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DARNALOS 6 MG CONCENTRATE FOR SOLUTION FOR INFUSION

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PACKAGE LEAFLET INFORMATION FOR THE USER
Darnalos 6 mg concentrate for solution for infusion
ibandronic acid

Read all of this leaflet carefully before you start using this medicine.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or your pharmacist.
This medicine has been prescribed for you . Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Darnalos is and what it is used for
2.
Before you receive Darnalos
3.
How to receive Darnalos
4.
Possible side effects
5.
How to store Darnalos
6.
Further information

1.

WHAT Darnalos IS AND WHAT IT IS USED FOR

Darnalos contains the active substance ibandronic acid. This belongs to a group of medicines called
bisphosphonates.
Darnalos is indicated in adults and prescribed to you if you have breast cancer that has spread to your
bones (called bone “metastases”).

It helps to prevent your bones from breaking (fractures).

It helps to prevent other bone problems that may need surgery or radiotherapy.
Darnalos can also be prescribed if you have a raised calcium level in your blood due to a tumour.
Darnalos works by reducing the amount of calcium that is lost from your bones. This helps to stop
your bones from getting weaker.

2.

BEFORE YOU RECEIVE Darnalos

During treatment your blood may be monitored to ensure that you are receiving the correct dose of
Darnalos.
Do not use Darnalos:
if you are allergic (hypersensitive) to the active substance or any of the other ingredients of
Darnalos.
if you have, or had in the past low blood calcium. Please consult your doctor.
Take special care with Darnalos:
If you know or believe that you may have hypersensitivity to other bisphosphonates.
Some patients need to be especially careful when using Darnalos. Tell your doctor:

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if you have or have ever had kidney problems, kidney failure or have needed dialysis, or if you
have any other disease that may affect your kidneys
if you have any disturbance of mineral metabolism (such as vitamin D deficiency)
You should take calcium and vitamin-D supplements while receiving Darnalos. If you are
unable to do so, you should inform your doctor.
If you are under dental treatment or will undergo dental surgery, tell your dentist that you are
being treated with Darnalos.

Children and adolescents
Darnalos should not be used in children and adolescents below age 18 years.
Using other medicines:
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
No interaction was observed when ibandronic acid was administered concomitantly with tamoxifen, or
melphalan/prednisolone.
In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called
“aminoglycoside” such as gentamicin. This is because aminoglycosides and Darnalos can both lower
the amount of calcium in your blood.
Caution should also be paid to the possible existence of simultaneous hypomagnesaemia (reduced
magnesium levels).
Pregnancy and breast-feeding
You should not be given Darnalos if you are pregnant or if you are breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicines.
Driving and using machines:
The effects of Darnalos on the ability to drive or to use machines have not been studied.
Important information about some of the ingredients of Darnalos
This medicinal product contains less than 1 mmol sodium (23 mg) per dose (3 ml), i.e. essentially
‘sodium-free’.

3.

HOW TO RECEIVE Darnalos

You will be given Darnalos as an infusion. Your doctor will determine how much Darnalos you will
be given depending on your illness. Your doctor may adjust your dose if you have kidney problems.
If you have any further questions on the use of this product, ask your doctor or pharmacist.

4.

POSSIBLE SIDE EFFECTS

Like all medicines, Darnalos can cause side effects, although not everybody gets them.
The side effects listed below were seen when ibandronic acid was given intravenously.
These side effects may occur with certain frequencies, which are defined as follows:
very common: affects more than 1 user in 10
common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000
rare: affects 1 to 10 users in 10,000
very rare: affects less than 1 user in 10,000
not known: frequency cannot be estimated from the available data.

