Menadiol sodium diphosphate
Menadiol sodium diphosphate Uses, Dosage, Side Effects, Food Interaction and all others data.
Menadiol sodium diphosphate is a Vitamin K derivative (chemically, it is menadiol sodium diphosphate), previously approved by FDA prior to 1982 and marketed by Lilly Marketing for this drug has been discontinued and is not available in North America . It has been found to have carcinogenic potential in mammalian cells as well as cytotoxic properties . Studies involving the active metabolite of this formulation, menadione, showed oocyte toxicity in a study of mice .
Menadiol sodium diphosphate is a highly water-soluble vitamin K analog. The presence of vitamin K is necessary for the formation of prothrombin, factor VII, factor IX and factor X. Lack of vitamin K results in an increased risk of hemorrhage, which can be minor or life-threatening .
| Trade Name | Menadiol sodium diphosphate |
| Generic | Kappadione |
| Kappadione Other Names | Menadiol sodium diphosphate |
| Type | |
| Formula | C11H8Na4O8P2 |
| Weight | Average: 422.084 Monoisotopic: 421.92851833 |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Anticoagulant-induced prothrombin deficiency caused by coumadin or indanedione derivatives, prophylaxis and therapy of hemorrhagic disease of the newborn, hypoprothrombinemia due to antibacterial therapy, hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K (for example, obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis, other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism) .
How Menadiol sodium diphosphate works
Menadiol sodium phosphate (vitamin K3) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of various proteins in the body, allowing for propagation of the clotting cascade that results in coagulation. These proteins are comprised of the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called G1a proteins .
Toxicity
This medication has been associated with increased risk of kernicterus and hemolytic anemia in premature infants . It is not advisable to administer this medication in newborns and those with G6PD, due to free radical cycling by this medication. This increases risk of free radical damage to the liver and hemolytic anemia .
Volume of Distribution
In a study of rabbits, the apparent volume of distribution (V(d)/F) in plasma was 30.833 ± 12.835 L .
Elimination Route
Menadiol sodium phosphate (vitamin K3), the synthetic analog of vitamin K, being water soluble, is advised in intestinal malabsorption or in states in which bile flow is deficient. The primary disadvantage is that it takes 24 h to initiate therapeutic effects, however, this effect lasts for several days. The dose is 5–40 mg orally, daily. Menadiol sodium phosphate, even in moderate doses, may lead to hemolytic anemia and, for this reason, neonates should not receive this medication. This precautionary measure is valid especially those that are deficient in glucose 6-phosphate dehydrogenase (G6PD); their immature livers are unable to compensate for the heavy bilirubin load and there is an increased risk of kernicterus .
Half Life
Mean elimination half-life of menadione was 27.17 min in the plasma of rabbits, in one study .
Clearance
The plasma clearance (CL/F) of VK3 was 0.822 ± 0.254 L min-1. [LI572]
Elimination Route
Vitamin K is heavily metabolized in the liver and excreted in the urine and bile. In tracer studies, it was found that approximately 20% of an injected dose of phylloquinone (Vitamin K metabolite) was found in the urine whereas about 40-50 % was excreted in the feces via the biliary system. The proportion of drug excreted was the same regardless of whether the injected dose was 1 mg or 45 µg. It can, therefore, be inferred that about 60-70% percent of the amounts of phylloquinone absorbed from each vitamin-K containing meal will be lost to the body by excretion .
Two major human excretion products have been identified: carboxylic acids with 5 and 7-carbon sidechains that are excreted in the urine as glucuronide conjugates. The biliary metabolites have not been clearly identified but are initially excreted as water-soluble conjugates and become lipid soluble during their passage through the gut, probably through deconjugation by the gut flora. There is no evidence for body stores of vitamin K being conserved by an enterohepatic circulation. Vitamin K itself is too lipophilic to be excreted in the bile and the sidechain-shortened carboxylic acid metabolites are not biologically active .
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