Details About Overdose or Poisoning Generic Salt :: Vitamin K1, Phytonadione
Vitamin K1 (Phytonadione)
Drug Pharmacology ::
I. Pharmacology. Vitamin K1 is an essential cofactor in the hepatic synthesis of coagulation factors II, VII, IX, and X. In adequate doses, vitamin K1 reverses the inhibitory effects of coumarin and indanedione derivatives on the synthesis of these factors. Note: Vitamin K3 (menadione) is not effective in reversing excessive anticoagulation caused by these agents. After parenteral vitamin K1administration, there is a 6- to 8-hour delay before vitaminK–dependent coagulation factors begin to achieve significant levels,and peak effects are not seen until 1–2 days after the initiation oftherapy. The duration of effect is 5–10 days. The response to vitamin K1is variable, and the optimal dosage regimen is unknown; it isinfluenced by the potency and amount of the ingested anticoagulant,vitamin K pharmacokinetics, and the patient’s hepatic biosyntheticcapability. Fresh frozen plasma or whole blood is indicated forimmediate control of serious hemorrhage.
Drug Indications ::
Indications
Excessive anticoagulation caused by coumarin and indanedione derivatives, as evidenced by elevated prothrombin time. Vitamin K1 is notindicated for empiric treatment of anticoagulant ingestion, as mostcases do not require treatment, and its use will delay the onset of anelevated prothrombin time as a marker of a toxic ingestion.
Vitamin K deficiency (eg, malnutrition, malabsorption, or hemorrhagic disease of the newborn) with coagulopathy.
Hypoprothrombinemia resulting from salicylate intoxication.
Drug Contra-Indications ::
III. Contraindications. Do not use in patients with known hypersensitivity to vitamin K or preservatives.
Drug Adverse Effects ::
IV. Adverse effects
Black box warning:Anaphylactoid reactions have been reported after intravenousadministration and have been associated with fatalities. Intravenoususe should be restricted to true emergencies; the patient must bemonitored closely in an intensive care setting.
Intramuscularadministration in anticoagulated patients may cause large, painfulhematomas. This can be avoided by using the oral or subcutaneous route.
Patientsreceiving anticoagulants for medical reasons (eg, deep vein thrombosisor prosthetic heart valves) may experience untoward effects fromcomplete reversal of their anticoagulation status. Preferably, suchpatients should receive small quantities of fresh frozen plasma orextremely small titrated doses (0.5–1 mg) of vitamin K until theprothrombin time is in the desired therapeutic range (eg, 1.5–2 timesnormal). Adjunctive anticoagulation with heparin may be required untilthe desired prothrombin time is achieved.
Use in pregnancy. FDA category C (indeterminate). Vitamin K1crosses the placenta readily. However, this does not preclude itsacute, short-term use in a seriously symptomatic patient (see TableIII–1).
Drug Lab Interactions ::
Drug or laboratory interactions. Empiricuse after an acute anticoagulant overdose will delay (for up to severaldays) the onset of elevation of prothrombin time, and this may give afalse impression of insignificant ingestion in a case of serious”superwarfarin” overdose (see Warfarin and Related Rodenticides).
Drug Dose Management ::
Dosage and method of administration
Oral. The usual dose of vitamin K1 (not menadione or vitamin K3)is 10–50 mg two to four times a day in adults and 5–10 mg (or 0.4mg/kg/dose) two to four times a day in children. Recheck theprothrombin time after 48 hours and increase the dose as needed. Note:Very high daily doses (7 mg/kg per day or more) have been required inadults with brodifacoum poisoning; in addition, treatment for severalweeks or months may be needed because of the long duration of effect ofthe “superwarfarin.” Because the only available oral vitamin K1formulation is 5 mg, high-dose treatment may require patients to ingestup to 100 pills per day, and long-term compliance with the regimen isoften problematic.
Parenteral injection isan alternative route of administration but is not likely to result inmore rapid reversal of anticoagulant effects and is associated withpotentially serious side effects. If hemorrhage is present, use freshfrozen plasma for rapid replacement of coagulation factors.Subcutaneous administration is preferred over IM injection, althoughboth can cause hematomas. The maximum volume is 5 mL or 50 mg per doseper injection site. The adult dose is 10–25 mg, and that for childrenis 1–5 mg; this may be repeated in 6–8 hours. Switch to oral therapy assoon as possible. Intravenous administration is used only rarelybecause of the risk of an anaphylactoid reaction. The usual dose is10–25 mg (0.6 mg/kg in children under 12 years), depending on theseverity of anticoagulation, diluted in preservative-free dextrose orsodium chloride solution. Give slowly at a rate not to exceed 1 mg/minor 5% of the total dose per minute, whichever is slower.
Drug Chemical Formulations ::
Formulations. Note: Do not use menadione (vitamin K3).
Parenteral. Phytonadione(AquaMEPHYTON and others), 2 mg/mL in 0.5-mL ampules and prefilledsyringes, and 10 mg/mL in 1-mL ampules (ampules contain fatty acidderivative and benzyl alcohol).
Oral. Phytonadione (Mephyton), 5-mg tablets.
The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 100 mg (20 tablets and ten 1-mL (10 mg) ampules or the equivalent).