Active ingredients: Protamine (Protamine hydrochloride)
Protamina Meda 50 mg / 5 ml - solution for injection for intravenous use
Why is Protamine used - Generic drug? What is it for?
Protamina Meda contains protamine hydrochloride and belongs to a group of medicines called antidotes, substances used to counteract the undesirable effects associated with excessive doses of other substances including heparin. Heparin is a compound used to keep the blood fluid and if taken in excessive doses it can cause bleeding (profuse blood loss).
Protamina Meda is indicated in adults to cancel the effect of heparin.
Contraindications When Protamine should not be used - Generic drug
You will not be given Protamine MEDA
- if you are allergic to protamine hydrochloride or any of the other ingredients of this medicine.
Precautions for use What you need to know before taking Protamine - Generic drug
Talk to your doctor, pharmacist or nurse before you are given this medicine.
Before you are given Protamine MEDA, tell your doctor:
- if you have a "fish allergy;"
- if you have had a vasectomy (an operation that makes the man sterile);
- if you have diabetes and are on insulin-zinc-protamine therapy;
- if you have already been given protamine, because you may have an allergic reaction, even a serious one (see section 4 "Possible side effects").
Children and adolescents
This medicine is not recommended in children and adolescents (0-18 years), due to the lack of safety and efficacy studies.
Interactions Which drugs or foods can modify the effect of Protamine - Generic Drug
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. In particular, tell your doctor:
- if you have been given an antibiotic (a medicine used to treat infections caused by bacteria), intravenously (injection into a vein) such as cefazolin;
- if you have taken a contrast agent (substance used before a diagnostic test such as a CT scan or nuclear magnetic resonance imaging).
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to have a baby or are breast-feeding, ask your doctor for advice before you are given this medicine.
Pregnancy
Protamina Meda will only be given to you during pregnancy when clearly needed and after your doctor has assessed the benefits for you and the risks to the fetus.
Feeding time
If you are breast-feeding and are to be given this medicine, you will need to stop breast-feeding.
Effects on ability to drive and use machines
There are no known effects this medicine has on the ability to drive or use machines.
Dose, Method and Time of Administration How to use Protamine - Generic drug: Posology
This medicine will be given to you under the strict supervision of qualified medical personnel.
How many
The most suitable dose for you will be determined after your doctor has assessed the amount of heparin in your blood.
Like
Protamine MEDA will be given to you drip into a vein as a drip (infusion).
Your blood pressure and heart function will be checked while you are being given this medicine.
Overdose What to do if you have taken too much Protamine - Generic Drug
If you are given too much Protamine MEDA, you may experience profuse blood loss (haemorrhage).
In case of ingestion / intake of an excessive dose of Protamine Meda, contact the nearest hospital or immediately inform your doctor who will adopt the appropriate supportive therapy.
If you have any further questions on the use of Protamine MEDA, ask your doctor or nurse.
Side Effects What are the side effects of Protamine - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you experience any of the following side effects as your doctor will take the necessary measures:
- severe allergic reaction including anaphylactic shock • narrowing of the bronchi with difficulty in breathing (bronchospasm)
- strong decrease in blood pressure due to a decrease in the amount of blood circulating (cardiovascular collapse)
- arrest of the heart.
The following side effects have been observed during treatment with Protamine MEDA with the frequencies indicated:
Common (may affect up to 1 in 10 people)
- swelling of the hands, feet, ankles, face, lips, tongue and / or throat (angioedema)
- allergic reaction and hives
- decrease in blood pressure
- dilation of blood vessels
- hot flashes
- feeling of heat
- narrowing of the bronchi with difficulty in breathing (bronchospasm)
Rare (may affect up to 1 in 1000 people)
- decreased function of the heart (right ventricular failure or heart failure) due to high blood pressure in the lungs
- reduction in heart rate, i.e. the number of heart beats per minute
- severe decrease or increase in blood pressure
- increased blood pressure in the lungs (pulmonary arterial hypertension)
- swelling of the lungs (pulmonary edema)
- difficulty in breathing (dyspnoea)
- nausea
- He retched
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 via the national reporting system at www.agenziafarmaco.it/ it / responsible. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Store at a temperature not exceeding 25 ° C.
Do not use this medicine after the expiry date which is stated on the package after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Protamine MEDA contains
Protamine MEDA 50 mg / 5 ml solution for injection
1 vial contains:
- the active ingredient is: protamine hydrochloride 50 mg
- the other ingredients are: sodium chloride, hydrochloric acid 25%, sodium hydroxide 27%, water for injections.
What Protamine MEDA looks like and contents of the pack
Protamine MEDA, solution for injection is presented as a clear colorless to light yellow solution, contained in glass ampoules.
