Konakion MM

Active ingredient: Phytomenadione (synthetic vitamin K₁).
Ampoules MM 10 mg/mL in a bile acid/lecithin mixed-micelle (MM) solution. One amber glass ampoule contains 1 ml of the clear mixed-micelle solution of 10 mg vitamin K₁ (filling volume 1.15 mL) for oral or parenteral administration.
Excipients/Inactive Ingredients: Ampoules: Glycocholic acid, sodium hydroxide, lecithin, hydrochloric acid, water for injections.

Pharmacology: Properties and effects: Vitamin K₁ (phytomenadione), the active ingredient of Phytomenadione (Konakion), is a procoagulant factor. As a component of a hepatic carboxylase system, vitamin K₁ is involved in the post-translational carboxylation of clotting factors II (prothrombin), VII, IX and X and the clotting inhibitors protein C and protein S. Coumarins inhibit the reduction of vitamin K₁ (quinone form) to vitamin K₁ hydroquinone and also prevent the vitamin K₁ epoxide arising after carboxylation from being reduced to the quinone form.
Vitamin K₁ is an antagonist of coumarin-type anticoagulants, e.g. phenprocoumon (active ingredient of Marcoumar). It does not, however, neutralize the activity of heparin (active ingredient of Liquemin); protamine is the antagonist of heparin. Vitamin K₁ is ineffective in hereditary hypoprothrombinemia or hypoprothrombinemia induced by severe hepatic failure. In the MM ampoules, vitamin K₁ is solubilized by means of a physiological colloid system of bile acid-lecithin micelles, a transport medium also found in the body.
Pharmacokinetics: Absorption: A pharmacokinetic study indicated that the MM solution of vitamin K₁ given orally is rapidly and effectively absorbed.
Oral doses of vitamin K₁ are absorbed primarily from the middle portions of the small intestine. Systemic availability following oral dosing is approximately 50%, with a wide range of interindividual variability. Onset of action occurs approximately 1-3 hours after intravenous administration and 4-6 hours after oral doses.
Distribution: The primary distribution compartment corresponds to the plasma volume. In blood plasma 90% of vitamin K₁ is bound to lipoproteins (VLDL fraction). Normal plasma concentrations of vitamin K₁ range from 0.4 to 1.2 ng/mL. After i.v. administration of 10 mg vitamin K₁ Phytomenadione (Konakion) MM, the plasma level after 1 hour is about 500 ng/mL and about 50 ng/mL at 12 hours. Vitamin K₁ does not readily cross the placenta and is poorly distributed into breast milk.
Metabolism: Vitamin K₁ is rapidly converted into more polar metabolites, including vitamin K₁-2,3-epoxide. Some of this metabolite is reconverted into vitamin K₁.
Elimination: Following metabolic degradation, vitamin K₁ is excreted in the bile and urine as glucuronide and sulfate conjugates. The terminal half-life in adults is 14 ± 6 h after i.v. administration and 10 ± 6 h after oral administration. Less than 10% of a dose is excreted unchanged in the urine.
Pharmacokinetics in special clinical situations: Intestinal absorption of vitamin K₁ is impaired by various conditions, including malabsorption syndromes, short bowel syndrome, biliary atresia and pancreatic insufficiency. The dosage for this patient group should therefore be at the lower end of the recommended range (see section Dosage & Administration).

Hemorrhage or risk of hemorrhage as a result of severe 'hypoprothrombinemia' (i.e. deficiency of clotting factors II, VII, IX and X) of various etiologies, including overdosage of coumarin-type anticoagulants, their combination with phenylbutazone and other forms of hypovitaminoses K (e.g. in obstructive jaundice as well as liver and intestinal disorders, and after prolonged treatment with antibiotics, sulfonamides or salicylates).
For prophylaxis and treatment of hemorrhagic disease in the newborn, Phytomenadione (Konakion) MM pediatric ampoules (2 mg/0.2 mL) should be used.

