Class: Vitamin K Activity
VA Class: VT702
CAS Number: 84-80-0
Brands: AquaMEPHYTON, Mephyton
- IV and IM Administration
Severe hypersensitivity reactions, including fatal anaphlaxis, have occurred during and immediately after IV or IM injection of phytonadione injection.b
Such severe reactions have occurred despite employing measures to prevent hypersensitivity reactions, including dilution of the injection and administration by slow infusion.b
These severe reactions are consistent with hypersensitivity or anaphylaxis, including shock and cardiac and/or respiratory arrest and have occurred after initial administration.b
Restrict IV and IM administration to those situations where sub-Q administration is not feasible and the serious risk associated with IV or IM administration is considered justified.b
.
Introduction
A fat-soluble naphthoquinone derivative; identical to naturally occurring vitamin K1.c
Uses for Phytonadione
Prophylaxis and treatment of coagulation disorders due to faulty formation of factors II, VII, IX and X caused by vitamin K deficiency or interference with vitamin K activity.a
More effective and is preferred to other vitamin K preparations in the presence of impending or actual hemorrhage.c
Anticoagulant-induced Hypoprothrombinemia
Drug of choice for the treatment of moderate or severe hemorrhage caused by overdosage of coumarin or indandione derivatives.a c
Withdrawal of oral anticoagulant alone usually corrects excessively prolonged prothrombin time or minor hemorrhage.c
Not effective against anticoagulant action of heparins, argatroban, bivalirudin, fondaparinux, or lepirudin.c
Hemorrhagic Disease of the Newborn
Prophylaxis and treatment of hemorrhagic disease of the newborn.b c f 34 135 136 137
AAP recommends routine IM administration to infants at birth to prevent hemorrhagic disease of the newborn.34 135 136 137 f
Treatment of vitamin K deficiency in infants who are breast-fed or receiving prolonged hyperalimentation.c
Drug-induced Hypoprothrombinemia
Treatment of hypoprothrombinemia secondary to drug therapy (e.g., salicylates, broad-spectrum anti-infectives, quinine, quinidine, sulfonamides) when it is definitely caused by interference with vitamin K activity.a b c
Discontinuance or dosage reduction of drug interfering with coagulation attempted first, if possible, as alternative to phytonadione.c
Other Causes of Hypoprothrombinemia
Treatment of hypoprothrombinemia secondary to obstructive jaundice or biliary fistulas; bile salts must be administered concomitantly with oral therapy.a
Ineffective in the treatment of hereditary hypoprothrombinemia.c
Vitamin K Deficiency
Treatment of vitamin K deficiency (e.g., in patients receiving prolonged hyperalimentation, as well as in the presence of malabsorption syndromes such as sprue, celiac disease, ulcerative colitis, regional enteritis, cystic fibrosis, prolonged diarrhea, obstructive jaundice, internal biliary fistula, dysentery, after extensive bowel resection).c
Dietary Requirements
Prevention of vitamin K deficiency and vitamin K-responsive hypothrombinemia.121 c
Adequate intake of vitamin K usually can be accomplished through consumption of foodstuffs.121 c
Spinach, collards, broccoli, iceberg lettuce, and plant oils are the major contributors of vitamin K in the diet of US adults and children.121 c
National Academies (formerly National Academy of Sciences; NAS) unable to establish accurate Recommended Dietary Allowances (RDAs) or Dietary Reference Intakes (DRIs) for vitamin K due to lack of adequate data.121
Adequate Intake (AI) for adults, adolescents, and children ≥1 year of age is based on reported vitamin K dietary intake in apparently healthy population groups (Third National Health and Nutrition Examination Survey [NHANES III]).121
Dietary intakes slightly lower in women than men.121
AI established for infants ≤6 months of age based on observed mean vitamin K intake of infants fed principally human milk.121
AI for infants 7–12 months of age set based on the AI for younger infants.121
Phytonadione Dosage and Administration
General
Restrict IV or IM administration to situations when sub-Q is not possible.a
Monitor prothrombin time regularly as dictated by clinical condition.b
If possible, discontinue or reduce dosage of drugs interfering with the coagulation mechanism as an alternative or adjunct to phytonadione therapy.c
Diagnosis of vitamin K deficiency may be based on tests for vitamin K-dependent clotting factors (e.g., prothrombin time, which is sensitive to the levels of factors II, VII, and X) or on a therapeutic trial of phytonadione.c
Administration
Administer orally or parenterally.a b
Parental therapy: Sub-Q preferred because of hypersensitivity risk with IV or IM administration.a (See Boxed Warning.)
