1. Name of the medicinal product

Phytomenadione Injection BP 10mg/1ml Taj Pharma

  1. Qualitative and quantitative composition

a) Phytomenadione Injection BP 10mg/1ml
Each ml contains:
Phytomenadione                                 10mg
Polyethylated fattyacid                       70mg
Dextrose                                          37.5mg
Benzyl alcohol                                     9mg
HCL for pH adjustment.

  1. Pharmaceutical form

Amber glass ampoules containing 10mg phytomenadione in 1ml. The ampoule 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 Injection is indicated as an antidote to anticoagulant drugs of the coumarin type in the treatment of haemorrhage or threatened haemorrhage, associated with a low blood level of prothrombin or factor VII.

4.2 Posology and method of administration

Phytomenadione Injection ampoules are for i.v. injection.

Adults

Severe or life-threatening haemorrhage, e.g. during anticoagulant therapy: The coumarin anticoagulant should be withdrawn and an intravenous injection of Phytomenadione Injection given slowly (over at least 30 seconds) at a dose of 5 – 10 mg together with prothrombin complex concentrate (PCC). Fresh frozen plasma (FFP) may be used if PCC is not available. The patient’s INR should be estimated three hours later and, if the response has been inadequate, the dose should be repeated. Not more than 40 mg of Phytomenadione Injection should be given intravenously in 24 hours. Coagulation profiles must be monitored on a daily basis until these have returned to acceptable levels; in severe cases more frequent monitoring is necessary.

Dose recommendations for vitamin K1 therapy in patients with major and life threatening bleeding:

Anticoagulant Condition Intravenous vitamin K1 Concomitant therapy
Warfarin Major bleeding 5.0 mg PCC1
Life-threatening bleeding 5.0 to 10.0 mg PCC1

PCC, prothrombin complex concentrate

1 Fresh frozen plasma (FFP) may be used if PCC is not available

Less severe haemorrhage:

Treatment of asymptomatic patients with elevated INR values depends on factors such as the underlying indication for anticoagulation, INR value, length of time spent outside the therapeutic INR range, patient characteristics (e.g. age, comorbidity, concomitant medication), and the associated risk of major bleeding. The following dose recommendations are provided for therapeutic guidance only:

Dose recommendations for vitamin K1 therapy in patients with asymptomatic high International Normalised ratio (INR) with or without mild haemorrhage:

Anticoagulant INR Intravenous vitamin K1
Warfarin 5-9 0.5 to 1.0 mg
>9 1.0 mg

For small doses one or more ampoules of Phytomenadione Injection Paediatric (2 mg/0.2 ml: same solution) can be used.

Reversal of anticoagulation prior to surgery

Patients who require emergency surgery that can be delayed for 6-12 hours can be given 5 mg intravenous vitamin K1 to reverse the anticoagulant effect. If surgery cannot be delayed, PCC can be given in addition to intravenous vitamin K1 and the INR checked before surgery.

Use with anticoagulants other than warfarin

The dosing recommendations above apply to patients taking warfarin. There are limited data regarding reversal of the effects of other anticoagulants, such as acenocoumarol or phenprocoumon. The half lives of these anticoagulants are different to warfarin and different doses of vitamin K1 may be required.

Special dosage instructions

Elderly

Elderly patients tend to be more sensitive to reversal of anticoagulation with Konakion MM. The dosage for this patient group should therefore be at the lower end of the ranges recommended.

Instructions for infusion in adults

Phytomenadione Injection Ampoules are for intravenous injection and should be diluted with 55ml of 5% glucose before slowly infusing the product. The solution should be freshly prepared and protected from light. Phytomenadione Injection Ampoule solution should not be diluted or mixed with other injectables, but may be injected into the lower part of an infusion apparatus.

Children aged 1 to 18 years

It is advisable that a haematologist is consulted about appropriate investigation and treatment in any child in whom Phytomenadione Injection is being considered.