Phytomenadione (Konakion) MM ampoules are for i.v. injection or oral use. The ampoule solution should not be mixed with other parenteral medications, but may be injected, where appropriate, into the lower part of the infusion set.
Because of the lower doses required, Phytomenadione (Konakion) MM pediatric should be used in neonates and infants under one year of age.
Standard dosage: Severe or life-threatening hemorrhage, e.g. during anticoagulant therapy: The coumarin anticoagulant should be withdrawn and an i.v. injection of Phytomenadione (Konakion) MM given slowly (in at least 30 seconds) in a dose of 5-10 mg together with fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC). The dose of Vitamin K₁ can be repeated as needed.
Dose recommendations for vitamin K₁ therapy in patients with asymptomatic high International Normalized Ratio (INR) with or without mild hemorrhage: (see Table 1).

Click on icon to see table/diagram/image

For small doses one or more ampoules of Phytomenadione (Konakion) MM pediatric (2 mg/0.2 mL; same solution) can be used.
Dose recommendations for vitamin K₁ therapy in patients with major and life-threatening bleeding: (see Table 2).

Click on icon to see table/diagram/image

Special dosage instructions: Use in the elderly: Elderly patients tend to be more sensitive to reversal of anticoagulation with Phytomenadione (Konakion). The dosage for this patient group should therefore be at the lower end of the ranges recommended. Small doses of 0.5 to 1.0 mg i.v. or oral Vitamin K₁ have shown to effectively reduce the INR to <5.0 within 24 hours (see section Pharmacology: Pharmacokinetics under Actions).
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 one tenth of the full i.v. adult dose of vitamin K₁ has been reported to be effective in reversing asymptomatic high (>8) INR in clinically well children.
Infants under one year of age: For this patient group, Phytomenadione (Konakion) MM pediatric should be used.
Oral use: Either with a Phytomenadione (Konakion) MM dispenser or a syringe.
Syringe: Phytomenadione (Konakion) MM solution can be given orally with a syringe as follows: withdraw required amount from ampoule using a syringe with attached needle. Remove needle from syringe and administer contents of syringe directly into patient's mouth. Wash down with fluid.

There is no known clinical syndrome attributable to hypervitaminosis of vitamin K₁. Reintroduction of anti-coagulation may be affected.

Phytomenadione (Konakion) is contraindicated in patients with known hypersensitivity to any of its constituents. Phytomenadione (Konakion) MM ampoules 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 hematoma formation.

At the time of use, the mixed-micelle ampoule solution must be clear. Following incorrect storage, the solution may become turbid or a phase separation may occur. In such cases, the ampoule must not be used.
Careful monitoring of the INR is necessary after administration of Phytomenadione (Konakion) MM in patients with severely impaired liver function.

Pregnancy, nursing mothers: No controlled studies of Phytomenadione (Konakion) have been performed in animals or pregnant women. On the basis of many years' clinical experience, however, it is safe to assume that neither vitamin K₁ nor the excipients contained in the Phytomenadione (Konakion) formulations have any reproductive toxicological effects when the drug is given at the recommended dosages. As with all medications, however, Phytomenadione (Konakion) should be given to pregnant women only if the benefit to the mother outweighs the risk to the fetus.
As vitamin K₁ does not readily cross the placental barrier, it is not recommended that Phytomenadione (Konakion) be given to expectant mothers as prophylaxis of hemorrhagic disease in the newborn.
Only a small fraction of administered vitamin K₁ enters the breast milk. At therapeutic doses, administration of Phytomenadione (Konakion) to nursing mothers accordingly does not pose a risk to their infants.
However, Phytomenadione (Konakion) is not recommended for nursing mothers as prophylaxis of hemorrhagic disease in the newborn.

Adverse events are listed as follows 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 intravenous administration of Phytomenadione (Konakion) MM.
General disorders and administration site conditions: Very rare: Venous irritation or phlebitis in association with intravenous administration of Phytomenadione (Konakion) MM.

Vitamin K₁ antagonizes the effect of coumarin-type anticoagulants. Coadministration of anticonvulsants can impair the action of vitamin K₁.

Phytomenadione (Konakion) MM ampoule solution should not be stored above 25°C. Keep the glass ampoule(s) in the outer carton in order to protect from light.
For stability reasons, the unused contents of open ampoules cannot be used and should be discarded.

Haemostatics

B02BA01 - phytomenadione ; Belongs to the class of vitamin K. Used in the treatment of hemorrhage.

Rx