Kanavit solution for injection 10 mg/ml ampoule 1 ml No. 5

Instructions for Kanavit solution for injection 10 mg/ml ampoule 1 ml No. 5

Composition

active ingredient: phytomenadione (vitamin K1);

1 ml of solution for injection contains 10 mg of phytomenadione;

Excipients: polysorbate 80, sodium acetate, disodium edetate, water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: slightly opalescent, green-yellow to yellow solution, without visible mechanical inclusions.

Pharmacotherapeutic group

Vitamin K and other hemostatics, phytomenadione.

ATX code B02B A01.

Pharmacological properties

Pharmacodynamics

The prophylactic and therapeutic use of vitamin K1 is based on its important role in the formation of coagulation factors in the liver and its positive effect on vitamin K1 deficiency after disruption of the intestinal flora by antibiotics and chemotherapy. Vitamin K1 affects the biosynthesis of factor II (prothrombin), factor VII (proconvertin), factor IX (Christmas factor) and factor X (Stewart–Prower factor).

Pediatric practice

A prospective randomized controlled trial included 44 breastfed infants (aged 1-26 weeks) with conjugated hyperbilirubinemia (idiopathic neonatal hepatitis - 17 patients, biliary atresia - 13, cholestasis associated with total parenteral nutrition - 3, Alagille syndrome - 2, alpha-1-antitrypsin deficiency - 2, bile thickening syndrome - 2, various diagnoses - 5; fructosemia, galactosemia, choledochal cyst, necrotizing enterocolitis, cytomegalovirus hepatitis).

A prospective randomized controlled trial included 44 infants (aged 1-26 weeks) with conjugated hyperbilirubinemia (idiopathic neonatal hepatitis - 17 patients, biliary atresia - 13, cholestasis associated with total parenteral nutrition - 3, Alagille syndrome - 2, alpha-1-antitrypsin deficiency - 2, bile thickening syndrome - 2, various diagnoses - 5; fructosemia, galactosemia, choledochal cyst, necrotizing enterocolitis, cytomegalovirus hepatitis).

The pharmacokinetics and efficacy of oral and intravenous prophylactic administration of micellar vitamin K in infants with cholestatic liver disease were compared.

The main measured values were serum vitamin K1 and prothrombin carboxylate (PIVKA-II) concentrations before and 4 days after administration of a single dose of 1 mg intravenously or 2 mg orally of micellar vitamin K1. Vitamin K1 levels after 24 hours of oral administration were also compared with those in 14 healthy newborns who received the same dose.

Results: At baseline, 18 children (41%) had elevated serum PIVKA-II levels and eight children (18%) had low vitamin K1 concentrations, indicating subclinical vitamin K deficiency. The mean serum vitamin K1 concentration was 0.92 vs. 1.15 ng/mL at baseline in the oral and intravenous vitamin K1 groups, respectively, and increased to 139 ng/mL 6 hours after intravenous administration, while after oral administration it was only 1.4 ng/mL.

In this latter group, the low mean (0.95 ng/mL) and wide range (<0.15–111 ng/mL) of serum vitamin K1 compared with the much higher levels (mean 77, range 11–263 ng/mL) measured in healthy infants given the same dose of vitamin K1 orally is not in favor of this group and indicates the insufficiency and unpredictability of intestinal absorption in infants with cholestasis.

The importance of malabsorption is such that only 4 of 24 (17%) infants with cholestasis achieved a gradual increase in serum vitamin K1 > 10 ng/mL.

Data from retrospective studies indicate that weekly oral prophylaxis is effective in preventing VKDB (Vitamin K Deficiency Bleeding). During this study, a total of 507,850 live births occurred between November 1992 and June 2000, of which 78% received oral prophylaxis and 22% intramuscular prophylaxis, resulting in 396,000 newborns receiving oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants for as long as they were predominantly breastfed. At birth, they were given 2 mg of vitamin K orally as phytomenadione, followed by weekly vitamin K prophylaxis; up to three months of age, parents were given 1 mg of phytomenadione. No cases of VKDB were detected, i.e. the ratio was 0–0.9:100,000 (95% CI).

Pharmacokinetics

Distribution

Vitamin K is completely absorbed after intramuscular administration. It is concentrated in the liver, but does not accumulate in it, its concentration decreases rapidly. A very small amount of vitamin K1 is stored in the tissues, but it also slowly disintegrates there.

Biotransformation

Phytomenadione is rapidly metabolized into polar metabolites.

