Active ingredients: Valsartan
Tareg 3 mg / ml oral solution
Tareg package inserts are available for pack sizes:- Tareg 3 mg / ml oral solution
- Tareg 40 mg film-coated tablets, Tareg 80 mg film-coated tablets, Tareg 160 mg film-coated tablets, Tareg 320 mg film-coated tablets
- Tareg 80 mg capsules, Tareg 160 mg capsules
Why is Tareg used? What is it for?
Tareg belongs to a class of medicines known as angiotensin II receptor antagonists, which help control high blood pressure. Angiotensin II is a substance in the body that causes blood vessels to narrow, thereby leading to blood pressure. "increased pressure. Tareg works by blocking the effect of angiotensin II. The result is that the blood vessels relax and the pressure decreases.
Tareg 3 mg / ml oral solution can be used to treat high blood pressure in children and adolescents aged 6 to 18 years. When blood pressure is high, the workload on the heart and arteries increases. In the long run, this can damage the blood vessels of the brain, heart and kidneys and can lead to a stroke, heart failure or kidney failure. High blood pressure increases the risk of heart attack. Bringing blood pressure back to normal reduces the risk of developing these diseases.
Contraindications When Tareg should not be used
Do not take Tareg
- if you are allergic (hypersensitive) to valsartan or any of the other ingredients of Tareg listed at the end of this leaflet.
- if you have severe liver disease.
- if you are more than three months pregnant (it is also better to avoid Tareg in early pregnancy - see pregnancy section).
- if you have diabetes mellitus or kidney function impairment and are being treated with a blood pressure lowering medicine called aliskiren.
If any of these apply to you, do not take Tareg.
Precautions for use What you need to know before taking Tareg
Take special care with Tareg:
- if you have liver disease.
- if you have severe kidney disease or if you are on dialysis.
- if you suffer from a narrowing of the renal artery.
- if you have recently had a kidney transplant (received a new kidney).
- if you have severe heart problems, your doctor will be able to check your kidney function.
- if you have ever had swelling of the tongue and face caused by an allergic reaction called angioedema when taking other medicines (including ACE inhibitors), please tell your doctor. If these symptoms occur when you take Tareg, stop taking Tareg immediately and never take it again. See section 4, "Possible side effects".
- if you are taking medicines that increase potassium levels in the blood. These include potassium supplements or potassium-containing salt substitutes or potassium and heparin-sparing medications. Your blood potassium level may need to be checked at regular intervals.
- if you are under 18 years of age and are taking Tareg in combination with other medicines that inhibit the renin-angiotensin-aldosterone system (blood pressure lowering medicines), your doctor will check your kidney function and your blood potassium levels regular intervals.
- if you suffer from aldosteronism, a disease in which the adrenal glands produce too much aldosterone hormone. In this case, the use of Tareg is not recommended.
- if you have had fluid loss (dehydration) caused by diarrhea, vomiting or diuretics in high doses.
- you should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Tareg is not recommended in early pregnancy and must not be taken after the third month of pregnancy as it may cause serious harm to the baby if used at that stage (see pregnancy section).
- if you are taking any of the following classes of medicines used to treat high blood pressure: - an "" ACE inhibitor "such as enalapril, lisinopril etc. - aliskiren
If any of these apply to you, tell your doctor before taking Tareg.
Interactions Which drugs or foods may change the effect of Tareg
Taking Tareg with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those obtained without a prescription.
The effect of the treatment may be influenced if Tareg is taken with certain other medicines. It may be necessary to adjust the dosage, take other precautions or, in some cases, stop taking one of the medicines. This applies to any medicine, even those without medical prescription, especially:
- other medicines that lower blood pressure, especially those that increase the elimination of fluids (diuretics), ACE inhibitors (such as enalapril, lisinopril, etc.) or aliskiren.
- medicines that increase blood potassium levels such as potassium supplements, potassium-containing salt substitutes, potassium-sparing drugs and heparin.
- some types of pain relievers called non-steroidal anti-inflammatory drugs (NSAIDs).
- some antibiotics (rifampicin group), a drug used against transplant rejection (cyclosporine) and an antiretroviral drug used to treat HIV / AIDS infections (ritonavir). These drugs can increase the effect of Tareg.
- lithium, a medicine used to treat some psychiatric diseases.
Taking Tareg with food and drink
Tareg can be taken with or without food
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
- You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). As a rule, your doctor will advise you to stop taking Tareg before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Tareg. Tareg is not recommended at the start of your pregnancy. pregnancy and should not be taken after the third month of pregnancy as it may cause serious harm to the baby if taken after the third month of pregnancy.
- Tell your doctor if you are breastfeeding, or about to start breastfeeding. Tareg is not recommended for women who are breastfeeding and your doctor may choose another treatment for you if you wish to breastfeed, especially if your baby is just born. or was born premature.
Driving and using machines
Before you drive a vehicle, operate machinery, or perform other activities that require concentration, you should know your reaction to Tareg. Like many other medicines used to treat high blood pressure, Tareg can in rare cases cause dizziness and affect your ability to concentrate.
