Consumer medicine information

Konakion MM Paediatric

Phytomenadione

BRAND INFORMATION

Brand name

Konakion MM Paediatric

Active ingredient

Phytomenadione

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

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

What is in this leaflet

This leaflet answers some common questions about KONAKION® MM Paediatric.

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 your baby receiving KONAKION MM Paediatric against the benefits they expect it will have for them.

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

Keep this leaflet. You may need to read it again.

What KONAKION MM Paediatric is used for

KONAKION MM Paediatric contains the active ingredient phytomenadione.

KONAKION MM Paediatric is used to treat blood clotting problems.

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

Vitamin K is used to prevent and treat Vitamin K Deficiency Bleeding (VKDB). This is when the newborn or older babies bleed excessively as the blood clotting system is not fully developed. Vitamin K works by reversing some of the causes of excessive bleeding.

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

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

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

Before KONAKION MM Paediatric is given

When your baby must not have it

Do not use KONAKION MM Paediatric if:

  1. Your baby has had an allergic reaction to KONAKION MM Paediatric, any other type of Vitamin K or any ingredients listed at the end of this leaflet.
  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 your baby should be receiving KONAKION MM Paediatric, talk to your doctor.

Before KONAKION MM Paediatric is given

Tell your doctor if:

  1. Your baby has any other health problems including:
  • Liver disease or blockage of the bile ducts.
  • Poor absorption of nutrients (called malabsorption).
  1. Your baby is allergic to any other medicines, foods, dyes or preservatives.
  2. You have taken any of the following medicines during pregnancy:
  • Warfarin (Coumadin®, Marevan®).
  • Phenindione (Dindevan®).
  • Antiepilepsy medicines.
  • Tuberculosis medicines.
  • Long-term antibiotics.

If you have not told your doctor about any of the above, tell them before your baby starts KONAKION MM Paediatric.

Taking other medicines

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

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

  • Long-term antibiotics.

These medicines may be affected by KONAKION MM Paediatric, or may affect how well it works. Your baby may need to use different amounts of medicine, or 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 your baby is receiving KONAKION MM Paediatric.

Ask your doctor or pharmacist if you are not sure about these medicines.

How Konakion MM Paediatric is given

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

They may differ from the information contained in this leaflet.

How it is used

KONAKION MM Paediatric can be used as an injection or as a liquid for the baby to swallow.

Usually, a doctor or nurse will give an injection into a muscle.

If it is given as a liquid into the baby's mouth, then the oral dispenser or another accurate measuring device should be used. After the liquid is placed in the baby's mouth, it is best to follow the dose with a feed, to ensure it is swallowed.

In the rare case that your baby already has a bleeding condition, then it may be given as an injection into a vein.

How long Konakion MM Paediatric is given for

Your doctor will usually prescribe one injection in the muscle or a number of doses given by mouth.

The length of therapy will vary according to whether your baby is breast-fed, on milk formula or if they are at particular risk of haemorrhagic disease.

If your baby is given KONAKION MM Paediatric orally, make sure they receive every dose as prescribed.

It is important that your baby receives every dose. If every dose is not given to your baby, KONAKION MM Paediatric may not work as well to prevent this disease.

In case of an overdose

Immediately telephone your doctor, or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital, if you think your baby or anyone else may have taken too much KONAKION MM Paediatric. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

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

While your baby is receiving KONAKION MM Paediatric

Things you must do

Tell your doctor or nurse if your baby vomits or has diarrhoea within 24 hours of receiving a dose of KONAKION MM Paediatric by mouth.

If your baby spits out or vomits an oral dose or if diarrhoea occurs within 24 hours, a repeat dose of Konakion MM Paediatric may be needed.

Tell all doctors and pharmacists who are treating your baby that they are receiving KONAKION MM Paediatric.

Be sure to attend all of your baby's follow-up appointments so that all oral doses can be given.

It is important that your baby receives every dose. For KONAKION MM Paediatric to work properly all doses must be given to your baby.

Things you must not do

Do not miss any of your baby's follow-up oral doses of KONAKION MM Paediatric.

For KONAKION MM Paediatric to work properly all doses must be given to your baby.

Do not give KONAKION MM Paediatric to anyone else, other than your baby even if they have the same condition.

