Novastan

Package leaflet: Information for the user Novastan 100 mg/ml concentrate

for solution for infusion
argatroban monohydrate
Please read all of this leaflet carefully before you start using this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Novastan is and what it is used for
2. What you need to know before you use Novastan
3. How to use Novastan
4. Possible side effects
5. How to store Novastan
6. Contents of the pack and other information

1. What Novastan is and what it is used for

Novastan is an anticoagulant (a medicine that helps prevent blood clots from forming). It works by blocking the action of thrombin, a substance in the blood that is important for blood clotting.
Novastan is used to treat a condition called heparin-induced thrombocytopenia type II (HIT type II). If you have HIT type II, you are at risk of developing blood clots that may lead to heart attacks, strokes, breathing problems, and problems with blood flow to the limbs. Novastan can help prevent these problems or stop them from getting worse.

2. What you need to know before using Novastan

Do not take Novastan
Novastan will not be prescribed to you:

• if you have significant bleeding.
• if you are allergic (hypersensitive) to argatroban or to any of the excipients in Novastan.
• if you have severe liver impairment.

Warnings and precautions
Novastan will be prescribed with caution:

• if you have an increased risk of bleeding
• if you have recently received injections or infusions of other anticoagulant medicines, such as heparin
• if you have liver disease

Children and adolescents
It is not recommended to give this medicine to children or adolescents, as a safe and effective dose of Novastan has not been clearly established.

Other medicines and Novastan
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
The combined use with other medicines that thin the blood or dissolve clots may increase the risk of bleeding.
Since Novastan contains ethanol, it may affect the action of other medicines containing metronidazole (used for infections) or disulfiram (used for alcoholism).

Pregnancy, breast-feeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breast-feeding, consult your doctor before taking this medicine.
As a precaution, it is preferable to avoid using Novastan during pregnancy.
Breast-feeding must be avoided during treatment with Novastan.
See also “Novastan contains alcohol”.

Driving and using machines
Since Novastan contains alcohol, you must not drive or operate machinery during treatment. See also “Novastan contains alcohol”.

Novastan contains alcohol
Before dilution, this product contains 400 mg/ml of alcohol (ethanol), 50% by volume, equivalent to 0.5% by volume after dilution as indicated in the instructions.
The daily dose may contain up to 5 ml (4 g) of alcohol, equivalent to 100 ml of beer or 40 ml of wine. This may be harmful for people with liver disorders, alcoholism or epilepsy, in case of brain injury or brain diseases, for women during pregnancy or breast-feeding, and for newborns. See also “Pregnancy, breast-feeding and fertility”.
If you are dependent on alcohol, speak with your doctor before taking this medicine.
The amount of alcohol in this medicine does not appear to have an effect on adults and adolescents.
The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.
Since this medicine is usually administered slowly over several hours, the effects of alcohol may be reduced.

Novastan contains sorbitol
This medicine contains 750 mg of sorbitol per vial (2.5 ml), equivalent to 300 mg/ml.
Sorbitol is a source of fructose. If your doctor has diagnosed you with hereditary fructose intolerance, a rare genetic disorder, you must not take this medicine. Patients with hereditary fructose intolerance are unable to metabolize fructose, and its accumulation can cause serious side effects.
Before taking this medicine, inform your doctor if you have hereditary fructose intolerance.

3. How to use Novastan

Novastan will always be administered to you by medical personnel. Novastan will be given by intravenous infusion (into a vein) as a continuous infusion. Your doctor will determine the dose and duration of your treatment.

4. Possible side effects

Like all medicines, Novastan can cause side effects, although not everyone experiences them.
The most common side effects are bleeding. Major bleeding may occur in about 5% of patients, while minor bleeding may occur in about 39% of patients. You must inform your doctor immediately if you notice any of the following symptoms:

• bleeding or bruising
• blood in urine or stools
• vomiting or coughing up blood
• dark stools
• difficulty breathing
• cold sweat
• dry mouth
• dilated pupils and/or weak or rapid pulse

These symptoms may indicate bleeding problems.
Common side effects ( may affect up to 1 in 10 people ):

• anaemia
• blood clot formation
• bleeding, including minor skin and mucous membrane bleeding (purpura)
• nausea

Uncommon side effects ( may affect up to 1 in 100 people ):