It is available in the following pack sizes 1 ampoule of 5 ml 10 ampoules of 5 ml.
Not all pack sizes may be marketed.
The following information is intended for medical or healthcare professionals only
Dose, method and time of administration
Protamine Meda is administered intravenously; instead it is inactive intramuscularly or subcutaneously. Intravenous administration should be done very slowly or by slow infusion after dilution. To avoid anaphylactic reactions in predisposed patients, a vial of Protamine Meda should preferably be administered as a drop by drop infusion, in 100-200 ml of physiological saline. The infusion solution should be used immediately after preparation. The amount of Protamine Meda actually needed depends on the amount of heparin circulating in the blood.
Inactivation of heparin after extracorporeal circulation
For the inactivation of heparin after the use of extracorporeal circulation, Protamina Meda can be used in the necessary quantities, modifying the dosage on the basis of repeated coagulation determinations (thrombin time, activated partial thromboplastin time).
One ml of protamine 1000 IU / ml (equal to 10 mg / ml) neutralizes about 1000 IU of heparin. The activity of coumarin anticoagulants is not neutralized by Protamine Meda.
Neutralization of unfractionated heparin
In case of severe bleeding after heparin administration, heparin treatment should be discontinued immediately and the protamine hydrochloride antagonist should be administered as follows:
Intravenously inject a vial of Protamine Meda. Depending on the severity it may be necessary to repeat the administration of a vial of Protamine Meda once or more times at 15 minute intervals.
The dose of protamine hydrochloride to be administered depends on the type and amount of heparin that must be neutralized in the circulating blood.
Usually, the dose of protamine hydrochloride that must be administered in cardiovascular surgery is determined by the activated clotting time (ACT), as it depends on both the amount of heparin administered and when the last heparin administration was given.
However, given the short half-life of heparin, the amount of protamine necessary for its neutralization is reduced as the time elapsed since injection increases.
Neutralization of low molecular weight heparin (LMW)
When low molecular heparin is neutralized, the possibility of a rapid and almost complete neutralization of their anti-factor IIa activity by protamine hydrochloride must be considered. Depending on the type of low molecular weight heparin, a " residual anti-factor Xa activity between 40 and 80%.
The dose of protamine hydrochloride needed to neutralize the different low molecular weight heparins is listed in the table below:
The administration of Protamine Meda should be considered only in severe cases, since the excess of protamine hydrochloride also exerts an anticoagulant effect and can induce anaphylactic reactions. To avoid giving too much protamine hydrochloride, Protamine Meda should only be administered until thrombin time is normalized.
Pediatric population
Safety and efficacy in children has not been established.
Overdose
During the neutralization of heparin, care must be taken to avoid an excess of protamine.
Signs and symptoms
In case of overdose of Protamina Meda, haemorrhages may occur as a result of the anticoagulant effect of the product.
Treatment
These bleeding can be stopped by controlled administration of heparin until the thrombin time is normalized.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PROTAMINA MEDA 50 MG / 5 ML SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial contains
Active principle:
Protamine hydrochloride 50 mg.
03.0 PHARMACEUTICAL FORM
Solution for injection for intravenous use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
To neutralize the action of heparin.
04.2 Posology and method of administration
Protamine Meda is administered intravenously; instead it is inactive intramuscularly or subcutaneously. Intravenous administration should be done very slowly. The amount of Protamine Meda actually needed depends on the amount of heparin circulating in the blood. Given the short half-life of heparin, the amount of protamine necessary for its neutralization is reduced as the time elapsed since the injection increases.
As a general guideline, in cases of heparin-induced bleeding it is recommended to administer a dose of Protamine Meda equal to 50% of the administered heparin dose (in I.U.) by administering slowly, i.e. within 2-5 minutes. If the heparin concentration is unknown, it is recommended not to administer more than 1 ml of protamine initially. If the bleeding does not stop within 15 minutes, the contents of a second vial of Protamine Meda will be injected.
Continue to give Protamine Meda only until the thrombin time has normalized to avoid giving too much protamine.
For the inactivation of heparin after the use of extracorporeal circulation, Protamina Meda can be used in the necessary quantities, modifying the dosage on the basis of repeated coagulation determinations (thrombin time, activated partial thromboplastin time).
One ml of Protamine Meda neutralizes 1000 I.U. of heparin. The activity of coumarin anticoagulants is not neutralized by Protamine Meda.
04.3 Contraindications
Known hypersensitivity to the drug or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Warnings:
Administration of Protamine carries the risk of anaphylactic reactions, which also include bronchospasm, cardiovascular collapse and cardiac arrest. For this reason, all necessary general and pharmacological measures must be taken to be able to treat such reactions. There are currently no studies on the safety and efficacy of Protamine Meda in children.
