Intravenous or intramuscular vitamin K has been associated rarely with anaphylactoid reactions, including shock, heart attack, respiratory arrest, and death. Therefore, these routes of administration should be avoided if possible. If given intravenously, preparations should be dilute and administration should be slow under strict medical supervision.
Skin hypersensitivity reactions are rare and may occur in particular with injections of vitamin K1 (Phytonadione®, AquaMEPHYTON®). A raised, itchy plaque may arise at the injection site that may take 1-2 months to resolve and can cause a scar.
Side Effects and Warnings
An unusual taste in the mouth has been rarely reported with vitamin K injections. Liver damage has been reported rarely in infants and children with use of the vitamin K preparation Menadiol (not available in the United States). Conditions that interfere with absorption of ingested vitamin K may lead to deficiency, including short gut, cystic fibrosis, malabsorption (various causes), pancreas or gall bladder disease, persistent diarrhea, sprue, or ulcerative colitis.
Red, painful swelling at vitamin K injection sites has been reported. A raised, itchy plaque can arise at the injection site that may take 1-2 months to resolve and can cause a scar. Transient flushing has been reported.
Dizziness has rarely been reported with vitamin K injections.
Damage to red blood cells causing anemia (hemolysis) has been reported rarely in infants and children with the use of the vitamin K preparation Menadiol (not available in the United States). This type of vitamin K should be avoided in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency because vitamin K may cause hemolytic episodes. Vitamin K deficiency decreases blood factors needed for clotting and increases the risk of bleeding.
Although initial concerns were voiced about the possible cancer risk of universally administering vitamin K by injection to newborns, there is no scientific evidence to support this risk. This is generally considered not to be a concern in the medical community.
Pregnancy and Breastfeeding
The U.S. Food and Drug Administration (FDA) has categorized vitamin K as Pregnancy Category C. There is not sufficient scientific evidence in animals or humans to clearly conclude the effects on the fetus. Vitamin K given to mothers soon before birth is generally not recommended. Regular supplementation with vitamin K during pregnancy (beyond normal dietary intake) may increase the risk of jaundice in the newborn.
The American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K1 to all newborns to prevent vitamin K deficiency bleeding (VKDB), a potentially life-threatening condition. Excessive amounts of vitamin K supplementation in newborns may lead to serious complications, including hemolytic anemia, hemoglobinuria, kernicterus, brain damage, or death. Reactions may be particularly severe in premature infants.
Vitamin K ingested by mothers is generally considered to be safe during breastfeeding. There is very little vitamin K transmitted to infants through breast milk (as opposed to many infant formulas, which do include vitamin K). It is not known if the amount of vitamin K in breast milk is increased if mothers take vitamin K supplements, but the scientific evidence suggests that this likely would make little if any difference. If an infant formula is used that is not fortified with vitamin K, a physician should be consulted to find another way for the infant to receive vitamin K.
Foods rich in vitamin K include green, leafy vegetables such as spinach, broccoli, asparagus, watercress, cabbage, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Cooking does not remove significant amounts of vitamin K from these foods.
Adults (over 18 years old)
Vitamin K deficiency management should be under medical supervision. If the PT is only slightly elevated and poor dietary intake is thought to be the cause, increasing the ingestion of vitamin K-rich foods can be tried. In non-emergency situations, oral vitamin K1 (Phytonadione®, AquaMEPHYTON®, Mephyton®, Konakion®) can be given in a daily dose of 5-10 milligrams (single doses up to 25 milligrams are given in some cases). If there is a concern of bile salt deficiency or malabsorption in the ileum, a water-soluble oral form of vitamin K can be considered. If necessary, vitamin K1 can be injected at a dose of 10 milligrams, repeated after 8-12 hours, or administered daily until the deficiency is corrected.
Elevated PT/INR (warfarin reversal) or acute liver dysfunction management should be under medical supervision.
Children (under 18 years old)
Vitamin K1 given by injection has been shown in newborns and young infants to prevent "hemorrhagic disease of newborn," also known as vitamin K deficiency bleeding (VKDB). The American Academy of Pediatrics therefore recommends administering a single intramuscular injection of 0.5 to 1 milligram of vitamin K1 to all newborns. Oral dosing is generally not regarded as adequate for prevention, particularly in breastfeeding infants.
Warfarin toxicity/reversal should be under strict medical supervision.
Menadiol (not available in the United States) should not be given to infants or children due to rare reports of liver damage and blood cell toxicity (hemolytic anemia).
Interactions with Drugs
Warfarin is a blood-thinning drug that functions by inhibiting vitamin K-dependent clotting factors. Warfarin is prescribed by doctors for people with various conditions such as atrial fibrillation, artificial heart valves, history of serious blood clot, clotting disorders (hypercoagulability), or placement of indwelling catheters/ports. Usually, blood tests must be done regularly to evaluate the extent of blood thinning using a test for prothrombin time (PT) or International Normalized Ratio (INR). Vitamin K can decrease the blood thinning effects of warfarin and will therefore lower the PT or INR value. This may increase the risk of clotting. Therefore, people taking warfarin are usually warned to avoid foods with high vitamin K content (such as green leafy vegetables) and to avoid vitamin K supplements. Conversely, vitamin K is used to treat overdoses or excess anticoagulant effects of warfarin and to reverse the effects of warfarin prior to surgery or other procedures. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. Vitamin K-depleted patients are sensitive to even small changes in vitamin K1 intake.
Some antibiotics may decrease the bacteria in the human gut (which synthesize a small amount of the human vitamin K requirement). Broad-spectrum antibiotics, particularly sulfonamides such as Bactrim®, may lower vitamin K levels and increase the risk of deficiency in people not ingesting adequate amounts.
High doses of salicylates (aspirin) may increase vitamin K requirements.
Sucralfate or high doses of aluminum hydroxide antacids may decrease absorption of fat-soluble vitamins such as vitamin K.
Cholestyramine (Questran®) mineral oil may decrease the absorption of oral vitamin K and increase vitamin K requirements.
Quinine, or quinidine, may increase vitamin K requirements.
Dactinomycin, a cancer chemotherapy drug, may decrease the effects of vitamin K and increase vitamin K requirements.
Menadiol sodium diphosphase is a form of vitamin K that is not used in the United States. Multiple drugs may cause complications when taken with menadiol.
Interactions with Herbs/Supplements
Vitamin K may decrease the blood thinning effects of herbs that act like warfarin (Coumadin®) in the body by decreasing clotting factors made in the liver. In particular, this may apply to herbs with coumarin constituents, such as alfalfa (Medicago sativa), American ginseng (Panax quinquefolius), and angelica (Angelica archangelica).
While the effects of vitamin K on bone density are still unclear, beneficial effects may be enhanced with vitamin D and calcium supplementation.