Active ingredients: Tranexamic acid
UGUROL 500 mg / 5 ml solution for injection for intravenous use, for oral and local use
Ugurol package inserts are available for packs:- UGUROL 500 mg / 5 ml solution for injection for intravenous use, for oral and local use
- UGUROL 250 mg tablets
Why is Ugurol used? What is it for?
UGUROL contains tranexamic acid, which belongs to a group of drugs called antihemorrhagics, antifibrinolytics, amino acids.
UGUROL is used in adults and children from one year of age to prevent and treat bleeding due to a process that inhibits blood clotting called fibrinolysis.
The specific indications are:
- heavy menstrual cycle;
- gastrointestinal bleeding;
- bleeding disorders of the urinary tract, following prostate surgery or urinary tract surgery;
- heart, abdomen or gynecological surgery;
- bleeding after treatment with other medicines to dissolve blood clots.
Contraindications When Ugurol should not be used
Do not take UGUROL:
- if you are allergic to tranexamic acid or any of the other ingredients of this medicine
- if you have a disease which leads to blood clots;
- if you have a condition called 'consumption coagulopathy' in which blood begins to clot in different parts of the body;
- if you have kidney problems;
- if you have had seizures in the past.
Due to the risk of cerebral edema and seizures, intrathecal and intraventricular injection and intracerebral application are not recommended.
If you think any of these apply to you, or if you have any other questions, talk to your doctor before taking UGUROL.
Precautions for use What you need to know before taking Ugurol
Tell your doctor if any of the following apply to you to help them decide if UGUROL is right for you:
- if you have noticed blood in your urine, this could be due to an obstruction in the urinary tract;
- if you are at risk for blood clots;
- if you have excessive clots or bleeding throughout your body (disseminated intravascular coagulation), UGUROL may not be suitable for you, unless you have acute severe bleeding and your blood tests have shown that the process that inhibits blood clotting, called fibrinolysis, be activated;
- if you have had seizures UGUROL should not be given. Your doctor should use the lowest possible dose to avoid seizures due to treatment with UGUROL;
- if you are undergoing prolonged treatment with UGUROL, attention should be paid to possible disturbances in color vision and, if necessary, treatment should be stopped. In case of prolonged use of UGUROL solution for injection, regular ophthalmological examinations are recommended (eye exams including visual acuity, color vision, fundus, field of vision, etc.). In case of pathological ophthalmological changes, in particular with diseases of the retina, your doctor must decide, after consulting a specialist, on the need for prolonged use of UGUROL solution for injection in your case.
Interactions Which drugs or foods can modify the effect of Ugurol
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription, vitamins, minerals, herbal medicines or dietary supplements.
In particular you should tell your doctor if you take:
- other medicines that help blood clot called antifibrinolytics;
- medicines that prevent blood clotting called thrombolytics;
- oral contraceptives.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor for advice if you are pregnant or breastfeeding before taking UGUROL.
Tranexamic acid is excreted in breast milk, therefore the use of UGUROL is not recommended during breastfeeding.
Driving and using machines
No studies on the ability to drive and use machines have been performed.
Dose, Method and Time of Administration How to use Ugurol: Posology
Take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or nurse.
Use in adults by the oral route
- Prophylaxis
If the solution is taken orally, diluting the contents of the ampoule with a little sugar water, the daily dosage is 1½-2 ampoules of Ugurol of 500 mg, starting the administration at least 1 day before the surgery and continuing the treatment for a period of not less than 3-4 days after the operation.
- Therapy
If the solution is taken orally, diluting the contents of the ampoule in a little sugar water, the daily dosage is 1-2 ampoules of Ugurol of 500 mg 3 times a day or ½-1 ampoule of Ugurol of 500 mg 6 times a day.
Oral administration is especially indicated:
- in hemorrhagic manifestations arising in internal medicine, otolaryngology and dentistry; for the preparation of surgical interventions in which it is assumed that haemorrhages from plasminic activation may arise;
- in hypermenorrhea;
- in gynecological gemices, cystitis and haemorrhagic proctitis following radiation therapy for genital carcinoma;
- for the maintenance of intravenous therapy in order to prevent recurrence of bleeding.
