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Vitamin K injection (package insert)

From MIMS 1 November 1999 - 31 January 2000

Konakion Paediatric Injection

MIMS Abbreviated Prescribing Information
Phytomenadione
Roche
Section: 2(l) Haemostatic agents - Cardiovascular System
Permitted in sport

Use: Prophylaxis and treatment of haemorrhage in neonates
Contraindications: Pronounced allergic diathesis
Precautions: Pregnancy
Adverse Reactions: Inj site pain

Konakion Paediatric Injection (Injection)
Phytomenadione
Pack 1 mg/0.5 mL 0.5 mL [10]
Dose Neonates. Haemorrhage, prophylaxis: 1 mg IMI immediately postpartum; therapy: 1 mg/kg IMI for 1-3 days; max 5 mg in the first few days of life
Refer: MIMS Annual 1999 p. 2-210

MIMS Full Prescribing Information
MIMS revision date: 05/01/1999
 Composition Active. Phytomenadione (vitamin K1).
Inactive. PEG-35 castor oil (solvent).
 Description Chemical name: 2-methyl-3- phytyl-1,4- naphthaquinone. It is a clear, yellow, very viscous, odourless or nearly odourless oil. MW: 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.

 Actions Pharmacology. Site and mode 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. 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.

Pharmacokinetics. 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. Systemic availability after oral or intramuscular administration is about 50%.
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 microgram/L. An intramuscular dose of vitamin K1 10 mg produces plasma concentrations of 10 to 20 microgram/L.
The elimination half-life in plasma is 1.5 to 3 hours. After metabolic degradation, vitamin K1 is bound to glucuronic acid and excreted in the bile and urine.
Less than 10% of the drug is excreted unchanged in the urine. Vitamin K1 has an active metabolite, vitamin K1-2,3-epoxide, which is reconverted into vitamin K1.
Impaired absorption may occur in conditions such as malabsorption syndromes, short bowel syndrome, biliary atresia and pancreatic insufficiency.

 Indications Haemorrhage in the newborn infant: prophylaxis and therapy.

 Contraindications Pronounced allergic diathesis.
The dosage of Konakion parenteral in neonates should not exceed 5 mg in the first few days of life because of the immaturity of the hepatic enzyme systems. Only 1 mg ampoules may be used in these patients.

 Precautions Konakion 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.

Use in pregnancy. There is no specific evidence regarding the safety of Konakionin pregnancy and no reproductive studies have been performed in animals. Therefore, as with most drugs, administration during pregnancy should only occur if the benefits outweigh the risks.

 Adverse Reactions Intravenous injection of Konakion may, in rare cases, cause severe, anaphylactoid reactions. Should an anaphylactoid reaction occur, the usual measures must be taken (e.g. administration of adrenaline and supportive measures as required).
Intramuscular administration may cause local pain, sometimes with erythema at the injection site. There may also be tenderness.

 Overdosage Hypervitaminosis of vitamin K1 has not been reported.
 Dosage and Administration For intramuscular administration.
Paediatric use. Haemorrhage or threatened haemorrhage in the newborn infant. Prophylaxis. 1 mg intramuscularly to the child immediately postpartum.
Therapy. 1mg/kg bodyweight intramuscularly for one to three days (on the second or third days, Konakion may be given orally in the milk). The dosage in neonates should not exceed 5 mg in the first few days of life because of the immaturity of the hepatic enzyme systems. Only 1 mg ampoules may be used in these patients.
Impaired hepatic and renal function. In severe hepatic disease, Konakion should be discontinued if no significant effect is noted within one to two days after the initial dose.
Incompatibilities. Do not mix with infusion solutions.
 Presentation Ampoules, 1 mg/0.5 mL: 10's.
 Storage Store below 30 deg. C. Protect from light. Shelf life: 3 years.
 Poison Schedule Unscheduled.
 Date of TGA approval or last amendment 19/01/1993