Konakion MM Paediatric Ampoules 2 mg/0.2 ml oral solution or solution for injection

Each ampoule contains 2 mg phytomenadione in 0.2 ml.

For a full list of excipients see section 6.1.

Oral solution or solution for injection.

A clear to slightly opalescent pale yellow solution.

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

Konakion MM Paediatric is further indicated for the treatment of overdoses with anticoagulants of the coumarin type in adults and older children (1 to 18 years) where small quantities of vitamin K are required. This may also include the treatment of haemorrhage or threatened haemorrhage, associated with a low blood level of prothrombin or factor VII.

Prevention and treatment of vitamin K deficiency bleeding (VKDB) in neonates and infants

Prophylaxis of vitamin K deficiency bleeding

Healthy neonates of 36 weeks gestation and older:

Either:

- 1 mg administered by intramuscular injection at birth or soon after birth, preferably within 2 hours of birth;

or

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

Preterm neonates of less than 36 weeks gestation weighing 2.5kg or greater, and term neonates at special risk (e.g. babies with birth asphyxia, obstructive jaundice, inability to swallow, bleeding problems, maternal use of anticoagulants or antiepileptics or maternal liver disease): 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. This parenteral dose should not be exceeded (see Section 4.4). The frequency of further doses should depend on coagulation status.

Exclusively breast-fed babies who received Konakion orally 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.

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

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 whole blood or blood clotting factors to compensate for severe blood loss and delayed response to vitamin K₁.

Treatment of coumarin anticoagulant overdose in adults and older children (1 to 18 years)

The dose selection for a specific patient should be based not only on the International Normalized Ratio (INR) value, but various other risk factors and clinical determinants such as patient characteristics, comorbid conditions and concomitant medications should also be appropriately considered. Hence the actual dose selection should be at the discretion of the treating physician.

The dosage recommendations detailed in the table below are provided for therapeutic guidance only.

Adults:

Dose recommendations for vitamin K₁ therapy in patients with asymptomatic high INR with or without mild haemorrhage:

For doses larger than 2mg, Konakion MM Ampoules 10mg/ml can be used.

Special dosage instructions

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 ranges recommended.

Elderly patients with asymptomatic high INR with or without mild haemorrhage

For an INR of 5.0 – 9.0, small doses of 0.5 to 1.0 mg i.v. or oral Vitamin K₁ have been shown to effectively reduce the INR to <5.0 within 24 hours.

Children

There are few data regarding the use of Konakion MM in children over 1 year. There have been no dose ranging studies in children with haemorrhage. The optimal dose should therefore be decided by the treating physician according to the indication, clinical situation and weight of the patient. However based on clinical experience, the following recommendation is suggested:

Children with asymptomatic high INR with or without mild haemorrhage

IV vitamin K₁ in doses of 30 μg/kg have been reported to be effective in reversing asymptomatic high (>8) INR in clinically well children.

Method of administration

Konakion MM Paediatric can be administered by intravenous injection or by oral administration. Administration by intramuscular injection is only suitable for the VKDB indication in babies.

Parenteral use: A 1 ml syringe or smaller, preferably with 0.01 ml graduations, is recommended for the administration of injection volumes of 0.04 ml (0.4 mg) to 0.1 ml (1 mg), for example, 1 ml B-D Plastipak Syringes.

Konakion MM Paediatric should not be diluted or mixed with other parenteral medications, but may be injected into the lower part of an infusion set.

Oral use:

For oral administration of 1mg or 2mg, oral dispensers are provided in the pack. After breaking the ampoule open, 0.2 ml of solution should be withdrawn into the oral dispenser until it reaches the mark on the dispenser (0.2 ml = 2 mg vitamin K). Drop the contents of the dispenser directly into the mouth by pressing the plunger.

Konakion MM Paediatric solution can also be given orally using a syringe (e.g. 1 ml syringe). The ampoule solution should not be diluted. The required amount should be withdrawn from the ampoule using a syringe with attached needle. The needle should then be removed from the syringe, the contents of syringe directly administered into the patient's mouth and washed down with fluid.

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

In adults and older children (1 to 18 years), Konakion MM solution should not be administered intramuscularly because the i.m. route exhibits depot characteristics and continued release of vitamin K₁ would lead to difficulties with the re-institution of anticoagulation therapy. Furthermore, i.m. injections given to anticoagulated subjects cause a risk of haematoma formation.

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.

Care should be taken when selecting the dose of Konakion MM Paediatric to ensure that a sub-therapeutic INR is not produced as these can be associated with either thrombosis or subsequent resistance to re-initiation of anticoagulant therapy. Smaller doses of 1mg have been found to reduce the INR effectively with less risk of over-correction than larger doses.

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

There is no specific evidence regarding the safety of Konakion MM Paediatric in pregnancy but, as with most drugs, the administration during pregnancy should only occur if the benefits outweigh the risks.

None known

There are only a few unconfirmed reports on the occurrence of possible anaphylactoid reactions after IV injection 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, increased GOT and GGT, abdominal pain, constipation, soft stools, malaise, agitation and cutaneous eruption. The causality of these adverse events cannot be established. The majority were, however, 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 vitamin K deficiency bleeding. 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.

A single 1 mg IM dose results in comparable vitamin K₁ concentrations at 1 month as two 2 mg oral doses (one given at birth and the second 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

Sodium hydroxide

Lecithin

Hydrochloric acid

Water for injection

Konakion MM paediatric ampoule solution should not be diluted or mixed with other parenteral medications. See section 4.2.

3 years.

Once opened use immediately

Do not store above 25°C. Do not freeze. Store in the original package in order to protect from light

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

Not all pack sizes may be marketed.

Konakion MM Paediatric Ampoule should not be diluted.

See section 4.2 for further details.

Do not use if the solution is turbid.

For single use only

Roche Products Limited

6 Falcon Way

Shire Park

Welwyn Garden City

AL7 1TW

United Kingdom

PA 50/76/2

Date of first authorisation: 20 April 1995

Date of last renewal: 19 April 2010

February 2011

Konakion is a registered trade mark.