Intravenous use in adults
UGUROL solution is given as a slow injection into a vein. Your doctor will decide on the right dose for you and how long you need to take it for.
Use in adults for local application
For the local application of UGUROL 500 mg / 5ml solution, use the contents of 1 vial and pour it directly on the bleeding site or apply it using a previously soaked gauze pad.
Direct local application or by means of gauze pads, previously soaked in the solution, is especially indicated for bleeding at the oro-nasopharyngeal level in which rapid haemostasis is desired.
Use in children
If UGUROL solution is given to a child from one year of age, the dose will be calculated based on the child's weight. Your doctor will decide on the right dose for your child and how long you need to take it for.
Use in the elderly
There is no need to reduce the dose unless there is proven renal insufficiency.
Use in patients with kidney problems
If you have kidney problems, your dose of tranexamic acid will be reduced based on a blood test (serum creatinine level).
Use in patients with liver problems
There is no need to reduce the dose.
Method of administration
UGUROL solution should be administered slowly into a vein
UGUROL solution must not be injected into a muscle.
Overdose What to do if you have taken too much Ugurol
If you are given more UGUROL than the recommended dose
If you are given more UGUROL than the recommended dose, you may have a transient drop in blood pressure. Tell your doctor or pharmacist immediately.
If you forget to take UGUROL
Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Ugurol
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been observed with UGUROL:
Common (may affect up to 1 in 10 patients)
- effects on the stomach and intestines: nausea, vomiting, diarrhea.
Uncommon (may affect 1 to 10 users in 1000)
- effects on the skin: rash
Not known (frequency cannot be estimated from the available data)
- malaise with hypotension (low blood pressure), particularly if the injection was given too quickly;
- blood clots;
- effects on the nervous system: convulsions;
- effects on the eyes: visual disturbances including impaired color vision;
- effects on the immune system: allergic reactions.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children
Do not use this medicine after the expiry date which is stated on the carton after "Expires on". 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.
What UGUROL contains
The active ingredient is tranexamic acid.
Each 5 ml vial contains 500 mg of tranexamic acid. The other component is water for injections.
What UGUROL looks like and contents of the pack
UGUROL 500 mg / 5ml solution for injection for intravenous use, for oral and local use, box of 5 ampoules
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
UGUROL 500 MG / 5 ML SOLUTION FOR INJECTION FOR INTRAVENOUS USE FOR ORAL OR LOCAL USE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
a 5 ml ampoule contains: active ingredient: tranexamic acid 500 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Solution for injection for intravenous use, for oral or local use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Prevention and treatment of bleeding due to generalized or local fibrinolysis in adults and children from one year of age.
The specific indications are:
• bleeding caused by generalized or local fibrinolysis such as:
- menorrhagia and metrorrhagia,
- gastrointestinal bleeding,
- urinary bleeding disorders, following prostatic surgery or surgical procedures involving the urinary tract;
• ENT surgery (adenoidectomy, tonsillectomy, dental extractions);
• gynecological surgery or obstetric disorders;
• thoracic and abdominal surgery and other major surgeries such as cardiovascular surgery;
• management of bleeding due to administration of a fibrinolytic.
04.2 Posology and method of administration
Dosage
Adults
- Oral prophylaxis
If the solution is taken orally, diluting the contents of the ampoule with a little sugar water, the daily dosage is 1½-2 ampoules of Ugurol of 500 mg, starting the administration at least 1 day before the surgery and continuing the treatment for a period of not less than 3-4 days after the operation.
- Oral therapy
If the solution is taken orally, diluting the contents of the ampoule in a little sugar water, the daily dosage is 1-2 ampoules of Ugurol of 500 mg 3 times a day or ½-1 ampoule of Ugurol of 500 mg 6 times a day.
