Consumer medicine information

Konakion MM Injection

Phytomenadione

BRAND INFORMATION

Brand name

Konakion MM

Active ingredient

Phytomenadione

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Konakion MM Injection.

What is in this leaflet

This leaflet answers some common questions about KONAKION MM.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you receiving KONAKION MM against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What KONAKION MM is used for

KONAKION MM contains the active ingredient phytomenadione.

KONAKION MM is used to treat excessive bleeding problems.

KONAKION MM belongs to a group of medicines called Vitamin K.

Vitamin K substances are used to treat excessive bleeding problems and work by reversing some of the causes of excessive bleeding. This risk of bleeding is usually caused by the use of too much medication to prevent blood clots (also known as anticoagulant medication).

There are many different types of medicines used to treat bleeding disorders. KONAKION MM belongs to one of these groups.

Your doctor, however, may have prescribed KONAKION MM for another purpose.

Ask your doctor if you have any questions about why KONAKION MM has been prescribed for you.

Before you receive KONAKION MM

When you must not have it

Do not have KONAKION MM if:

  1. You have had an allergic reaction to KONAKION MM, any other type of Vitamin K or any ingredients listed at the end of this leaflet.
Some symptoms of an allergic reaction may include:
  • 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 skinIf you use this medicine after the expiry date has passed it may not work as well
  1. You are pregnant or plan to become pregnant.
  2. The ampoule is damaged or shows signs of tampering.
  3. The expiry date (EXP) printed on the pack has passed.
If you use this medicine after the expiry date has passed it may not work as well.
  1. The solution is cloudy or separated.

If you are not sure if you should be receiving KONAKION MM, talk to your doctor.

Do not give KONAKION MM to children less than one year of age.

KONAKION MM is for use in adults. KONAKION MM Paediatric is recommended for use in children under one year of age.

Before you receive KONAKION MM:

Tell your doctor if:

  1. You are pregnant or plan to become pregnant.
It is not known whether KONAKION MM is harmful to an unborn baby when used by a pregnant woman. You must not use KONAKION MM if you are pregnant or plan to become pregnant.
  1. You are breast-feeding or plan to breast-feed.
KONAKION MM may pass into breast milk. It is not known what effect KONAKION MM may have on your baby. Your doctor will discuss the risks and benefits of you receiving KONAKION MM while you are breast-feeding.
  1. You have any other health problems including:
  • Liver disease.
  1. You are allergic to any other medicines, foods, dyes or preservatives.

If you have not told your doctor about any of the above, tell them before you start receiving KONAKION MM.

Taking other medicines

Tell your doctor if you are taking any other medicines including any that you have bought from a pharmacy, supermarket or health food shop.

Some medicines may interfere with KONAKION MM. These medicines include:

  • Warfarin (Coumadin®, Marevan®), a medicine used to prevent blood clots
  • Phenindione (Dindevan®), a medicine used to prevent and treat blood clots
  • Some medicines used to treat epilepsy
  • Aspirin and other salicylates
  • Some cephalosporin antibiotics
  • Some medicines used to treat tuberculosis

These medicines may be affected by KONAKION MM, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while you are receiving KONAKION MM.

Ask your doctor or pharmacist if you are not sure about this list of medicines.

How to take KONAKION MM

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

How much to take

KONAKION MM should be used exactly as your doctor has prescribed.

KONAKION MM is given as an injection or as a liquid for you to swallow. Your doctor will decide which is the best way for you to receive KONAKION MM.

If you receive KONAKION MM as an injection your doctor will usually prescribe a single injection or short course of injections. You may also receive it as a liquid to swallow.

How to use it

KONAKION MM is usually given as an injection into a vein by a doctor or nurse.

If you receive KONAKION MM as a liquid to swallow it will be administered with a suitable measuring device. It should be followed with a drink such as water.

How long to take it

Your dose or length of therapy may be adjusted according to your blood clotting response.

KONAKION MM may be given as a single injection or a short course of injections. You may then receive a course of oral Vitamin K depending on your response.

If you take too much (overdose)

Immediately tell your doctor, or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital, if you think that you may have received too much KONAKION MM, even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you are not sure what to do, contact your doctor or pharmacist.

Keep telephone numbers for these places handy.

While you are taking KONAKION MM

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are taking KONAKION MM.

Tell your doctor if you feel the injection is not helping your condition.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Things you must not do

Do not take any other medicines whether they require a prescription or not without first telling your doctor or consulting a pharmacist.

