Phylloquinone

Phylloquinone Uses, Dosage, Side Effects, Food Interaction and all others data.

Vitamin K-1 (Phytomenadione) is a procoagulant factor. As a component of a hepatic carboxylase system, vitamin K- 1 is involved in the post translational carboxylation of clotting factors II (prothrombin), VII, IX and X and the clotting inhibitors protein C and protein S. Vitamin K-1 is ineffective in hereditary hypoprothrombinemia or hypoprothrombinemia induced by severe hepatic failure. Lack of vitamin K-1 leads to an increased tendency to haemorrhagic disease in the newborn. Vitamin K-1 administration, which promotes synthesis of the above-mentioned coagulation factors by the liver, can reverse an abnormal coagulation status and bleeding due to vitamin K-1 deficiency.

Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K. It has a long duration of action as vitamin K is cycled in the body, and a wide therapeutic index as large doses can be tolerated. Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.

Trade Name Phylloquinone
Generic Phylloquinone
Phylloquinone Other Names 3-Phytylmenadione, alpha-Phylloquinone, Fitomenadiona, Phyllochinon, Phyllochinonum, Phylloquinone, Phythyl-menadion, Phytomenadione, Phytomenadionum, Phytonadione, Phytonadionum, Phytylmenadione, trans-Phylloquinone, Vitamin K, Vitamin K1
Type
Formula C31H46O2
Weight Average: 450.6957
Monoisotopic: 450.349780716
Groups Approved, Investigational
Therapeutic Class Vitamin-K Preparations
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Phylloquinone
Phylloquinone

Uses

Prophylaxis and treatment of haemorrhagic disease in the newborn.

Haemorrhage or risk of haemorrhage as a result of severe hypoprothrombinemia (i.e. deficiency of clotting factors II, VII, IX and X) of various etiologies, including overdosage of courmarin-type anticoagulants, their combination with phenylbutazone, and other forms of hypovitaminosis K (e.g. in obstructive jaundice as well as liver and intestinal disorders, and after prolonged treatment with antibiotics, sulphonamides or salicylates).

Prevention and treatment of bleeding due to vitamin K deficiency.

Phylloquinone is also used to associated treatment for these conditions: Coagulation Disorders, Hypoprothrombinemia, Hemorrhagic disease of the newborn, Vitamin supplementation

How Phylloquinone works

Vitamin K is a cofactor of gamma-carboxylase. Gamma carboxylase attaches carboxylic acid functional groups to glutamate, allowing precursors of factors II, VII, IX, and X to bind calcium ions. Binding of calcium ions converts these clotting factors to their active form, which are then secreted from hepatocytes into the blood, restoring normal clotting function.

Vitamin K may also carboxylate matrix proteins in chondrocytes, inhibiting calcification of joints, and may increase type II collagen. The role of vitamin K in osteroarthritis, bone density, and vascular calcification is currently under investigation.

Dosage

Phylloquinone dosage

Prophylaxis: Mild Hemorrhage or hemorrhagic tendency: The usual dose for Neonates is 2 mg orally at or just after birth. Then 2 mg on 4 th-5 th day and another 2 mg on 28 th - 30 th day orally. If the oral route is unsuitable then 2 mg of drug can be administered by IM or IV route. Children over 1 year of age are could be given 5-10 mg orally.

A single 1 mg (0.1 ml) dose IM is recommended in children who are not assured of receiving a second oral dose or, in the case of breast-fed children, who are not assured of receiving a third oral dose.

Therapy: Initially, 1 mg by intravenous injection, with further doses as required, based on the clinical picture and coagulation status. Neonates with special risk factors[Pre-maturity, birth asphyxia (inadequate intake of oxygen by the baby during birth process), obstructive jaundice, inability to swallow, maternal use of anticoagulants or anti-epileptics]:

  • 1 mg intramuscularly or intravenously at birth or shortly after birth if the oral route is unsuitable.
  • Intramuscular and intravenous doses should not exceed 0.4 mg/kg in premature infants weighing less than 2.5 kg.
  • The size and frequency of further doses should be based on coagulation status

To ensure a total protection of the newborns, 3 prophylactic doses of Vitamin K should be administered orally following the dosing schedule mentioned above.

