1. Name Of The Medicinal Product
Konakion MM.
2. Qualitative And Quantitative Composition
Each Konakion MM Ampoule contains 10.0mg vitamin K1 (phytomenadione) Ph. Eur in 1ml.
3. Pharmaceutical Form
Amber glass ampoules containing 10mg phytomenadione in 1ml. 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.
4. Clinical Particulars
4.1 Therapeutic Indications
Konakion MM is indicated as an antidote to anticoagulant drugs of the coumarin type in the treatment of haemorrhage or threatened haemorrhage, associated with a low blood level of prothrombin or factor VII.
4.2 Posology And Method Of Administration
Adults: As an antidote to anticoagulant drugs
For potentially fatal and severe haemorrhages: Konakion MM therapy should be accompanied by a more immediate effective treatment such as transfusions of whole blood or blood clotting factors. The anticoagulant should be withdrawn and an intravenous injection of Konakion MM given slowly in a dose of 10 – 20mg. The prothrombin level should be estimated three hours later and, if the response has been inadequate, the dose should be repeated. Not more than 40mg of Konakion MM should be given intravenously in 24 hours. Coagulation profiles must be monitored on a daily basis until these have returned to acceptable levels; in severe cases more frequent monitoring is necessary and where there is no immediate efficacy, transfusion of whole blood or blood clotting factors should be used.
Less severe haemorrhage: Oral treatment with Konakion tablets may be used.
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.
Instructions for infusion in adults
Konakion MM Ampoules are for intravenous injection and should be diluted with 55ml of 5% glucose before slowly infusing the product. The solution should be freshly prepared and protected from light. Konakion MM Ampoule solution should not be diluted or mixed with other injectables, but may be injected into the lower part of an infusion apparatus.
Children aged 1 to 18 years
It is advisable that a haematologist is consulted about appropriate investigation and treatment in any child in whom Konakion MM is being considered.
Likely indications for using vitamin K in children are limited and may include:
1. Children with disorders that interfere with absorption of vitamin K (chronic diarrhoea, cystic fibrosis, biliary atresia, hepatitis, coeliac disease).
2. Children with poor nutrition who are receiving broad spectrum antibiotics.
3. Liver disease.
4. Patients receiving anticoagulant therapy with warfarin in whom the INR is increased outside the therapeutic range and therefore are at risk of, or are bleeding, and those with an INR in the therapeutic range who are bleeding.
For patients on warfarin therapy, therapeutic intervention must take into consideration the reason for the child being on warfarin and whether or not anticoagulant therapy has to be continued (e.g. in a child with mechanical heart valve or repeated thromboembolic complications) as vitamin K administration is likely to interfere with anticoagulation with warfarin for 2 – 3 weeks.
It should be noted that the earliest effect seen with vitamin K treatment is at 4 – 6 hours and therefore in patients with severe haemorrhage replacement with coagulation factors may be indicated (discuss with haematologist).
Dose of vitamin K
There are few data available regarding use of Konakion MM in children over 1 year. There have been no dose ranging studies in children with haemorrhage. Suggested dosages based on clinical experience are as follows:
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Prothrombin levels should be measured 2 to 6 hours later and if the response has not been adequate, the dose may be repeated. Frequent monitoring of vitamin K dependent clotting factors is essential in these patients.
Children on warfarin therapy who need to remain anticoagulated are not included in the above dosage recommendations.
Neonates and babies
Konakion MM Paediatric should be used in these patients. (See separate prescribing information.)
4.3 Contraindications
Use in patients with a known hypersensitivity to any of the constituents.
4.4 Special Warnings And Precautions For Use
When treating patients with severely impaired liver function, it should be borne in mind that one Konakion MM Ampoule 10mg/1ml contains 54.6mg glycocholic acid and this may have a bilirubin displacing effect.
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.
In potentially fatal and severe haemorrhage due to overdosage of coumarin anticoagulants, intravenous injections of Konakion MM must be administered slowly and not more than 40mg should be given during a period of 24 hours. Konakion MM therapy should be accompanied by a more immediate effective treatment such as transfusion of whole blood or blood clotting factors. When patients with prosthetic heart valves are given transfusions for the treatment of severe or potentially fatal haemorrhages, fresh frozen plasma should be used.
Large doses of Konakion MM (more than 40mg per day) should be avoided if it is intended to continue with anticoagulant therapy because there is no experience with doses above this maximum of 40mg per day and higher doses may give rise to unexpected adverse events. Clinical studies have shown a sufficient decrease in the prothrombin time with the recommended dosage. If haemorrhage is severe, a transfusion of fresh whole blood may be necessary whilst awaiting the effect of the vitamin K1.
Vitamin K1 is not an antidote to heparin.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
No significant interactions are known other than antagonism of coumarin anticoagulants.
4.6 Pregnancy And Lactation
There is no specific evidence regarding the safety of Konakion MM in pregnancy but, as with most drugs, the administration during pregnancy should only occur if the benefits outweigh the risks.
4.7 Effects On Ability To Drive And Use Machines
None.
4.8 Undesirable Effects
There are only few unconfirmed reports of the occurrence of possible anaphylactoid reactions after intravenous injection of Konakion MM. Very rarely, venous irritation or phlebitis has been reported in association with intravenous administration of Konakion mixed micelle solution. Injection site reactions have been reported after intramuscular injection of Konakion.
4.9 Overdose
Hypervitaminosis of vitamin K1 is unknown.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Konakion MM is a synthetic preparation of vitamin K. The presence of vitamin K (i.e. vitamin K or substances with vitamin K activity) is essential for the formation within the body of prothrombin, factor VII, factor IX and factor X. Lack of vitamin K leads to an increased tendency to haemorrhage. When an antidote to an anticoagulant is necessary it is essential to use vitamin K1 itself, as vitamin K analogues are much less effective.
In the mixed micelles solution, vitamin K1 is solubilised by means of a physiological colloidal system, also found in the human body, consisting of lecithin and bile acid. Owing to the absence of organic solvents, the Konakion mixed micelles solution is well tolerated on intravenous administration.
5.2 Pharmacokinetic Properties
In blood plasma, 90% of vitamin K1 is bound to lipoproteins. Following an intramuscular dose of 10mg vitamin K, plasma concentrations of 10 – 20mcg/l are produced (normal range 0.4 – 1.2mcg/l). Systemic availability following intramuscular administration is about 50% and elimination half-life in plasma is approximately 1.5 – 3 hours.
5.3 Preclinical Safety Data
None applicable.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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6.2 Incompatibilities
None.
6.3 Shelf Life
The recommended shelf-life of Konakion MM Ampoules is 36 months.
6.4 Special Precautions For Storage
The recommended maximum storage temperature is 25°C. Do not use if the solution is turbid.
6.5 Nature And Contents Of Container
Konakion MM is supplied in amber glass ampoules containing 10mg phytomenadione in 1ml. 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.
6.6 Special Precautions For Disposal And Other Handling
See section 4.2.
7. Marketing Authorisation Holder
Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom.
8. Marketing Authorisation Number(S)
PL 0031/0254
9. Date Of First Authorisation/Renewal Of The Authorisation
April 2008
10. Date Of Revision Of The Text
April 2008
LEGAL STATUS
POM
Konakion is a registered trade mark
Item Code
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