Likely indications for using vitamin K in children are limited and may include:

  1. Children with disorders that interfere with absorption of vitamin K (chronic diarrhoea, cystic fibrosis, biliary atresia, hepatitis, coeliac disease).
  2. Children with poor nutrition who are receiving broad spectrum antibiotics.
  3. Liver disease.
  4. Patients receiving anticoagulant therapy with warfarin in whom the INR is increased outside the therapeutic range and therefore are at risk of, or are bleeding, and those with an INR in the therapeutic range who are bleeding.

For patients on warfarin therapy, therapeutic intervention must take into consideration the reason for the child being on warfarin and whether or not anticoagulant therapy has to be continued (e.g. in a child with mechanical heart valve or repeated thromboembolic complications) as vitamin K administration is likely to interfere with anticoagulation with warfarin for 2 – 3 weeks.

It should be noted that the earliest effect seen with vitamin K treatment is at 4 – 6 hours and therefore in patients with severe haemorrhage replacement with coagulation factors may be indicated (discuss with haematologist).

Dose of vitamin K

There are few data available regarding use of Phytomenadione Injection in children over 1 year. There have been no dose ranging studies in children with haemorrhage. The optimal dose should therefore be decided by the treating physician according to the indication, clinical situation and weight of the patient. Suggested dosages based on clinical experience are as follows:

Children with major and life threatening bleeding

A dose of 5 mg vitamin K1 i.v. is suggested (together with PCC if appropriate, or FFP if PCC is not available).

Children with asymptomatic high International Normalised Ratio (INR) with or without mild haemorrhage

Intravenous vitamin K1 at doses of 30 micrograms/kg have been reported to be effective in reversing asymptomatic high (>8) INR in clinically well children.

The patient’s INR should be measured 2 to 6 hours later and if the response has not been adequate, the dose may be repeated. Frequent monitoring of vitamin K dependent clotting factors is essential in these patients.

Neonates and babies

Phytomenadione Injection Paediatric 2 mg/0.2 ml should be used in these patients (see separate prescribing information).

4.3 Contraindications

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

Phytomenadione Injection ampoules should not be administered intramuscularly because the i.m. route exhibits depot characteristics and continued release of vitamin K1 would lead to difficulties with the re-institution of anticoagulation therapy. Furthermore, i.m. injections given to anticoagulated subjects cause a risk of haematoma formation.

4.4 Special warnings and precautions for use

When treating patients with severely impaired liver function, it should be borne in mind that one Phytomenadione Injection Ampoule 10 mg/1ml contains 54.6mg glycocholic acid and this may have a bilirubin displacing effect. Careful monitoring of the INR is necessary after administration of Phytomenadione Injection in patients with severely impaired liver function.

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

In potentially fatal and severe haemorrhage due to overdosage of coumarin anticoagulants, intravenous injections of Phytomenadione Injection must be administered slowly and not more than 40 mg should be given during a period of 24 hours. Phytomenadione Injection therapy should be accompanied by a more immediate effective treatment such as transfusion of whole blood or blood clotting factors. When patients with prosthetic heart valves are given transfusions for the treatment of severe or potentially fatal haemorrhage, fresh frozen plasma should be used. The use of vitamin K1 in patients with mechanical heart valves is generally to be avoided, unless there is major bleeding.

Large doses of Phytomenadione Injection (not more than 40 mg per day) should be avoided if it is intended to continue with anticoagulant therapy because there is no experience with doses above this maximum of 40 mg per day and higher doses may give rise to unexpected adverse events. Clinical studies have shown a sufficient decrease in the INR with the recommended dosage. If haemorrhage is severe, a transfusion of fresh whole blood may be necessary whilst awaiting the effect of the vitamin K1.

Vitamin K1 is not an antidote to heparin.

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

There is no specific evidence regarding the safety of Phytomenadione Injection in pregnancy but, as with most drugs, the administration during pregnancy should only occur if the benefits outweigh the risks.

Konakion is not recommended for pregnant women as prophylaxis of vitamin K deficiency bleeding in the newborn.

