Konakion MM Paediatric 2mg/0.2ml

Each ampoule contains 2mg phytomenadione in 0.2ml.

The ampoule solution is clear to slightly opalescent, pale yellow in colour and contains the active constituent in a mixed micelles vehicle of glycocholic acid and lecithin.

Konakion MM Paediatric is indicated for the prophylaxis and treatment of vitamin K deficiency bleeding (VKDB) in neonates and infants.

Konakion MM Paediatric can be used, following specialist advice from a haematologist, as an antidote to anticoagulant drugs of the coumarin type in infants and children. For use as an antidote to anticoagulant drugs of the coumarin type in adolescents and adults, refer to Konakion MM Ampoules 10mg/ml.

Prophylaxis of vitamin K deficiency bleeding (VKDB)

Healthy neonates of 36 weeks gestation and older:

Either:

- 1mg administered by intramuscular injection at birth or soon after birth

or

- 2mg orally at birth or soon after birth. The oral dose should be followed by a second dose of 2mg at 4-7 days.

Exclusively breast-fed babies who received oral Konakion at birth: In addition to the doses at birth and at 4-7 days, a further 2mg oral dose should be given 1 month after birth. Further monthly 2mg oral doses until formula feeding is introduced have been advised, but no safety or efficacy data exist for these additional doses.

Preterm neonates of less than 36 weeks gestation weighing 2.5kg or greater, and term neonates at special risk: 1mg IM or IV at birth or soon after birth, the size and frequency of further doses depending on coagulation status.

Preterm neonates of less than 36 weeks gestation weighing less than 2.5kg: 0.4mg/kg (equivalent to 0.04ml/kg) IM or IV at birth or soon after birth, see dosing table below. This parenteral dose should not be exceeded (see Special warnings and special precautions for use). The frequency of further doses should depend on coagulation status.

CAUTION: care is required when calculating and measuring the dose in relation to the baby's weight (10x errors are common).

Dosing information for preterm babies at birth for the prophylaxis of VKDB

Therapy of early and/or late vitamin K deficiency bleeding (VKDB)

Initially 1mg IV and further doses as required, depending on clinical picture and coagulation status. Konakion therapy may need to be accompanied by a more immediate effective treatment, such as transfusion of blood or blood clotting factors to compensate for severe blood loss and delayed response to vitamin K₁.

Antidote therapy to anticoagulant drugs of the coumarin type

There have been no dose ranging studies performed to recommend a specific dose of Konakion MM Paediatric used as an antidote to anticoagulant drugs of the coumarin type in infants and children. Suggested doses are detailed below. Konakion MM Paediatric must be administered by intravenous injection in these patients. It is advisable that a haematologist is consulted about appropriate investigation and treatment in any infant or child in whom Konakion MM Paediatric is being considered.

For patients on warfarin therapy, therapeutic intervention must consider the reason for the patient being on warfarin and whether or not anticoagulant therapy has to be continued (e.g. in a patient with mechanical heart valve or repeated thrombo-embolic complications) as vitamin K administration is likely to interfere with anticoagulation with warfarin for 2 - 3 weeks. For patients continuing to receive warfarin, the suggested dose for the partial reversal of anticoagulation is 30 micrograms/kg administered by IV injection. Konakion MM Paediatric is only suitable for the administration of doses of 30 micrograms/kg in children weighing over 13 kg.

The suggested dose of vitamin K for patients requiring a complete reversal of a warfarin overdose is 250300 micrograms/kg administered by IV injection. It should be noted that the earliest effect seen with vitamin K treatment is at 4 to 6 hours and therefore, in patients with severe haemorrhage, replacement with coagulation factor concentrates may be indicated (discuss with haematologist). Konakion MM Paediatric is only suitable for the administration of doses of 250300 micrograms/kg in children weighing over 1.6 kg. Prothrombin time should be measured 2 to 6 hours later and if the response has not been adequate, Konakion MM Paediatric administration may be repeated. Frequent monitoring of vitamin K dependent clotting factors is essential in these patients.

Method of administration

Konakion MM Paediatric can be administered by intramuscular or intravenous injection or by oral administration depending on the indication.

Parenteral use: For the administration of injection volumes of 0.04ml (0.4mg) to 0.1ml (1mg), 0.5ml syringes with 0.01ml gradations are recommended, see section 6.6 Instructions for use/handling.

