.

NOR NOR API JUL20 V1

Girls with Turner syndrome generally have an increased risk of otitis media, which is why

otological evaluation is recommended on at least an annual basis.

Chronic renal disease

The dosage in children with chronic renal disease is individual and must be adjusted

according to the individual response to therapy (see section 4.2). The growth disturbance

should be clearly established before somatropin treatment by following growth on optimal

treatment for renal disease over one year. Conservative management of uraemia with

customary medicinal product and if needed dialysis should be maintained during somatropin

therapy.

Patients with chronic renal disease normally experience a decline in renal function as part of

the natural course of their illness. However, as a precautionary measure during somatropin

treatment, renal function should be monitored for an excessive decline or increase in the

glomerular filtration rate (which could imply hyperfiltration).

Scoliosis

Scoliosis is known to be more frequent in some of the patient groups treated with somatropin

for example Turner syndrome and Noonan syndrome. In addition, rapid growth in any child

can cause progression of scoliosis. Somatropin has not been shown to increase the

incidence or severity of scoliosis. Signs of scoliosis should be monitored during treatment.

Blood glucose and insulin

In Turner syndrome and SGA children it is recommended to measure fasting insulin and

blood glucose before start of treatment and annually thereafter. In patients with increased

risk of diabetes mellitus (e.g. familial history of diabetes, obesity, severe insulin resistance,

acanthosis nigricans), oral glucose tolerance testing (OGTT) should be performed. If overt

diabetes occurs, somatropin should not be administered.

Somatropin has been found to influence carbohydrate metabolism, therefore, patients should

be observed for evidence of glucose intolerance.

IGF-1

In Turner syndrome and SGA children it is recommended to measure the IGF-1 level before

start of treatment and twice a year thereafter. If on repeated measurements IGF-1 levels

exceed +2 SD compared to references for age and pubertal status, the dose should be

reduced to achieve an IGF-1 level within the normal range.

Some of the height gain obtained with treating short children born SGA with somatropin may

be lost if treatment is stopped before final height is reached.

Adults

Growth hormone deficiency in adults

Growth hormone deficiency in adults is a lifelong disease and needs to be treated

accordingly, however, experience in patients older than 60 years and in patients with more

than five years of treatment in adult growth hormone deficiency is still limited.

General

Neoplasms

There is no evidence for increased risk of new primary cancers in children or in adults treated

with somatropin.

In patients in complete remission from tumours or malignant disease, somatropin therapy

has not been associated with an increased relapse rate.

An overall slight increase in second neoplasms has been observed in childhood cancer

survivors treated with growth hormone, with the most frequent being intracranial tumours.

The dominant risk factor for second neoplasms seems to be prior exposure to radiation.

NOR NOR API JUL20 V1

Patients who have achieved complete remission of malignant disease should be followed

closely for relapse after commencement of somatropin therapy.

Leukaemia

Leukaemia has been reported in a small number of growth hormone deficient patients, some

of whom have been treated with somatropin. However, there is no evidence that leukaemia

incidence is increased in somatropin recipients without predisposition factors.

Benign intracranial hypertension

In the event of severe or recurrent headache, visual problems, nausea, and/or vomiting, a

funduscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of

benign intracranial hypertension should be considered and if appropriate the somatropin

treatment should be discontinued.

At present there is insufficient evidence to guide clinical decision making in patients with

resolved intracranial hypertension. If somatropin treatment is restarted, careful monitoring for

symptoms of intracranial hypertension is necessary.

Patients with growth hormone deficiency secondary to an intracranial lesion should be

examined frequently for progression or recurrence of the underlying disease process.

Thyroid function

Somatropin increases the extrathyroidal conversion of T4 to T3 and may, as such, unmask

incipient hypothyroidism. Monitoring of thyroid function should therefore be conducted in all

patients. In patients with hypopituitarism, standard replacement therapy must be closely

monitored when somatropin therapy is administered.

In patients with a pituitary disease in progression, hypothyroidism may develop.

Patients with Turner syndrome have an increased risk of developing primary hypothyroidism

associated with anti-thyroid antibodies. As hypothyroidism interferes with the response to

somatropin therapy patients should have their thyroid function tested regularly and should

receive replacement therapy with thyroid hormone when indicated.

Insulin sensitivity

Because somatropin may reduce insulin sensitivity, patients should be monitored for

evidence of glucose intolerance (see section 4.5). For patients with diabetes mellitus, the

insulin dose may require adjustment after somatropin containing product therapy is instituted.

