Phytomenadione Prefilled Syringe 1mg/0.5ml Taj Pharma

  1. Name of the medicinal product

Phytomenadione Prefilled Syringe 1mg/0.5ml Taj Pharma

  1. Qualitative and quantitative composition

Each 0.5ml Prefilled Syringe contains
Phytomenadione                                 1mg
Excipients                                           q.s.

  1. Pharmaceutical form

The Prefilled Syringe solution is clear to slightly opalescent, pale yellow in colour and contains the active constituent in a mixed micelles vehicle of glycocholic acid and lecithin.

  1. Clinical particulars

4.1 Therapeutic indications

Phytomenadione Prefilled Syringe is indicated for the prophylaxis and treatment of vitamin K deficiency bleeding (VKDB) in neonates and infants.

Phytomenadione Prefilled Syringe can be used, following specialist advice from a haematologist, as an antidote to anticoagulant drugs of the coumarin type in infants and children. For use as an antidote to anticoagulant drugs of the coumarin type in adolescents and adults, refer to Phytomenadione Prefilled Syringe  1mg/0.5ml.

4.2 Posology and method of administration

Prophylaxis of vitamin K deficiency bleeding (VKDB)

Healthy neonates of 36 weeks gestation and older:

Either:

– 1 mg administered by intramuscular injection at birth or soon after birth

or

– 2 mg orally at birth or soon after birth. The oral dose should be followed by a further dose of 2 mg at 4-7 days of age. A further 2 mg oral dose should be given at 1 month after birth. In exclusively formula fed infants the third oral dose can be omitted

Preterm neonates of less than 36 weeks gestation weighing 2.5 kg or greater, and term neonates at special risk (e.g. prematurity, birth asphyxia, obstructive jaundice, inability to swallow, maternal use of anticoagulants or antiepileptics): 1 mg IM or IV at birth or soon after birth. The amount and frequency of further doses should be based on coagulation status.

Preterm neonates of less than 36 weeks gestation weighing less than 2.5 kg: 0.4 mg/kg (equivalent to 0.04 ml/kg) IM or IV at birth or soon after birth. This parenteral dose should not be exceeded. The amount and frequency of further doses should be based on coagulation status.

There is evidence that oral prophylaxis is insufficient in patients with underlying cholestatic liver disease and malabsorption (see section 5.1).

CAUTION: care is required when calculating and measuring the dose in relation to the baby’s weight (10 times dosing errors are common).

Dosing information for preterm babies at birth for the prophylaxis of Vitamin K deficiency bleeding

Weight of the babyDose of vitamin K at birthInjection volume
1 kg0.4 mg0.04 ml
1.5 kg0.6 mg0.06 ml
2 kg0.8 mg0.08 ml
2.5 kg1 mg0.1 ml
Over 2.5 kg1 mg0.1 ml

Further oral doses in breast-fed infants have been advised, but safety or efficacy data for these additional doses is limited (see section 5.1).

Therapy of early and/or late vitamin K deficiency bleeding (VKDB)

Initially 1mg IV and further doses as required, depending on clinical picture and coagulation status. Vitamin K therapy may need to be accompanied by a more immediate effective treatment, such as transfusion of blood or blood clotting factors to compensate for severe blood loss and delayed response to vitamin K1.

Antidote therapy to anticoagulant drugs of the coumarin type

There have been no dose ranging studies performed to recommend a specific dose of Phytomenadione Prefilled Syringe used as an antidote to anticoagulant drugs of the coumarin type in infants and children. Suggested doses are detailed below. Phytomenadione Prefilled Syringe must be administered by intravenous injection in these patients. It is advisable that a hematologist is consulted about appropriate investigation and treatment in any infant or child in whom Phytomenadione Prefilled Syringe is being considered.

For patients on warfarin therapy, therapeutic intervention must consider the reason for the patient being on warfarin and whether or not anticoagulant therapy has to be continued (e.g. in a patient with mechanical heart valve or repeated thrombo-embolic complications) as vitamin K administration is likely to interfere with anticoagulation with warfarin for 2 – 3 weeks. For patients continuing to receive warfarin, the suggested dose for the partial reversal of anticoagulation is 30 micrograms/kg administered by IV injection. Phytomenadione Prefilled Syringe is only suitable for the administration of doses of 30 micrograms/kg in children weighing over 13 kg.