Route of administration depends on the severity of the prothrombin deficiency and the risks associated with administration by each route.c
Oral Administration
Avoid oral route when the clinical disorder would prevent proper absorption.b
Patients with decreased bile secretion: Give bile salts (e.g., ox bile extract 300 mg or dehydrocholic acid 500 mg) with each oral dose of phytonadione to ensure absorption.b c
The parenteral preparation has also been administered orally† to neonates.34 35 37 102 103 104 105 136
IV, IM, or Sub-Q Administration
Because of the possibility of severe hypersensitivity reactions, IV or IM administration is indicated only when the serious risk involved is considered justified and other routes of administration are not feasible.b (See Boxed Warning.)
Parenteral administration is indicated in patients unable to retain or absorb the drug from the GI tract.c
Sub-Q or IM administration may be contraindicated in hypoprothrombinemia because of the possibility of inducing hemorrhage or hematoma at the site of injection.c
Dilution
Dilute for infusion with preservative-free 5% dextrose, 0.9% sodium chloride, or 5% dextrose in 0.9% sodium chloride injection; other diluents should not be used.c
Administer IV immediately after dilution, and any unused portion of the dilution and the unused contents of the ampul should be discarded.c The infusion container must be protected from light at all times.c (See Storage under Stability.)
Rate of Administration
Inject IV very slowly, at a rate ≤1 mg/minute.b (See Boxed Warning.)
Dosage
Dose, frequency of administration, and duration of treatment depend on the severity of the prothrombin deficiency and the response of the patient.c
Pediatric Patients
Hemorrhagic Disease of the Newborn
Prophylaxis
IM
AAP recommends a single IM dose of 0.5–1 mg within 1 hour of delivery.34 113 135 136 c f
Oral
Alternatively, 1–2 mg orally† (can use injection formulation) immediately after delivery.135 136 137 Several oral doses, administered over a period of up to 3 months, may be required (e.g., at 1–2 weeks and 4 weeks of age in breast-fed infants, repeatedly if diarrhea occurs in breast-fed infants).135 136 137 f
Treatment
Empiric administration should not replace proper laboratory evaluation of the coagulation mechanism.b
A prompt response (shortening of the prothrombin time in 2–4 hours) following phytonadione usually is diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.b
IM or Sub-Q
1 mg sub-Q or IM.b Higher doses may be necessary if the mother has been receiving oral anticoagulants.b
Dietary and Replacement Requirements
Healthy Infants ≤6 Months of Age
Oral
2 mcg daily.121
Healthy Infants 7–12 Months of Age
Oral
2.5 mcg daily.121
Healthy Children 1–3 Years of Age
Oral
30 mcg daily.121
Healthy Children 4–8 Years of Age
Oral
55 mcg daily.121
Healthy Children 9–13 Years of Age
Oral
60 mcg daily.121
Healthy Children 14–18 Years of Age
Oral
75 mcg daily.121
Adults
Anticoagulant-induced Hypoprothrombinemia
Oral
Usual initial dosage: 2.5–10 mg.a Initial doses up to 25 mg have been used.a
Subsequent frequency and dosage should be determined by prothrombin time response and/or clinical condition.a
Dose may be repeated in 12–48 hours.a
Rarely, larger doses (e.g., 50 mg) may be required; however, administer lowest effective dosage so that refractoriness to further anticoagulant therapy is minimized and prothrombin time is not decreased below the effective anticoagulant level.a c
IV, IM, or Sub-Q
Usual initial dosage: 2.5–10 mg.b Initial doses up to 25 mg have been used.b
Subsequent frequency and dosage should be determined by prothrombin time response and/or clinical condition.b
Dose may be repeated in 6–8 hours.b
