Consumer medicine information

Heparin Interpharma Injection

Heparin sodium

BRAND INFORMATION

Brand name

Heparin Interpharma

Active ingredient

Heparin sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Heparin Interpharma Injection.

SUMMARY CMI

HEPARIN INTERPHARMA INJECTION

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using HEPARIN INTERPHARMA INJECTION?

HEPARIN INTERPHARMA INJECTION contains the active ingredient heparin sodium derived from porcine (pig) intestinal mucosa. HEPARIN INTERPHARMA INJECTION is used to prevent the blockage of blood vessels by blood clots in adults 18 years and over. For more information, see Section 1. Why am I using HEPARIN INTERPHARMA INJECTION? in the full CMI.

2. What should I know before I use HEPARIN INTERPHARMA INJECTION?

Do not use if you have ever had an allergic reaction to heparin or pork products, any medicine derived from heparin or any of the ingredients listed at the end of the CMI. Do not take heparin if you have or have had major bleeding disorders, injury to the brain, stomach or bowel problems, or bacterial infections of the heart.

For more information, see Section 2. What should I know before I use HEPARIN INTERPHARMA INJECTION? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with HEPARIN INTERPHARMA INJECTION and affect how it works. Heparin may lead to an increase of potassium in your blood. Therefore, you should tell your doctor if you are taking any medicines that raise your potassium level. A list of medicines that may affect how Heparin works is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use HEPARIN INTERPHARMA INJECTION?

  • Your doctor will determine the dose you require and duration of use.
  • HEPARIN INTERPHARMA INJECTION should not be injected by self-administration until you have been shown how to inject Heparin Sodium Injection using the prefilled syringe. It is injected by slow injection under the skin. It can also be injected into a vein by a doctor or nurse.

More instructions and how to use HEPARIN INTERPHARMA INJECTION can be found in Section 4. How do I use HEPARIN INTERPHARMA INJECTION? in the full CMI.

5. What should I know while using HEPARIN INTERPHARMA INJECTION?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using HEPARIN INTERPHARMA INJECTION
  • Tell your doctor if you are pregnant or breastfeeding
  • Tell your doctor if you have diabetes, impaired kidney or liver function
  • Tell your doctor if you are taking any medicines to raise the potassium level in your blood
Things you should not do
  • Do not use HEPARIN INTERPHARMA INJECTION if you have:
    - active bleeding (eg. from open wounds);
    - you have any illnesses or organ injuries that may be associated with increased bleeding tendency, including low blood platelet count, blood coagulation disorders, severe diseases of liver or pancreas;
  • Do not stop using this medicine or change the dosage without checking with your doctor.
  • Do not mix heparin sodium injection with other injections or fluids.
  • Do not inject HEPARIN INTERPHARMA INJECTION into your muscle
Drinking alcohol
  • Heavy alcohol drinkers are at greater risk of major heparin associated bleeding than moderate or non-drinkers
Looking after your medicine
  • Store below 25°C. Do not refrigerate or freeze.
  • For single use only in one patient. Discard any residue

For more information, see Section 5. What should I know while using HEPARIN INTERPHARMA INJECTION? in the full CMI.

6. Are there any side effects?

Less serious side effects include local irritation at the injection site, or mild pain around the injection site. Serious side effects that may occur include: allergic reactions, swelling or changing skin colour at injection site, easy bruising and increased bleeding. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

HEPARIN INTERPHARMA INJECTION

Active ingredient: heparin sodium (from porcine intestinal mucosa)

Consumer Medicine Information (CMI)

This leaflet provides important information about using HEPARIN INTERPHARMA INJECTION.

This medicine is likely to be used while you are at the clinic or in hospital. If possible, please read this leaflet carefully, before this medicine is given to you. In some cases, this leaflet may be given to you after the medicine has been administered. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using HEPARIN INTERPHARMA INJECTION.

Where to find information in this leaflet:

1. Why am I using HEPARIN INTERPHARMA INJECTION?
2. What should I know before I use HEPARIN INTERPHARMA INJECTION?
3. What if I am taking other medicines?
4. How do I use HEPARIN INTERPHARMA INJECTION?
5. What should I know while using HEPARIN INTERPHARMA INJECTION?
6. Are there any side effects?
7. Product details

1. Why am I using HEPARIN INTERPHARMA INJECTION?

HEPARIN INTERPHARMA INJECTION contains the active ingredient heparin sodium. HEPARIN INTERPHARMA INJECTION is for use in patients over 18 years of age. This medicine belongs to a group of medicines known as anti-coagulants. Anti-coagulants work by decreasing the clotting ability of the blood and help stop clots forming in the blood vessels.

Anti-coagulants are sometimes called "blood thinners", although they do not actually thin the blood. Heparin will not dissolve blood clots that have already formed, but it may prevent any clots that have already formed from becoming larger and causing serious problems.

This medicine is used to prevent and treat diseases caused by blood clots, such as deep vein thrombosis (DVT) and certain blood vessel, heart and lung conditions.