Things to be careful of

Be careful driving or operating machinery until you know how KONAKION MM affects you.

However, KONAKION MM is not expected to affect your ability to drive a car or operate machinery.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are receiving KONAKION MM.

KONAKION MM helps most people with bleeding problems but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • Irritation, soreness or redness near the injection site.
  • Unusual taste, flushing or sweating.

Tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • An allergic reaction (which may include rash, swelling or breathing difficulties).

This is a serious side effect. You may need urgent medical attention. Serious side effects are rare.

Side effects would usually occur within hours of the dose being administered.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After KONAKION MM is given

Storage

KONAKION MM will be stored in the pharmacy, or at the doctors surgery. It is kept in a cool dry place where the temperature stays below 25°C.

KONAKION MM should be protected from light.

Product description

Availability

KONAKION MM comes in one adult strength: 10 mg/1 mL.

KONAKION MM comes in packs of 5 ampoules.

KONAKION MM is also available as a paediatric strength injection.

What KONAKION MM looks like

KONAKION MM is an amber glass ampoule containing a clear, yellow solution.

Ingredients

Active ingredient:

  • phytomenadione (also called Vitamin K1).
  • each 1mL ampoule contains 10 mg of phytomenadione.

Inactive ingredients:

  • Glycocholic acid.
  • Lecithin (322).
  • Sodium hydroxide.
  • Hydrochloric acid (507).
  • Water for injection.

KONAKION MM is lactose and gluten free.

Distributor

KONAKION MM is distributed by:

Pharmaco (Australia) Ltd
Suite 1A, Level 2, 802 Pacific Highway,
Gordon NSW 2072,
Australia

Under license of CHEPLAPHARM Arzneimittel GmbH, Germany

Please check with your pharmacist for the latest Consumer Medicine Information.

Australian Registration Number:

  • AUST R 61654.

This leaflet was prepared on 19 March 2019

Published by MIMS June 2019

BRAND INFORMATION

Brand name

Konakion MM

Active ingredient

Phytomenadione

Schedule

Unscheduled

 

1 Name of Medicine

Phytomenadione (vitamin K1).

2 Qualitative and Quantitative Composition

Konakion MM contains as the active ingredient phytomenadione (vitamin K1) which is 2-methyl- 3-phytyl- 1,4-naphthaquinone. Phytomenadione is a clear, yellow, very viscous, odourless or nearly odourless oil with a molecular weight of 450.7. It is insoluble in water, soluble 1 in 70 in alcohol, more soluble in dehydrated alcohol; soluble in benzene, chloroform, ether and vegetable oils. It is stable in air but decomposes on exposure to light.
The ampoule contains the active ingredient phytomenadione 10 mg/1 mL in a mixed micelles (MM) solution (the micelles are composed of glycocholic acid and lecithin in an aqueous solution).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Haemorrhage or threatened haemorrhage as a result of severe hypoprothrombinaemia (i.e. deficiency of coagulation factors II, VII, IX and X) due, for instance, to overdosage of anticoagulants of the dicoumarol type or to other forms of hypovitaminosis K (e.g. obstructive jaundice, liver and intestinal disorders, or prolonged administration of antibiotics, sulfonamides or salicylates).

4.2 Dose and Method of Administration

Konakion MM ampoules are for IV injection or oral use.
For important information about the expiry, see Section 6.3 Shelf Life.
Slow IV injection must be reserved for potentially fatal haemorrhage due to overdosage of anticoagulants of the coumarin and indandione series. There is currently no data to advise on the appropriate vitamin K1 dosage in the event of an indandione overdose.
Excessive doses of Konakion MM impede the resumption of anticoagulant therapy without offering any advantages.
If there is a recurrence of thrombosis while Konakion MM is being used, IV administration of heparin is recommended as a first measure.
Konakion MM should not be diluted or mixed with other injectables except, where appropriate, into the lower part of the infusion set during continuous infusion of sodium chloride 0.9% or dextrose 5%.

Standard dosage.

Severe or life threatening haemorrhage, e.g. during anticoagulant therapy.

The coumarin anticoagulant should be withdrawn and an IV injection of Konakion MM given slowly (in at least 30 seconds) in a dose of 5-10 mg together with fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Vitamin K1 is essential for sustaining the reversal achieved by FFP or PCC. The prothrombin level should be estimated 3 hours later and, if the response has been inadequate, the dose of vitamin K1 can be repeated as needed. See Table 1.
Close monitoring of all patients with frequent review of INR (international normalised ratio) is recommended.
Oral administration of vitamin K1 is not recommended for patients with major or life threatening bleeding.