Rarely, larger doses (e.g., 50 mg) may be required; however, administer lowest effective dosage so that refractoriness to further anticoagulant therapy is minimized and prothrombin time is not decreased below the effective anticoagulant level.b c
Hypoprothrombinemia from Other Causes
Oral
Usual initial dosage: 2.5–25 mg, depending on deficiency, severity, and response.a Rarely, larger doses (e.g., 50 mg) may be required.a
Determine subsequent frequency and dosage by prothrombin time response and/or clinical condition in addition to reduction or discontinuance of drug (if drug therapy causing hypoprothrombinemia).a
IV, IM, or Sub-Q
Usual initial dosage: 2.5–25 mg, depending on deficiency severity and response.a Rarely, larger doses (e.g., 50 mg) may be required.a
Determine subsequent frequency and dosage by prothrombin time response and/or clinical condition in addition to reduction or discontinuance of interfering drug (if drug therapy causing hypoprothrombinemia).a
Dietary and Replacement Requirements
Healthy Men ≥ 19 Years of Age
Oral
120 mcg daily.121
Healthy Women ≥19 Years of Age
Oral
90 mcg daily.121
Limited data suggest that the vitamin K status in pregnant women does not differ from that in nonpregnant women.121 Therefore, NAS states that the AI of vitamin K does not need to be increased during pregnancy (i.e., pregnant women can receive the usual AI appropriate for their age).121
Available evidence indicates that the vitamin K status of lactating women is comparable to that of nonlactating women.121 Vitamin K is not distributed in clinically important amounts into milk, and the AI for lactating women does not differ from that for nonlactating women.121
Special Populations
Geriatric Patients
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a
Cautions for Phytonadione
Contraindications
Warnings/Precautions
Warnings
IV or IM Administration
Restrict IV and IM administration to those situations where sub-Q administration is not feasible and the risk of anaphylaxis associated with IV or IM administration is considered justified.b (See Boxed Warning.)
Delayed Coagulant Effect
Coagulant effect is not immediate after parenteral administration; measurable improvement in prothrombin time generally occurs after a minimum of 1–2 hours.b
Whole blood or component therapy may also be necessary for severe bleeding.b
Heparins and Other Non-coumarin/Indandione Coagulants
Does not counteract the anticoagulant effect of heparins, argatroban, bivalirudin, fondaparinux, or lepirudin.b
Anticoagulant-induced Hypoprothrombinemia
Use minimum effective dosage when treating anticoagulant-induced hypoprothrombinemia to avoid subsequent anticoagulant refractoriness; monitor prothrombin time regularly according to clinical conditions.b
When used to treat excessive anticoagulant-induced hypoprothrombinemia and continued anticoagulant therapy is indicated, clotting hazards that existed prior to anticoagulant therapy should be considered.b Phytonadione is not a clotting agent, but excessive dosage may restore conditions originally underlying the thromboembolic phenomena.b
Hepatic Disease
Repeated large doses are not indicated in liver disease if the response to initial therapy with the vitamin is unsatisfactory.b
Lack of response may indicate the condition is inherently unresponsive to phytonadione.b
Sensitivity Reactions
Hypersensitivity Reactions
Serious and fatal hypersensitivity reactions, including anaphylaxis, after IV or IM administration.b (See Boxed Warning.)
Pruritic Plaques
Infrequently, usually after repeated injection, erythematous, indurated, pruritic plaques reported; rarely, progression to persistent sclerodermalike lesions.b Also, may resemble erythema perstans.b
General Precautions
Light-Sensitivity
Rapidly degraded by light; protect phytonadione injection from light.b Store in closed original carton until use.b (See Stability.)