Heparin may be used for the treatment of other conditions that are not mentioned above. Your doctor will be able to tell you about the specific condition for which you have been prescribed heparin.

2. What should I know before I use HEPARIN INTERPHARMA INJECTION?

Warnings

Do not use HEPARIN INTERPHARMA INJECTION if:

  • you are allergic to heparin, pork products or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • you have any of the following medical conditions:
    - conditions where bleeding may be a problem, such as haemophilia, hiatus hernia, bleeding haemorrhoids (piles)
    - retinopathy (a disease of the retina)
    - problems with weak blood vessels
    - endocarditis (inflammation of the lining of the heart)
    - ascorbic acid (Vitamin C) deficiency
    - stroke (bleeding on the brain)
    - very high blood pressure
    - stomach or intestinal ulcers or other conditions which may bleed, such as ulcerative colitis
    - severe kidney or liver disease
    - major surgery involving the eyes, brain or spinal cord
    - immediately after childbirth, or imminent miscarriage
    - low blood platelet count (thrombocytopenia)
    - a drop in blood platelet count due to heparin or pentosan polysulfate.

If you are not sure whether you should be given this medicine, talk to your doctor.

Check with your doctor if you:

  • have or have had any of the following medical conditions:
    - asthma
    - liver or kidney disease
    - high blood pressure (hypertension)
    - ulcer disease
    - vascular disease
    - recent medical, surgical or dental procedures
    - a heart infection, or other heart problems
    - recent surgery on your eyes, brain or spinal cord
    - chronic alcoholism
  • take any medicines for any other conditions

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

Children

Do not give HEPARIN INTERPHARMA INJECTION to a child.

Patients to be Closely Monitored:

Elderly patients or Critically ill patients

You will be monitored closely if you are:

  • an elderly patient, especially an elderly woman,
  • critically ill (e.g. you need to stay in an intensive care unit)
  • also receiving certain medicines that affect blood clotting or clotting system (see section 3. What if I am taking other medicines?)

Liver or kidney disorders

Your doctor will carefully supervise and monitor your blood clotting values during therapy with this medicine if you have disorders of your kidneys or liver.

Heparin resistance

Resistance to heparin can occur and is suspected if people require unusually high doses. Increased doses should only be prescribed if monitoring of the effect of the medication occurs (anti-Xa level measurement).

Monitoring

Before the start and during your heparin therapy, blood samples will be taken at certain time intervals, to determine your blood clotting time values and the blood platelet count.

Heparin may lead to an increase of potassium in your blood. Therefore, the potassium level should be monitored if you are at risk to develop high potassium level in your blood. This can be the case if you have, e.g. diabetes, an impaired kidney function or if you are taking drugs that raise the potassium level in the blood (please refer to section 3. What if I am taking other medicines?)

Your doctor will check your water and salt balance during heparin therapy, if you receive the medicine for a prolonged time or whenever your doctor decides that a check of these parameters is required.

During and immediately following spinal anaesthesia Heparin sodium will only be administered to you with extreme caution since there is increased risk of bleeding.

Heparin Sodium Injection will only be given to you after thorough weighing of risks against benefits in your individual case.

For safety reasons it is recommended to observe a puncture-free interval of 4 hours between the last administration of heparin and the next administration of heparin or the removal of a spinal/peridural catheter. Earliest 1 hour thereafter, a new injection of Heparin can be administered. If, during heparin therapy, blood vessels become blocked by blood clots, your doctor will take into consideration that you may suffer from a special disease associated with low blood cell counts called heparin-induced thrombocytopenia type II. Then, your doctor will initiate blood platelet counts.

After prolonged use of heparin, you may develop the brittle bone disease (osteoporosis). This may happen more likely to elderly people (especially women), pregnant or breast-feeding women or to children.

This medicine may intensify and prolong menstrual bleeding. If bleeding is unusually heavy and irregular, you should undergo a gynaecological examination in order to rule out organic causes.

Your doctor will take special care if you are allergic to other heparins, like so called low-molecular-weight heparin.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and HEPARIN INTERPHARMA INJECTION may interfere with each other.

Medicines that may increase the effect of HEPARIN INTERPHARMA INJECTION include:

  • corticosteroids, such as prednisolone and hydrocortisone,
  • medicines for rheumatoid arthritis, such as hydroxychloroquine,
  • medicines for reducing swelling of the body such as etacrynic acid,
  • medicines for treating gout such as probenecid,
  • high-dose acetylsalicylic acid (aspirin),
  • drugs used to dissolve existing blood clots (fibrinolytics),
  • anticlotting medicines such as: warfarin, tirofiban, streptokinase, urokinase, alteplase; anistreplase
  • some non-steroidal anti-inflammatory drugs such as ibuprofen, diclofenac and ketorolac,
  • antibiotics, such as cefamandole and penicillin at high doses,
  • asparaginase (cytostatic anti-cancer drug)
  • epoprostenol (a prostaglandin used for pulmonary arterial hypertension)
  • medicines to restore lost blood containing dextrans,
  • medicines used for epilepsy (seizures) such as valproic acid
  • medicines used for thyroid problems such as propylthiouracil
  • substances used to enhance the contrast of structures or fluids within the body in medical imaging

The action of these substances is intensified, which may be associated with an increased risk of bleeding.