Dose recommendations for vitamin K1 therapy in patients with asymptomatic high international normalised ratio (INR) with or without mild haemorrhage.

Warfarin should be withdrawn prior to administration of vitamin K1. See Table 2.
Konakion MM may be administered orally with a syringe. Administration with a syringe can be performed as follows: withdraw the required amount from the ampoule using a syringe with a needle attached. Remove the needle from the syringe and administer the contents of the syringe directly into the patient's mouth. Wash down with fluid.
For small doses one or more ampoules of Konakion MM paediatric (2 mg/0.2 mL; same solution) can be used.

Special dosage instructions.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Use in the elderly. Small doses of 0.5 to 1.0 mg IV or oral vitamin K1 have been shown to effectively reduce the INR to < 5.0 within 24 hours (see Section 5.2 Pharmacokinetic Properties).

Children over one year of age.

The optimal dose should be decided by the treating physician according to the indication and weight of the patient. A single dose of 30 microgram/kg or one tenth of the full IV adult dose of vitamin K1 has been reported to be effective in reversing asymptomatic high (> 8) INR in clinically well children. Konakion MM must not be injected intramuscularly to children on oral anticoagulant.

Infants under one year of age.

For this patient group, Konakion MM paediatric should be used.

4.3 Contraindications

Konakion MM is contraindicated in patients with known hypersensitivity to any of its constituents.
Konakion MM should not be used for patients with pronounced allergic diathesis.
Konakion MM ampoules should not be administered intramuscularly as this route of administration exhibits depot characteristics which may cause difficulties in the reinstitution of anticoagulant therapy. Furthermore, IM administration of medications to anticoagulated patients cause a risk of haematoma formation.

4.4 Special Warnings and Precautions for Use

Konakion MM should be considered as adjunctive therapy to blood transfusions for severe haemorrhage due to anticoagulant therapy; it is not effective when heparin-like compounds have been used for anticoagulant therapy; minimal doses should be used to offset refractoriness to coumarin-like anticoagulants if long-term anticoagulant therapy is intended.

Thromboembolism.

Vitamin K inhibits the therapeutic effect of coumarin anticoagulants and hence creates a risk of thrombosis. In patients in whom Konakion MM is being used to reverse the effect of coumarin anticoagulation, careful consideration must be given to the fact that restoring the blood's clotting ability restores the risk of thrombosis, possibly even to an increased extent.

Mutagenesis.

Neither phytomenadione nor phytomenadione in the mixed micellar formulation showed evidence of mutagenic activity in Salmonella typhimurium. No evidence of chromosomal aberration in human lymphocytes was demonstrated in vitro for phytomenadione, but no tests of potential for DNA damage have been conducted.

Use in hepatic impairment.

Careful monitoring of the INR (international normalized ratio) is necessary after administration of Konakion MM in patients with severely impaired liver function. In severe liver disease, Konakion MM should be discontinued if no significant effect is noted within 1-2 days after the initial dose.

Use in the elderly.

Elderly patients tend to be more sensitive to reversal of anticoagulation with Konakion MM. Dosage in this group should be at the lower end of the range (see Section 4.2 Dose and Method of Administration, Special dosage instructions).

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Konakion MM should not be mixed with infusion solutions (see Section 4.2 Dose and Method of Administration).
Vitamin K1 antagonises the effects of coumarin-type anticoagulants. Coumarins inhibit epoxide reductase in the vitamin K cycle and hence the cofactor function of vitamin K in the carboxylation reaction. Aspirin and other salicylates also attenuate the effect of vitamin K by inhibiting the carboxylase reductase system.
Cephalosporins with the N-methylthiotetrazole group inhibit vitamin K epoxide reductase and hence the effect of vitamin K.
Co-administration of anticonvulsants can impair the action of vitamin K1. Anticonvulsants such as phenobarbital and phenytoin, as well as the antituberculosis drugs isoniazid and rifampicin, may cause vitamin K deficiency bleeding on the first day of life in newborns whose mothers have taken these drugs during pregnancy. The exact mechanism is still unclear.
Vitamin K inhibits the therapeutic effect of coumarin anticoagulants and hence creates a risk of thrombosis (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There have been no studies investigating the effect of phytomenadione on reproductive fertility.
Vitamin K1 does not readily cross the placental barrier. There are no specific studies regarding the safety of Konakion MM in pregnancy and no reproductive studies have been performed in animals. Konakion MM is contraindicated in pregnant women.
 Vitamin K1 is poorly excreted into breast milk. Konakion MM is not recommended for nursing mothers as prophylaxis of haemorrhagic disease in the newborn.