Patients with diabetes or glucose intolerance should be monitored closely during somatropin

therapy.

Antibodies

As with all somatropin containing products, a small percentage of patients may develop

antibodies to somatropin. The binding capacity of these antibodies is low, and there is no

effect on growth rate. Testing for antibodies to somatropin should be carried out in any

patient who fails to respond to therapy.

Acute adrenal insufficiency

Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum

cortisol concentrations. In patients treated with somatropin, previously undiagnosed central

(secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be

required.

In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed

hypoadrenalism may require an increase in their maintenance or stress doses, following

initiation of somatropin treatment (see section 4.5).

Use with oral oestrogen therapy

NOR NOR API JUL20 V1

If a woman taking somatropin begins oral oestrogen therapy, the dose of somatropin may

need to be increased to maintain the serum IGF-1 levels within the normal age-appropriate

range. Conversely, if a woman on somatropin discontinues oral oestrogen therapy, the dose

of somatropin may need to be reduced to avoid excess of growth hormone and/or side

effects (see section 4.5).

Slipped capital femoral epiphysis

In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses

of the hip may occur more frequently than in the general population. A patient treated with

somatropin who develops a limp or complains of hip or knee pain should be evaluated by a

physician.

Clinical trial experience

Two placebo-controlled clinical trials of patients in intensive care units have demonstrated an

increased mortality among patients suffering from acute critical illness due to complications

following open heart or abdominal surgery, multiple accidental trauma or acute respiratory

failure, who were treated with somatropin in high doses (5.3-8 mg/day). The safety of

continuing somatropin treatment in patients receiving replacement doses for approved

indications who concurrently develop these illnesses has not been established. Therefore,

the potential benefit of treatment continuation with somatropin in patients having acute critical

illnesses should be weighed against the potential risk.

One open-label, randomised clinical trial (dose range 0.045-0.090 mg/kg/day) with patients

with Turner syndrome indicated a tendency for a dose-dependent risk of otitis externa and

otitis media. The increase in ear infections did not result in more ear operations/ tube

insertions compared to the lower dose group in the trial.

4.5

Interaction with other medicinal products and other forms of interaction

Concomitant treatment with glucocorticoids inhibits the growth-promoting effect of

Norditropin

. Patients with ACTH deficiency should have their glucocorticoid replacement

therapy carefully adjusted to avoid any inhibitory effect on growth.

Growth hormone decreases the conversion of cortisone to cortisol and may unmask

previously undiscovered central hypoadrenalism or render low glucocorticoid replacement

doses ineffective (see section 4.4).

In women on oral oestrogen replacement, a higher dose of growth hormone may be required

to achieve the treatment goal (see section 4.4)

Data from an interaction study performed in growth hormone deficient adults suggest that

somatropin administration may increase the clearance of compounds known to be

metabolised by cytochrome P450 isoenzymes. The clearance of compounds metabolised by

cytochrome P450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine)

may be especially increased resulting in lower plasma levels of these compounds. The

clinical significance of this is unknown.

The effect of somatropin on final height can also be influenced by additional therapy with

other hormones, e.g. gonadotropin, anabolic steroids, oestrogen and thyroid hormone.

In insulin treated patients adjustment of insulin dose may be needed after initiation of

somatropin treatment (see section 4.4).

Paediatric population

Interaction studies have only been performed in adults.

4.6

Fertility, pregnancy and lactation

NOR NOR API JUL20 V1

Pregnancy

Animal studies are insufficient with regard to effects on pregnancy, embryo-foetal

development, parturition or postnatal development. No clinical data on exposed pregnancies

are available.

Therefore, somatropin containing products are not recommended during pregnancy and in

women of childbearing potential not using contraception.

Breast-feeding

There have been no clinical studies conducted with somatropin containing products in

breast-feeding women. It is not known whether somatropin is excreted in human milk.

Therefore caution should be exercised when somatropin containing products are

administered to breast-feeding women.

Fertility

Fertility studies with Norditropin® have not been performed.

4.7

Effects on ability to drive and use machines

Norditropin

NordiFlex

has no or negligible influence on the ability to drive and use

machines.

4.8

Undesirable effects

Growth hormone deficient patients are characterised by extracellular volume deficit. When

treatment with somatropin is initiated, this deficit is corrected. Fluid retention with peripheral

oedema may occur especially in adults. Carpal tunnel syndrome is uncommon, but may be

seen in adults. The symptoms are usually transient, dose dependent and may require

transient dose reduction.