Medicines that may reduce the effect of HEPARIN INTERPHARMA INJECTION include:

  • tetracycline antibiotics
  • insulin, an injection used to treat diabetes
  • medicines for heart and circulation problems such as digitalis or digoxin
  • vitamin C (ascorbic acid)
  • quinine
  • glyceryl trinitrate (used to treat angina to help restore oxygen supply to the heart)
  • alkaline medicines (e.g. phenothiazine, tricyclic antidepressants, antihistamines)
  • Nicotine abuse (smokers):
    Nicotine may increase the elimination of heparin from your body and the effect of blood thinning of heparin may be weaker than intended.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect HEPARIN INTERPHARMA INJECTION.

4. How do I use HEPARIN INTERPHARMA INJECTION?

How much to use and when to use

  • HEPARIN INTERPHARMA INJECTION dose and the duration of use will be determined by your doctor.
  • The dose depends on your clotting values, the nature and course of your illness, your response to the therapy, side effects, weight and age.
  • Follow the instructions provided by your doctor and use HEPARIN INTERPHARMA INJECTION until your doctor tells you to stop.

How it is given

HEPARIN INTERPHARMA INJECTION is given as an injection under the skin (subcutaneously) or as a slow injection into a vein (intravenously). It should not be given as an injection into a muscle (intramuscularly).

HEPARIN INTERPHARMA INJECTION should not be injected by self-administration until you have been shown how to inject HEPARIN INTERPHARMA INJECTION using the prefilled syringe.

How to administer HEPARIN INTERPHARMA INJECTION

Subcutaneous injection

  • HEPARIN INTERPHARMA INJECTION should be given by slow injection under the skin.
    Do not inject yourself or someone else until you have been shown how to inject HEPARIN INTERPHARMA INJECTION using the prefilled syringe.
  • Your doctor, nurse or pharmacist will show you how to inject HEPARIN INTERPHARMA INJECTION properly using the prefilled syringe with needle shield; and how to cover the needle after injection. The needle shield will help prevent needle stick injuries to anyone who handles the prefilled syringe.
  • Keep the HEPARIN INTERPHARMA INJECTION prefilled syringe in the blister packaging until you are ready to use it.
    HEPARIN INTERPHARMA INJECTION prefilled syringes are for single, one-time use only. Do not re-use a HEPARIN INTERPHARMA INJECTION prefilled syringe.
  • The prefilled syringe may have air bubbles. To avoid loss of medicine when using the prefilled syringe, do not push out (expel) any air bubbles from the prefilled syringe before giving the injection.

HEPARIN INTERPHARMA INJECTION prefilled syringe parts:

Step 1: Gather supplies needed for your injection

Included in the HEPARIN INTERPHARMA INJECTION box: A HEPARIN INTERPHARMA INJECTION prefilled syringe.

Not included in the box:

  • 1 alcohol wipe
  • sharps disposal container
  • 1 piece of gauze
  • 1 adhesive bandage (optional)

Step 2: Wash your hands well with soap and water

Dry your hands

Step 3: Remove the prefilled syringe from the blister packaging

Do not remove by pulling on the plunger as this may damage the syringe. Place the syringe on a flat surface.

Step 4: Choose and clean your injection site.

Sit or lie down in a comfortable position. Choose an injection site on your stomach area (abdomen) to give your injection.

  • Choose a different injection site each time you give yourself an injection, alternating between the left and right side of your stomach area.
  • Clean the injection site with the alcohol wipe. Let it dry before injecting.

Step 5: Prepare the prefilled syringe.

  • Pick up the prefilled syringe. Bend the needle shield towards the body of the prefilled syringe by approximately a 90-degree angle.
  • Hold the body of the prefilled syringe firmly in one hand. Remove the protective needle cap by pulling it straight off the syringe. Throw away the needle cap in the sharps disposal container.

Do not touch the needle or let it come in contact with any surface before you give your injection.

Step 6: Give your injection.

  • Gently pinch the skin that has been cleaned to make a fold. Hold the fold between the thumb and the fore finger of one hand.
  • Using the other hand, hold the prefilled syringe Firmly and insert the full length of the needle at a 90-degree angle into the skin fold. The skin fold should be held during the entire injection.
  • Inject all the medicine in the prefilled syringe by pressing down on the plunger as far as it will go. Inject the product slowly. When all the medicine has been injected, remove the needle from the skin fold.
  • Press the injection site with a piece of gauze for a few seconds to minimize bruising, do not rub the injection site after you have given your injection. There may be a small amount of blood at the injection site. You may cover the injection site with a small adhesive bandage if needed.