The suggested dose of vitamin K for patients requiring a complete reversal of a warfarin overdose is 250-300 micrograms/kg administered by IV injection. It should be noted that the earliest effect seen with vitamin K treatment is at 4 to 6 hours and therefore, in patients with severe haemorrhage, replacement with coagulation factor concentrates may be indicated (discuss with hematologist). Phytomenadione Prefilled Syringe is only suitable for the administration of doses of 250-300 micrograms/kg in children weighing over 1.6 kg. Prothrombin time should be measured 2 to 6 hours later and if the response has not been adequate, Phytomenadione Prefilled Syringe administration may be repeated. Frequent monitoring of vitamin K dependent clotting factors is essential in these patients.

Method of administration

Phytomenadione Prefilled Syringe can be administered by intramuscular or intravenous injection or by oral administration depending on the indication.

Parenteral use: For the administration of injection volumes of 0.04 ml (0.4 mg) to 0.1 ml (1 mg), 0.5 ml syringes with 0.01 ml graduations are recommended, see section 6.6 Instructions for use/handling.

Administration of Phytomenadione Prefilled Syringe by i.v. infusion is not recommended because Phytomenadione Prefilled Syringe must not be diluted or mixed with other parenteral medications. However, Phytomenadione Prefilled Syringe may be administered by injecting the dose into the lower part of an infusion set containing 5% dextrose or 0.9% sodium chloride running at ≥ 0.7 ml/minute, see section 6.2 Incompatibilities.

Oral use: For oral administration, oral dispensers are provided in the pack. After breaking the Prefilled Syringe open, 0.2 ml of solution should be withdrawn into the oral dispenser until it reaches the mark on the dispenser (0.2 ml = 2 mg vitamin K). Drop the contents of the dispenser directly into the baby’s mouth by pressing the plunger.

4.3 Contraindications

Use in patients with a known hypersensitivity to any of the constituents.

4.4 Special warnings and precautions for use

At the time of use, the Prefilled Syringe contents should be clear. Following incorrect storage, the contents may become turbid or present a phase-separation. In this case the Prefilled Syringe must no longer be used.

Parenteral administration to premature babies weighing less than 2.5kg may increase the risk for the development of kernicterus (bilirubin encephalopathy).

Infants with cholestatic disease must receive Phytomenadione Prefilled Syringe by intramuscular or intravenous injection since oral absorption is impaired in these patients.

Phytomenadione Prefilled Syringe must be administered by intravenous injection when used as an antidote to anticoagulant drugs of the coumarin type, as intramuscular injections may result in significant bleeding in these patients.

4.5 Interaction with other medicinal products and other forms of interaction

No significant interactions are known other than antagonism of coumarin anticoagulants.

4.6 Fertility, pregnancy and lactation

Not applicable

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

There have been reports of anaphylactoid reactions after intravenous injections of Phytomenadione Prefilled Syringe

Local irritation may occur at the injection site but is unlikely due to the small injection volume. Rarely, injection site reactions may occur which may be severe, including inflammation, atrophy and necrosis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

4.9 Overdose

There is no known clinical syndrome attributable to hypervitaminosis of vitamin K1.

The following adverse events have been reported concerning overdose with use of Phytomenadione Prefilled Syringe in neonates and infants: jaundice, hyperbilirubinaemia, increase GOT and GGT, abdominal pain, constipation, soft stools, malaise, agitation and cutaneous eruption. The causality of those cannot be established. The majority of these adverse events were considered non-serious and resolved without any treatment.

Treatment of suspected overdose should be aimed at alleviating symptoms.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihaemorrhagics (vitamins)

Phytomenadione Prefilled Syringe  is a preparation of synthetic phytomenadione (vitamin K1). The presence of vitamin K1 is essential for the formation within the body of prothrombin, factor VII, factor IX and factor X, and of the coagulation inhibitors, protein C and protein S.

Vitamin K1 does not readily cross the placental barrier from mother to child and is poorly excreted in breast milk.

Lack of vitamin K1 leads to an increased tendency to haemorrhagic disease in the newborn. Vitamin K1 administration, which promotes synthesis of the above-mentioned coagulation factors by the liver, can reverse an abnormal coagulation status due to vitamin K1 deficiency.