Breeding

Phytomenadione is rapidly metabolized to polar metabolites that are excreted in bile and urine (after conjugation as glucuronides).

Indication

Prevention and treatment of bleeding due to reduced blood clotting caused by hypovitaminosis or avitaminosis K, as well as inhibition of blood clotting factors II, VII, IX and X of various etiologies.
Hemorrhagic complications during treatment with indirect anticoagulants of the coumarin type (such as, for example, warfarin).

Hypocoagulation after prolonged obstruction of the biliary tract and in the early stages of liver cirrhosis. Intestinal diseases associated with malabsorption, after prolonged treatment with antibiotics, sulfonamides and salicylates. Hemorrhagic phenomena in newborns, uterine bleeding. For prophylactic purposes before childbirth to protect the mother and newborn from bleeding, treatment of bleeding in newborns. In surgery with long-term biliary drainage and in preoperative preparation of patients with reduced blood clotting.

Contraindication

Hypersensitivity to the components of the drug; glucose-6-phosphate dehydrogenase deficiency; hypercoagulation; thromboembolism; hemolytic disease of the newborn; severe liver failure.

Interaction with other medicinal products and other types of interactions

Phenacetin, sulfonamides, quinine - simultaneous use of Kanavit may increase the risk of hemolytic effects.

Drugs that can displace bilirubin from protein compounds (e.g., sulfonamides) - simultaneous use of Kanavit in newborns with increased hemolysis may increase the risk of kernicterus.

Cholestyramine - reduces the absorption of vitamin K1 from the intestines.

Antagonism with coumarin anticoagulants.

Application features

Caution is necessary in chronic liver disease.

For patients with known glucose-6-phosphate dehydrogenase deficiency, where vitamin K can cause hemolysis of red blood cells, the benefit-risk ratio should be considered before using the drug.

In biochemical studies, phytomenadione increases serum bilirubin test results.

The use of Kanavit for blood clotting disorders caused by causes other than those mentioned above (e.g., treatment of gynecological bleeding) is inappropriate.

Intravenous administration to infants weighing less than 2.5 kg may increase the risk of bilirubin encephalopathy.

The contents of the ampoule must be clean. If a precipitate appears, turbidity appears, or the solution separates into phases, do not use the medicine.

Ability to influence reaction speed when driving vehicles or other mechanisms

Kanavit has no or negligible influence on the ability to drive or use machines.

Use during pregnancy or breastfeeding

Pregnancy

Phytomenadione crosses the placental barrier.

Because reproductive toxicity was observed in animal studies and there are no studies on safety during human pregnancy, phytomenadione should only be used when the benefit of treatment outweighs the risk to the fetus.

Breast-feeding

Phytomenadione passes into breast milk in small amounts.

Premature infants and newborns have poorly developed liver enzyme systems, therefore, they may develop kernicterus, jaundice, and hemolytic anemia due to slow biotransformation of phytomenadione in the liver.

Fertilization

The effect on fertilization is unknown.

Method of administration and doses

Intravenous and intramuscular, as well as oral administration (for this, after filling, use a syringe without a needle).

Infusion administration is not recommended.

Adults and elderly patients:

Bleeding after anticoagulant therapy:

In severe cases, use 10 to 20 mg (1 to 2 ampoules) of Kanavit, diluted in 5–10 ml of water for injection or 5% glucose solution, administered slowly (at least 30 seconds) intravenously. If bleeding does not stop, then repeated administration is possible after 3–4 hours, but not more than 40 mg per day. In emergency situations, infusion of fresh blood or frozen plasma is mandatory. In milder cases, Kanavit is administered intramuscularly. It is imperative to remember that the effect of vitamin K1 is long-lasting, especially when using large doses and with concomitant discontinuation of anticoagulant therapy, it can be achieved within a maximum of 24 hours, when an undesirable increase in blood clotting is possible. For this reason, it is recommended to proceed with caution and, if possible, to administer Canavit orally or intramuscularly and in lower doses to avoid the patient developing new thromboembolic complications due to the rapid increase in the level of blood clotting factors.

Continuous monitoring of blood clotting parameters is necessary until they stabilize.

With a slight decrease in blood clotting factors, use 5 to 10 mg of the drug intramuscularly 3 times a week. With a more severe decrease in blood clotting and with open bleeding, use 1–2 ml ampoules intramuscularly 1–2 times a week until the level of the prothrombin complex normalizes. With less advanced stages of liver cirrhosis, administer 20 to 30 mg of Kanavit intramuscularly 3 times a week.