Step 7: Secure needle in needle shield.

Do not try to secure the needle in the needle shield with your fingers. Secure the needle in the groove of the safety shield by pressing it against a stable surface.

Step 8: Dispose of used HEPARIN INTERPHARMA INJECTION prefilled syringes.

Put the used prefilled syringe in a sharps disposal container right away after use. Do not throw away the prefilled syringe in the household trash. If you do not have a sharps disposal container, you may use a household container that is:

  • Made of heavy-duty plastic.
  • Can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out.
  • Upright and stable during use.
  • Leak-resistant, and
  • Properly labelled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, ask your pharmacist about how to dispose of it safely. Do not throw the used sharps disposal container into the trash.
  • Do not recycle your used sharps disposal container.

Important: Always keep the sharps disposal container out of the reach of children.

If you forget to use HEPARIN INTERPHARMA INJECTION

HEPARIN INTERPHARMA INJECTION should be used regularly at the same time each day. If you miss your dose at the usual time, skip the dose and wait until your next dose.

If it is almost time for your next dose of heparin, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much HEPARIN INTERPHARMA INJECTION

As HEPARIN INTERPHARMA INJECTION is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience any severe side effects after being given this medicine, tell your doctor or nurse immediately, or, if you are not in hospital, go to the Accident and Emergency department at your nearest hospital.

You may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • Go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using HEPARIN INTERPHARMA INJECTION?

Things you should do

If you are about to be started on any new medicine, remind your doctor, dentist or pharmacist that you are being given HEPARIN INTERPHARMA INJECTION.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine. It may affect other medicines used during surgery.

Tell your doctor immediately if you become pregnant.

If you are about to have any blood tests, tell your doctor that you are being given this medicine. It may interfere with the results of some tests.

If you have any serious, physical accidents once you leave hospital, advise your treating doctor or nurse that you have been given this medicine recently.

Things you should not do

  • Do not stop using this medicine or change the dosage without checking with your doctor
  • Do not inject into a muscle
  • Do not give this medicine to anyone else even if they have the same condition as you.
  • Do not use this medicine to treat any other complaints unless a doctor tells you to.
  • Do not mix this medicine with other injections or infusion fluids. Certain medicines or solutions contain ingredients that could interact with HEPARIN INTERPHARMA INJECTION

Driving or using machines

Be careful before you drive or use any machines or tools until you know how HEPARIN INTERPHARMA INJECTION affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Heavy alcohol drinkers are at greater risk of major heparin associated bleeding than moderate or non-drinkers.

Looking after your medicine

  • Store below 25°C. Do not refrigerate or freeze.
  • Keep syringes in the pack until it is time to use them.
  • HEPARIN INTERPHARMA INJECTION is for single use only.

Keep it where young children cannot reach it.

When to discard your medicine

HEPARIN INTERPHARMA INJECTION and its packaging must not be disposed of via household waste. Ask your doctor or pharmacist how the product and its packaging should be disposed.

Any unused solution should be discarded.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this HEPARIN INTERPHARMA INJECTION after the expiry date which is stated on the label. The expiry date refers to the last date of that month.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Injection site-related
  • Local reactions, like mild pain or irritation
Hair and skin
  • temporary hair loss (alopecia) after long-term use,
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergy-related
  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body;
  • rash, itching or hives on the skin, chills or fever.
Skin
  • any changes in skin colour or pain around the injection site,
  • the skin starts to swell, gets warm/red, becomes numb or starts to blister
Bleeding-related
  • easy bruising or bleeding (e.g., nose bleeds, heavy menstrual periods, bleeding from gums when brushing teeth) during or after treatment
  • passing blood in the urine or faeces, dark coloured faeces, or vomiting blood
Bones
  • osteoporosis (brittle bones) – after long term treatment
Reproductive System
  • persistent painful erection
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Other side effects not listed above may also occur in some people. Some side effects may only be seen by your doctor.

If you are over 60 years of age you may have an increased chance of getting side effects, especially if you are female.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What HEPARIN INTERPHARMA INJECTION contains

Active ingredient
(main ingredient)		Heparin sodium (from porcine mucosal membrane)
Other ingredients
(inactive ingredients)		Water for injection
Sodium hydroxide
Hydrochloric acid

Do not take this medicine if you are allergic to any of these ingredients.

What HEPARIN INTERPHARMA INJECTION looks like

HEPARIN INTERPHARMA INJECTION is a clear, colourless solution.

HEPARIN INTERPHARMA INJECTION contains heparin sodium 5,000 IU in 0.5 mL solution in a pre-filled syringe with a 27 gauge x ½ inch needle attached. It is available in packs of 10 pre-filled syringes. (AUST R 394930).

Who distributes HEPARIN INTERPHARMA INJECTION

InterPharma Pty Ltd
Suite 103, 39 East Esplanade
MANLY NSW 2095 AUSTRALIA
Ph.: 02 9976 6876
[email protected]

This leaflet was prepared in Nov 2023.