Important information about some of the ingredients of Tareg solution
- Tareg solution contains 0.3 g of sucrose per milliliter. Take this into account if you have diabetes mellitus. If your doctor has told you that he has an "intolerance to some sugars, contact him before taking Tareg solution. The amount of sucrose in Tareg solution can be harmful to your teeth."
- Tareg solution contains methyl parahydroxybenzoate (E218), which may cause allergic reactions even some time after taking the solution. The signs may include rash, itching, hives. If any of the side effects get serious, tell your doctor.
- Tareg solution contains poloxamer, which can make stools soft.
Dose, Method and Time of Administration How to use Tareg: Posology
Always take Tareg exactly as your doctor has told you to get the best results and reduce the risk of side effects. If in doubt, you should consult your doctor or pharmacist. Those with high blood pressure often don't notice any signs of this problem, and many feel as good as usual. For this reason it is very important that you keep regular appointments with your doctor, even when you are feeling well.
Read the instructions at the end of this chapter before using the oral syringe or measuring cup.
How much Tareg to take
Tareg solution should be taken once a day
- If you weigh less than 35 kg: the usual dose is 20 mg of valsartan (corresponding to 7 ml of solution).
- If you weigh 35 kg or more: o the usual dose is 40 mg of valsartan (corresponding to 13 ml of solution).
In some cases, your doctor may ask you to take:
- up to 40 mg of valsartan (corresponding to 13 ml of solution) for those weighing less than 35 kg;
- up to 80 mg of valsartan (corresponding to 27 ml of solution) for those who weigh 35 kg or more than 35 kg.
You can take Tareg with or without food.
Take Tareg at about the same time each day.
INSTRUCTIONS FOR USE OF THE ORAL SYRINGE AND DOSER GLASS
Read these instructions carefully before taking your medicine. They will help you to use the oral syringe and measuring cup correctly.
What will you use
A pressure adapter for the bottle:
- which must be inserted into the neck of the bottle.
- once inserted, it must not be removed.
A bottle containing the medicine:
- which has a child resistant screw cap.
- Always screw the cap back on after use.
One oral syringe:
- consisting of a transparent plastic tube with a piston inside.
- The oral syringe fits into the bottle adapter and is used to dose the required amount of medicine from the bottle. Use a new bottle adapter and oral syringe each time you start a new bottle of medicine.
A measuring cup:
- which can be used if the prescribed dose requires filling the syringe several times.
- After use and cleaning, always put the measuring cup back on top of the cap.
Insert the bottle pressure adapter into a new medicine bottle
- Remove the cap from the bottle by pressing down firmly and turning counterclockwise (as indicated above the cap).
- Holding the opened bottle upright on a table, push the bottle adapter firmly into the bottle neck as far as it will go.
Note: You may not be able to push the bottle adapter all the way in but this is not a problem as it will be forced into the bottle by screwing the cap back on. - Screw the cap back onto the bottle.
Preparation of a dose of the medicine
- Remove the cap from the bottle by firmly pressing down and turning counterclockwise (as indicated above the cap).
- Check that the plunger is fully pushed into the oral syringe.
- Holding the bottle upright, insert the oral syringe firmly into the bottle adapter.
- While holding the oral syringe in place, carefully turn the bottle and oral syringe upside down.
- Before measuring the dose, any large bubbles that may be retained in the oral syringe should be cleared. To do this:
- slowly pull the plunger down to completely fill the oral syringe with the medicine;
- then push the plunger in the opposite direction upwards so that the syringe is completely empty
Measurement of the dose of the medicine
Note: The total amount of solution that can be measured in the oral syringe is 5 ml. Depending on the prescribed dose, it may be necessary to repeat steps 10 to 16 several times. For example, if the prescribed dose is 13 ml, it will be necessary to dose the solution in three different steps: 5 ml + 5 ml + 3 ml.
- Identify the notch on the oral syringe that corresponds to the required amount of medicine.
- Slowly pull the plunger until the apex of the edge of the black ring inside is exactly aligned with the notch.
- Carefully return the bottle and oral syringe to an upright position.
- Remove the oral syringe from the bottle adapter with a gentle twisting motion.
Taking the medicine
- Stand upright.
- Put the end of the oral syringe into your mouth.
- Slowly press the plunger and swallow the medicine directly from the oral syringe.
- If the prescribed dose requires filling the syringe several times, you can pour the measured doses of medicine from the syringe into the measuring cup and then check the total volume of the solution.
- Drink all of the solution immediately.
- Screw the child resistant capsule back on after use.
- Cleaning the oral syringe
- Clean the outside of the oral syringe with a clean, dry cloth.
- Do this each time after using the oral syringe.
- Cleaning the measuring cup Rinse the measuring cup with water. Dry the measuring cup with a clean cloth and place it back on the cap of the bottle.