4.7 Effects on ability to drive and use machines

None

4.8 Undesirable effects

There have been reports of anaphylactoid reactions after intravenous injections of Konakion MM. Very rarely, venous irritation or phlebitis has been reported in association with intravenous administration of Konakion mixed micelle solution.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Hypervitaminosis of vitamin K1 is unknown.

Reintroduction of anti-coagulation may be affected.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihaemorrhagics (vitamins),

Phytomenadione Injection is a synthetic preparation of vitamin K. The presence of vitamin K (i.e. vitamin K or substances with vitamin K activity) is essential for the formation within the body of prothrombin, factor VII, factor IX and factor X. Lack of vitamin K leads to an increased tendency to haemorrhage. When an antidote to an anticoagulant is necessary it is essential to use vitamin K1 itself, as vitamin K analogues are much less effective.

In the mixed micelles solution, vitamin K1 is solubilised by means of a physiological colloidal system, also found in the human body, consisting of lecithin and bile acid. Owing to the absence of organic solvents, the Konakion mixed micelles solution is well tolerated on intravenous administration.

5.2 Pharmacokinetic properties

In blood plasma, 90% of vitamin K1 is bound to lipoproteins. Following an intramuscular dose of 10mg vitamin K, plasma concentrations of 10 – 20mcg/l are produced (normal range 0.4 – 1.2mcg/l). Systemic availability following intramuscular administration is about 50% and elimination half-life in plasma is approximately 1.5 – 3 hours.

5.3 Preclinical safety data

None applicable.

  1. Pharmaceutical particulars

6.1 List of excipients

Glycocholic acid HSE
Sodium hydroxide Ph. Eur
Lecithin (phospholipon 100) HSE
Hydrochloric acid Ph. Eur.
Water for injection Ph. Eur.

6.2 Incompatibilities

None

6.3 Shelf life

The recommended shelf-life of Phytomenadione Injection Ampoules is 36 months.

6.4 Special precautions for storage

The recommended maximum storage temperature is 25°C. Do not use if the solution is turbid.

6.5 Nature and contents of container

Phytomenadione Injection is supplied in amber glass ampoules containing 10mg phytomenadione in 1ml. The ampoule 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.

6.6 Special precautions for disposal and other handling

See Section 4.2.

 

7.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 Injection BP 10mg/1ml Taj Pharma

Package Leaflet: Information for the patient

solution for injection

Phytomenadione (vitamin K1)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it
  • If you have any further questions, ask your doctor or
  • If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaflet, please tell your doctor or

What is in this leaflet:

  1. What Phytomenadione Injection is and what it is used for
  2. What you need to know before you are given Phytomenadione Injection
  3. How Phytomenadione Injection is given
  4. Possible side effects
  5. How to store Phytomenadione Injection
  6. Contents of the pack and further information

1. What Phytomenadione Injection is and what it is used for

Phytomenadione Injection contains a medicine called phytomenadione. This is a man-made vitamin called vitamin K1. Phytomenadione Injection is used for the following:

  • To prevent and treat bleeding after the use of certain medicines to thin the blood (called anti-coagulants).
  • To treat children (aged 1 year and older) who have liver disease or low levels of vitamin K in their body because of illness. Phytomenadione Injection is normally used to treat these children after advice from a specialist haematologist (blood doctor).

Phytomenadione Injection works by helping your body make blood clotting factors. These blood clotting factors help stop bleeding.

  1. What you need to know before you are given Phytomenadione Injection

You must not be given Phytomenadione Injection if you are allergic (hypersensitive) to phytomenadione or any of the other ingredients of Phytomenadione Injection (listed in Section 6: Further information).

If you are not sure if this applies to you, talk to your doctor or nurse before having Konakion.