Paediatric population

A prospective randomised controlled study included 44 infants (1-26 weeks of age) with conjugated hyperbilirubinaemia (idiopathic neonatal hepatitis – 17 patients, biliary atresia – 13, total parenteral nutrition cholestasis – 3, Alagille’s syndrome -2, alpha 1 antitrypsin deficiency – 2, inspissated bile syndrome – 2, and 5 miscellaneous diagnoses (fructosaemia, galactosaemia, choledochal cyst, necrotising enterocolitis, cytomegalovirus hepatitis). The pharmacokinetics and efficacy of oral versus intravenous mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease was compared.

Main outcome measures were serum concentrations of vitamin K1 and undercarboxylated prothrombin (PIVKA-II) before and for up to 4 days after a single dose of mixed micellar K1 1 mg intravenously or 2 mg orally. A comparison was also made between K1 levels 24 hours after oral K1 administration with those of 14 healthy newborns given the same dose.

Results: At admission, 18 infants (41%) had elevated levels of serum PIVKA-II and eight (18%) had low K1 concentrations, indicative of subclinical vitamin K deficiency. Median serum K1 concentrations were similar in the oral and intravenous groups at baseline (0.92 v 1.15 ng/ml), rising to 139 ng/ml six hours after intravenous K1 but to only 1.4 ng/ml after oral administration. In the latter group, the low median value (0.95 ng/ml) and wide range (< 0.15–111 ng/ml) of serum K1 compared unfavourably with the much higher levels (median 77, range 11–263 ng/ml) observed in healthy infants given the same oral dose, and suggested impaired and erratic intestinal absorption in cholestatic infants. The severity of malabsorption was such that only 4/24 (17%) achieved an incremental rise in serum K1 > 10 ng/ml.

The data from a retrospective study indicate that weekly oral prophylaxis was effective in the prevention of VKDB. A total of 507 850 live babies were born during the study period, November 1992 to June 2000. Of these infants, 78% and 22% received oral and intra-muscular prophylaxis, respectively; i.e. about 396000 neonates received oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants as long as they were mainly breastfed. Oral vitamin K prophylaxis at birth 2 mg phytomenadione, followed by weekly oral vitamin K prophylaxis; 1 mg was administered by the parents until 3 months of age. No cases of VKDB were revealed, i.e. the incidence was 0–0.9:100000 (95% CI).

5.2 Pharmacokinetic properties

In the mixed micelle solution, vitamin K1 is solubilised by means of a physiological colloidal system consisting of lecithin and a bile acid.

Following oral administration vitamin K1 is absorbed from the small intestine. The systemic availability following oral dosing is approximately 50%, with a wide range of interindividual variability. Absorption is limited in the absence of bile.

After intramuscular administration vitamin K1 release into the circulation is prolonged, i.e. the IM route acts as a depot. A single 1mg IM dose results in comparable vitamin K1 concentrations at 1 month as two 2 mg doses (one given at birth and the other at one week).

Vitamin K1 accumulates predominantly in the liver, is up to 90% bound to lipoproteins in the plasma and is stored in the body only for short periods of time.

Vitamin K1 is transformed to more polar metabolites, such as phytomenadione-2,3-epoxide.

The half-life of vitamin K1 in plasma is approximately 72 hours in neonates and about 1.5 to 3 hours in adults. Vitamin K1 is excreted in bile and urine as the glucuronide and sulfate conjugates.

5.3 Preclinical safety data

None applicable

  1. Pharmaceutical particulars

6.1 List of excipients

Glycocholic acid, lecithin, sodium hydroxide, hydrochloric acid and water

6.2 Incompatibilities

Phytomenadione Prefilled Syringe must not be diluted before injection.

Do not dilute with sodium chloride containing solutions as precipitation may occur, see section 4.2 Posology and Method of Administration.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Phytomenadione Prefilled Syringe Ampoule solution should be stored below 25°C and be protected from light. The solution should not be frozen. Do not use if the solution is turbid.

6.5 Nature and contents of container

Amber glass Prefilled Syringes containing 2 mg phytomenadione in 0.2 ml. Plastic oral dispensers. Packs of 5.