Oral administration is especially indicated:
- in hemorrhagic manifestations arising in internal medicine, otolaryngology and dentistry;
- for the preparation of surgical interventions in which it is assumed that bleeding from plasminic activation may arise;
- in hypermenorrhea;
- in gynecological gemices, cystitis and haemorrhagic proctitis following radiation therapy for genital carcinoma;
- for the maintenance of therapies initiated intravenously in order to prevent recurrence of haemorrhage.
- Intravenous therapy
Adults
Unless otherwise prescribed, the following doses are recommended:
1. standard treatment of local fibrinolysis:
0.5 g (1 x 5 ml ampoule) to 1 g (2 x 5 ml ampoules) of tranexamic acid by slow intravenous injection (= 1 ml / minute) two or three times a day
2. standard treatment of generalized fibrinolysis:
1 g (2 ampoules of 5 ml) of tranexamic acid by slow intravenous injection (= 1 ml / minute) every 6-8 hours, equal to 15 mg / kg body weight.
Kidney failure
In case of renal insufficiency which may involve a risk of accumulation, the use of tranexamic acid is contraindicated in patients with severe renal insufficiency (see section 4.3). For patients with mild to moderate renal impairment, the dose of tranexamic acid should be reduced based on the serum creatinine level.
Hepatic insufficiency
No dose adjustments are required in patients with hepatic insufficiency.
Senior citizens
There is no need to reduce the dose unless there is proven renal insufficiency.
- Therapy for local application
The content of 1 ampoule is normally used, which must be poured directly onto the site of the bleeding or applied with a previously soaked gauze pad.
Direct local application or by means of gauze pads, previously soaked in the solution, is especially indicated for bleeding at the oral, rhino-pharyngeal level in which rapid haemostasis is desired.
Pediatric population
Data on efficacy, posology and safety for the currently approved indications, as described in section 4.1, are limited.
- Oral prophylaxis
Administer the solution orally at a daily dose of 5-10 mg / kg starting the administration at least 1 day before the operation and continuing the treatment for a period of not less than 3-4 days after the operation.
In the case of taking the solution by mouth, dilute the contents of the vial with a little sugar water.
- Oral therapy
Administer the solution orally at a dose of 10-20 mg / kg 3 times a day or 5-10 mg / kg 6 times a day.
To take the solution see "Prophylaxis".
- Intravenous therapy
In children from one year of age, for the current approved indications described in section 4.1, the dose is around 20 mg / kg / day. However, there are few data on efficacy, posology and safety for these indications.
There are no comprehensive evaluations of the efficacy, posology and safety of tranexamic acid in children undergoing cardiac surgery. Currently available data are limited and are presented in section 5.1.
Method of administration
a) Intravenously
Administration must compulsorily take place by slow intravenous injection.
b) Orally
Orally, the solution is mainly indicated in children or in patients with swallowing difficulties.
c) For local application
Instructions for opening the vial
The vials are equipped with a safety pre-opening and must be opened as follows:
- position the vial as indicated in figure 1;
- exert pressure with the thumb placed over the COLORED DOT as shown in figure 2.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Acute venous or arterial thrombosis (see section 4.4).
Fibrinolytic conditions due to consumption coagulopathy except in cases where there is predominant activation of the fibrinolytic system with acute severe bleeding (see section 4.4).
Severe renal insufficiency (risk of accumulation).
History of seizures.
Intrathecal and intraventricular injection, intracerebral application (risk of cerebral edema and convulsions).
04.4 Special warnings and appropriate precautions for use
The above indications and method of administration must be strictly observed:
• intravenous injections should be given slowly
• Tranexamic acid must not be administered intramuscularly.
Convulsions
Cases of seizures have been reported in association with tranexamic acid treatment. In coronary artery bypass grafting (CABG) surgery, most cases have occurred following intravenous (IV) injection of high doses of tranexamic acid. with the lower recommended doses of tranexamic acid, the incidence of postoperative seizures was the same as in untreated patients.