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Talk to a nurse or a doctor straight away if you notice any of the following serious side effects you may need urgent medical treatment:
rash, itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may
be having an allergic reaction to the medicine
problems breathing.
pain or sore in your mouth or jaw
eye pain and inflammation (if prolonged).
Other possible side effects
Very common
rise in body temperature.
Common
stomach pain, indigestion, being sick or having diarrhoea
low calcium or phosphate levels in your blood
changes in blood test results such as Gamma GT or creatinine
a heart problem called “bundle branch block”
flu-like symptoms (including fever, chills, bone pain and aching muscles). These symptoms
usually disappear within a couple of hours or days
pain or stiffness in your muscles
headache, feeling dizzy or feeling weak
feeling thirsty, sore throat, changes in taste
swollen legs or feet
aching joints, arthritis, or other joint problems
problems with your parathyroid gland
bruising
infections
a problem with your eyes called cataracts
skin problems
tooth problems.
Uncommon
shaking or shivering
your body temperature getting too low (hypothermia)
a condition affecting the blood vessels in your brain called “cerebrovascular disorder”
heart and circulatory problems (including palpitations, heart attack, hypertension and varicose
veins)
changes in your blood cells (anaemia)
a high level of alkaline phosphatase in your blood
fluid build up and swelling (“lymphoedema”)
fluid in your lungs
stomach problems such as “gastroenteritis” or “gastritis”
gallstones
being unable to pass water (urine), cystitis
migraine
pain in your nerves, damaged nerve root
deafness
increased sensitivity of sound, taste or touch or changes in smell
difficulty swallowing
mouth ulcers, swollen lips (“cheilitis”), oral thrush
itching or tingling skin around your mouth
pelvic pain, discharge, itching or pain in the vagina
a skin growth called a “benign skin neoplasm”
memory loss
sleep problems, feeling anxious, emotional instability, or mood swings
hair loss

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pain or injury at the injection site
weight loss
kidney cyst
phosphate level of the blood decreased
redness of the skin
an abnormal, high-pitched sound produced by turbulent airflow through a partially obstructed
airway called stridor

Rare
eye pain or inflammation.
Very rare
a condition involving exposed bone in the mouth called “osteonecrosis of the jaw”.
Unusual fracture of the thigh bone particularly in patients on long-term treatment for osteoporosis may
occur rarely. Contact your doctor if you experience pain, weakness or discomfort in your thigh, hip or
groin as this may be an early indication of a possible fracture of the thigh bone.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.

5.

HOW TO STORE Darnalos

Keep out of the reach and sight of children.
Store in the original package in order to protect from light. This medicinal product does not require
any special temperature storage conditions.
After dilution the infusion solution should be used immediately.
From a microbiological point of view, the product should be used immediately. If not used
immediately, in-use storage times and conditions prior to use are the responsibility of the user and
would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in
controlled and validated aseptic conditions.
Chemical and physical in-use stability has been demonstrated for 48 hours at 2-8°C.
Do not use Darnalos after the expiry date which is stated on the carton after “Exp”. The expiry date
refers to the last day of that month.
Do not use Darnalos if you notice that the solution is not clear or contains particles.
Unused solution should be discarded.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.

6.

FURTHER INFORMATION

What Darnalos contains
-

The active substance is ibandronic acid. One vial with 6 ml concentrate for solution for infusion
contains 6 mg ibandronic acid, (as 6.75 mg ibandronate sodium monohydrate).1ml of
concentrate for solution for infusion contains 1mg of ibandronic acid.

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The other ingredients are sodium chloride, acetic acid, sodium acetate trihydrate and water for
injections. Sodium hydroxide and hydrochloric acid (for pH adjustment).