Overdose What to do if you have taken too much Tareg
If you take more Tareg than you should
In case of severe dizziness and / or fainting, contact your doctor immediately and lie down. If you have inadvertently taken too much Tareg solution, contact your doctor, pharmacist or hospital.
If you forget to take Tareg
If you forget to take a dose, take it as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose.
Do not take a double dose to make up for a forgotten dose.
If you stop taking Tareg
Stopping treatment with Tareg may cause your disease to get worse. Do not stop using the medicine unless your doctor tells you to.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Side Effects What are the side effects of Tareg
Like all medicines, Tareg can cause side effects, although not everybody gets them.
These side effects can occur with certain frequencies, defined as follows:
- very common: occurs in more than one in 10 patients
- common: affects 1 to 10 out of 100 patients
- uncommon: affects 1 to 10 users in 1,000
- rare: affects 1 to 10 out of 10,000 patients
- very rare: affects less than 1 in 10,000 patients
- not known: frequency cannot be estimated from the available data.
Some symptoms require immediate medical attention:
See your doctor right away if you have symptoms of angioedema (a particular allergic reaction), such as:
- swelling of the face, lips, tongue or pharynx
- difficulty in breathing or swallowing
- hives, itching
If you get any of these symptoms, stop taking Tareg and contact your doctor immediately (see also section 2 'Take special care with Tareg').
The side effects are:
common
- dizziness
- low blood pressure with or without symptoms such as dizziness and fainting when standing up
- reduced values of kidney function tests (sign of kidney dysfunction)
Uncommon
- angioedema (see section "Some symptoms require immediate medical attention")
- sudden loss of consciousness (syncope)
- feeling dizzy (vertigo)
- severely reduced kidney function (sign of acute kidney failure)
- muscle cramps, abnormal heart rhythm (signs of high blood potassium levels)
- shortness of breath, difficulty breathing when lying down, swelling of the feet or legs (signs of heart failure)
- headache
- cough
- abdominal pain
- nausea
- diarrhea
- tiredness
- weakness
Not known
- blistering of the skin (sign of bullous dermatitis)
- allergic reactions such as rash, itching and hives, fever symptoms, swollen joints and joint pain, muscle pain, swollen lymph nodes and / or flu-like symptoms (signs of serum sickness) may occur
- red papules, fever, itching (signs of an inflammation of the vessels also known as vasculitis)
- bleeding or bruising more frequently than usual (signs of thrombocytopenia)
- muscle pain (myalgia)
- fever, sore throat or mouth ulcers due to infections (symptoms of white blood cell deficiency, also called neutropenia)
- decrease in hemoglobin levels and decrease in the percentage of erythrocytes in the blood (which can lead to "anemia in severe cases)
- increased levels of potassium in the blood (which can cause muscle cramps and abnormal heart rhythms in severe cases)
- elevated liver function values (which may indicate liver damage) including elevated levels of bilirubin in the blood (which can cause yellow skin and eyes in severe cases)
- increased levels of blood urea nitrogen and serum creatinine levels (which may indicate an abnormal renal function)
The frequency of some of the side effects may vary depending on your condition. For example, effects such as dizziness and decreased liver function values were observed less frequently in adult patients treated for high blood pressure than in adult patients treated for heart failure or after a recent heart attack.
In children and adolescents the side effects are similar to those in adults.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
- Do not store above 30 ° C.
- Once opened, the bottle can be stored for up to 3 months at a temperature below 30 ° C.
- Keep out of the reach and sight of children
- Do not use Tareg after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.
- Do not use Tareg if you notice that the pack is damaged or shows signs of tampering.
- Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Tareg contains
- The active ingredient is valsartan.
- 1 ml of oral solution contains 3 mg of valsartan.
- The other ingredients are sucrose, methyl parahydroxybenzoate (E218), potassium sorbate, poloxamer, citric acid anhydrous, sodium citrate, cranberry flavored artificial, propylene glycol (E1520), sodium hydroxide, hydrochloric acid, purified water.
Description of what Tareg looks like and contents of the pack
Tareg 3 mg / ml oral solution is a clear, colorless to pale yellow solution.
- The solution is supplied in a pack containing a 180 ml amber glass bottle with a child resistant screw cap and a yellow guarantee ring. The bottle contains 160 ml of solution. It is available with a kit containing a push-in bottle adapter, a 5 ml polypropylene oral dosing syringe and a 30 ml polypropylene dosing cup.
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
TAREG 3 MG / ML ORAL SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of solution contains 3 mg of valsartan.
Excipients: each ml of solution contains 0.3 g of sucrose, 1.22 mg of methyl parahydroxybenzoate (E218) and 5 mg of poloxamer.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Clear, colorless to pale yellow solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of hypertension in children and adolescents aged 6 to 18 years.
04.2 Posology and method of administration
Dosage
Children and adolescents between the ages of 6 and 18
For children and adolescents who cannot swallow tablets, the use of Tareg oral solution is recommended. Systemic exposure and peak plasma concentration of valsartan is approximately 1.7-fold and 2.2-fold higher with the solution. than tablets.
The starting dose for Tareg oral solution is 20 mg (corresponding to 7 ml of solution) once daily in children and adolescents weighing less than 35 kg and 40 mg (corresponding to 13 ml of solution) once daily in children of weight equal to or greater than 35 kg. The dose should be adjusted based on blood pressure response up to a maximum dose of 40 mg of valsartan once daily (corresponding to 13 ml of solution) for children and adolescents weighing less than 35 kg and 80 mg of valsartan. (corresponding to 27 ml of solution) for children and adolescents with a body weight of 35 kg or more.
Switching from Tareg tablets to Tareg oral solution
Switching from Tareg tablets to Tareg solution is not recommended unless clinically necessary. If switching from Tareg tablets to Tareg oral solution is considered clinically indispensable, the dose of valsartan should be adjusted as described in the table below and blood pressure should be carefully monitored. The dose should be gradually adjusted based on blood pressure response and tolerability.
If switching from Tareg oral solution to Tareg tablets is considered clinically necessary, the same dose in milligrams should be administered initially. Subsequently, frequent checks of blood pressure should be performed, considering the possibility of an under-dosage and the dose should be further adjusted based on the blood pressure response and tolerability.
Children under the age of 6
Available data are described in sections 4.8, 5.1 and 5.2. However, the safety and efficacy of Tareg in children aged 1 to 6 years have not been established.
Use in pediatric patients aged 6 to 18 years with renal impairment
Use in pediatric patients with creatinine clearance on dialysis has not been studied, therefore valsartan is not recommended in these patients. No dose adjustment is required in pediatric patients with creatinine clearance> 30 ml / min. Renal function and Serum potassium should be monitored closely (see sections 4.4 and 5.2). In patients with renal impairment the concomitant use of Tareg with aliskiren is contraindicated (GFR 2) (see section 4.3).
Diabetes mellitus
In patients with diabetes mellitus the concomitant use of Tareg with aliskiren is contraindicated (see section 4.3).
Use in pediatric patients aged 6 to 18 years with hepatic impairment
As in adults, Tareg is contraindicated in pediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis (see sections 4.3, 4.4 and 5.2). Experience with the use of Tareg in pediatric patients with mild to moderate hepatic impairment is limited. In these patients the dose of valsartan should not exceed 80 mg.
Pediatric heart failure and recent myocardial infarction
Tareg is not recommended for the treatment of heart failure and recent myocardial infarction in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
Method of administration
Tareg can be taken with or without meals.
04.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients.
- Severe hepatic impairment, biliary cirrhosis and cholestasis.
- Second and third trimester of pregnancy (see sections 4.4 and 4.6).
- Concomitant use of angiotensin receptor antagonists (ARBs) - including Tareg - or angiotensin converting enzyme (ACEI) inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (GFR 2) (see sections 4.4 and 4.5).
04.4 Special warnings and appropriate precautions for use
Hyperkalemia
Concomitant use with potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other substances that may increase potassium levels (heparin, etc.) is not recommended. Blood potassium levels should be appropriately controlled. .
Kidney damage
To date, there is no experience on the safe use in patients with creatinine clearance 10 ml / min. (see sections 4.2 and 5.2). In patients with renal impairment the concomitant use of ARBs - including Tareg - or ACEIs with aliskiren is contraindicated (GFR 2) (see sections 4.3 and 4.5).
Hepatic insufficiency
In patients with mild or moderate hepatic impairment without cholestasis, Tareg should be used with caution (see sections 4.2 and 5.2).
Patients with sodium and / or volume depletion
In patients with severe sodium and / or volume depletion, such as those receiving high doses of diuretics, symptomatic hypotension may, in rare cases, occur after initiation of Tareg therapy. Sodium and / or volume depletion should be corrected before starting treatment with Tareg, e.g. by reducing the dose of the diuretic.
Renal artery stenosis
The safe use of Tareg in patients with bilateral renal artery stenosis or single kidney stenosis has not been established.
Short-term administration of Tareg to twelve patients with reno-vascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal haemodynamics, serum creatinine or blood urea nitrogen (BUN). However, since others Substances affecting the renin-angiotensin system may increase BUN and serum creatinine in patients with unilateral renal artery stenosis, monitoring of renal function is recommended during treatment with valsartan.
Kidney transplant
To date, there is no experience on the safe use of Tareg in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary aldosteronism should not be treated with Tareg as their renin-angiotensin system is not activated.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with all other vasodilators, special caution is required in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy (HOCM).
Diabetes
Tareg oral solution contains 0.3 g of sucrose per milliliter. This must be taken into account in patients with diabetes mellitus.
Hereditary fructose intolerance, glucose-galactose malabsorption or insufficiency of bagrasi-isomaltase
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take Tareg oral solution as it contains sucrose.
Methyl parahydroxybenzoate
Tareg oral solution contains methyl parahydroxybenzoate which may cause allergic reactions (including delayed).
Tareg oral solution contains poloxamer which may cause loose stools.
Pregnancy
Angiotensin II receptor antagonist therapy (AIIRA) should not be initiated during pregnancy. An alternative antihypertensive treatment with an established safety profile for use in pregnancy should be used for patients planning pregnancy. unless continued therapy with an AIIRA is considered essential. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Previous episodes of angioedema
Episodes of angioedema, with enlargement of the larynx and glottis, resulting in airway obstruction and / or swelling of the face, lips, pharynx and / or tongue, have been reported in patients treated with valsartan; some of these patients had had previous episodes of angioedema with other medicines, including ACE inhibitors. In patients who develop angioedema, treatment with Tareg should be stopped immediately and not restarted (see section 4.8).
Other conditions with stimulation of the renin-angiotensin system
In patients whose renal function may be dependent on the activity of the renin-angiotensin system (eg, patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and / or progressive azotaemia and, rarely, acute renal failure and / or death. Since valsartan is an angiotensin II receptor antagonist, it cannot be excluded that the use of Tareg may be associated with renal failure.
Double blockade of the Renin-Angiotensin-Aldosterone System (RAAS)
Hypotension, syncope, stroke, hyperkalaemia and changes in renal function (including acute renal failure) have been reported in susceptible individuals, especially when several medicinal products acting on this system are combined. Dual blockade of the renin-angiotensin-aldosterone system by combining aliskiren with an angiotensin converting enzyme (ACEI) inhibitor or angiotensin II receptor blocker (ARB) is therefore not recommended.
The use of aliskiren in combination with Tareg is contraindicated in patients with diabetes mellitus or renal impairment (GFR 2) (see section 4.3).
Pediatric population
Change of pharmaceutical form
Tareg oral solution is not bioequivalent to the tablet formulation and patients should not switch formulations unless clinically necessary. For dose guidance in this case, see section 4.2.
Kidney damage
Use in pediatric patients with creatinine clearance 30 ml / min (see sections 4.2 and 5.2). Renal function and serum potassium should be closely monitored during treatment with valsartan. In particular this applies when valsartan is administered in the presence other conditions (fever, dehydration) that can compromise kidney function.
In patients with renal impairment the concomitant use of ARBs - including Tareg - or ACEIs with aliskiren is contraindicated (GFR 2) (see sections 4.3 and 4.5).
Hepatic impairment
As in adults, Tareg is contraindicated in pediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis (see sections 4.3 and 5.2). Clinical experience with the use of Tareg in pediatric patients with mild or moderate hepatic impairment is limited. In these patients the dose should not exceed 80 mg.
04.5 Interactions with other medicinal products and other forms of interaction
Double blockade of the Renin-Angiotensin-Aldosterone System (RAAS) with ARB, ACEI or aliskiren
Caution is required when co-administering ARBs, including Tareg, with other RAAS blocking agents such as ACEIs or aliskiren (see section 4.4).
Concomitant use of ARBs - including Tareg - or ACEIs with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR 2) (see section 4.3).
Concomitant use not recommended
Lithium
In case of concomitant use of lithium with angiotensin converting enzyme inhibitors or with angiotensin II receptor antagonists, including Tareg, reversible increases in serum concentrations and in lithium toxicity have been reported. combination proves necessary, careful monitoring of serum lithium levels is recommended. If a diuretic is also given, the risk of lithium toxicity may presumably increase further.
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and other medicines that may increase potassium levels
If the use of the combination of valsartan and a medicinal product that alters potassium levels is necessary, monitoring of serum potassium levels is advised.
Concomitant use requiring caution
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid> 3 g / day), and non-selective NSAIDs
When angiotensin II antagonists are co-administered with non-steroidal anti-inflammatory drugs, attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of worsening of renal function. and induce an increase in serum potassium.At the beginning of the treatment it is therefore recommended to check the renal function, as well as an adequate hydration of the patient.
Conveyors
Data in vitro indicate that valsartan is a substrate of the hepatic uptake transporters OATP1B1 / OATP1B3 and the hepatic efflux transporter MRP2. The clinical relevance of this observation is unknown. Co-administration of uptake transporter inhibitors (eg rifampicin, cyclosporine) or efflux transporter (eg ritonavir) may increase systemic exposure to valsartan. Particular care should be taken when initiating or terminating concomitant treatment with these drugs.
Others
In interaction studies, no pharmacokinetic interactions of clinical relevance were found with valsartan or with any of the following medicinal products: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Pediatric population
In hypertensive children and adolescents, where underlying renal abnormalities are common, caution is advised in concomitant use of valsartan and other substances that inhibit the renin-angiotensin-aldosterone system and which may increase serum potassium. Renal function and serum potassium. must be checked carefully.
04.6 Pregnancy and lactation
Pregnancy
The use of angiotensin II receptor antagonists (AIIRAs) is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).
Epidemiological evidence on the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Although no controlled epidemiological data on risk with angiotensin II receptor antagonists (AIIRAs) are available, a similar risk may also exist for this class of medicinal products. An alternative antihypertensive treatment should be used for patients planning pregnancy. with a proven safety profile for use in pregnancy unless continued therapy with an AIIRA is considered essential. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and, if appropriate, alternative therapy should be started.
Exposure to AIIRAs during the second and third trimesters is known to induce fetal toxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). See also section 5.3 "Preclinical safety data".
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Neonates whose mothers have taken AIIRAs should be closely monitored for hypotension (see sections 4.3 and 4.4).
Feeding time
Since no data are available regarding the use of valsartan during lactation, the use of Tareg is not recommended and alternative therapies with a proven safety profile should be preferred for use during lactation, especially if breastfeeding. newborns and premature babies.
Fertility
Valsartan had no adverse effects on the reproductive capacity of male or female mice at oral doses up to 200 mg / kg / day. This dose is 6 times the maximum recommended human dose in terms of mg / m2 (the calculation is based on an oral dose of 320 mg / day and a patient of 60 kg).
04.7 Effects on ability to drive and use machines
No studies on the effect on the ability to drive have been performed. When driving vehicles or using machines, the possibility of occasional dizziness or tiredness should be considered.
04.8 Undesirable effects
In controlled clinical trials in adult hypertensive patients, the overall incidence of adverse reactions was comparable to that seen with placebo and is consistent with the pharmacology of valsartan. The incidence of adverse reactions did not appear to be related to dose or duration of treatment. nor was any association found with gender, age or ethnicity.
Adverse reactions reported in clinical trials, post-marketing experience and laboratory test results are listed in the table below by system organ class.
Adverse reactions are ranked by frequency, the most frequent first, according to the following definition: very common (≥ 1/10); common (≥ 1/100, 1/10); uncommon (≥ 1/1000,
It is not possible to attribute a frequency to adverse reactions reported from post-marketing experience and in laboratory test results and therefore these are reported with a frequency "not known".
- Hypertension
Pediatric population
Hypertension
The antihypertensive effect of valsartan was evaluated in two double-blind, randomized clinical trials in 561 pediatric patients aged 6-18 years. With the exception of isolated gastrointestinal disturbances (such as abdominal pain, nausea, vomiting) and dizziness, no relevant differences in the type, frequency and severity of adverse reactions were identified between the safety profile of pediatric patients aged 6 to 18 years and the previously reported profile in adult patients.
Neurocognitive and developmental evaluation of pediatric patients aged 6 to 16 years overall revealed no clinically relevant adverse influences after treatment with Tareg for up to one year.
In a double-blind, randomized study of 90 children aged 1 to 6 years, which was followed by an "one-year open label extension, two deaths and isolated cases of a marked elevation of transaminases were observed. These cases occurred in a population that had significant comorbidities. A causal relationship with Tareg has not been established. In a second study, in which 75 children aged 1 to 6 years were randomized, they did not occur. significant elevations in transaminases or deaths with valsartan treatment.
Hyperkalaemia has been observed most frequently in children and adolescents aged 6 to 18 years with underlying chronic kidney disease.
The safety profile observed in controlled clinical trials in post-infarct and / or heart failure adult patients differs from the general safety profile observed in patients with hypertension. This observation may be related to the underlying pathology. Adverse reactions observed in post-infarct and / or heart failure adult patients are listed below:
- Post-myocardial infarction and / or heart failure (studied in adult patients only)
04.9 Overdose
Symptoms
Overdose of Tareg can cause marked hypotension, which can lead to a reduced level of consciousness, circulatory collapse and / or shock.
Treatment
Therapeutic measures depend on the time of ingestion and the type and severity of the symptoms, giving priority to normalizing the circulatory conditions.
In case of hypotension it is best to place the patient in the supine position and quickly administer saline solutions.
It is unlikely that valsartan can be removed by hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Angiotensin II antagonists, unassociated.
ATC code: C09CA03.
Valsartan is a specific, potent orally active angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT1 receptor subtype, responsible for the known actions of angiotensin II. The increase in plasma Ang II levels resulting from valsartan's blockade of AT1 receptors may stimulate unblocked AT2 receptors, which appears to counterbalance the action of AT1 receptors. Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has a much greater (approximately 20,000-fold) affinity for the AT1 receptor than for the AT2 receptor.
Valsartan does not bind or block other hormone receptors or ion channels known for their importance in cardiovascular regulation.
Valsartan does not inhibit ACE, also known as kininase II, which converts Ang I to Ang II and degrades bradykinin. Since there is no effect on ACE or potentiation of the effects of bradykinin or substance P, angiotensin receptor antagonists are unlikely to be associated with cough. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (P
Use in adults
Administration of Tareg to patients with arterial hypertension leads to a reduction in blood pressure without affecting the heart rate.
In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs within 2 hours and peak blood pressure reduction is achieved within 4-6 hours. The antihypertensive effect persists for more than 24 hours after administration. In case of repeated administration, the antihypertensive effect is substantially present within 2 weeks and the maximum reduction in blood pressure is usually achieved within 4 weeks and is maintained over the course of one treatment. long-term. A further significant reduction in blood pressure is obtained by associating the drug with hydrochlorothiazide.
Abrupt discontinuation of Tareg was not associated with rebound hypertension or other adverse clinical events.
In hypertensive patients with type 2 diabetes and microalbuminuria, valsartan has been shown to reduce urinary albumin excretion. The MARVAL (Micro Albuminuria Reduction with Valsartan) study evaluated the reduction in urinary albumin excretion (UAE) with valsartan ( 80 - 160 mg / od) vs. amlodipine (5-10 mg / od), in 332 patients with type 2 diabetes (mean age: 58 years; 265 males) with microalbuminuria (valsartan: 58 mcg / min; amlodipine: 55.4 mcg / min), normal or elevated blood pressure and intact kidney function (creatinine
After 24 weeks, UAE decreased (p
The Tareg Reduction of Proteinuria (DROP) study further investigated the efficacy of valsartan in reducing urinary albumin excretion (UAE) in 391 hypertensive patients (BP = 150/88 mmHg) with type 2 diabetes, albuminuria (mean = 102 mcg / min; 20-700 mcg / min) and intact renal function (mean serum creatinine = 80 mcmol / l). Patients were randomized to one of three different valsartan dosages (160, 320, and 640 mg / od) and treated for 30 weeks. The aim of this study was to determine the optimal dose of valsartan to reduce UAE in hypertensive patients with type 2 diabetes. After 30 weeks, the percentage change in UAE was significantly reduced by 36% from baseline. with valsartan 160 mg (95% CI: 22% to 47%), and 44% with valsartan 320 mg (95% CI: 31% to 54%). It was found that 160-320 mg of valsartan produced clinically significant reductions in UAE in hypertensive patients with type 2 diabetes.
Hypertension (pediatric population)
The antihypertensive effect of valsartan was studied in four double-blind, randomized clinical trials conducted in 561 pediatric patients aged 6 to 18 years and in 165 pediatric patients aged 1 to 6 years. Renal and urinary disorders and obesity were the most common underlying medical conditions that could potentially contribute to the hypertension of the children enrolled in these studies.
Clinical experience in children aged 6 years and older
In a clinical study involving 261 hypertensive pediatric patients aged 6 to 16 years, patients weighing systolic blood pressure of 8, 10, 12 mmHg from baseline, respectively. Patients were re-randomized, either to continue receiving the same dose of valsartan or to switch to placebo. In patients who continued to receive medium and high doses of valsartan, downstream systolic blood pressure was -4 and -7 mmHg lower than in placebo-treated patients. In patients who received the low dose of valsartan, the downstream systolic blood pressure was similar to that of patients treated with placebo. Overall, the dose-dependent antihypertensive effect of valsartan was consistent across all demographic subgroups.
In another clinical study involving 300 hypertensive pediatric patients aged 6 to 18 years, eligible patients were randomized to receive either valsartan or enalapril tablets for 12 weeks. Children weighing ≥18 kg and diastolic blood pressure, with reductions of 9.1 mmHg with valsartan and 8.5 mmHg with enalapril.
Clinical experience in children under 6 years of age
Two clinical studies were conducted, with 90 and 75 patients aged 1 to 6 years, respectively. Children less than 1 year of age were not enrolled in these studies. In the first study, the efficacy of valsartan was confirmed compared to placebo, but a dose-response relationship was not demonstrated. In the second study, higher doses of valsartan were associated with a greater reduction in blood pressure, but the dose-response relationship. did not reach statistical significance and the treatment difference from placebo was not significant Due to these discrepancies, valsartan is not recommended in this age group (see section 4.8).
The European Medicines Agency has waived the obligation to submit the results of studies with Tareg in heart failure and heart failure after recent myocardial infarction in all subsets of the pediatric population. For information on pediatric use see section 4.2.
05.2 Pharmacokinetic properties
Absorption:
After oral administration alone, peak concentrations of valsartan are reached after 2-4 hours for the tablets and after 1-2 hours for the solution formulation. Its mean absolute bioavailability is 23% and 39% for the tablet and solution formulation, respectively. Food decreases the exposure (measured by the AUC, area under the plasma concentration curve) to valsartan by approximately 40% and the peak plasma concentration by approximately 50%, although approximately 8 hours after drug administration the concentrations plasma values of valsartan are similar in both fasted and non-fasted subjects. However, this reduction in AUC is not accompanied by a clinically significant reduction in therapeutic effect, therefore valsartan can be taken with or without food.
Distribution:
The steady-state volume of distribution of valsartan following intravenous administration is approximately 17 liters, indicating that valsartan does not distribute extensively to tissues. Valsartan is highly (94-97%) bound to serum proteins, primarily serum albumin.
Biotransformation:
Valsartan is not biotransformed to a high degree, as only about 20% of the dose is recovered as metabolites.Low concentrations of a hydroxylated metabolite (less than 10% of the AUC of valsartan) have been identified in plasma. This metabolite is pharmacologically inactive.
Excretion:
Valsartan exhibits multiexponential decay kinetics (t½α faeces (approximately 83% of the dose) and via the kidneys in urine (approximately 13% of the dose), primarily as unchanged drug. After intravenous administration, plasma clearance is approximately 2 l / h and its renal clearance is 0.62 l / h (approximately 30% of the total plasma clearance). The elimination half-life of valsartan is 6 hours.
Special patient groups
Altered kidney function
As would be expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no correlation was observed between renal function and systemic exposure to valsartan. Therefore, no dosage adjustment is required in patients with renal insufficiency (creatinine clearance> 10 ml / min). To date, no data are available on the safe use of the medicinal product in patients with creatinine clearance
Valsartan is extensively bound to plasma proteins and is unlikely to be removed by hemodialysis.
Altered liver function
About 70% of the absorbed dose is excreted in the bile, mainly in the unchanged form.
Valsartan does not undergo any noteworthy biotransformation. In patients with mild to moderate hepatic impairment, an exposure (AUC) practically double that seen in healthy subjects was observed. However, no correlation was observed between plasma concentrations of valsartan and the degree of hepatic dysfunction. Tareg it has not been studied in patients with severe hepatic dysfunction (see sections 4.2, 4.3 and 4.4).
Pediatric population
In a study of 26 hypertensive pediatric patients (aged 1 to 16 years) administered a single dose of a suspension of valsartan (mean 0.9 to 2 mg / kg, with a maximum dose of 80 mg), clearance (liters / h / kg) of valsartan was comparable over the age range of 1 to 16 years and similar to that of adults receiving the same formulation.
Kidney failure
Use in pediatric patients with creatinine clearance 30 ml / min. Renal function and serum potassium should be closely monitored (see sections 4.2 and 4.4).
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential.
In rats, maternally toxic doses (600 mg / kg / day) during the last days of pregnancy and lactation resulted in lower survival rates, lower weight gain and delayed development (cartilage detachment and canal opening). ear) in offspring (see section 4.6). These doses in rats (600 mg / kg / day) are approximately 18 times the maximum human dose on a mg / m2 basis (calculations assume a dose of 320 mg / day for a patient 60 kg weight).
In the course of non-clinical safety studies, high doses of valsartan (200 to 600 mg / kg body weight) caused a reduction in red cell parameters (erythrocytes, hemoglobin, hematocrit) and changes in red cell parameters in the rat. renal haemodynamics (slight increase in plasma urea and hyperplasia of the renal tubules and basophilia in males). These doses in rats (200 to 600 mg / kg / day) correspond to approximately 6 and 18 times the maximum human dose on a mg / m2 basis, respectively (calculations assume a dosage of 320 mg / day for a 60 kg patient weight).
In monkeys, similar doses caused similar, though more severe, changes, particularly in the kidneys, where evolution to nephropathy, including increases in urea and creatinine, occurred. Hypertrophy of the kidney juxtaglomerular cells was also observed in both species. All changes were attributed to the pharmacological activity of valsartan which causes prolonged hypotension, especially in monkeys. Renal juxtaglomerular cell hypertrophy does not appear to have any relevance for therapeutic doses of valsartan in humans.
Pediatric population
Daily oral administration of valsartan to neonatal and juvenile rats (days 7 to 70 after birth) at low doses, such as 1 mg / kg / day (approximately 10-35% of the maximum recommended pediatric dose of 4 mg / kg / day based on systemic exposure) resulted in persistent and irreversible kidney damage. These effects represent an expected exaggerated pharmacological event of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. Such effects are observed if rats are treated during the first 13 days of life.
This period coincides with 36 weeks of gestation in mankind, which could occasionally extend up to 44 weeks after conception. In the juvenile valsartan study, rats were treated up to day 70 and effects on renal development (postnatal weeks 4-6) cannot be excluded. In humans, the development of renal function is a continuous process during the first year of life. Consequently, a clinical relevance in children of older age cannot be excluded.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sucrose
Methyl parahydroxybenzoate (E218)
Potassium sorbate
Poloxamer
Anhydrous citric acid
Sodium citrate
Artificial blueberry flavoring (538926 C)
Propylene glycol (E1520)
Sodium hydroxide
Hydrochloric acid
Purified water
06.2 Incompatibility
Not relevant.
06.3 Period of validity
18 months.
06.4 Special precautions for storage
Do not store above 30 ° C.
Once opened, the bottle can be stored for up to 3 months at a temperature below 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
180 ml type III amber glass bottle with a white child resistant polypropylene cap, including a polyethylene seal and a yellow guarantee ring; the package also includes a kit containing a 5 ml polypropylene dosing syringe for oral administration, a pressure adapter for the bottle and a 30 ml polypropylene measuring cup.
Package: 1 bottle containing 160 ml of oral solution
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
UK
08.0 MARKETING AUTHORIZATION NUMBER
033178423 - "3 mg / ml oral solution" 1 glass bottle of 160 ml + dosing syringe of 5 ml + measuring cup of 30 ml
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
20/07/2010