• infections, such as urinary tract infections
• abnormalities in blood test results
• blood clot formation
• loss of appetite
• low blood sugar levels
• low blood sodium levels
• confusion
• dizziness
• fainting
• headache
• stroke
• muscle disorders
• speech difficulties
• vision problems
• deafness
• heart attack
• fluid accumulation in the pericardium
• changes in heart rhythm
• tachycardia
• low blood pressure
• high blood pressure
• inflammation of the veins
• shock
• reduced oxygen supply to tissues
• breathing difficulties
• fluid accumulation around the lungs
• hiccups
• coughing up blood, vomiting blood or blood in stools
• constipation
• diarrhoea
• gastritis
• difficulty swallowing
• tongue disorders
• altered liver function
• jaundice (yellowing of the skin and eyes)
• changes in liver function blood test results
• skin rash, including urticaria
• itching
• increased sweating
• hair loss
• muscle weakness
• muscle pain
• impaired kidney function
• fever
• pain
• fatigue
• reactions at the site of administration
• leg swelling
• increased wound exudate
• changes in laboratory test results

Not known (frequency cannot be estimated from the available data)

• Cases of intracranial haemorrhage have been reported.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Novastan

Keep this medicine out of the sight and reach of children.
Store the vial in the outer packaging to protect the medicine from light.
Do not refrigerate or freeze.
Once diluted, solutions must not be exposed to direct sunlight.
Do not use the solution if it appears cloudy or if particles are observed in suspension.
Diluted solution: chemical and physical stability has been demonstrated for up to 14 days after dilution, both at 25°C and between 2°C and 8°C, in infusion solutions of sodium chloride 9 mg/mL (0.9%), glucose 50 mg/mL (5%), or in a sodium lactate-based intravenous infusion compound.
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2°C and 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.
Novastan must not be used after the expiry date which is stated on the carton/vial after “Exp”. The expiry date refers to the last day of the month.

6. Contents of the pack and other information

What Novastan contains
The active substance in Novastan is argatroban monohydrate 100 mg/ml.
1 ml of concentrate for infusion solution contains 100 mg of argatroban monohydrate.
1 vial with 2.5 ml of concentrate for infusion solution contains 250 mg of argatroban monohydrate.
The other components are anhydrous ethanol, sorbitol and water for injections.

Description of the appearance of Novastan and contents of the pack
This medicinal product is a clear, colourless to slightly yellow concentrate for infusion solution. Each vial contains 2.5 ml of solution. Vials are packed in cardboard cartons containing 1 or 6 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Ethypharm, 194, Bureaux de la Colline, Bâtiment D, 92213 Saint-Cloud cedex, France.

Manufacturer
Tjoapack Netherlands B.V., Nieuwe Donk 9, Etten-Leur, 4879AC, The Netherlands.

For further information, contact:
Recordati Rare Diseases (Italy) s.r.l
Via M. Civitali 1
20148 Milano

This medicinal product has been authorised in the EEA Member States under the following names:
Denmark Novastan
Italy Novastan
Norway Novastan
Spain Arganova
Sweden Novastan
______________________________________________________________________________

The following information is intended exclusively for healthcare professionals

Instructions for use, handling and disposal
Novastan must be diluted in a 9 mg/ml (0.9%) sodium chloride solution for infusion, in a 50 mg/ml (5%) glucose solution for infusion, or in an intravenous infusion preparation of sodium lactate, to a final concentration of 1 mg/ml. If the solution appears cloudy or if insoluble precipitate is observed, the vial must be discarded.
Each 2.5 ml vial must be diluted 1:100 in 250 ml of diluent. Use 250 mg (2.5 ml) per 250 ml of diluent or 500 mg (5 ml) per 500 ml of diluent. The reconstituted solution must be mixed by repeatedly inverting the bag or bottle for one minute. The diluted solution should be clear and practically free from visible suspended particles. After preparation, the solution may show slight transient cloudiness due to the formation of microprecipitates, which however dissolve rapidly upon mixing. The pH of the intravenous solution prepared according to instructions is 3.2 – 7.5.
Protective measures against light, such as the use of protective film for intravenous lines, are not required. No significant loss of product potency has been observed after simulated delivery of the solution through intravenous tubing.
Any unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.