Published by MIMS April 2024

BRAND INFORMATION

Brand name

Heparin Interpharma

Active ingredient

Heparin sodium

Schedule

S4

 

1 Name of Medicine

Heparin sodium.

2 Qualitative and Quantitative Composition

Each pre-filled syringe contains 5,000 IU heparin sodium from porcine intestinal mucosa.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clear, colourless solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of deep vein thrombosis for use in patients 18 years and older.

4.2 Dose and Method of Administration

Heparin may be given by intermittent intravenous injection, intravenous infusion or deep subcutaneous injection. It should not be given intramuscularly because of the danger of haematoma formation.
A guide to dosage schedules for prophylaxis and treatment is presented in Table 1.

Laboratory monitoring for efficacy and safety.

Adjust the dosage of Heparin Interpharma according to the patient's coagulation test results. Dosage is considered adequate when the activated partial thromboplastin time (aPTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. After deep subcutaneous injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injections.
Periodic platelet counts and haematocrits are recommended during the entire course of Heparin Interpharma therapy, regardless of the route of administration.

Use in hepatic impairment.

Dose adjustment may be needed in patients with hepatic impairment. Also see Section 4.4 Special Warnings and Precautions for Use.

Use in renal impairment.

Dose adjustment may be needed in patients with renal impairment. Also see Section 4.4 Special Warnings and Precautions for Use.

Use in the elderly.

Dose requirements for heparin might be adjusted in the elderly (patients aged 60 years and over) depending on their individual condition (e.g. kidney function). Also see Section 5.2 Pharmacokinetic Properties.

Smokers.

Depending on the amount of nicotine present in the body dose adjustments might be necessary. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

Obese patients.

Clinical trials suggest that in order to provide sufficient anti-coagulation in morbidly obese patient's dose adjustment of heparin might be needed. However, no specific dosage recommendations can be made.
Contains no antimicrobial agent. This is for single use only in a single patient. Any residue should be discarded.

4.3 Contraindications

Heparin therapy is contraindicated in patients who are hypersensitive to the drug.
It should not be used in the following cases:
in the presence of actual or potential haemorrhagic states, e.g. haemophilia, ascorbic acid deficiency, increased capillary fragility, hiatus hernia, neoplasms, retinopathy, bleeding haemorrhoids or other organic lesions likely to bleed;
with an uncontrollable active bleeding state (see Section 4.4 Special Warnings and Precautions for Use), except when this is due to disseminated intravascular coagulation;
haemorrhagic vascular accident;
threatened abortion;
immediate postpartum period;
subacute bacterial endocarditis or acute infectious endocarditis;
severe hypertension;
gastric or duodenal ulcers or other ulcerative conditions which may have a tendency to haemorrhage, e.g. ulcerative colitis;
advanced renal or hepatic disease;
during and immediately after spinal or major surgery, especially those involving the brain, eye or spinal cord;
shock;
severe thrombocytopenia or a history of thrombocytopenia (type II) with any kind of heparin or with pentosan polysulfate;
patients in whom suitable blood coagulation tests, e.g. whole blood clotting time, partial thromboplastin time, etc, cannot be performed at appropriate intervals (this contraindication refers to full dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low dose heparin);
hypersensitivity to heparin or to any of the excipients or pork products (e.g. anaphylactoid reactions).

4.4 Special Warnings and Precautions for Use

Heparin should not be given by intramuscular injection, due to the risk of haematoma formation.
When neuraxial anaesthesia (epidural/spinal anaesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with unfractionated heparin or low molecular weight heparins/heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long term or permanent paralysis. The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by concomitant use of drugs affecting haemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. Patients should be frequently monitored for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. The physician should consider the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
Heparin should be used with extreme caution in patients with continuous tube drainage of the stomach or small intestine.
Any action which may cause vascular injury, with the exception of necessary intravenous or subcutaneous injections, should be avoided where possible.
Heparin may lead to an increase and prolongation of menorrhagia. In case of unusual strong or acyclic uterine bleeding, any organic disease requiring specific treatment should be excluded by a supplementary gynaecological examination.
Heparin should be administered with caution to patients with hypertension, a history of ulcers, or with vascular diseases of the chorio-retina, impaired hepatic function, hemostasis disorder, endocarditis, or during surgery of the eyes and central nervous system.
Increased resistance to heparin is frequently encountered with fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and in post-surgical patients.
Outpatients should be warned of the haemorrhagic risks in case of possible trauma.
After prolonged administration, osteoporosis may develop, especially in predisposed patients (i.e. older people - especially postmenopausal women, pregnant and breastfeeding women). Also see Section 4.6; Section 4.8.

Oral surgery.

Heparin therapy increases the risk of localised haemorrhage during and following oral surgical (dental) procedures. Temporary heparin dosage reduction or withdrawal may therefore be advisable prior to oral surgery.

Serum transaminase.