Prevention of bleeding before surgical interventions in patients with reduced levels of coagulation factors.

Before emergency surgery, administer from half an ampoule to two ampoules intravenously, in less urgent cases - 5 mg intravenously. If surgery is planned, the drug should be administered 6-12 hours in advance.

Other bleeding

With reduced levels of factors II, VII and X, with bleeding of various origins, use 1–2 ampoules intramuscularly to correct coagulation and stop bleeding.

The highest single dose is 20 mg, the highest daily dose of Kanavit is 40 mg for both methods of administration.

Note: For intravenous use, dilute the emulsion for injection 1:5 (with water for injection or 5% glucose solution), inject slowly at a rate of about 1 ml per 20 seconds.

Elderly people are more sensitive to the effects of the drug, so the lowest recommended doses should be prescribed for this age group.

Pediatric practice (under 18 years of age)

The drug can be administered intramuscularly, intravenously, or orally.

Do not mix with other medicinal products. However, it may be administered by injecting the dose into the lower part of an infusion set containing 5% dextrose or 0.9% sodium chloride at an infusion rate ≥ 0.7 mL/min.

Healthy newborns 36 weeks gestational age or older - 1 mg injection administered intramuscularly at birth or shortly after birth.

Or 2 mg orally at birth or shortly after birth. An additional 2 mg dose should be given at 4 to 7 days of age after the oral dose. Another 2 mg oral dose should be given 1 month after birth. In the exclusively formula-fed group of infants, the third oral dose may be omitted.

Premature infants (less than 36 weeks gestational age with a body weight of 2.5 kg or more) and those at particular risk of being born at term (e.g., prematurity, birth asphyxia, obstructive jaundice, inability to swallow, maternal anticoagulant or antiepileptic drug administration).

1 milligram injection intramuscularly or intravenously at birth or shortly after birth. The number of subsequent doses and their frequency should be determined based on coagulation status.

In the treatment of overdose with coumarin-type anticoagulants, the recommended dose is 250 - 300 micrograms/kg intravenously for children weighing more than 1.6 kg.

For patients continuing to receive warfarin, the recommended dose for partial reversal of anticoagulation is 30 mcg/kg administered by intravenous injection in children weighing more than 13 kg.

Premature newborns (less than 36 weeks of gestational age with a body weight of less than 2.5 kg):

0.4 mg/kg (equivalent to 0.04 ml/kg) intramuscularly or intravenously at birth or shortly after birth. This parenteral dose should not be exceeded. The number of subsequent doses and their frequency should be determined on the basis of the coagulation status.

It has been proven that oral prophylaxis is insufficient in patients with cholestatic liver disease as the underlying disease and with malabsorption.

WARNING: it is necessary to pay attention to the calculation and measurement of doses in relation to the child's body weight (frequent errors in terms of use - such as 10 times the dose exceeded).

Doses for premature infants as prophylaxis for vitamin K deficiency bleeding are given in the table:

Infants are recommended to receive an additional oral dose, but data regarding the safety and efficacy of these subsequent doses are limited.

Recommended doses for children

Children

The drug can be used in pediatric practice.

Overdose

Phytomenadione has low toxicity, and overdose does not usually cause clinical problems. Intravenous administration of phytomenadione medicinal products may cause an acute hypersensitivity or anaphylactic reaction, manifested by flushing, sweating, chest pain, difficulty breathing, cyanosis, bronchoconstriction, and cardiovascular collapse. These reactions are likely caused by histamine release by excipients, not by the medicinal substance.

Treatment: In case of overdose, treatment is not required unless there are any serious clinical symptoms, as the biological half-life of phytomenadione is short (1.2 to 3.5 hours).

Adverse reactions

The following table lists the adverse reactions, which are divided into groups according to MedDRA (Medical Dictionary for Regulatory Activities) terminology, indicating the frequency of occurrence: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

*with G-6-P-dehydrogenase deficiency.

Expiration date

3 years.

Storage conditions

Store in a dry place, protected from light and out of reach of children,

Store in original packaging at a temperature not exceeding 25°C, do not refrigerate.

Incompatibility

Kanavit in solution is incompatible with dextrin, vitamin B12, hydantoins, and barbiturates.

Packaging

1 ml in a brown glass ampoule. 5 ampoules placed in a PVC film package.

One plastic package in a cardboard box.

Vacation category

According to the recipe.

Producer

HBM Pharma s.r.o., Slovak Republic.

Location of the manufacturer and its business address

Sklabinsk 30, 036 80 Martin, Slovak Republic.