Specific Populations
Pregnancy
Category C.a g
Lactation
Distributes into milk, but amount is too low to protect against hermorrhagic disease of newborn.c g Caution if used in nursing women,a b but maternal use considered compatible with breast-feeding.g
Pediatric Use
Oral administration: Safety and efficacy of oral phytonadione not established.a b
Severe hemolytic anemia, hyperbilirubinemia, and jaundice reported rarely in neonates, particularly premature neonates, following large doses (10–20 mg).a c However, the incidence of these adverse effects is much less with phytonadione than with other vitamin K preparations.c
Phytonadione injection contains 9 mg/mL of benzyl alcohol as a preservative.113 Administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.113 114 115 116 117 118 119 120 Toxicity appears to have resulted from administration of large amounts (i.e., 100–400 mg/kg daily) of benzyl alcohol in these neonates.114 115 116 117 118 119 120
Whenever possible use of drugs or diluents preserved with benzyl alcohol should be avoided in neonates;114 116 however, AAP states that the small amount of the preservative in commercially available injection should not proscribe its use when indicated in neonates114 and the manufacturers state that there is no evidence that the amount of benzyl alcohol contained in the injections is associated with toxicity when the drug is used as recommended.113
Geriatric Use
Response in patients≥65 years of age does not appear to differ from that in younger adults; however, select dosage with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.a
Common Adverse Effects
Parenteral Administration: Pain, swelling, and tenderness at the injection site, transient “flushing sensations,“ “peculiar” sensations of taste.b
Fatal anaphylactic reaction reported after IV and IM administration.b (See Boxed Warning.)
Interactions for Phytonadione
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Anticoagulants, oral (coumarins and indandiones)
|
Vitamin K1 is a pharmacologic antagonistc
|
Avoid concomitant use; only use concomitant phytonadione for treatment of excessive hypoprothrombinemiac
Consider alternate to prothrombin-depressing anticoagulant (e.g., heparins) if neccesaryb
|
Orlistat
|
Possible decreased GI absorption of fat-soluble vitamins, inlcuding phytonadione (vitamin K1)122
|
Separate oral administration of orlistat and phytonadione by ≥2 hours 122 124 128 130
|
Phytonadione Pharmacokinetics
Absorption
Abosorbed from the GI tract only in the presence of bile salts.c
Onset
Oral administration: blood coagulation factors increase in 6–10 hours.c
Parenteral administration: blood coagulation factors increase within 1–2 hours.c
Parenteral administration: bleeding usually controlled within 3–6 hours, and a normal prothrombin time often obtained within 12–14 hours.c
Distribution
Extent
May be concentrated in the liver for a short time after absorption; only small amounts are stored in body tissues.c
Appears to cross the placenta to a limited extent.c
Distributes into milk.34 35 102 107 108 109 110 111 g
Elimination
Route of excretion of vitamin K is not known.c High fecal concentrations of vitamin K probably result from bacterial synthesis in the intestine.c
Stability
Storage
Oral
Tablets
Tight, light resistant, original container at 25°C (may be exposed to 15–30°C).a
Always protect from light.a
Parenteral
Injection
Protect from light.b Store in carton to protect from light until used.b
Infusion solutions should be protected from light by wrapping the container with aluminum foil or other opaque material.c
Use immediately after dilution; discard unused portion of ampul and dilution.c
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution CompatibilityHID
Compatible
|
|---|
Amino acids 4.25%, dextrose 25%
|
Dextran 6% in dextrose 5%
|
Dextran 6% in sodium chloride 0.9%
|
Dextrose 2½, 5, or 10% in water
|
Dextrose–Ringer’s injection combinations
|
Dextrose–Ringer’s injection, lactated, combinations
|
Dextrose–saline combinations
|
Fat emulsion 10%, IV
|
Fructose 10% in sodium chloride 0.9%
|
Fructose 10% in water
|
Invert sugar 5 and 10% in sodium chloride 0.9%
|
Invert sugar 5 and 10% in water
|
Ionosol products
|
Ringer’s injection
|
Ringer’s injection, lactated
|
Sodium chloride 0.45 or 0.9%
|
Sodium lactate (1/6) M
|
Incompatible
|
|---|
Amino acids 2%, dextrose 12.5%
|
Dextran 12%
|
Drug Compatibility
Admixture CompatibilityHID
Compatible
|
|---|
Amikacin sulfate
|
Chloramphenicol sodium succinate
|
Cimetidine HCl
|
Sodium bicarbonate
|
Incompatible
|
|---|
Ranitidine HCl
|
Y-site CompatibilityHID
Compatible
|
|---|
Ampicillin sodium
|
Epinephrine HCl
|
Famotidine
|
Heparin sodium
|
Hydrocortisone sodium succinate
|
Potassium chloride
|
Vitamin B complex with C
|
Incompatible
|
|---|
Dobutamine HCl
|
ActionsActions
Same activity as naturally occurring vitamin K1, which is required for the synthesis of blood coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor or plasma thromboplastin component), and X (Stuart-Prower factor) in the liver.c
Involved in carboxylation of the preformed, inactive precursors of these coagulation factors, resulting γ-carboxyglutamyl residues are required for the calcium-dependent phospholipid binding exhibited by active vitamin K-dependent clotting factors.c
Reverses the inhibitory effect of coumarin and indandione derivatives on the synthesis of these factors.c
Advice to Patients
Importance of advising patients receiving coumarin or indandione anticoagulants
to avoid vitamin K supplementation or foods high in vitamin K (e.g., spinach, collards, broccoli, iceberg lettuce, plant oils).
