Vitamin K1 (phytonadione (vit K1))

Dose, frequency of administration, and duration of treatment with phytonadione depend on the severity of the prothrombin deficiency and the response of the patient; the lowest effective dose of phytonadione should be used.

Phytonadione may be administered orally or parenterally (IV, IM, or subcutaneously). The parenteral preparation also has been administered orally+ in neonates. The route of administration of phytonadione depends on the severity of the prothrombin deficiency and the risks associated with administration by each route. The manufacturers state that because of the possibility of severe adverse reactions (see Cautions: Adverse Effects), IV or IM administration is indicated only when other routes of administration are not feasible and the serious risk is justified. However, the effects of phytonadione have been reported to be delayed and/or unpredictable following subcutaneous injection, and subcutaneous administration may be less effective for reversal of excessive anticoagulation than IV or oral administration. The American College of Chest Physicians (ACCP) and other clinicians recommend IV administration of phytonadione in emergency situations for major bleeding due to vitamin K-antagonist anticoagulants because of its more rapid onset; these clinicians recommend that subcutaneous administration be avoided.

Oral administration of phytonadione usually reduces international normalized ratio (INR) levels in 24-48 hours and generally is recommended over parenteral administration in selected asymptomatic (nonbleeding) patients with hypoprothrombinemia due to vitamin K-antagonist anticoagulants. In patients with decreased bile secretion, bile salts (e.g., ox bile extract 300 mg or dehydrocholic acid 500 mg) should be given with each oral dose of phytonadione to ensure absorption. Parenteral administration is indicated in patients who are unable to retain or absorb the drug from the GI tract.

When phytonadione injection is administered IV, it should be injected at a rate not exceeding 1 mg/minute. The drug may be diluted for infusion with 0.9% sodium chloride, 5% dextrose, or 5% dextrose in 0.9% sodium chloride injection; other diluents that may contain benzyl alcohol should not be used. (See Cautions: Pediatric Precautions.) The drug should be administered immediately after dilution, and any unused portion of the dilution and the unused contents of the ampul or vial should be discarded. The infusion container must be protected from light at all times. (See Chemistry and Stability: Stability.)

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Because vitamin K1 is a pharmacologic antagonist to coumarin and indandione derivatives, patients being treated with these anticoagulants should not receive phytonadione except for the treatment of excessive hypoprothrombinemia. Phytonadione does not antagonize the anticoagulant effects of heparin, low molecular weight heparins, fondaparinux, or direct-acting oral anticoagulants.

Orlistat may result in decreased GI absorption of fat-soluble vitamins such as phytonadione (vitamin K1). At least 2 hours should elapse between (before or after) any orlistat dose and phytonadione administration; administering fat-soluble vitamins at bedtime may be a convenient time. Although the manufacturer of orlistat recommends that a vitamin supplement containing fat-soluble vitamins (A, D, E, and K) be used during orlistat therapy, such vitamin concentrations in clinical studies with the drug remained within the normal range for most patients despite decreases, and vitamin supplementation was only occasionally needed.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Vitamin K/Selected Anticoagulants (Vitamin K Antagonists)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Anticoagulants interfere with the activation of vitamin K-dependent clotting factors. Vitamin K administration may reverse this effect.

CLINICAL EFFECTS: The pharmacological effect of anticoagulants may be reversed resulting in thrombus formation.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving anticoagulants should avoid eating unusual increases in foods high in vitamin K content. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Numerous reports have demonstrated that vitamin K interferes with the hypoprothrombinemic effects of anticoagulants. However, reports of clinically important consequences are uncommon. A clearer understanding of the mechanism by which these drugs act has made it possible to use vitamin K to control bleeding side effects of warfarin therapy. One should be aware of the vitamin K content of enteral feeding products being administered to patients on anticoagulant therapy. Prothrombin time should be monitored when these products are given.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Fat Soluble Vitamins/Colesevelam

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

CLINICAL EFFECTS: Colesevelam may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by colesevelam should be borne in mind during implementation of a vitamin supplementation strategy. Oral multivitamin supplements should be taken at least four hours before the dose of colesevelam.(1)

DISCUSSION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

Fat Soluble Vitamins/Orlistat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The acetate ester forms of vitamin A and vitamin E must undergo hydrolysis for absorption from the gastrointestinal tract.(1) The enzyme responsible for this hydrolysis is inhibited by orlistat.(2)

CLINICAL EFFECTS: Orlistat may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by orlistat should be borne in mind during implementation of a vitamin supplementation strategy. Patients should be strongly encouraged to take a multivitamin supplement which contains fat soluble vitamins, particularly Vitamin D as it appears most susceptible to this interaction.(4,5) Multivitamin supplements should be taken at least two hours before or after the dose of orlistat, or at bedtime.(4) Patients with chronic malabsorption syndromes should not receive orlistat.(4)

DISCUSSION: Adult patients taking orlistat without supplementation showed a greater reduction in vitamin A,D,E and beta-carotene levels compared to placebo during two or more consecutive visits in studies of 1-2 years duration; these patients had normal baseline values prior to orlistat therapy. Low vitamin values in orlistat patients were as follows: low Vitamin D 12%, low beta-carotene 6.1%, low Vitamin E 5.8%, low Vitamin A 2.2%.(4) A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption and a 60% decreased in vitamin E acetate absorption with concomitant orlistat.(4) In a study, orlistat produced the vitamin net concentration by approximately 43%.(1) In a study, no statistically significant decrease in vitamin A absorption was observed with concurrent orlistat.(2) In a study, mean vitamin D levels were significantly reduced compared with baseline after one month of orlistat therapy despite multivitamin supplementation.(5)

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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No enhanced messaging available.

Reproduction studies have not been conducted in animals, and it is not known if phytonadione has teratogenic effects.

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No enhanced messaging available.