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)

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000) and very rare (< 1/10,000) including isolated reports.

Immune system disorders.

Very rare: anaphylactoid reactions after IV administration of Konakion MM. Should an anaphylactoid reaction occur, the usual measures must be taken (e.g. administration of adrenaline and supportive measures as required).

General disorders and administration site conditions.

Very rare: venous irritation or phlebitis in association with IV administration of Konakion MM. Facial flushing and sweating and unusual taste have been reported.

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

There is no known clinical syndrome attributable to hypervitaminosis of vitamin K1. Reintroduction of anticoagulation may be affected.
Treatment of suspected overdose should consist of general supportive measures.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

As a component of an enzyme system, vitamin K1 promotes the formation in the liver of coagulation factors II (prothrombin), VII, IX and X and of the coagulation inhibitors protein C and protein S, within the body. Anticoagulants of the coumarin and indandione series cause a reversible displacement of vitamin K1 from this enzyme system, thereby inhibiting the synthesis of these factors. Since this is a competitive displacement, Konakion MM is a specific antagonist for warfarin and similar anticoagulants. It is not capable, however, of terminating the action of heparin; for this purpose a salt of protamine should be used.
Vitamin K1 administration, which promotes synthesis of the abovementioned coagulation factors by the liver, can reverse an abnormal coagulation status or bleeding due to vitamin K1 deficiency. Vitamin K1 is ineffective in hereditary hypoprothrombinaemia or hypoprothrombinaemia induced by severe hepatic failure.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

A pharmacokinetic study indicated that the MM solution of vitamin K1 administered orally is rapidly and effectively absorbed. Orally ingested phytomenadione is absorbed primarily in the middle portions of the small intestine. Systemic availability after oral administration is about 50%, with a wide range of interindividual variability. Onset of action occurs approximately 1-3 hours after intravenous (IV) administration and 4-6 hours after oral doses.
Impaired gastrointestinal absorption may occur in conditions such as malabsorption syndromes, short bowel syndrome, biliary atresia and pancreatic insufficiency. The oral dosage for this patient group should therefore be at the higher end of the recommended range (see Section 4.2 Dose and Method of Administration).

Distribution.

The primary distribution compartment corresponds to the plasma volume. In blood plasma, 90% of vitamin K1 is bound to lipoproteins (VLDL portion). Vitamin K1 plasma concentration is normally between 0.4 and 1.2 nanogram/mL. After IV administration of 10 mg Konakion MM the plasma level after 1 hour is approximately 500 nanogram/mL and approximately 50 nanogram/mL at 12 hours.

Metabolism.

Vitamin K1 is rapidly converted into more polar metabolites, including an active metabolite vitamin K1-2,3-epoxide. Some of this metabolite is reconverted into vitamin K1.

Excretion.

After metabolic degradation, vitamin K1 is excreted in the bile and urine as the glucuronide and sulphate conjugates. In one pharmacokinetic study of patients on phenprocoumon (another coumarin), which used a sensitive assay, the terminal half-life in adults was 14 ± 6 hours after IV administration of Konakion MM. Less than 10% of the medicine is excreted unchanged in the urine.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No studies on the potential carcinogenic activity of phytomenadione have been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Glycocholic acid, lecithin, sodium hydroxide, hydrochloric acid, water for injection.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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.
During the shelf-life of Konakion MM it is known that impurities will develop. Although there has been no definite evidence of a safety problem due to these impurities, there are also no adequate safety and toxicity data in relation to the impurities. In order to minimise the amount of impurities, prescribers are encouraged to use the product early in the shelf-life wherever possible.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.
At the time of use, the ampoule solution should be clear. Following incorrect storage, the solution may become turbid or present a phase separation. In this case the ampoule must not be used. Konakion MM ampoules should be used early in the shelf-life wherever possible (see Section 6.3 Shelf Life).

6.5 Nature and Contents of Container

Konakion MM is available in ampoules. MM Ampoules 10 mg/1 mL, IV, 5s.

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.

CAS-84-80-0.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes