Active ingredients: Urapidil
URAPIDIL STRAGEN 25 mg solution for injection
URAPIDIL STRAGEN 50 mg solution for injection
Why is Urapidil Stragen used? What is it for?
URAPIDIL STRAGEN contains the active substance Urapidil.
URAPIDIL STRAGEN belongs to the alpha blocker group of medicines. The action of this medicine is localized in the blood vessels (eg arteries and veins). It reduces blood pressure by relaxing the walls of the blood vessels.
URAPIDIL STRAGEN is used to treat severe cases of high blood pressure:
- in the event of an emergency when blood pressure is high, with organ injury that is rapidly life threatening;
- during and / or after surgery.
Contraindications When Urapidil Stragen should not be used
Do not use URAPIDIL STRAGEN
- if you are allergic to urapidil or any of the other ingredients of this medicine (listed in section 6).
- if you have a cardiac abnormality known as aortic stenosis or a blood vessel abnormality known as a cardiac shunt (except cardiac shunt from patients on dialysis).
Precautions for use What you need to know before taking Urapidil Stragen
Before using URAPIDIL STRAGEN your doctor should check:
- if you have ever had diarrhea or vomiting (or any other cause of reduced fluid in the body);
- if the sodium in the blood has decreased.
Interactions Which drugs or foods can modify the effect of Urapidil Stragen
Tell your doctor if you are taking or have recently taken any other medicines.
Tell your doctor before using this medicine if you are taking any of the following medicines as they may interact with URAPIDIL STRAGEN i.v. and this could alter their effectiveness or more likely cause side effects:
- Alpha blocker drugs used for urinary problems caused by prostate disease
- Any medicine that reduces blood pressure
- Beclofene (used to treat muscle spasms)
- Cimetidine (used to inhibit stomach acid production)
- Imipramine and neuroleptics (used to treat depression)
- Corticoids (anti-inflammatory agents, sometimes called "steroids").
URAPIDIL STRAGEN and alcohol
Take care if you drink alcohol while being treated with URAPIDIL STRAGEN. It can increase the effect of Urapidil.
Warnings It is important to know that:
Pregnancy and breastfeeding
The use of URAPIDIL STRAGEN i.v. during pregnancy is not recommended. There is no adequate information to evaluate the safety of the use of Urapidil in pregnant women.
If you experience a rise in blood pressure during pregnancy and need to be treated with this medicine, the decrease in blood pressure should be gradual and, in any case, should always be monitored by a doctor.
There are no data regarding the passage of Urapidil into breast milk. For safety reasons, breastfeeding is not recommended during treatment with URAPIDIL STRAGEN.
If you are pregnant, breast-feeding, think you may be pregnant or are planning to become pregnant, ask your doctor for advice before taking this medicine.
Driving and using machines
The use of URAPIDIL STRAGEN may affect your ability to drive or use machines, in particular: - at the start of treatment or in case of changes to treatment; - in case of simultaneous consumption of alcoholic beverages. If you feel unwell, it is not recommended to drive or operate machinery until the symptoms go away. U
RAPIDIL STRAGEN contains polypropylene glycol. This ingredient can cause alcohol-like symptoms.
URAPIDIL STRAGEN contains less than 23 mg of sodium per vial, ie it is essentially "sodium free". This means that you can use it even if you are on a low-salt diet.
Dose, Method and Time of Administration How to use Urapidil Stragen: Posology
Always take URAPIDIL STRAGEN exactly as your doctor has told you and if administered by trained healthcare professionals.
Dosage
Your doctor will decide on the appropriate dosage based on your health status.
Special patient groups
- Use in children below 18 years of age is not recommended due to a lack of information on safety and efficacy.
- For older people (over 65), a reduction in intake may be necessary.
- If you have liver disease (severe liver failure), the dosage should be reduced.
- If you have kidney disease (kidney dysfunction), tests may be needed to check your blood circulation.
- If you have heart failure caused by mechanical impairment, special precautions should be taken.
Method of administration
URAPIDIL STRAGEN is administered into a vein.