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.c
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Phytonadione
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Tablets
|
5 mg
|
Mephyton (scored)
|
Merck
|
Parenteral
|
Injection
|
2 mg/mL*
|
AquaMEPHYTON (with polyoxyethylated fatty acid derivative, dextrose, and benzyl alcohol 0.9%)
|
Merck
|
|
|
|
Phytonadione Injection
|
Hospira, IMS
|
|
|
10 mg/mL*
|
AquaMEPHYTON (with polyoxyethylated fatty acid derivative, dextrose, and benzyl alcohol 0.9%)
|
Merck
|
|
|
|
Phytonadione Injection
|
Hospira
|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
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35. American Academy of Pediatrics Committee on Nutrition. Vitamin K supplementation for infants receiving milk substitute infant formulas and for those with fat malabsorption. Pediatrics. 1971; 48:483-7. [PubMed 5109893]
37. Vest M. Vitamin K in medical practice—pediatrics. Vitam Horm. 1966; 24:649-63. [PubMed 5340884]
100. Shearer MJ, Barkhan P, Webster GR. Absorption and excretion of an oral dose of titrated vitamin K1 in man. Br J Haematol. 1970; 18:297-308. [PubMed 5491582]
101. Hollander D. Intestinal absorption of vitamins A, E, D, and K. J Lab Clin Med. 1981; 97:449-62. [PubMed 7205056]
102. Lane PA, Hathaway WE. Vitamin K in infancy. J Pediatr. 1985; 106:351-9. [IDIS 197121] [PubMed 3973772]
103. Sann L, Leclercq M, Bourgeois J et al. Pharmacokinetics of vitamin K1 in newborn infants. Pediatr Res. 1983; 17:155A.
104. Dunn PM. Vitamin K1 for all newborn babies. Lancet. 1982; 2:770. [IDIS 158995] [PubMed 6125839]
105. Shoskes M. “Solubilized” vitamin K1 (phytonadione) in neonatal hypoprothrombinemia. J Pediatr. 1961; 58:27-31.
106. Hemorrhage in the newborn infant. In: Behrman RE, Vaughn RC III, eds. Nelson textbook of pediatrics. 12th ed. Philadelphia: WB Saunders Company; 1983:389-90.
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108. Haroon Y, Shearer MJ, Rahim S et al. The content of phylloquinone (vitamin K1) in human milk, cow’s milk and infant formula foods determined by high-performance liquid chromatography. J Nutr. 1982; 112:1105-17. [PubMed 7086539]
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110. Sutherland JM, Glueck HI, Gleser G. Hemorrhagic disease of the newborn: breast feeding as a necessary factor in the pathogenesis. Am J Dis Child. 1967; 113:524-33. [PubMed 6071586]
111. Keenan WJ, Jewett T, Glueck HI. Role of feeding and vitamin K in hypoprothrombinemia of the newborn. Am J Dis Child. 1971; 121:271-7. [PubMed 5108035]
112. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998. (Prepublication copy uncorrected proofs.)