6.6 Special precautions for disposal and other handling

See section 4.2 Posology and method of administration, section 4.4 Special warnings and precautions for use and section 6.2 Incompatibilities for advice regarding the administration of Phytomenadione Prefilled Syringe Paediatric.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

Phytomenadione Prefilled Syringe 1mg/0.5ml Taj Pharma

Patient Information Leaflet

Phytomenadione (vitamin K1)

Please read all of this leaflet carefully before your baby or child is given this medicine.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask the doctor, nurse or midwife.

This medicine has been prescribed for your child. Do not pass it on to others. It may harm them even if their symptoms are the same.

If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaflet, please tell the doctor, nurse or midwife.

In this leaflet:

  1. What Phytomenadione Prefilled Syringe 1mg/0.5ml is and what it is used for
  2. Before your baby or child is given Phytomenadione Prefilled Syringe
  3. How Phytomenadione Prefilled Syringe 1mg/0.5mlis given
  4. Possible side effects
  5. How Phytomenadione Prefilled Syringe 1mg/0.5mlis stored
  6. Further information
  7. What Phytomenadione Prefilled Syringe 1mg/0.5ml is and what it is used for

Phytomenadione Prefilled Syringe 1mg/0.5mlcontains a medicine called phytomenadione. This is a man-made vitamin called vitamin K1. Phytomenadione Prefilled Syringe 1mg/0.5mlis used for the following:

Babies who do not have enough vitamin K in their bodies. Giving Phytomenadione Prefilled Syringe 1mg/0.5mlprevents and treats bleeding caused by a lack of vitamin K. This is called ‘vitamin K deficiency bleeding’ (VKDB). This is a serious, but rare condition. All newborn babies are given vitamin K1 with their parent’s permission.

Babies and young children who may have had too much of certain medicines to thin their blood (called anticoagulants). Phytomenadione Prefilled Syringe 1mg/0.5mlis normally used to treat these children after advice from a specialist haematologist (blood doctor).

Phytomenadione Prefilled Syringe 1mg/0.5mlworks by helping your body make blood clotting factors. These blood clotting factors help stop bleeding.

  1. Before your baby or child is given Phytomenadione Prefilled Syringe

Your child must not be given Phytomenadione Prefilled Syringe 1mg/0.5mlif they are allergic (hypersensitive) to:

Phytomenadione or any of the other ingredients of Phytomenadione Prefilled Syringe 1mg/0.5ml (listed in Section 6: Further information).

If you are not sure if this applies to your child, talk to the doctor, nurse or midwife before they are given Phytomenadione Prefilled Syringe.

Take special care with Phytomenadione Prefilled Syringe

Check with your doctor, nurse or midwife before your child has Konakion if:

They have a problem with the flow of bile in their body (cholestatic disease). Bile is important in helping the body to use some vitamins.

Taking other medicines

Please tell your doctor, nurse or midwife if your child is taking or has recently taken any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Phytomenadione Prefilled Syringe 1mg/0.5ml can affect the way some medicines work. Also, some other medicines may affect the way Phytomenadione Prefilled Syringe 1mg/0.5ml works.

In particular, tell your doctor, nurse or midwife if your baby or child is taking medicines to stop their blood clotting (anticoagulants).

Important information about some of the ingredients of Phytomenadione Prefilled Syringe

Phytomenadione Prefilled Syringe 1mg/0.5ml is essentially ‘sodium free’ as it contains less than 1 millimole sodium (2.64 mg in each millilitre).

  1. How Phytomenadione Prefilled Syringe 1mg/0.5ml is given

Phytomenadione Prefilled Syringe 1mg/0.5mlcan be given to your child by injection into a vein or muscle or by mouth (orally). How it is given will depend upon what the medicine is being used for and whether your baby was born prematurely. The doctor will decide how much Phytomenadione Prefilled Syringe 1mg/0.5mlyour child needs.

Healthy babies delivered at or nearly full term

These babies will be given either:

A single injection (1 mg) either at birth or soon after, or

By mouth (oral) a first dose (2 mg) at birth or soon after. This is followed by a second 2 mg dose after 4 to 7 days and third 2 mg dose at 1 month. In exclusively formula fed infants the third oral dose can be omitted.

Premature babies or full-term babies at special risk of bleeding

These babies will be given Phytomenadione Prefilled Syringe 1mg/0.5ml as an injection at birth or soon after.