Significant elevations of AST and ALT levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin. Since AST determinations are important in the differential diagnosis of myocardial infarction, liver disease and pulmonary embolism, rises that might be caused by drugs (like heparin) should be interpreted with caution.

Heparin resistance.

Resistance to heparin is encountered in patients with antithrombin III deficiency. Adjustment of heparin doses based on anti Factor Xa levels may be warranted.

Monitoring during treatment.

Heparin therapy should be monitored carefully. Adequate monitoring of therapy reduces the risk of overdosage and consequent risk of haemorrhage and is an important guide to the development of serious adverse reactions such as delayed onset thrombocytopenia.
Platelet counts should be monitored in patients receiving heparin for more than a few days, since heparin may cause thrombocytopenia with severe thromboembolic complications. Heparin should be discontinued if thrombocytopenia develops.

Heparin-induced thrombosis-thrombocytopenia syndrome (HITTS or "white clot syndrome").

Patients on heparin may rarely develop heparin-induced thrombosis-thrombocytopenia syndrome: new thrombus formation in association with thrombocytopenia, as a result of irreversible platelet aggregation. This may lead to severe thromboembolic complications such as skin necrosis, gangrene of the extremities, myocardial infarction, pulmonary embolism and stroke. Heparin administration should therefore be discontinued if a patient develops new thrombosis in association with thrombocytopenia. These effects are probably of immuno-allergic nature and occur mostly between the fifth and 21st day of treatment in patients being treated with heparin for the first time.

Delayed onset of HIT and HITT.

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis (HITT) can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT.

Hyperkalemia.

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalemia, in patients at risk of increased potassium levels such as patients with diabetes mellitus, renal insufficiency or taking drugs that may increase plasma potassium levels such as ACE inhibitors. The risk of hyperkalemia appears to increase with the duration of treatment but is normally reversible.

Use in hepatic impairment.

Heparin should be administered with caution to patients with hepatic disease. Dosage reduction may be necessary in patients with advanced hepatic disease.

Use in renal impairment.

Heparin should be administered with caution to patients with renal disease. Dosage reduction may be necessary in patients with advanced renal disease.

Use in the elderly.

Dosage should be reduced in elderly people. Patients aged 60 years or over, especially women, may be more susceptible to haemorrhage during heparin therapy. Patients should be carefully monitored.

Paediatric use.

There are no adequate and well controlled studies on heparin use in paediatric patients. Heparin Interpharma is in a prefilled syringe and should not be administered to children since it does not allow a dose adjustment.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Enhancement of the heparin effect.

Heparin may prolong the one-stage prothrombin time. Therefore, when heparin is given with oral anticoagulants such as warfarin, a period of at least 5 hours after the last intravenous dose, or 24 hours after the last subcutaneous dose of heparin, should elapse before blood is drawn for a valid prothrombin time to be obtained.
Medicines which affect platelet function, e.g. aspirin, other salicylates and other non-steroidal anti-inflammatory agents, platelet aggregation inhibitors, glycoprotein IIb/IIIa antagonists, thienopyridines, dextran, dipyridamole and systemic corticosteroids, may increase the risk of haemorrhage and should be used with caution in patients receiving heparin. Where concomitant use cannot be avoided, careful clinical and biological monitoring should be undertaken.
Other medicines which may potentiate the effect of heparin include hydroxychloroquine, sulphinpyrazone, probenecid, ethacrynic acid, vitamin K antagonists, cytostatic agents, cephamandole, cefotetan, plicamycin, valproic acid and propylthiouracil. High doses of penicillins, some contrast media, asparaginase and epoprostenol may also affect the coagulation process and increase the risk of haemorrhage.
Concomitant use of thrombolytic agents such as alteplase, anistreplase, streptokinase or urokinase may also increase the risk of haemorrhage.

Weakening of the heparin effect.

Antihistamines, digitalis glycosides, tetracyclines, nicotine, ascorbic acid and quinine may reduce the anticoagulant effect of heparin.
Glyceryl trinitrate has been reported to reduce the activity of heparin when both drugs are administered simultaneously intravenously. This effect may be due to the presence of propylene glycol as a solvent in many glyceryl trinitrate parenteral preparations. No interaction has been reported when the glyceryl trinitrate was administered immediately after the heparin. Adjustment of heparin dosage during and following administration of intravenous glyceryl trinitrate may be required.

Alcohol.

Heavy alcohol drinkers are at greater risk of major heparin associated bleeding than moderate or non-drinkers.

Nicotine abuse.

Nicotine may increase the clearance of heparin and therefore partially counteracts the anticoagulant effect of heparin. Also see Section 4.2 Dose and Method of Administration.

Influence of heparin on the effect of other drug substances.

Drugs that lead to an increase of the serum potassium level (e.g. aliskiren, ACE inhibitors) should only be administered together with heparin under careful monitoring. Also see Section 4.4 Special Warnings and Precautions for Use.
Heparin is known to activate plasma lipoprotein lipase, which should be taken into consideration when heparin is administered concomitantly together with drugs with known high plasma protein binding and narrow therapeutic width (e.g. cardiac glycosides).