Visual disturbances
Attention should be paid to possible visual disturbances, including visual impairment, blurred vision, impaired color vision and, if necessary, treatment should be stopped. In case of prolonged use of the tranexamic acid solution for injection, regular ophthalmological examinations are recommended (eye exams including visual acuity, color vision, fundus, visual field, etc.). In case of pathological ophthalmological changes, in particular with pathologies of the retina, the physician should decide, after consulting a specialist, on the need for prolonged use of tranexamic acid solution for injection in each individual case.
Hematuria
In case of upper urinary tract hematuria, there is a risk of urethral obstruction.
Thromboembolic events
Before using tranexamic acid, risk factors for thromboembolic disease should be considered. In patients with a history of thromboembolic disease or in those with a "high incidence of thromboembolic events in the" family history (patients at high risk of thrombophilia), Tranexamic acid solution for injection should only be administered if expressly indicated by the doctor, after consultation with an expert in haemostaseology and under close medical supervision (see section 4.3).
Tranexamic acid should be administered with caution in patients taking oral contraceptives due to the increased risk of thrombosis (see section 4.5).
Disseminated intravascular coagulation
Patients with disseminated intravascular coagulation (DIC) in most cases cannot be treated with tranexamic acid (see section 4.3). If a decision is made to administer tranexamic acid, this should only be done in patients in whom there is a "predominant activation of the fibrinolytic system with acute severe bleeding. Normally the haematological profile approaches the following: reduced time of lysis of the euglobulin clot; prolonged prothrombin time; decreased plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin and alpha-2 macroglobulin; normal plasma levels of the prothrombin complex, i.e. factors II (prothrombin), VIII and X; elevated plasma levels of fibrinogen breakdown products; normal platelet count. The above assumes that the underlying disease does not change. for itself the various elements of this profile. In these acute cases a single dose of 1 g of tranexamic acid usually or is it enough to control bleeding. The administration of tranexamic acid in DIC should only be considered if adequate haematological laboratory equipment is available and in the presence of expert personnel.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed. Concomitant treatment with anticoagulants can only take place under the close supervision of a physician experienced in this field. Medicinal products acting on haemostasis should be administered with caution in patients treated with tranexamic acid. There is a theoretical risk of a potential increase in thrombus formation, as occurs with estrogen. Alternatively, the antifibrinolytic action of the drug can be antagonized with thrombolytic drugs.
04.6 Pregnancy and breastfeeding
Women of childbearing potential must use effective contraceptives during treatment.
Pregnancy
There are insufficient clinical data on the use of tranexamic acid in pregnant women. Consequently, even if animal studies do not report teratogenic effects, as a precaution for use, the use of tranexamic acid is not recommended during the first trimester of pregnancy. Limited clinical data on the use of tranexamic acid in various bleeding conditions during the second and third trimester of pregnancy have not reported a deleterious effect to the fetus. Tranexamic acid can be used during pregnancy only if the expected benefits justify the potential risk.
Feeding time
Tranexamic acid is excreted in breast milk, therefore breastfeeding is not recommended.
Fertility
There are no clinical data on the effects of tranexamic acid on fertility.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
04.8 Undesirable effects
Adverse drug reactions reported in clinical trials and on the basis of post-marketing experience are listed below by system organ class.
Table with the list of adverse reactions
Adverse reactions reported are included in the table below and are listed by MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency. Within each frequency category, adverse reactions are listed in order of decreasing severity. Frequency categories are defined as follows: very common (≥1 / 10); common (≥1 / 100
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Street address.
04.9 Overdose
No cases of overdose have been reported.
The signs and symptoms can be dizziness, headache, hypotension and seizures. Seizures have been shown to occur more frequently with increasing dose.
Management of overdose should consist of supportive care.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihaemorrhagics, antifibrinolytics
ATC code: B02AA02
Tranexamic acid has an anti-haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.
A complex is formed which includes tranexamic acid and plasminogen; tranexamic acid binds to plasminogen when it is transformed into plasmin.
The activity of the tranexamic acid-plasmin complex on fibrin activity is lower than the activity of free plasmin alone.