Side Effects

There are isolated unconfirmed reports on the possible occurrence of anaphylactoid reactions and venous irritation or phlebitis after parenteral use of Phytomenadione injections.

Toxicity

High doses of vitamin K1 are not associated with toxicity. Intravenous administration has been associated with an increased risk of toxicity. These patients should be treated with symptomatic and supportive measures.

The intravenous LD50 in mice is 1170 mg/kg and the oral LD50 is >24180 mg/kg.

Precaution

Careful monitoring of the coagulation parameters is necessary for patients with severely impaired liver function after administration of Phytomenadione .

Interaction

Vitamin K-1 antagonises the effect of coumarin-type anticoagulants. Coadministration of anticonvulsants can impair the action of vitamin K-1.

Food Interaction

No interactions found.

Volume of Distribution

The steady state volume of distribution of phylloquinone is 20 ± 6 L in subjects who are also taking phenprocoumon therapy.

Elimination Route

A 4 µg oral dose of phylloquinone is 13% ± 9% bioavailable, with a Tmax of 4.7 ± 0.8 hours. 1.5 ± 0.8 nmol is found in the plasma compartment, and 3.6 ± 3.4 nmol is found in the second compartment.

A 10 mg intramuscular phylloquinone dose is 89.2% ± 25.4% bioavailable. The same dose reaches a mean Cmax of 67 ± 30 ng/mL, with a mean Tmax of 9.2 ± 6.6 hours, and an AUC of 1700 ± 500 h*ng/mL.

A 10 mg intravenous phylloquinone dose has a mean AUC of 1950 ± 450 h*ng/mL.

Half Life

Intravenous phylloquinone has an initial half life of 22 minutes, followed by a half life of 125 minutes.

Clearance

Intravenous phylloquinone is 90% cleared in 2 hours, and 99% cleared in 8 hours. A 10 mg intravenous dose of phylloquinone has a mean clearance of 91 ± 24 mL/min.

Elimination Route

Intravenous phylloquinone is 36% eliminated in the feces in 5 days and 22% recovered in urine in 3 days.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

It is contraindicated in patients with known hypersensitivity to any of its constituents.

Storage Condition

Store at 15-30° C.

Innovators Monograph

You find simplified version here Phylloquinone

Phylloquinone contains Phylloquinone see full prescribing information from innovator Phylloquinone Monograph, Phylloquinone MSDS, Phylloquinone FDA label

http://classyfire.wishartlab.com/tax_nodes/C0000000
http://classyfire.wishartlab.com/tax_nodes/C0000012
http://classyfire.wishartlab.com/tax_nodes/C0000259
http://classyfire.wishartlab.com/tax_nodes/C0001534
http://classyfire.wishartlab.com/tax_nodes/C0001547
http://classyfire.wishartlab.com/tax_nodes/C0001551
http://classyfire.wishartlab.com/tax_nodes/C0000153
http://classyfire.wishartlab.com/tax_nodes/C0002495
http://classyfire.wishartlab.com/tax_nodes/C0003670
http://classyfire.wishartlab.com/tax_nodes/C0003940
http://classyfire.wishartlab.com/tax_nodes/C0004150
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:18067
http://www.lipidmaps.org/data/LMSDRecord.php?LMID=LMPR02030028
http://www.hmdb.ca/metabolites/HMDB0015157
http://www.genome.jp/dbget-bin/www_bget?drug:D00148
http://www.genome.jp/dbget-bin/www_bget?cpd:C02059
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5284607
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504528
https://www.chemspider.com/Chemical-Structure.4447652.html
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=24782
https://mor.nlm.nih.gov/RxNav/search?searchBy=RXCUI&searchTerm=8308
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=18067
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL1550
https://zinc.docking.org/substances/ZINC000003831332
http://bidd.nus.edu.sg/group/cjttd/ZFTTDDRUG.asp?ID=DNC001500
http://www.pharmgkb.org/drug/PA450961
https://www.ebi.ac.uk/pdbe-srv/pdbechem/chemicalCompound/show/PQN
http://www.rxlist.com/cgi/generic3/phytonadione.htm
https://www.drugs.com/cdi/phytonadione.html
https://en.wikipedia.org/wiki/Phytomenadione
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