Do not use KONAKION MM Paediatric to treat other complaints that your baby has unless your doctor says to.

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

Side effects

Tell your doctor or pharmacist as soon as possible if you think your baby does not feel well while they are receiving KONAKION MM Paediatric.

KONAKION MM Paediatric helps prevent haemorrhagic disease (bleeding) in most babies but may have unwanted side effects in a few.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Your baby may need medical treatment if they 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, rarely this may be severe.
  • Unusual 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. Your baby may need urgent medical attention. Serious side effects are rare.

Side effects 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 babies and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making your baby 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. Your baby may not experience any of them.

After KONAKION MM Paediatric is given

Storage

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

KONAKION MM Paediatric should be protected from light.

Product description

Availability

KONAKION MM Paediatric comes in one paediatric strength:

2 mg/0.2 mL.

KONAKION MM Paediatric comes in packs of 5 ampoules with 5 dispensers. The dispensers are for use if it is given by mouth.

KONAKION MM Paediatric is also available as an adult injection or tablet.

What KONAKION MM Paediatric looks like

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

Ingredients

Active ingredient:

  • Phytomenadione (also called Vitamin K1).
  • Each 0.2 mL ampoule contains 2 mg of phytomenadione.

Inactive ingredients:

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

KONAKION MM Paediatric is lactose and gluten free.

Distributor

KONAKION MM Paediatric 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 71758.

This leaflet was prepared on 19 March 2019

Published by MIMS June 2019

BRAND INFORMATION

Brand name

Konakion MM Paediatric

Active ingredient

Phytomenadione

Schedule

Unscheduled

 

1 Name of Medicine

Phytomenadione (vitamin K1).

6.7 Physicochemical Properties

Chemical structure.


CAS number.

CAS-84-80-0.

2 Qualitative and Quantitative Composition

Konakion MM Paediatric 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 2 mg/0.2 mL in a mixed micelles (MM) solution (the micelles are composed of glycocholic acid and lecithin in an aqueous solution). The formulation is available in two volumes, phytomenadione 10 mg/1 mL (adult) and 2 mg/0.2 mL (paediatric).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Injection, solution.

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 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.
Lack of vitamin K1 leads to an increased tendency of vitamin K deficiency bleeding (VKDB). Administration of vitamin K1 promotes synthesis of above mentioned coagulation factors, can reverse an abnormal coagulation status or bleeding due to vitamin K1 deficiency and thereby reduces the risk of early, classic or late VKDB.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Orally ingested phytomenadione is absorbed primarily in the middle portions of the small intestine. Optimum absorption is possible only in the presence of bile and pancreatic juice. The absolute bioavailability following intramuscular (IM) administration is approximately 80%. The 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.

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/L. After IV administration of 10 mg Konakion MM to adults the plasma level after 1 hour is approximately 500 nanogram/mL and approximately 50 nanogram/mL at 12 hours. Vitamin K1 is stored in the body for only short periods of time, does not readily cross the placenta and is poorly distributed into breast milk.

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. Metabolism of vitamin K1 after birth through epoxidation may occur more rapidly in premature infants.

Excretion.

The elimination half-life in plasma is 1.5-3 hours. After metabolic degradation, vitamin K1 is excreted in the bile and urine as the glucuronide and sulphate conjugates. 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.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of vitamin K deficiency bleeding (VKDB).

4.3 Contraindications

Konakion MM Paediatric is contraindicated in patients with known hypersensitivity to any of the ingredients.

4.4 Special Warnings and Precautions for Use

Anticoagulant therapy.

Konakion MM Paediatric 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.

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 the elderly.

Please see Konakion MM 10 mg/1 mL Product Information for recommendations for this group.

Paediatric use.

Parenteral administration is associated with a possible risk of kernicterus in premature infants weighing less than 2.5 kg.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Vitamin K1 antagonises the effects of coumarin and indanedione type anticoagulants (e.g. warfarin, phenindione).
Coadministration of anticonvulsants can impair the action of vitamin K1.
Konakion MM Paediatric should not be mixed with infusion solutions (see Section 4.2 Dose and Method of Administration).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There have been no studies investigating the effect of phytomenadione on reproductive fertility.
Not applicable, please see Konakion MM 10 mg/1 mL Product Information.
Vitamin K1 is poorly excreted into breast milk. Konakion is not recommended for nursing mothers as prophylaxis of haemorrhagic disease in the newborn.