Mild arthralgia, muscle pain and paresthesia may also occur but are usually self-limiting.

Adverse reactions in children are uncommon or rare.

Clinical trial experience:

System organ

classes

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)

Metabolism and

nutrition disorders

In adults

Diabetes

mellitus type 2

Nervous system

disorders

In adults

headache and

paraesthesia

In adults carpal

tunnel

syndrome. In

children

headache

Skin and

subcutaneous

tissue disorders

In adults

pruritus

In children rash

Musculoskeletal,

connective tissue

In adults

arthralgia, joint

In adults muscle

In children

arthralgia and

NOR NOR API JUL20 V1

disorders

stiffness and

myalgia

stiffness

myalgia

General disorders

and administration

site conditions

In adults

peripheral

oedema (see

text above)

In adults and

children

injection site

pain. In children

injection site

reaction

In children

peripheral

oedema

In children with Turner syndrome increased growth of hands and feet has been reported

during somatropin therapy.

A tendency for increased incidence of otitis media in Turner syndrome patients treated with

high doses of Norditropin

has been observed in one open-label randomised clinical trial.

However, the increase in ear infections did not result in more ear operations/tube insertions

compared to the lower dose group in the trial.

Clinical Trials in Children with Noonan Syndrome

Norditropin

was studied in 21 pediatric patients, 3 years to 14 years of age at doses of

0.033

mg/kg/day

0.066

mg/kg/day.

After

two-year

study,

patients

continued

Norditropin

treatment until final height was achieved; randomized dose groups were not

maintained. Adverse reactions were later collected retrospectively from 18 pediatric patients;

total follow-up was 11 years. An additional 6 pediatric patients were not randomized, but

followed the protocol and are included in this assessment of adverse reactions.

The most frequent adverse reactions were upper respiratory infection, gastroenteritis, ear

infection, and influenza. Cardiac disorders was the system organ class with the second most

adverse reactions reported. Scoliosis was reported in 1 and 4 pediatric patients receiving

doses of

0.033 mg/kg/day

and 0.066 mg/kg/day

respectively.

The following

additional

adverse reactions also occurred once: insulin resistance and panic reaction for the 0.033

mg/kg/day dose group; injection site pruritus, bone development abnormal, depression, and

self-injurious ideation in the 0.066 mg/kg/day dose group. Headache occurred in 2 cases in

the 0.066 mg/kg/day dose group.

Post-marketing experience:

In addition to the above mentioned adverse drug reactions, those presented below have

been spontaneously reported and are by an overall judgement considered possibly related to

Norditropin® treatment. Frequencies of these adverse events cannot be estimated from the

available data:

Neoplasms benign and malignant (including cysts and polyps): Leukaemia has been

reported in a small number of growth hormone deficiency patients (see section 4.4)

Immune system disorders: Hypersensitivity (see section 4.3). Formation of antibodies

directed against somatropin. The titres and binding capacities of these antibodies

have been very low and have not interfered with the growth response to Norditropin

administration

Endocrine disorders: Hypothyroidism. Decrease in serum thyroxin levels (see section

4.4)

Metabolism and nutrition disorders: Hyperglycaemia (see section 4.4)

Nervous system disorders: Benign intracranial hypertension (see section 4.4)

Musculoskeletal and connective tissue disorders: Legg-Calvé-Perthes disease. Legg-

Calvé-Perthes disease may occur more frequently in patients with short stature

Investigations: Increase in blood alkaline phosphatase level.

Reporting of suspected adverse reactions

NOR NOR API JUL20 V1

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form:

https://sideeffects.health.gov.il

4.9

Overdose

Acute overdosage can lead to low blood glucose levels initially, followed by high blood

glucose levels. These decreased glucose levels have been detected biochemically, but

without clinical signs of hypoglycaemia. Long-term overdosage could result in signs and

symptoms consistent with the known effects of human growth hormone excess.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Somatropin and somatropin agonists. ATC: H01AC01.

Mechanism of action

Norditropin

NordiFlex

contains somatropin, which is human growth hormone produced by

recombinant DNA-technology. It is an anabolic peptide of 191 amino acids stabilised by two

disulphide bridges with a molecular weight of approximately 22,000 Daltons.

The major effects of somatropin are stimulation of skeletal and somatic growth and

pronounced influence on the body’s metabolic processes.

Pharmacodynamic effects

When growth hormone deficiency is treated a normalisation of body composition takes place

resulting in an increase in lean body mass and a decrease in fat mass.

Somatropin exerts most of its actions through insulin-like growth factor 1 (IGF-1), which is

produced in tissues throughout the body but predominantly by the liver.

More than 90% of IGF-1 is bound to binding proteins (IGFBPs) of which IGFBP-3 is the most

important.

A lipolytic and protein sparing effect of the hormone becomes of particular importance during

stress.

Somatropin also increases bone turnover indicated by an increase in plasma levels of

biochemical bone markers. In adults bone mass is slightly decreased during the initial

months of treatment due to more pronounced bone resorption, however, bone mass

increases with prolonged treatment.

Clinical efficacy and safety

In clinical trials in short children born SGA doses of 0.033 and 0.067 mg/kg/day have been

used for treatment until final height. In 56 patients who were continuously treated and have

reached (near) final height, the mean change from height at start of treatment was

+1.90 SDS (0.033 mg/kg/day) and +2.19 SDS (0.067 mg/kg/day). Literature data from

untreated SGA children without early spontaneous catch-up suggest a late growth of

0.5 SDS. Long-term safety data are still limited.

A growth promoting effect was observed following 104 weeks (primary endpoint) and 208

weeks treatment with once-daily dosing of Norditropin® 0.033 mg/kg/day and 0.066

mg/kg/day in 51 children aged 3 to <11 years with short stature due to Noonan syndrome.

NOR NOR API JUL20 V1

A statistically significant increase from baseline in mean height SDS at 104 weeks (primary

endpoint) was observed with 0.033 mg/kg/day (0.84 SDS) and 0.066 mg/kg/day (1.47 SDS).

A mean difference of 0.63 SDS [95 % CI: 0.38; 0.88] was observed between the groups at

104 weeks; the difference was greater after 208 weeks with an mean difference of 0.99 SDS

[95 % CI: 0.62; 1.36] (figure 1).

Change from baseline in height SDS

Change from baseline in height SDS

Full analysis set, LOCF imputed data.

Error bars are 1*SEM.

Norditropin 0.033 mg/kg/day

Norditropin 0.066 mg/kg/day

Figure 1

Height SDS (national) change from baseline to week 208

The mean height velocity and height velocity SDS increased markedly from baseline during

the first year of treatment with a greater increase with 0.066 mg/kg/day than with 0.033

mg/kg/day. The mean height velocity SDS was maintained above 0 in both groups after a

two-year treatment and also after four years of treatment in the 0.066 mg/kg/day group. The

height velocity SDS was greater with 0.066 mg/kg/day than with 0.033 mg/kg/day throughout

the trial period (figure 2).

NOR NOR API JUL20 V1

Group = Norditropin 0.033 mg/kg/day

Group = Norditropin 0.066 mg/kg/day

Time since randomisation (weeks)

Full analysis set, LOCF imputed data.

Baseline: Height velocity from 1 year prior to screening to week 0.

Error bars are 1*SEM.

Height velocity SDS

2.80

-1.99

0.58

-0.39

-0.73

5.01

2.65

1.44

0.92

-1.70

Baseline

Baseline

Figure 2

Height velocity SDS (national) from baseline to week 208

Final height data were collected in 24 paediatric patients (18 included in a two-year

prospective, open label, randomised, parallel group study and six who had followed the

protocol without randomisation). After the initial two-years prospective study, Norditropin®

continued until final height. At the end of the treatment the majority of the subjects (16/24)

achieved a final height within the normal national reference range (> 2 SDS).

5.2

Pharmacokinetic properties

I.v. infusion of Norditropin

(33 ng/kg/min for 3 hours) to nine growth hormone deficient

patients, gave the following results: serum half-life of 21.1±1.7 min., metabolic clearance rate

of 2.33±0.58 ml/kg/min. and a distribution space of 67.6±14.6 ml/kg.

S.c. injection of Norditropin

SimpleXx

(Norditropin

®

SimpleXx

®

is the cartridge

containing the solution for injection in Norditropin

®

NordiFlex

®

) 2.5 mg/m

in 31 healthy

subjects (with endogenous somatropin suppressed by continuous infusion of somatostatin)

gave the following results:

Maximal concentration of human growth hormone (4246 ng/ml) after approximately 4 hours.

Thereafter human growth hormone declined with a half-life of approximately 2.6 hours.

In addition the different strengths of Norditropin

SimpleXx

were demonstrated to be

bioequivalent to each other and to Norditropin

for reconstitution after subcutaneous injection

to healthy subjects.

5.3

Preclinical safety data

The general pharmacological effects on the CNS, cardiovascular and respiratory systems

following administration of Norditropin

SimpleXx

with and without forced degradation were

investigated in mice and rats; renal function was also evaluated. The degraded product

showed no difference in effect when compared with Norditropin

SimpleXx

and Norditropin

All three preparations showed the expected dose dependent decrease in urine volume and

retention of sodium and chloride ions.

NOR NOR API JUL20 V1

In rats, similar pharmacokinetics has been demonstrated between Norditropin

SimpleXx

and Norditropin

. Degraded Norditropin

SimpleXx

has also been demonstrated to be

bioequivalent with Norditropin

SimpleXx

.

Single and repeated dose toxicity and local tolerance studies of Norditropin

SimpleXx

the degraded product did not reveal any toxic effect or damage to the muscle tissue.

The toxicity of poloxamer 188 has been tested in mice, rats, rabbits, and dogs and no

findings of toxicological relevance were revealed.

Poloxamer 188 was rapidly absorbed from the injection site with no significant retention of

the dose at the site of injection. Poloxamer 188 was excreted primarily via the urine.

Clinical Studies

A prospective, open label, randomized, parallel group study with 21 pediatric patients was

conducted for 2 years to evaluate the efficacy and safety of Norditropin

. Additional 6

children were not randomized, but did follow the protocol. Inclusion criteria included bone

age determination showing no significant acceleration, prepubertal status, height SDS <-2,

and HV SDS <1 during the 12 months pre-treatment. Exclusion criteria were previous or

ongoing treatment with growth hormone, anabolic steroids or corticosteroids, congenital

heart disease or other serious disease perceived to possibly have major impact on growth,

FPG >6.7 mmol/L (>120 mg/dL), or growth hormone deficiency (peak GH levels <10 ng/mL).

The twenty-four, 12 female and 12 male, patients 3 – 14 years of age received either 0.033

mg/kg/day or 0.066 mg/kg/day of Norditropin

subcutaneously which was adjusted based on

growth response after the first 2 years.

After the initial two-year study, Norditropin

treatment continued until final height.

Retrospective final height was collected from 18 patients in the study and the 6 who had

followed the protocol without randomization. Historical reference materials of height velocity

and adult height analyses of Noonan patients served as the controls.

Patients obtained a final height (FH) gain from baseline of 1.5 and 1.6 SDS estimated

according to the national and the Noonan reference, respectively. A height gain of 1.5 SDS

(national) corresponds to a mean height gain of 9.9 cm in boys and 9.1 cm in girls at 18

years of age, while a height gain of 1.6 SDS (Noonan) corresponds to a mean height gain of

11.5 cm in boys and 11.0 cm in girls at 18 years of age.

A comparison of HV between the two treatment groups during the first two years of treatment

for the randomized subjects was 10.1 and 7.6 cm/year with 0.066 mg/kg/day versus 8.55 and

6.7 cm/year with 0.033 mg/kg/day, for Year 1 and Year 2, respectively.

Norditropin

SimpleXx

is the cartridge containing the solution for injection in Norditropin®

NordiFlex

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Mannitol

Poloxamer 188

Phenol

Histidine

Water for injection

Hydrochloric acid for pH adjustment

Sodium hydroxide for pH adjustment.

6.2

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other

medicinal products.

NOR NOR API JUL20 V1

6.3

Shelf life

The expiry date of the product is indicated on the packaging materials. .

After first opening: Store for a maximum of 4 weeks in a refrigerator (2

C – 8

Alternatively, the medicinal product may be stored for a maximum of 3 weeks below 25

6.4

Special precautions for storage

Store in a refrigerator (2°C – 8°C) in the outer carton, in order to protect it from light. Do not

freeze.

Do not store close to any cooling elements.

For storage conditions after first opening of the medicinal product, see section 6.3. Do not

freeze.

When in use, always replace the pen cap on the Norditropin

NordiFlex

pre-filled pen after

each injection. Always use a new needle for each injection.

The needle must not be screwed onto the pre-filled pen when it is not in use.

6.5

Nature and contents of container

Norditropin

NordiFlex

10 mg/1.5 ml is a multi-dose disposable pre-filled pen, which

consists of a cartridge (Type I colourless glass) permanently sealed in a plastic pen-injector.

The cartridge is closed at the bottom with a rubber stopper (Type I rubber closures) shaped

as a plunger and at the top with a laminated rubber stopper (Type I rubber closures) shaped

as a disc and sealed with an aluminium cap. The push button on the pen-injector is coloured

blue. Pack sizes of 1 pre-filled pen and multipacks with 5 and 10 x 1 pre-filled pens. Not all

pack sizes may be marketed.

Norditropin

NordiFlex

15 mg/1.5 ml is a multi-dose disposable pre-filled pen, which

consists of a cartridge (Type I colourless glass) permanently sealed in a plastic pen-injector.

The cartridge is closed at the bottom with a rubber stopper (Type I rubber closures) shaped

as a plunger and at the top with a laminated rubber stopper (Type I rubber closures) shaped

as a disc and sealed with an aluminium cap. The push button on the pen-injector is coloured

green. Pack sizes of 1 pre-filled pen and multipacks with 5 and 10 x 1 pre-filled pens. Not all

pack sizes may be marketed.

The pre-filled pen is packed in a carton.

6.6

Special precautions for disposal and other handling

Norditropin

NordiFlex

is a pre-filled pen designed to be used with NovoFine

or NovoTwist

disposable needles up to a length of 8 mm.

Norditropin

NordiFlex

10 mg/1.5 ml delievers a maximum of 3.0 mg somatropin per dose,

in incerments of 0.050 mg somatropin.

Norditropin

NordiFlex

15 mg/1.5 ml delievers a maximum of 4.5 mg somatropin per dose,

in incerments of 0.075 mg somatropin.

To ensure proper dosing and avoid injection of air, check the growth hormone flow before the

first injection. Do not use Norditropin

NordiFlex

if a drop of growth hormone does not

appear at the needle tip. A dose is selected by turning the dose selector, until the desired

dose appears at the window of the housing. If the wrong dose is selected , the dose can be

corrected by turning the dosage selector the opposite way. The push button is pressed to

inject the dose.

NOR NOR API JUL20 V1

Norditropin

NordiFlex

should not be shaken vigorously at any time.

Do not use Norditropin

NordiFlex

if the growth hormone solution for injection is cloudy or

discoloured. Check this by turning the pen upside down once or twice.

Any unused medicinal product or waste material should be disposed of in accordance with

local requirements.

7. Marketing Authorisation Holder:

Novo Nordisk Ltd.

1 Athir Yeda St.,

Kfar-Saba

4464301

8. Manufacturer:

Novo Nordisk A/S

DK-2880 Bagsvaerd

Denmark

9. Registration number:

Norditropin

10 mg/1.5 ml:118 74 29921 00

Norditropin

15mg/1.5 ml: 118 73 29920 00

This leaflet was revised in July 2020.

העדוה העדוה

לע לע

הרמחה הרמחה

(

(

עדימ עדימ

)תוחיטב )תוחיטב :ךיראת

08/08/2012

םש

רישכת

:תילגנאב

Norditropin SimpleXx

רפסמ

:םושיר

118

75

29922

,

118

74

29921

,

118

73

29920

םש

לעב

:םושירה

ובונ

קסידרונ

ש"עתה 'חר ,מ"עב

20

רוזא ,

אבס-רפכ ,הישעתה

44425

םייונישה

ןולעב

םינמוסמ

לע

עקר

בוהצ ןולעב ןולעב

אפור אפור םיטרפ

לע

םי/יונישה

םי/שקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

4.3

Contraindicati

ons

evidence

active

malignant

tumours.

Intracranial neoplasm must be inactive

and anti-tumour therapy should be

completed

prior

institution

therapy.

Somatropin must not be used when

there is any evidence of activity of a

tumour. Intracranial tumours must be

inactive and antitumour therapy must

be completed prior to starting growth

hormone (GH) therapy. Treatment

should be discontinued if there is

evidence of tumour growth

.

4.6

Pregnancy

and lactation

Therefore, somatropin containing

products are not recommended during

pregnancy

Therefore, somatropin containing

products are not recommended during

pregnancy and in women childbearing

potential not using contraception

.

ןכרצל ןולעב ןכרצל ןולעב םיטרפ

לע

םי/יונישה

םי/שקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

2

ינפל .

שומישה הפורתב םא

התא

הלוח

םא ,ןטרסב

ךניה

לבוס לודיגמ

וא

ךלהמב

לופיט

לודיגב ךל שי םא .)ןטרס( ליעפ לודיג לודיגה תא םייסל בייח ךנהו ליעפ אל תויהל ךירצ תלחתה ינפל ,ינטרס יטנאה לופיטה סקלפידרונ ןיפורטידרונב לופיטה

2

שומיש . תופורתב

תורחא אל

עיפוה תא תונשל ךרוצ היהיו ןכתי – ןילוסניא הנמה

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