More injections may be given later if your baby is still at risk of bleeding.

Further doses:

Babies who are given vitamin K by mouth and who are breast-fed (not given formula milk) may need more doses of vitamin K by mouth.

Bottle-fed babies given the two doses of vitamin K by mouth may not need any more doses of vitamin K. This is because it is included in formula milk.

The instructions ‘How to give your baby Phytomenadione Prefilled Syringe 1mg/0.5ml by mouth’ are given later in this section (section 3).

Treatment of vitamin K deficiency bleeding (VKDB)

These babies will be given Phytomenadione Prefilled Syringe 1mg/0.5ml as an injection (usually 1 mg).

More injections may be given later if your baby is still at risk of bleeding. Some babies may also need a blood transfusion.

Treatment of too much blood thinning medicine

Treatment of children who have had too much blood thinning medicine is usually decided by a haematologist (blood doctor).

Phytomenadione Prefilled Syringe 1mg/0.5ml will be given by injection into one of your child’s veins (IV injection).

The doctor will usually check your child’s blood for the levels of clotting factors.

This check will be made 2 to 6 hours after giving Phytomenadione Prefilled Syringe.

If your child still does not have enough blood clotting factors, the doctor may give additional doses of Phytomenadione Prefilled Syringe.

If your baby gets more Phytomenadione Prefilled Syringe 1mg/0.5ml than they should

If your baby has had more Phytomenadione Prefilled Syringe 1mg/0.5ml than they should, talk to a doctor, nurse or midwife.

The following effects may happen to your baby; jaundice (signs of which are yellowing of the skin or the whites of the eyes), tummy ache, constipation, soft stools (poo), seeming unwell, being agitated (upset), a rash and changes to how well their liver works (shown up by blood tests).

If you forget to give your baby Phytomenadione Prefilled Syringe

If you forget to give your baby their dose of Phytomenadione Prefilled Syringe 1mg/0.5ml, talk to your health visitor, midwife or doctor about when to give the next dose.

Do not give your baby a double dose to make up for a forgotten dose.

If someone else takes your baby’s Phytomenadione Prefilled Syringe 1mg/0.5ml by mistake, they should talk to a doctor. If you have any further questions on the use of this medicine, ask your doctor, nurse or midwife.

  1. Possible side effects

Like all medicines, Phytomenadione Prefilled Syringe 1mg/0.5ml can cause side effects, although not everyone gets them.

The following side effects may happen with this medicine:

Allergic reactions

The signs may include:

Swelling of your baby’s or child’s throat, face, lips and mouth. This may make it difficult for them to breathe or swallow.

Sudden swelling of your baby’s or child’s hands, feet and ankles.

If your baby or child has an allergic reaction, tell a doctor straight away.

A reaction where the injection was given

Rarely this may be severe. Signs include redness, swelling, pain and it may cause a scar.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly.

  1. How Phytomenadione Prefilled Syringe 1mg/0.5ml is stored

Phytomenadione Prefilled Syringe 1mg/0.5ml Prefilled Syringe should be stored in their original packaging to protect them from light.

Phytomenadione Prefilled Syringe 1mg/0.5ml should be stored at a temperature below 25°C.

Keep out of the reach and sight of children.

Do not use Phytomenadione Prefilled Syringe 1mg/0.5ml after the expiry date printed on the pack.

Do not throw away any whole left-over Prefilled Syringe. Instead, return them to your pharmacist so that they can be disposed of carefully. Only keep them if your doctor tells you to.

  1. Further information

What Phytomenadione Prefilled Syringe 1mg/0.5ml contains

The active substance in Phytomenadione Prefilled Syringe 1mg/0.5ml2 mg/0.2 ml is vitamin K1 (phytomenadione). Each 0.2 ml of liquid medicine contains 2 mg vitamin K1.

Other ingredients are glycocholic acid, sodium hydroxide, lecithin, hydrochloric acid and water for injections.

What Phytomenadione Prefilled Syringe 1mg/0.5ml looks like and contents of the pack

Phytomenadione Prefilled Syringe 1mg/0.5ml is a slightly opalescent, pale yellow liquid (‘solution for injection).

Phytomenadione Prefilled Syringe 1mg/0.5ml is supplied as a Prefilled syringe.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com