Incompatibility.

Experimental evidence suggests that heparin may antagonise the actions of ACTH, corticosteroids and insulin. Heparin is incompatible with certain substances in aqueous solution. Reference to specialised literature should be made to verify in which solution the incompatibility was noted. The following incompatibilities have been reported: hydrocortisone; hyaluronidase; hydroxyzine; some antihistamines, narcotic analgesics, phenothiazines and antibiotics. See Section 6.2 Incompatibilities.
Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during co-administration of heparin and intravenous nitroglycerin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies to evaluate the effects of heparin on fertility and embryonic development have not been conducted in animals.
(Category C)
Animal reproduction studies have not been conducted with heparin sodium.
Unfractionated heparin sodium is not known to cross the placenta. Whilst the possibility of fetal harm or effect on reproduction cannot be excluded, a direct fetal effect is unlikely.
During pregnancy, complications resulting from underlying illness and/or therapy cannot be excluded. Long-term administration (> 3 to 5 months) of heparin may increase the risk of osteoporosis in pregnant women (also see Section 4.4 Special Warnings and Precautions for Use).
The tendency for skin lesions is higher in pregnant women compared to non-pregnant women (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
For the use of heparin in epidural anaesthesia during labour (see Section 4.4 Special Warnings and Precautions for Use).
For imminent abortion, also see Section 4.3 Contraindications.
 Heparin is not excreted in breastmilk. Long-term administration of heparin may increase the risk of osteoporosis in breast-feeding women (also see Section 4.4 Special Warnings and Precautions for Use).

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The most frequent undesirable effects are bleeding events from any organ or tissue.
Besides this, local reactions at the site of administration may occur.
Heparin-induced thrombocytopenia of type II occurs rarely (≥ 1/10,000 to < 1/1,000) but this adverse reaction may become serious. It is assumed to be a hypersensitivity reaction mediated by specific antibodies. For details, see below.
Other undesirable effects may include local or systemic allergic reactions.
Undesirable effects are listed according to their frequencies as follows: 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 (frequency cannot be estimated from the available data).
All reactions that are derived from post-marketing experience (spontaneous reports and literature) only are based on a patient population which is largely unknown. Therefore, exact incidences cannot be provided and are referred to with the frequency 'not known'. See Table 2.

Information on particular undesirable effects.

Heparin induced thrombocytopenia type II.

Severe heparin-induced, antibody-mediated thrombocytopenia (type II thrombocytopenia, HIT II) is characterised by platelet counts markedly below 100,000 per microlitre or a rapid decrease to less than 50 percent of the initial value and accompanied by arterial or venous thromboses or embolism, consumption coagulopathy, skin necroses at the site of injection. The anticoagulatory effect of heparin may be reduced.
In patients without pre-existing hypersensitivity to heparin the decrease of the platelet count typically begins between 5 to 14 days after commencement of the heparin therapy. In patients with existing antibodies to heparin such decrease may begin already after a few hours. The greater the degree of trauma and thus the release of PF4, the more likely patients went on to develop HIT antibodies and clinical HIT.
As soon as type II thrombocytopenia occurs, heparin administration must be discontinued immediately. Emergency treatment depends on the nature and severity of the symptoms. Re-exposure of the patient to parenteral heparin is absolutely contraindicated.

Patients undergoing extracorporeal circulation.

Principally the same ADRs that occur in other patients might occur. Haemodialysis patients might be at an increased risk for developing anaphylactic or anaphylactoid reactions.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

The main complication associated with heparin overdose is over-anticoagulation and haemorrhage. Examples of types of bleeding observed in patients receiving heparin sodium following subcutaneous administration include melanemia, haematoma, haematuria, ecchymoses, epistaxis, haematemesis, intracranial haemorrhages, pulmonary haemorrhage and other haemorrhage.

Treatment.

Mild symptoms.

Slight haemorrhage due to overdosage can usually be treated by withdrawing the drug.

Severe symptoms.

Severe bleeding may be reduced by the administration of protamine sulphate. Protamine sulphate should be administered intravenously. To avoid circulatory side effects, the injection should be given slowly over a period of about 10 minutes. Not more than 50 milligrams should be given at any one time. The dose of protamine sulphate required is governed by the amount of heparin that has to be neutralised; approximately 1 milligram of protamine sulphate neutralises 100 units of heparin (mucous) that has been injected in the previous 15 minutes. Since heparin is being continuously excreted, the dose should be reduced as more time elapses after the heparin injection. Ideally, the dose of protamine sulphate required should be accurately determined by titration methods as the antagonist itself, in gross excess, acts as an anticoagulant.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Anti-thrombotic agents, heparin group, ATC code B01A B01.

Mechanism of action.