Administration of Konakion MM Paediatric by i.v. infusion is not recommended because Konakion MM Paediatric must not be diluted or mixed with other parenteral medications. However, Konakion MM Paediatric may be administered by injecting the dose into the lower part of an infusion set containing 5% dextrose or 0.9% sodium chloride running at 0.7ml/minute, see section 6.2 Incompatibilities.

Oral use: For oral administration, oral dispensers are provided in the pack. After breaking the ampoule open, 0.2ml of solution should be withdrawn into the oral dispenser until it reaches the mark on the dispenser (0.2ml = 2mg vitamin K). Drop the contents of the dispenser directly into the baby's mouth by pressing the plunger.

Use in patients with a known hypersensitivity to any of the constituents.

At the time of use, the ampoule contents should be clear. Following incorrect storage, the contents may become turbid or present a phase-separation. In this case the ampoule must no longer be used.

Parenteral administration to premature babies weighing less than 2.5kg may increase the risk for the development of kernicterus (bilirubin encephalopathy).

Infants with cholestatic disease must receive Konakion MM Paediatric by intramuscular or intravenous injection since oral absorption is impaired in these patients.

Konakion MM Paediatric must be administered by intravenous injection when used as an antidote to anticoagulant drugs of the coumarin type, as intramuscular injections may result in significant bleeding in these patients.

No significant interactions are known other than antagonism of coumarin anticoagulants.

Not applicable.

Not applicable.

There have been reports of anaphylactoid reactions after intravenous injections of Konakion MM. Local irritation may occur at the injection site but is unlikely due to the small injection volume. Rarely, injection site reactions may occur which may be severe, including inflammation, atrophy and necrosis.

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, increase GOT and GGT, 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 non-serious and resolved without any treatment.

Treatment of suspected overdose should be aimed at alleviating symptoms.

Konakion MM is a preparation of synthetic phytomenadione (vitamin K₁). The presence of vitamin K₁ is essential for the formation within the body of prothrombin, factor VII, factor IX and factor X, and of the coagulation inhibitors, protein C and protein S.

Vitamin K₁ does not readily cross the placental barrier from mother to child and is poorly excreted in breast milk.

Lack of vitamin K₁ leads to an increased tendency to haemorrhagic disease in the newborn. Vitamin K₁ administration, which promotes synthesis of the above-mentioned coagulation factors by the liver, can reverse an abnormal coagulation status due to vitamin K₁ deficiency.

In the mixed micelle solution, vitamin K₁ is solubilised by means of a physiological colloidal system consisting of lecithin and a bile acid.

Following oral administration vitamin K₁ is absorbed from the small intestine. The systemic availability following oral dosing is approximately 50%, with a wide range of interindividual variability. Absorption is limited in the absence of bile.

After intramuscular administration vitamin K₁ release into the circulation is prolonged, i.e. the IM route acts as a depot. A single 1mg IM dose results in comparable vitamin K₁ concentrations at 1 month as two 2 mg doses (one given at birth and the other at one week).

Vitamin K₁ accumulates predominantly in the liver, is up to 90% bound to lipoproteins in the plasma and is stored in the body only for short periods of time.

Vitamin K₁ is transformed to more polar metabolites, such as phytomenadione-2,3-epoxide.

The half-life of vitamin K₁ in plasma is approximately 72 hours in neonates and about 1.5 to 3 hours in adults. Vitamin K₁ is excreted in bile and urine as the glucuronide and sulphate conjugates.

None applicable.

Glycocholic acid, lecithin, sodium hydroxide, hydrochloric acid and water.

Incompatibilities have been observed with diluted Konakion MM solution and certain siliconised syringes, therefore, Konakion MM Paediatric must not be diluted before injection.

Do not dilute with sodium chloride containing solutions as precipitation may occur, see section 4.2 Posology and Method of Administration.

3 years.

Konakion MM Paediatric ampoule solution should be stored below 25°C and be protected from light. The solution should not be frozen. Do not use if the solution is turbid.

Amber glass ampoules containing 2mg phytomenadione in 0.2ml. Plastic oral dispensers. Packs of 1, 5 or 10.

See section 4.2 Posology and method of administration, section 4.4 Special warnings and precautions for use and section 6.2 Incompatibilities for advice regarding the administration of Konakion MM Paediatric.

Undiluted Konakion MM Paediatric is compatible with 0.5ml syringes supplied by B.Braun.

Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom.

PL 00031/0346

11 March 2008

10 January 2011

POM

Konakion is a registered trade mark

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