Kanavit


1. NAME OF THE MEDICINAL PRODUCT

                                            KANAVIT

2.     QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient:     phytomenadione (vitamin K 1), 10 mg in 1 ml.
All the excipients are listed in section 6.1.

3. PHARMACEUTICAL FORM

Solution for injections.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prevention and treatment of bleeding based on decreased blood coagulation caused by vitamin K hypovitaminosis or avitaminosis, haemorrhagic complication of the treatment with indirect anticoagulants (Pelenthane, Pelenthanettae), hypocoagulability after long-term bile ways obstruction, in intestinal diseases connected with malabsorption, after long-term treatment with antibiotics, sulphonamides and salicylates, hypocoagulability in initial stages of hepatic cirrhoses. Prior to delivery as a prevention of bleeding in mother and newborn, neonatal haemorrhages treatment. 
In surgery in longer running bile drainages and pre-op preparation of patients with decreased blood coagulation.

4.2 Posology and method of administration

a) Dosage for children
Newborns haemorrhages: In indicated cases, Kanavit is administered to the woman in childbed 48 hours prior to the expected delivery, latest 2 hours prior delivery 1-2 ampoules of Kanavit intramuscularly or to the new-born immediately after birth intramuscularly in a dose not exceeding 1 mg. In serious cases, a second and third dose is administered to the new-born, preferably in the form of drops in milk,
Recommended doses for children:
Newborns          not exceed 1 mg
till 1 year of age            1-2.5 mg
from 1 to 6 years           2.5-5 mg
from 6 to 15 years          5-10 mg
always intramuscularly.

b) Dosage for adults
Bleeding after indirect anticoagulants:
In serious cases, 10-20 mg (1 to 2 ampoules) of Kanavit, diluted with 5 to 10 ml of water for injection or 5% glucose solution, is administered slowly intravenously. If the bleeding persists, it is possible to repeat the dose after three to four hours. In emergent situations an infusion of fresh blood is necessary. In less emergent cases, Kanavit is administered orally (in the form of drops) or intramuscularly. The protracted effect of vitamin K1 should be always kept in mind, and mainly in high doses and simultaneous discontinuation of anticoagulant treatment, it may reach the maximum after 24 hours, when the undesirable blood coagulation increase may occur. Therefore, it is necessary to proceed carefully, prefer oral or intramuscular application and rather lower doses, not to endanger the patient with a thromboembolic event due to a sudden increase of levels of coagulant factors.

Prevention and treatment of bleeding in bile ways and liver diseases:
In the case of moderate decrease of coagulation factors, 5 -10 mg is applied intramuscularly 3 times a week. In the case of more serious blood coagulation decrease and manifest bleeding, 1-2 ampoules are applied intramuscularly 1 to 2 times daily until the prothrombin complex level is normalized. In less advanced stages of hepatic cirrhosis, 20-30 mg of Kanavit is applied intramuscularly 3 times a week.

Prevention of bleeding prior to surgical interventions in patients with decreased coagulation factors level:
Prior to emergent interventions a half to two ampoules is applied intravenously, in less urgent cases daily 10 to 20 mg intramuscularly.

Other haemorrhagic conditions:
In decreased factor II, VII and X levels and bleeding of various etiology, 1-2 ampoules intramuscularly until the normalisation of coagulation conditions and bleeding termination. The maximal single dose is 20 mg, the maximal daily dose 40 mg for all methods of application!

Note:
For an intravenous application, the injection solution has to be diluted five times (by water for Injection or 5% glucose solution), applied slowly at a rate of 1 ml within 20 seconds,

4.3 Contraindications
Hypersensitivity to the preparation, individuals with known G-6-P dehydrogenase deficiency.

4.4 Special warnings and precautions for use
Care is necessary in advanced state of hepatic disease. In biochemical examination, phytomenadione increases the serum bilirubin test values. Kanavit is not an universal antihaemorrhagic drug and its administration in hemorrhagic conditions, caused by other than mentioned reasons (e.g. for treatment of gynaecologic bleedings) is not suitable.

4.5 Interaction with other medicinal products and other forms of interaction
The preparation may increase the risk of haemolytic effects of other drugs (e.g. phenacetin, sulphonamide, quinine), in newborns with increased haemolysis it may increase the risk of nuclear icterus, first of all in interaction with drugs pushing out bilirubin from the binding with proteins (e.g. sulphonamides). Cholestyramine decreases vitamin K1 resorption from the digestive tube.

4.6 Pregnancy and lactation
Phytomenadione passes the placental barrier and in small amount also into breast milk. In premature infants, and new-borns the hepatal enzymatic system Is insufficiently developed and therefore nuclear icterus, icterus gravis and haemolytic anaemia may occur due to slow phytomenadlone biotransformation in the liver.

4.7 Effects on ability to drive and use machines
No effect on attention.

4.8 Undesirable effects
Occurrence in 0.5-1% of patients. Most frequently skin eruptions (0.2-0.4%), reactions at the place of administration (inflammation, burning pain in about 0.2%). In isolated cases cardiovascular collapse, sweating, cyanosis, bronchospasm. Haemolytic anaemia in G-6-P dehydrogenase deficiency, hyperbilirubinaemia in newborns.

4.9 Overdose
The toxicity of phytomenadione is low and an overdose does not cause clinical problems. Intravenous administration of a phytomenadione containing preparation may cause acute hypersensitive or anaphylactic reaction manifested by flush, sweating, pain in thorax, dyspnoea, cyanosis, bronchoconstriction and cardiovascular collapse, In new-borns, especially premature, high dose may cause haemolytic anaemia. Risk of nuclear icterus, caused by bilirubin push out from the binding on albumin, also threatens.
Treatment: In overdosage a treatment is not necessary, because the biological half-life of phytomenadione is short (1.2-3.5 hours),

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamin K and other hemostatics
ATC code: B02BA01

Preventive and therapeutic use of vitamin K1 is based on its important role in coagulation factors production in the liver and in favourable effect on K1 avitaminosis after intestinal flora impairment by antibiotics and chemotherapeutics. Vitamin K1 is active in factor II (prothrombin), factor VII (proconvertin), factor IX (Hageman's factor) and factor X (Stuart-Prower's factor) biosynthesis.

5.2 Pharmacokinetic properties
In the case of intramuscular application, vitamin K Is completely absorbed . It concentrates in the liver, but it does not stockpile, its concentration decreases quickly. A very small amount of vitamin K is laid down in tissues but it is also slowly decomposed.
Phytomenadlone is quickly biotransformed into more polar metabolites, excreted by the bile and urine (after conjugation as glucuronides).

5.3 Preclinical safety data
Embryotoxic, cytotoxic, teratogenic and carcinogenic effects of are not known. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Polysorbate 80
Sodium acetate anhydrous
Disodium edentate
Water for injection
Sodium content: 0.180 mg/mL, what corresponds to 0.0078 mMol/mL

6.2 Incompatibilities
The preparation is in a solution incompatible with dextrane, vitamin B12, hydantoins and barbiturates.

6.3 Shelf life
3 years

6.4 Special precautions for storage
Store at temperature 10 - 25°C. Store ampoules in outer carton, in order protect from light.

6.5 Nature and contents of container
Carton contains brown glass ampoule in PVC mould.
Package size : 5 ampoules of 1 ml.

6.6 Special precautions for disposal and other handling
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.


7. MARKETING AUTHORISATION HOLDER
 BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic 
8. MARKETING AUTHORISATION NUMBER(S) 
86 / 767 / 92-S / C 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
December 14th,1992/ September 22nd,1999
10. DATE OF REVISION OF THE TEXT