Heparin is a naturally occurring mucopolysaccharide which inhibits the clotting of blood in vitro and in vivo. It enhances the rate at which antithrombin III neutralises thrombin and activated factor X (Xa). Antithrombin III also neutralises other activated coagulation factors, e.g. factors IX, XI, XII and plasmin.
With low dose heparin therapy, anticoagulation appears to result from neutralisation of Xa which prevents the conversion of prothrombin to thrombin. With full dose heparin therapy, anticoagulation appears to result primarily from neutralisation of thrombin which prevents the conversion of fibrinogen to fibrin. Full dose heparin therapy also prevents the formation of a stable fibrin clot by inhibiting activation of fibrin stabilising factor.

Clinical trials.

The safety and efficacy of unfractionated heparin has been demonstrated by decades of use in the clinic.
The safety and efficacy of Heparin Interpharma was assessed in a single dose cross over comparison with a foreign registered product in healthy adults. A total of 10 adverse events were reported by 7 (23%) of the 30 subjects who participated in this study. All of the AEs were mild (9/10; 90%) or moderate (1/10, 10%) in severity. No severe AEs, deaths or withdrawals were reported.
Studies published in the literature and post-market surveillance data have not identified new safety concerns for heparin sodium.

5.2 Pharmacokinetic Properties

Absorption.

Because of its high relative molecular mass and its negative surface charge heparin is not absorbed from the intestine. Intake by the parenteral route intravenous or subcutaneous is used. Intake by inhalation is possible.
Once administered subcutaneous heparin follows non-linear kinetics, as there is a combination of saturable and non-saturable mechanisms of clearance. This effect thereby reduces the unbound fraction of heparin and also heparin's anticoagulant activity at low concentrations. Additionally, binding of heparin to Von-Willebrand factor inhibits platelet function. The bioavailability of subcutaneously administered heparin is dose dependent. The bioavailability of the anti-factor Xa activity increases with the dose delivered and tends from approximately 30% with low doses toward 100% at high doses. Therefore, after subcutaneous injection, the onset of the heparin effect is delayed for approximately 0.5 - 1 hour after administration.

Distribution.

Heparin is strongly bound to plasma proteins (LDL, globulins, in particular AT and fibrinogen). Therefore, the distribution volume is generally limited to the plasma volume. This is also valid for adults undergoing dialysis; here the volume of distribution has been reported to be approximately 0.07 L/kg.

Metabolism.

The saturable phase of heparin clearance is attributed to binding to the reticulo-endothelial system (e.g. endothelial cell receptors, macrophages), where it is internalized and depolymerised followed by its degradation in the liver by heparinises and urinary excretion mainly in the form of depolymerized inactivated heparin.

Excretion.

After parenteral administration heparin is eliminated from the blood through a combination of rapid saturable mechanism of zero-order and much slower first-order mechanism. The interindividual half-life has been reported to be approximately 1 - 2 hours. It depends on the actual dose administered, on liver and kidney function and on accompanying diseases.

5.3 Preclinical Safety Data

Nonclinical data sourced from published literature reveal no special hazard for humans based on conventional data of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, toxicity to reproduction and development.
In animal studies, only effects have been observed that have already been described also for humans in Section 4.8 Adverse Effects (Undesirable Effects), such as osteoporosis and bleeding.

Genotoxicity.

In vitro data suggest heparin is associated with DNA inhibition, unscheduled DNA synthesis, and unspecified DNA damage in various bacterial and mammalian cell types. No in vivo data are available.

Carcinogenicity.

No studies in animals have been performed to evaluate the carcinogenic potential of heparin sodium.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections; sodium hydroxide (for pH adjustment); hydrochloric acid (for pH adjustment).

6.2 Incompatibilities

Incompatibility has been reported between heparin (sodium) and alteplase, amikacin sulphate, amiodarone, ampicillin sodium, benzylpenicillin sodium, cephalothin sodium, ciprofloxacin lactate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, dobutamine hydrochloride, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin sulphate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin sulphate, methicillin sodium, netilimicin sulphate, opioid analgesics, oxytetracycline hydrochloride, polymyxin B sulphate, promazine hydrochloride, promethazine hydrochloride, streptomycin sulphate, sulphafurazole diethanolamine, tetracycline hydrochloride, tobramycin sulphate, vancomycin hydrochloride and vinblastine sulphate.
Heparin sodium has also been reported to be incompatible with cisatracurium besylate, labetalol hydrochloride and nicardipine hydrochloride.
Admixture with glucose can have variable effects. Incompatibility has been reported between heparin and fat emulsion.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate or freeze.
Only use the product if the solution is clear and the container is intact. Do not use if solution is yellow or contains precipitates.

6.5 Nature and Contents of Container

Heparin Interpharma is supplied in ready to use type I clear glass prefilled syringes containing 0.5 mL sterile solution for injection. Each syringe is provided with an affixed siliconised 27 g x ½" stainless steel needle with a needle shield.
Pack size - 10 x prefilled syringe.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

9041-08-1.

7 Medicine Schedule (Poisons Standard)

S4 - (Prescription only medicine).