4.8 Adverse Effects (Undesirable Effects)

In rare cases anaphylactoid reactions have been reported after parenteral use of Konakion MM Paediatric. Should an anaphylactoid reaction occur, the usual measures must be taken (e.g. administration of adrenaline and supportive measures as required).
Very rarely, injection site reaction, venous irritation or phlebitis has been reported in association with parenteral administration of Konakion MM solution to adults. This reaction is unlikely in neonates due to the small injection volume (0.2 mL). Rarely, injection site reactions may occur which may be severe, including inflammation, atrophy and necrosis.
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.

4.2 Dose and Method of Administration

Konakion MM Paediatric may be given by intramuscular, oral or intravenous routes. Care should be taken to ensure the correct dose is given for the chosen route of administration.

Prophylaxis.

All healthy neonates.

1 mg (0.1 mL) IM at birth is recommended. Alternatively, 2 mg (0.2 mL) orally at birth, at the time of newborn screening (3-5 days of age) and at 4 weeks.
For predominately formula fed neonates the last oral dose may be omitted.

Neonates with special risk factors.

1 mg IM at birth is recommended in neonates with special risk factors. If the neonate has special risk factors and weighs less than 1.5 kg, then 0.5 mg (0.05 mL) is recommended (see Section 4.4 Special Warnings and Precautions for Use).
The size and frequency of further doses should be based on clinical grounds and coagulation status.
Clotting and PIVKA-II (proteins induced in vitamin K absence) tests are not to be relied upon as indications of deficiency as the relationship between biochemical evidence of deficiency and late VKDB is not clear.

Special risk factors.

Early and/or classical VKDB.

Risk factors include: prematurity, birth asphyxia, delay in establishment of oral feeding, maternal use of anticoagulants, antiepileptics or tuberculostatics and antibiotic treatment.

Late VKDB.

Risk factors include: liver dysfunction including obstructive jaundice, malabsorption and prolonged use of antibiotics.

Therapy.

Initially, 1 mg by intravenous injection, with further doses as required, based on the clinical grounds and coagulation status. In certain circumstances, treatment with Konakion MM Paediatric may need to be accompanied by more direct forms of effective haemorrhage control, such as transfusion of whole blood or coagulation factors, to compensate for severe blood loss and the delayed response to vitamin K1.
VKDB should be suspected with any minor bleed in infants less than 6 months of age, even if coagulation tests are within normal limits. Clotting and PIVKA-II tests are not to be relied upon as indications of deficiency as the relationship between biochemical evidence of deficiency and late VKDB is not clear.

Administration.

Parenteral use.

Konakion MM Paediatric should not be diluted or mixed with other parenteral medications.

Oral use (with the dispenser included in the package).

After breaking the ampoule, place the dispenser vertically into the ampoule.
Withdraw the solution from the ampoule into the dispenser until the solution reaches the marking on the dispenser (= 2 mg vitamin K1).
Administer the contents of the dispenser directly into the infant's mouth.
Repeated doses are advised if the infant spits out or vomits an oral dose or alternatively diarrhoea occurs within 24 hours of administration.

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.

4.9 Overdose

There is no known clinical syndrome attributable to hypervitaminosis of vitamin K1.
The following adverse events have been reported concerning overdose with use of Konakion in neonates and infants: jaundice, hyperbilirubinaemia, increased glutamine-oxaloacetic transferase and gamma-glutamyl transferase, abdominal pain, constipation, soft stools, malaise, agitation and cutaneous eruption. The causality of those cannot be established. The majority of these adverse events were considered nonserious and resolved without any treatment.
Treatment of suspected overdose should be aimed at alleviating symptoms and consist of general supportive measures.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Unscheduled.

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 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 MM ampoule solution should be clear. Following incorrect storage, the solution may become turbid or phase-separation may occur. In this case the ampoule must not be used.

6.5 Nature and Contents of Container

Konakion MM Paediatric ampoules 2 mg/0.2 mL (filling volume 0.3 mL): pack of five amber glass ampoules and 5 dispensers (graduated oral plastic syringes).

6.6 Special Precautions for Disposal

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

Summary Table of Changes