113. Merck. AquaMEPHYTON (phytonadione) injection aqueous colloidal solution of vitamin K1 prescribing information (dated 1997 Sep). In: Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:2042-3
114. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]
115. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10-1. [PubMed 7188569]
116. Anon. Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]
117. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]
118. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]
119. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]
120. Food and Drug Administration. Parenteral drug products containing benzyl alcohol or other antimicrobial preservatives; intent and request for information. [Docket No. 85N-0043] Fed Regist. 1985; 50:20233-5.
121. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2002:162-98. (Prepublication copy uncorrected proofs.)
122. Roche Laboratories Inc. Xenical (orlistat) capsules prescribing information. Nutley, NJ; 1999 April.
123. Sjöström L, Rissanen A, Andersen T et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998; 352:167-72. [IDIS 407969] [PubMed 9683204]
124. Davidson MH, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999; 281:235-42. [IDIS 417495] [PubMed 9918478]
125. Hollander PA, Elbein SC, Hirsch IB et al. Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care. 1998; 21:1288-94. [IDIS 411429] [PubMed 9702435]
126. Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol. 1996; 36:647-53. [IDIS 370479] [PubMed 8844448]
127. Zhi J, Melia AT, Koss-Twardy SG et al. The effect of orlistat, an inhibitor of dietary fat absorption, on the pharmacokinetics of β-carotene in healthy volunteers. J Clin Pharmacol. 1996; 36:152-9. [IDIS 364805] [PubMed 8852391]
128. Roche Laboratories Inc. Xenical (orlistat) capsules patient information. Nutley, NJ; 1999 April.
129. James WP, Avenell A, Broom J et al. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes Relat Metab Disord. 1997; 21(Suppl 3):S24-30. [PubMed 9225173]
130. Roche Laboratories Inc, Nutley, NJ: Personal communication on Orlistat 56:40.
131. Anon. Practice parameter: management issues for women with epilepsy (summary statement). Neurology. 1998; 51:944-8. [PubMed 9781510]
132. American College of Obstetricians and Gynecologists. ACOG educational bulletin No. 231: seizure disorders in pregnancy. Dec 1996.
133. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs. 1999; 57:535-44. [PubMed 10235691]
134. Merck. Mephyton (phytonadione) tablets vitamin K1 prescribing information (dated 1998 Aug). In: Physicians’ desk reference. 56th ed. Montevale, NJ: Medical Economics Company Inc; 2002:2129-30.
135. American Academy of Pediatrics Vitamin K ad hoc task force. Controversies concerning vitamin K and the newborn. Pediatrics. 1993; 91:1001-3. [IDIS 313728] [PubMed 8474790]
136. Buck ML. Vitamin K for the prevention of bleeding in newborns. Pediatric Pharmacotherapy. 2001. From the web site ().
137. American Academy of Pediatrics Committee on Nutrition. Pediatric nutrition handbook. 4th ed. Elk Groove Village, IL: American Academy of Pediatrics; 1998:14,277-8.
a. Merck. Mephyton (phytonadione) vitamin K1 tablets prescribing information. Whitehouse Station, NJ; 2002 Feb.
b. Merck. AquaMEPHYTON (phytonadione) injection aqueous colloidal solution of vitamin K1 prescribing information.Whitehouse Station, NJ; 2002 Feb.
c. AHFS drug information 2004. McEvoy GK, ed. Phytonadione. Bethesda, MD: American Society of Health-System Pharmacists; 2004:3525-27.
d. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.
HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1347-50.
f. American Academy of Pediatrics. Nutritional needs of preterm infant. In: Pediatric nutrition handbook. 5th ed. 2004.
g. Briggs GG, Freeman RK, Yaffe SJ. Phytonadione. In: Drugs in pregnancy and lactation. 6th ed. Baltimore: Lippincott Williams & Wilkins; 1128-1131.
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Compare Phytonadione with other medications
- Hypoprothrombinemia, Anticoagulant Induced
- Hypoprothrombinemia, Not Associated with Anticoagulant Therapy
- Hypoprothrombinemia, Prophylaxis
- Vitamin K Deficiency