Warnings and precautions

Check with your doctor or nurse before having Phytomenadione Injection if:

  • You have severe problems with your
  • You have an artificial heart

Other medicines and Phytomenadione Injection

Please tell your doctor or nurse if you are taking or have recently taken any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Phytomenadione Injection can affect the way some medicines work. Also some other medicines may affect the way Phytomenadione Injection works. In particular, tell your doctor or nurse if you are taking medicines to stop your blood clotting (anticoagulants).

Pregnancy and breast-feeding

Talk to your doctor before having Konakion if you are pregnant, think you are pregnant, or breastfeeding. Your doctor will then decide if you should receive Konakion.

Driving and using machines

Phytomenadione Injection is not likely to affect you being able to drive or use any tools or machines. Talk to your doctor if you notice any problems that might affect driving, using tools or machines while having Konakion.

Important information about some of the ingredients of Phytomenadione Injection

Phytomenadione Injection is essentially ‘sodium (a type of salt) free’ as it contains less than 1 mmol sodium (2.64 mg per 1 ml).

  1. How Phytomenadione Injection is given

Phytomenadione Injection will be given to you by a doctor or nurse. It will be given to you by injection into a vein or through a small tube into one of your veins (intravenous infusion).

Adults

  • For people who are bleeding after taking blood-thinning (anticoagulant) medicines, the usual dose is 5 to 10
  • For people who have severe bleeding the Konakion dose (5 to 10 mg) is usually given with a blood transfusion.
  • For people with mild bleeding or at risk of bleeding, the usual dose is 0.5 to 1
  • If you need to have emergency surgery you may be given 5 mg Konakion before surgery to reverse the effects of blood-thinning (anticoagulant)
  • The maximum dose is usually no more than 40 mg Konakion in 24

Your doctor will usually check your blood for the levels of clotting factors, 3 hours after having Phytomenadione Injection and, if you need them give you more doses of Phytomenadione Injection .

Elderly

Because elderly adults are sometimes more sensitive to Phytomenadione Injection your doctor may decide to start you on a lower dose. This dose may be increased or repeated if necessary.

Children (aged 1 to 18 years)

Phytomenadione Injection is normally used to treat children following advice from a specialist haematologist (blood doctor).

  • The dose is usually no more than 5
  • Some children may also need a blood transfusion.

The doctor will usually check the child’s blood for the levels of clotting factors, 2 to 6 hours after they have Phytomenadione Injection and, if necessary, give more doses of Phytomenadione Injection .

If you are given more Phytomenadione Injection than you should

Because Phytomenadione Injection is given by a doctor or nurse, it is unlikely that you or your child will be given too much or that you or your child will miss a dose. However, if you are worried talk to your doctor or nurse.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

  1. Possible side effects

Like all medicines Phytomenadione Injection may cause side effects, although not everyone will get them. The following side effects may happen with this medicine:

Allergic reactions

The signs may include:

  • Swelling of the throat, face, lips and mouth. This may make it difficult to breathe or
  • Sudden swelling of the hands, feet and

If you have an allergic reaction, tell a doctor straight away.

A reaction where the injection was given

The signs may include swelling and redness along the vein where the medicine was given, which is very tender or painful when touched.

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

  1. How to store Phytomenadione Injection
  • Your doctor or pharmacist is responsible for storing Phytomenadione Injection . They are also responsible for disposing of any unused Phytomenadione Injection correctly.
  • Keep out of the sight and reach of
  • Do not use Phytomenadione Injection after the expiry date printed on the pack.
  • Phytomenadione Injection ampoules should be stored at a temperature below 25°C.
6. Contents of the pack and other information

What Phytomenadione Injection contains

The active substance in Phytomenadione Injection Ampoules 10 mg/ml is vitamin K1 (phytomenadione). Each 1 ml of liquid medicine contains 10 mg vitamin K1.

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

What Phytomenadione Injection looks like and contents of the pack

Phytomenadione Injection is a slightly opalescent, pale yellow liquid (‘solution for infusion’). This liquid will be further diluted to make it weaker before it is given to you.

Phytomenadione Injection is supplied in amber coloured glass ampoules in packs of 10.

 

7.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