Phytomenadione (Vitamin K1)

Source: UK SPC (eMC) for Phytomenadione 10 mg/1 ml solution for injection (Konakion MM), §4.2 (https://www.medicines.org.uk/emc/product/11708/smpc). Coagulation profiles must be monitored daily until they have returned to acceptable levels; in severe cases more frequent monitoring is necessary. SPC DOSE TABLE — WARFARIN, MAJOR AND LIFE-THREATENING BLEEDING: major bleeding, 5.0 mg IV vitamin K1 with PCC; life-threatening bleeding, 5.0 to 10.0 mg IV vitamin K1 with PCC (FFP if PCC is not available). LESS SEVERE HAEMORRHAGE / ASYMPTOMATIC HIGH INR (therapeutic guidance only — treatment depends on the underlying indication for anticoagulation, INR value, time spent outside the therapeutic range, patient characteristics such as age, comorbidity and concomitant medication, and the associated risk of major bleeding): on warfarin, INR 5-9 give 0.5 to 1.0 mg IV; INR > 9 give 1.0 mg IV. For small doses, one or more ampoules of the Konakion MM Paediatric / Phytomenadione 2 mg/0.2 mL solution for injection (same solution) can be used. REVERSAL BEFORE SURGERY: patients requiring emergency surgery that can be delayed for 6-12 hours can be given 5 mg intravenous vitamin K1 to reverse the anticoagulant effect; if surgery cannot be delayed, PCC can be given in addition to intravenous vitamin K1 and the INR checked before surgery. ANTICOAGULANTS OTHER THAN WARFARIN: the above recommendations apply to warfarin; there are limited data on reversing acenocoumarol or phenprocoumon, whose half-lives differ from warfarin, and different vitamin K1 doses may be required. Vitamin K1 is NOT an antidote to heparin. ELDERLY: elderly patients tend to be more sensitive to reversal of anticoagulation, so dose at the lower end of the recommended ranges. SEVERE HEPATIC IMPAIRMENT: one 1 mL ampoule contains 54.6 mg glycocholic acid which may have a bilirubin-displacing effect — monitor the INR carefully after administration. MECHANICAL HEART VALVES: the use of vitamin K1 in patients with mechanical heart valves is generally to be avoided unless there is major bleeding; when such patients are transfused for severe or potentially fatal haemorrhage, fresh frozen plasma should be used. If haemorrhage is severe, a transfusion of fresh whole blood may be necessary while awaiting the effect of vitamin K1. The ampoule contents should be clear at the time of use — if turbid or showing phase separation after incorrect storage, the ampoule must not be used. NEONATES AND BABIES: this 10 mg/1 mL presentation is not for them — Konakion MM Paediatric / Phytomenadione 2 mg/0.2 mL solution for injection should be used, see its separate prescribing information. CHILDREN 1 TO 18 YEARS: see the structured paedDose field for the one per-kg figure given; note the SPC advises that a haematologist is consulted about appropriate investigation and treatment in any child being considered for this medicine, that there are few data in children over 1 year and no dose-ranging studies in children with haemorrhage, so the optimal dose should be decided by the treating physician according to indication, clinical situation and patient weight. For children with MAJOR AND LIFE-THREATENING BLEEDING a dose of 5 mg vitamin K1 IV is suggested (with PCC if appropriate, or FFP if PCC is unavailable) — that is a fixed dose, not per-kg. Likely paediatric indications are limited and may include disorders interfering with vitamin K absorption (chronic diarrhoea, cystic fibrosis, biliary atresia, hepatitis, coeliac disease); poor nutrition with broad-spectrum antibiotics; liver disease; and warfarin-treated patients with a raised INR who are at risk of or are bleeding, or who bleed with an INR in range. For children on warfarin, intervention must take account of why the child is anticoagulated and whether anticoagulation must continue (e.g. mechanical heart valve, repeated thromboembolic complications), as vitamin K administration is likely to interfere with warfarin anticoagulation for 2-3 weeks. The earliest effect of vitamin K treatment is at 4-6 hours, so in severe haemorrhage replacement with coagulation factors may be indicated (discuss with a haematologist). Verify all paediatric dosing against a children's formulary.

Children aged 1 to 18 years with ASYMPTOMATIC HIGH INR with or without mild haemorrhage only: intravenous vitamin K1 at doses of 30 micrograms/kg have been reported to be effective in reversing asymptomatic high (> 8) INR in clinically well children. Frequent monitoring of vitamin K dependent clotting factors is essential in these patients. This is NOT the regimen for paediatric major or life-threatening bleeding, for which the SPC suggests a fixed dose of 5 mg vitamin K1 IV (with PCC if appropriate, or FFP if PCC is unavailable). The SPC states there are few data in children over 1 year and no dose-ranging studies in children with haemorrhage; the optimal dose should be decided by the treating physician according to indication, clinical situation and weight, and a haematologist should be consulted. Neonates and babies must receive the separate Konakion MM Paediatric / Phytomenadione 2 mg/0.2 mL presentation instead. Verify against a children's formulary before use. Source: UK SPC (eMC), Phytomenadione 10 mg/1 ml solution for injection, §4.2.