Education in vitro showed that high doses of tranexamic acid reduced complement activity.
Pediatric population
Children from one year:
In the literature, 12 efficacy studies in pediatric cardiac surgery were identified which included 1073 children, 631 treated with tranexamic acid. Most of the studies were placebo controlled. The population studied was heterogeneous in terms of age, type of surgery, and dosage regimens. Results from tranexamic acid studies indicate less blood loss and less need for blood products in pediatric cardiac surgery with cardiopulmonary bypass (CPB) when there is a high risk of bleeding, especially in cyanotic patients or in patients undergoing repeated surgical interventions. The most appropriate dosage schedule was found to be:
- first bolus of 10 mg / kg after induction of anesthesia and before skin incision,
- continuous infusion of 10 mg / kg / h or injection into the priming fluid of the CPB pump at a dose appropriate to the CPB procedure, or according to the patient's weight at a dose of 10 mg / kg, or according to the priming volume of the pump CPB, with the last injection of 10 mg / kg at the end of the cardiopulmonary bypass operation.
Although the studies involved a very limited number of patients, the few available data indicate that continuous infusion is preferable, as it maintained therapeutic plasma concentrations throughout surgery.
No specific dose-effect and pharmacokinetic studies have been performed in children.
05.2 Pharmacokinetic properties
Absorption
Peak plasma concentrations of tranexamic acid are reached rapidly after a short intravenous infusion, after which plasma concentrations decrease in a multi-exponential manner.
Distribution
The plasma protein binding of tranexamic acid is approximately 3% at therapeutic plasma levels and appears to be entirely due to its binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is approximately 9-12 liters.
Tranexamic acid crosses the placenta. Following the administration of an intravenous injection of 10mg / kg to 12 pregnant women, the serum tranexamic acid concentration was between 10 and 53 mcg / ml, while that in the blood umbilical cord was between 4 and 31 mcg / ml. Tranexamic acid diffuses rapidly into the synovial fluid and synovial membrane. Following the administration of an intravenous injection of 10 mg / kg to 17 patients undergoing knee surgery, the concentrations in the synovial fluid were similar to those observed in the related serum samples. The concentration of tranexamic acid in a number of other tissues corresponds to a fraction of that observed in the blood (one hundredth in breast milk; one tenth in cerebrospinal fluid; one tenth in aqueous humor). Tranexamic acid was detected in semen, where it inhibits fibrinolytic activity but does not affect sperm migration.
Excretion
It is mainly excreted in the urine as unchanged drug. Urinary excretion via glomerular filtration is the major route of elimination. Renal clearance is equal to plasma clearance (110-116 ml / min). Tranexamic acid excretion is approximately 90% in the first 24 hours following intravenous administration of 10 mg / kg body weight. The half-life of tranexamic acid is approximately 3 hours.
Special populations
Plasma concentrations increase in patients with renal insufficiency.
No specific pharmacokinetic studies have been performed in children.
05.3 Preclinical safety data
Non-clinical data reveal no specific hazard in humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.
Epileptogenic activity was observed in the case of intrathecal use of tranexamic acid in animals.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
A 500 mg vial of tranexamic acid / 5 ml contains:
water for injections.
06.2 Incompatibility
None.
06.3 Period of validity
5 years
06.4 Special precautions for storage
None
06.5 Nature of the immediate packaging and contents of the package
box of 5 ampoules of 500 mg / 5 ml
box of 6 ampoules of 500 mg / 5 ml
06.6 Instructions for use and handling
07.0 MARKETING AUTHORIZATION HOLDER
Rottapharm S.p.A. - Galleria Unione, 5 - 20122 Milan
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. 021458029 - "500 mg / 5 ml solution for injection for intravenous use, for oral and local use" 5 ampoules
A.I.C. 021458031 - "500 mg / 5 ml solution for injection for intravenous use, for oral and local use" 6 ampoules
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Ugurol has been on the market since May 1970 / May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
December 2013