Precautions for use:
The intravenous injection of the drug must be given slowly (2-5 minutes). After 15 minutes from the first, a second vial can be injected. Further administrations of Protamina Meda must be preceded by laboratory tests on blood coagulation.
An excess of Protamine Meda causes a lengthening of the coagulation time.
If an allergic reaction to protamine is considered possible, basic antiallergic drug therapy should be administered in a sufficient dose and a test dose given before use of protamine.
Keep out of reach of children.
04.5 Interactions with other medicinal products and other forms of interaction
Protamina Meda neutralizes heparin to form a complex. Protamina Meda must not be mixed with other drugs, particularly antibiotics or contrast media, as it can lead to the formation of precipitates.
04.6 Pregnancy and breastfeeding
It is not known whether protamine can cause fetal harm when administered to pregnant women or whether it can affect reproductive capabilities. Therefore Protamina Meda should be administered to pregnant women only when clearly needed and when the possible benefits outweigh the potential risks to the fetus.
It is not known whether protamine is excreted in human milk; if its administration is indicated in a breastfeeding woman, it is advisable to interrupt breastfeeding.
04.7 Effects on ability to drive and use machines
You don't notice.
04.8 Undesirable effects
Nausea, vomiting, sensation of heat, bradycardia, dyspnoea, severe hypotension, may appear, especially following rapid intravenous administration. In rare cases, allergic reactions, even severe ones, with a state of shock have been observed.
Hypersensitivity reactions to the drug, of various kinds and at different sites, seem to develop in predisposed subjects, particularly in patients with a history of fish allergy, in patients undergoing vasectomy, in diabetic patients on insulin-zinc-protamine therapy or in case of of previous protamine exposure to neutralize heparin.
Contrary to what happens with other protamine salts, with protamine hydrochloride no heparin rebound phenomenon has been observed (this means reduction of heparin inactivation before the elimination of heparin-protamine complexes after extracorporeal circulation).
It has not been established whether the non-cardiogenic pulmonary edema associated with elevated albumin levels, which is observed with the use of protamine in cardiopulmonary bypass surgery, constitutes a particular clinical picture of anaphylactic reactions.
04.9 Overdose
In case of Protamine Meda overdose, haemorrhages may occur as a result of the anticoagulant effect of the product. Such haemorrhages can be stopped by controlled administration of heparin until thrombin time is normalized.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Protamines are strongly basic low molecular weight proteins. They consist of a relatively small number of amino acids, among which arginine predominates. Protamines are obtained from the testes of various salmon species. Protamines act in vitro and in vivo as antagonists of heparin, which is a strong acid, forming of inactive complexes, which have no anticoagulant effect. To neutralize 100 I.U. of heparin, approximately 1 mg of protamine (in the form of hydrochloride) is required in vitro. In practice, however, even a smaller amount is sufficient to inactivate any excess heparin, since the injected heparin quickly disappears from the circulation.
Protamine activity occurs within 1-2 minutes after intravenous administration. Given alone, protamine can have an anticoagulant effect.
05.2 Pharmacokinetic properties
Metabolism:
Protamine is enzymatically inactivated in plasma. Although the metabolic processes of the heparin-protamine complex are not known, it is possible that this complex is metabolized by the enzymes responsible for fibrinolysis, causing heparin to be released.
Distribution:
Following intravenous administration to animals, the highest tissue concentrations were found in the liver and kidneys.
Elimination:
protamine is eliminated mainly through the renal emunctorium and, to a small extent, also through the liver and biliary tract. It forms inactive complexes with heparin. The half-life of these complexes in the animal is 24 minutes.
05.3 Preclinical safety data
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
1 vial contains:
4 mg methyl p-hydroxybenzoate; propyl p-hydroxybenzoate 0.5 mg; water for injections ml 5.
06.2 Incompatibility
Protamina Meda neutralizes heparin forming a complex. Protamina Meda must not be mixed with other drugs, particularly antibiotics or contrast media, as it can lead to the formation of precipitates.
06.3 Period of validity
Stability in intact packaging: 5 years.
There is no reconstitution of the product.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
1 or 10 glass vials enclosed in the cardboard box together with the package leaflet.
06.6 Instructions for use and handling
There are no special instructions for using the product.
07.0 MARKETING AUTHORIZATION HOLDER
Meda Pharma S.p.A. - Viale Brenta, 18 - 20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Protamina Meda pack of 1 vial - AIC: 004698027
Protamina Meda pack of 10 ampoules - AIC: 004698039
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal June 2010
10.0 DATE OF REVISION OF THE TEXT
April 2010