Duration of treatment
The duration of treatment of URAPIDIL STRAGEN should not exceed 7 days.
Overdose What to do if you have taken too much Urapidil Stragen
The main event of an overdose is a sudden drop in blood pressure when standing up, causing dizziness, lightheadedness or fainting (orthostatic hypotension). In this case, the patient should be placed on the back with the legs raised. If symptoms persist, contact your doctor immediately.
If you have any further questions on the use of this medicine, ask your doctor.
Side Effects What are the side effects of Urapidil Stragen
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur during treatment. You should contact your doctor, who will decide whether to stop or continue the treatment.
Common: may affect up to 1 in 10 patients: Nausea, dizziness and headache.
Uncommon: may affect up to 1 in 100 patients: Palpitations, increased or decreased heart rate, feeling of pressure in the chest and difficulty in breathing, vomiting, fatigue and sweating.
Rare: may affect up to 1 in 1000 patients: prolonged and painful erection, nasal congestion, allergic skin reactions (itching, unusual redness of the skin, rash).
Very rare: may affect up to 1 in 10,000 patients: Reduction in the number of platelets (clotting red blood cells); weakness, restlessness.
If any of the side effects gets serious, or if you notice any of the side effects mentioned in this leaflet, please contact your doctor.
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet.
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 and vial after EXP. The expiry date refers to the last day of that month.
Store below 30 ° C.
After first opening / dilution
Physical and chemical stability has been demonstrated for 50 hours at 15-25 ° C.
From a microbiological point of view, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user and would not be longer than 24 hours at 2 to 8 ° C, unless reconstitution / dilution has taken place under controlled and validated conditions.
For single use only.
Use immediately after first opening the vial.
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.
Deadline "> Other information
What URAPIDIL STRAGEN contains
The active ingredient is Urapidil.
- One 5 ml ampoule contains 25 mg of Urapidil.
- One 10 ml ampoule contains 50 mg of Urapidil.
- One 20 ml ampoule contains 100 mg of Urapidil.
The other ingredients are: Propylene glycol (see section 2), Sodium dihydrogen phosphate dihydrate, Hydrochloric acid (37% w / w), Disodium phosphate dihydrate, Hydrochloric acid (3.7% w / w), Sodium hydroxide (4% w / p), Water for injections.
What URAPIDIL STRAGEN looks like and contents of the pack
URAPIDIL STRAGEN 25 mg is a solution for injection in ampoule.
URAPIDIL STRAGEN 50 mg is a solution for injection in ampoule.
URAPIDIL STRAGEN 100 mg is a concentrate for solution for infusion in ampoule.
One box contains 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 -
URAPIDIL STRAGEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
1 ml contains 5 mg of urapidil.
The 5 ml ampoule contains 25 mg of urapidil.
The 10 ml vial contains 50 mg of urapidil.
The 20 ml vial contains 100 mg of urapidil.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
25 mg / 50 mg: Solution for injection, which can also be diluted for infusion.
100 mg: Concentrate for solution for infusion.
Clear, colorless solution with a pH of 5.6 to 6.6.
Free of visible particles.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Hypertensive emergencies (e.g. critical increase in blood pressure), severe and very severe forms of hypertensive disease, treatment-resistant hypertension.
Controlled lowering of blood pressure in hypertensive patients during and / or after surgery.
04.2 Posology and method of administration -
Hypertensive emergencies, severe and very severe forms of hypertension, and treatment resistant hypertension
Intravenous injection
10-50 mg of urapidil is administered slowly by intravenous injection under constant control of blood pressure. The hypotensive action usually occurs within 5 min.
from administration. The injection of 10-50 mg of urapidil can be repeated in relation to the trend in blood pressure.
The intravenous infusion or syringe pump is used to maintain the blood pressure level achieved with the injection.
For instructions on dilution of the medicinal product before administration, see section 6.6.
The maximum compatible amount is 4 mg urapidil per ml of solution for infusion.
Rate of administration: The rate of infusion is determined by the individual blood pressure situation. Infusion rate of the recommended starting dose: 2 mg / min.
Maintenance dose: On average 9 mg / h, referred to 250 mg of urapidil added to 500 ml of solution for infusion equivalent to 1 mg = 44 drops = 2.2 ml.
Controlled lowering of blood pressure in the event of an increase in blood pressure during and / or after surgery
The intravenous infusion or syringe pump is used to maintain the blood pressure level achieved with the injection.
Dosage
Note
Urapidil Stragen i.v. it is administered intravenously by infusion or injection to the patient in the supine position. The dose can be given as one or more injections or as a slow intravenous infusion. The injections can be combined with subsequent slow infusion.
Senior citizens
In older patients, antihypertensive drugs should be used with caution and initially in lower doses, since in these patients the sensitivity towards preparations of this kind is often modified.
Patients with impaired renal and / or hepatic function
In patients with impaired hepatic and renal function the dosage of urapidil may need to be reduced.
Pediatric population
The safety and efficacy of urapidil for intravenous use in children aged 0-18 years have not been established. No recommendation on a posology can be made.
Duration of treatment
From a toxicological point of view it is considered safe for a treatment period of 7 days; generally, this period should not be exceeded with parenteral antihypertensive drugs. Repeated parenteral treatment is possible if blood pressure rises again.
The overlap of acute parenteral therapy with the switch to continuous treatment with oral blood pressure lowering agents is possible.
04.3 Contraindications -
Urapidil Stragen must not be used in case of hypersensitivity (allergy) to the active substance or to any of the excipients. Urapidil Stragen i.v. it must not be used in cases of aortic stenosis of the isthmus or with arteriovenous shunt (except in the case of non-haemodynamically active dialysis shunt).
04.4 Special warnings and appropriate precautions for use -
Precautions for use
- In heart failure, caused by functional damage of mechanical origin, such as stenosis of the aortic or mitral valve, pulmonary embolism or weakening of cardiac action due to pericardial disease;
- In patients with liver function disorders;
- In patients with moderate to severe renal impairment;
- In elderly patients;
- In patients receiving concomitant treatment with cimetidine (see section 4.5
"Interactions with other medicinal products and other forms of interaction").
If urapidil has not been administered as a first-line antihypertensive agent, this should not be used until the effect of the previously administered antihypertensive drug has passed. The dosage of urapidil should be lower accordingly.
An excessively rapid fall in blood pressure can cause bradycardia or cardiac arrest.
When Urapidil Stragen is administered i.v., due to the presence of propylene glycol, alcohol-like symptoms may be observed.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, essentially sodium-free.
04.5 Interactions with other medicinal products and other forms of interaction -
The antihypertensive action of urapidil could be enhanced by the intake of alpha receptor blockers, including those administered for urological states, vasodilators and other drugs that lower blood pressure, volume depleted states (diarrhea, vomiting) and alcohol.
The combination of urapidil with baclofen should be considered very carefully, as baclofen may enhance the antihypertensive effect.
The concomitant use of cimetidine inhibits the metabolism of urapidil. The concentration of urapidil in serum may increase by 15%, so dose reduction may be considered.
The following concomitant administrations should be considered:
- imipramine (antihypertensive effect and risk of orthostatic hypotension);
- neuroleptics (antihypertensive effect and risk of orthostatic hypotension);
- corticoids (reduction of the antihypertensive effect through sodium water retention).
As adequate information is not yet available on the concomitant use of ACE inhibitors, this treatment is not recommended for now.
04.6 Pregnancy and breastfeeding -
Pregnancy
Administration of Urapidil Stragen during pregnancy is not recommended. There is no adequate information on the use of urapidil in pregnant women.
Animal studies have shown reproductive toxicity without teratogenicity (section 5.3). Due to limited studies, the potential risk in humans is unknown.
Feeding time
Due to the lack of data on excretion in breast milk, breastfeeding is not recommended in case of treatment with urapidil.
04.7 Effects on ability to drive and use machines -
This medicinal product has a minor influence on the ability to drive and use machines.
Individual response to treatment may vary from patient to patient. This is particularly true at the start of treatment, when changing treatment, or when taken concomitantly with alcohol.
04.8 Undesirable effects -
Many of the following side effects are due to a sudden drop in blood pressure, but experience has shown that they disappear within minutes, even during slow infusion; however, in relation to the severity of the undesirable effects, a suspension of treatment should also be considered.
04.9 Overdose -
Symptoms
Symptoms of overdose are: dizziness, orthostatic hypotension, collapse, fatigue and reduced reaction rate.
Overdose treatment
Excessive pressure drop can be alleviated by raising the legs or by restoring blood volume. If these measures are inadequate, a vasoconstrictor drug should be administered slowly intravenously, monitoring blood pressure. In very rare cases, intravenous injection of catecholamines is required ( e.g. adrenaline 0.5-1.0 diluted to 10 ml with isotonic sodium chloride solution).
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Peripherally acting antiadrenergic substances, alpha-adrenergic receptor blockers.
ATC code: C02CA06
Urapidil induces a lowering of systolic and diastolic pressure by reducing peripheral resistance.
Heart rate remains largely constant.
Cardiac output is unchanged: while it can increase in cases where it is reduced due to an increase in afterload.
Mechanism of action
Urapidil has both central and peripheral effects.
• Peripheral: Urapidil mainly blocks the postsynaptic alpha receptors and consequently inhibits the vasoconstrictor effect of catecholamines.
• At the central level: Urapidil also has a central action. It modulates the activity of the brain centers that control the circulatory system. Thus it inhibits a reflex increase in the tone of the sympathetic nervous system or reduces the sympathetic tone.
05.2 "Pharmacokinetic properties -
After intravenous administration of 25 mg of urapidil there is a biphasic trend of its concentration in the blood (initial phase of distribution, final phase of elimination). The distribution phase has a half-life of approximately 35 minutes. The volume of distribution is 0.8 (0.6-1.2) l / kg.
Urapidil is mainly metabolised in the liver. The main metabolite is urapidyl hydroxylated in position 4 of the phenyl ring, which does not possess an appreciable antihypertensive activity. The O-desmethyl urapidil metabolite has approximately the same biological activity as urapidil, but present only in small amounts.
The elimination of urapidil and its metabolites in humans is up to 50-70% renal; of which 15% of the administered dose is pharmacologically active urapidil; the remainder, mainly consisting of para-hydroxylated urapidyl without antihypertensive activity, is excreted via the faecal route.
The serum half-life after intravenous bolus administration is 2.7 h (1.8-3.9 h). The plasma protein binding of urapidil in human serum is 80% in vitro. This relatively low binding affinity of urapidil to plasma proteins may explain why there are no known interactions between urapidil and strongly plasma protein binding drugs.
In elderly patients and in subjects with marked hepatic and / or renal insufficiency, the volume of distribution and clearance of urapidil are reduced and the plasma half-life is longer. Urapidil crosses the blood-brain barrier and passes the placenta.
05.3 Preclinical safety data -
Acute toxicity
Studies with urapidil hydrochloride were conducted in mice and rats to test for acute toxicity.
The LD50 (referred to urapidil base) after oral administration is between 508 and 750 mg / kg body weight and after intravenous administration, between 140 and 260 mg / kg body weight. Toxicity was mainly observed as sedation, ptosis, reduced motility, loss of protective reflex and hypothermia, shortness of breath, cyanosis, tremors and convulsions before death.
Chronic toxicity / Sub-chronic toxicity
Chronic toxicity studies were conducted in rats following oral administration with food for over 6 and 12 months, using doses up to 250 mg / kg body weight / day. Sedation, ptosis, decreased weight gain, prolongation of the menstrual cycle and decreased uterus weight have been observed.
Chronic toxicity has been observed in dogs in studies over 6 and 12 months with doses up to 64 mg / kg body weight / day. Doses above 30 mg / kg body weight / day caused sedation, hypersalivation and tremor. No signs of clinical or histopathological changes were observed.
Potential to induce genetic mutation and tumor
In bacterial studies (AMES test, host-mediated assay), investigations on human lymphocytes and in the mouse bone marrow metaphase test, urapidil did not show any mutagenic characteristics. A DNA repair test on rat hepatocytes tested negative.
Carcinogenic studies in mice and rats at 18 and 24 months provided no relevant indication to humans of tumor inducing potential. In special studies in rats and mice, urapidil contributed to the increase in the level of prolactin. In rodents, the increase in the level of prolactin leads to growth of breast tissue. In view of what is known about the mechanism of action, this effect is not expected in humans receiving therapeutic doses, and cannot be determined in clinical trials.
Reproductive toxicity
Reproductive toxicity studies in rats, mice and rabbits did not provide any indication on the teratogenic effect.
Studies in rats and rabbits did not show reproductive toxicity of urapidil. Side effects resulted in a reduction in the pregnancy rate in rats; in a reduced increase in body weight and food and water intake in rabbits; a reduction in the percentage of live rabbit fetuses; and a reduction in the survival rate of perinatal fetuses and increased body weight of neonatal rats.
The reproduction study established that the menstrual cycle of the female rats was prolonged, as was also established by the chronic toxicity study. This effect, like the decrease in the weight of the uterus in the chronic test, is considered to be a result of the increase in the level of prolactin, which occurs in rodents after treatment with urapidil. Female fertility is not compromised.
However, due to the considerable differences between species, these results cannot be considered applicable to humans. In long-term clinical studies it was not possible to establish any influence on the pituitary gonadal axis in women.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Propylene glycol,
Sodium dihydrogen phosphate dihydrate,
Hydrochloric acid (37% w / w),
Disodium phosphate dihydrate,
Hydrochloric acid (3.7% w / w),
Sodium hydroxide (4% w / w),
Water for injections.
06.2 Incompatibility "-
This medicinal product cannot be mixed with other medicinal products except those mentioned in section 6.6.
The following active substances [or solution for reconstitution / dilution] must not be administered simultaneously:
alkaline solutions for injection and infusion.
This can cause cloudiness or flocculation.
06.3 Period of validity "-
3 years.
After first opening / dilution:
Physical and chemical stability has been demonstrated for 50 hours at 15-25 ° C.
From a microbiological point of view, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user and would not be longer than 24 hours at 2 to 8 ° C, unless reconstitution / dilution has taken place under controlled and validated conditions.
06.4 Special precautions for storage -
Store below 30 ° C.
For storage conditions of the diluted medicinal product, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package -
Clear glass vials (type I, Ph. Eur.)
Packaging: 5 ampoules.
06.6 Instructions for use and handling -
The 100 mg vial can be used to stabilize blood pressure by infusion. For initial treatment, ampoules containing 25 mg and 50 mg of urapidil are available. These dosages can also be used for intravenous infusion after dilution.
The dilution takes place under aseptic conditions.
The solution should be visually inspected prior to administration for the presence of particles and discolouration. Only clear, colorless solutions should be used.
Preparation of the diluted solution
- Intravenous infusion:
Add 250 mg of urapidil (2 vials of 100 mg of urapidil + 1 vial of 50 mg of urapidil) to 500 ml of one of the compatible solvents.
- Syringe pump:
Withdraw 100 mg of urapidil by means of a syringe pump and dilute to a volume of 50 ml with one of the compatible solvents.
Compatible solvents for dilution
- Sodium chloride 9 mg / ml (0.9%) solution for infusion
- Glucose 50 mg / ml (5%)
- Glucose 100 mg / ml (10%)
For single use only.
Any residual unused solution and the "bags / sachets" must be properly disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Stragen Nordic A / S
Helsingorsgade 8C
DK-3400 Hillerød
Denmark
08.0 MARKETING AUTHORIZATION NUMBER -
AIC n.040876017 - "25 mg Solution for injection" 5 5 ml glass ampoules
AIC n.040876029 - "50 mg Solution for injection" 5 glass ampoules of 10 ml
AIC n.040876031 - "100 mg Concentrate for solution for infusion" 5 Glass ampoules
of 20 ml
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
13.05.2013
10.0 DATE OF REVISION OF THE TEXT -
13.05.2013