What Darnalos looks like and contents of the pack
Darnalos is a colourless, clear solution, practically free from particles, pH 3.5 – 4.5.
Darnalos 6 mg concentrate for solution for infusion is supplied as packs containing 1, 5 or 10 vials (6
ml glass vials).
Colourless Type I glass vial (6R) with rubber stopper (20mm) and cap (20 mm) with plastic seal.
Not all pack sizes may be marketed.
Manufacturer
Gedeon Richter Plc.
1103 Budapest,
Gyömrői út 19-21.
Hungary

This leaflet was last approved in 09/2011
------------------------------------------------------------------------------------------------------------------------The following information is intended for medical or healthcare professionals only
Dosage: Prevention of Skeletal Events in Patients with Breast Cancer and Bone Metastases
The recommended dose for prevention of skeletal events in patients with breast cancer and bone
metastases is 6 mg intravenously given every 3-4 weeks. The dose should be infused over at least 15
minutes.
Patients with renal impairment
For patients with mild renal impairment (CLcr ≥50 and <80 ml/min) no dosage adjustment is
necessary. For patients with moderate renal impairment (CLcr ≥30 and <50 ml/min) or severe renal
impairment (CLcr <30 ml/min) being treated for the prevention of skeletal events in patients with
breast cancer and metastatic bone disease the following dosing recommendations should be followed:
Creatinine Clearance
(ml/min)
≥50 CLcr <80

6 mg / 15 minutes

100 ml

4 mg / 1 hour

500 ml

<30

2

Infusion volume2

≥30 CLcr <50

1

Dosage / Infusion time1

2 mg / 1 hour

500 ml

Administration every 3 to 4 week
0.9% sodium chloride solution or 5% glucose solution

A 15 minute infusion time has not been studied in cancer patients with CLCr <50 ml/min.
Dosage: Tumour-induced Hypercalcemia
Darnalos is usually administered in a hospital setting. The dose is determined by the doctor
considering the following factors.

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Prior to treatment with Darnalos the patient should be adequately rehydrated with 9 mg/ml (0.9%)
sodium chloride. Consideration should be given to the severity of the hypercalcaemia as well as the
tumour type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3
mmol/l or ≥12 mg/dl) 4 mg will be an adequate single dosage. In patients with moderate
hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose.
The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms
of efficacy.
* Note albumin-corrected serum calcium concentrations are calculated as follows:
Albumin-corrected
serum calcium (mmol/l)
Albumin-corrected
serum calcium (mg/dl)

=

Serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8

or
=

Serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)]

To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4.
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The
median time to relapse (reincrease of serum albumin corrected serum calcium above 3 mmol/l) was
18-19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg.
Method and route of administration
Darnalos concentrate for solution for infusion should be administered as an intravenous infusion.
For this purpose the contents of the vial are to be used as follows:
Hypercalcaemia - added to 500 ml isotonic sodium chloride solution or 500 ml 5% glucose
solution and infused over 1-2 hours.
Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5%
glucose solution and infused over at least 15 minutes. See also dosage section above for patients
with renal impairment.
Note:
In order to avoid potential incompatibilities, Darnalos concentrate for solution for infusion should only
be mixed with isotonic sodium chloride solution or with 5% glucose solution. Calcium containing
solutions should not be mixed with Darnalos concentrate for solution for infusion.
Diluted solutions are for single use. Only clear solutions without particles should be used.
It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “HOW
TO STORE Darnalos”).
As the inadvertent intra-arterial administration of preparations not expressly recommended for this
purpose as well as paravenous administration can lead to tissue damage, care must be taken to ensure
that Darnalos concentrate for solution for infusion is administered intravenously.
Frequency of administration
For treatment of tumour induced hypercalcemia, Darnalos concentrate for solution for infusion is
generally given as a single infusion.
For the prevention of skeletal events in patients with breast cancer and bone metastases, the Darnalos
infusion is repeated at 3-4 week intervals.
Duration of treatment
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia.
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy.

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For patients with breast cancer and bone metastases, Darnalos infusion should be administered every
3-4 weeks. In clinical trials, therapy has continued for up to 96 weeks.
Overdose
Up to now there is no experience of acute poisoning with ibandronic acid concentrate for solution for
infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical
studies with high doses, kidney and liver function should be monitored.
Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous
administration of calcium gluconate.

7

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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