Active ingredients: Telmisartan
Pritor 20 mg tablets
Pritor package inserts are available for pack sizes:- Pritor 20 mg tablets
- Pritor 40 mg tablets
- Pritor 80 mg tablets
Indications Why is Pritor used? What is it for?
Pritor belongs to a class of medicines known as angiotensin II receptor antagonists. Angiotensin II is a substance in the body that causes blood vessels to constrict, thereby increasing blood pressure. Pritor blocks the effect of angiotensin II, causing the blood vessels to relax and thus lowering blood pressure.
Pritor is used to treat essential hypertension (high blood pressure) in adults. 'Essential' means that high blood pressure is not caused by any other condition.
High blood pressure, if left untreated, can damage blood vessels in many organs, which can sometimes lead to heart attack, heart or kidney failure, stroke, or blindness. Normally, high blood pressure has no symptoms before such damage occurs. Therefore, it is important to take regular blood pressure measurements to see if it is average.
Pritor is also used to reduce cardiovascular events (e.g. heart attack or stroke) in adults who are at risk because their blood supply to the heart or legs is reduced or blocked or they have had a stroke or have high diabetes. risk. Your doctor can tell you if you are at high risk for these events.
Contraindications When Pritor should not be used
Do not take Pritor
- if you are allergic to telmisartan or any of the other ingredients of this medicine
- if you are more than 3 months pregnant (it is also better to avoid Pritor in early pregnancy - see pregnancy section).
- if you have severe liver problems such as cholestasis or biliary obstruction (problems with the drainage of bile from the liver and gallbladder) or any other severe liver disease.
- if you have diabetes or impaired kidney function and you are being treated with a blood pressure lowering medicine containing aliskiren.
If you have any of the conditions listed above, tell your doctor or pharmacist before taking Pritor.
Precautions for use What you need to know before taking Pritor
Talk to your doctor if you have or have ever suffered from any of the following conditions or diseases:
- Kidney disease or kidney transplant.
- Renal artery stenosis (narrowing of the blood vessels of one or both kidneys).
- Diseases of the liver.
- Heart problems.
- Increased aldosterone levels (water and salt retention in the body with imbalance of several minerals in the blood).
- Low blood pressure (hypotension), which is more likely to occur if you are dehydrated (excessive loss of water from the body) or have a salt deficiency due to diuretic therapy ('diuretics'), a low-salt diet, diarrhea or vomiting.
- High levels of potassium in the blood.
- Diabetes.
Talk to your doctor before taking Pritor:
- if you are taking any of the following medicines used to treat high blood pressure:
- an ACE inhibitor (for example enalapril, lisinopril, ramipril), particularly if you have diabetes-related kidney problems.
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (such as potassium) in your blood at regular intervals. See also information under the heading "Do not take Pritor".
- if you are taking digoxin.
You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Pritor is not recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section).
In case of surgery or administration of anesthetics, you should tell your doctor that you are taking Pritor.
Pritor may be less effective in lowering blood pressure in ethnic African patients.
Children and adolescents
Pritor is not recommended for use in children and adolescents up to 18 years.
Interactions Which drugs or foods can change the effect of Pritor
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Your doctor may decide to change the dose of these other medicines or take other precautions. In some cases it may be necessary to stop taking one of these medicines. This mainly applies to the medicines listed below, taken at the same time as Pritor:
- Medicines containing lithium to treat some types of depression.
- Medicines that may increase blood potassium levels such as potassium-containing salt substitutes, potassium-sparing diuretics (some "diuretics"), ACE inhibitors, angiotensin II receptor antagonists, NSAIDs (non-steroidal anti-inflammatory drugs,
- eg. aspirin or ibuprofen), heparin, immunosuppressants (eg cyclosporine or tacrolimus) and the antibiotic trimethoprim.
- Diuretics, especially when taken at high doses with Pritor, can induce excessive loss of body water and low blood pressure (hypotension).
- If you are taking an ACE inhibitor or aliskiren (see also information under the headings: "Do not take Pritor" and "Warnings and precautions").
- Digoxin.
The effect of Pritor may be reduced when you take NSAIDs (non-steroidal anti-inflammatory medicines, eg aspirin or ibuprofen) or corticosteroids.
Pritor may increase the effect of other medicines used to lower blood pressure or medicines that have the potential to lower blood pressure (eg baclofen, amifostine).
In addition, low blood pressure may be aggravated by alcohol, barbiturates, narcotics or antidepressants. You may feel this low blood pressure as dizziness on standing up. Consult your doctor if you need to change the dose of your other medicines while taking Pritor
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Pritor before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Pritor. Pritor is not recommended at all. early pregnancy and must not be taken if you are more than 3 months pregnant as it may cause serious harm to your baby if taken after the third month of pregnancy.
Feeding time
Tell your doctor if you are breastfeeding or about to start breastfeeding. Pritor is not recommended for women who are breastfeeding and your doctor may choose another treatment for you if you wish to breastfeed, especially if the baby is newborn or was born prematurely. .
Driving and using machines
Some patients may feel dizzy or sleepy when taking Pritor. If these effects occur, do not drive or use machines.
Pritor contains sorbitol.
If you are intolerant to any sugars, consult your doctor before taking Pritor.
Dosage and method of use How to use Pritor: Dosage
Always take Pritor exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose of Pritor is one tablet a day. Try to take the tablet at the same time each day. You can take Pritor with or without food. The tablets should be swallowed with some water or another non-alcoholic drink. It is important to take Pritor every day until your doctor tells you otherwise. If you have the impression that the effect of Pritor is too strong or too weak, consult your doctor or pharmacist.
For the treatment of high blood pressure, the recommended dose of Pritor for most patients is one 40 mg tablet per day to control blood pressure over a 24 hour period. Your doctor has recommended a lower dose of 20 mg per day. Pritor can also be used in combination with diuretics such as hydrochlorothiazide, which have been shown to have an additive effect with Pritor in terms of blood pressure lowering.
For the reduction of cardiovascular events, the usual dose of Pritor is one 80 mg tablet once a day. At the start of preventive therapy with Pritor 80 mg, blood pressure should be checked frequently.
If your liver is not functioning properly, the usual dose of 40 mg per day should not be exceeded.
Overdose What to do if you have taken too much Pritor
If you take more Pritor than you should
If you have taken too many tablets by mistake, contact your doctor or pharmacist, or the nearest hospital emergency department immediately.
If you forget to take Pritor
If you forget to take your medicine, don't worry. Take it as soon as you remember, then continue as before. If you miss the dose on one day, take your normal dose the next day. 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 Pritor
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects can be serious and need immediate medical attention:
You should see your doctor immediately if you experience any of the following symptoms:
Sepsis * (often called "blood infection" is a serious infection with an inflammatory response of the whole body), rapid swelling of the skin and mucous membranes (angioedema); these side effects are rare (may affect up to 1 in 1,000 people), but extremely serious and patients should stop taking the medicine and consult their doctor immediately. If left untreated, they can be fatal.
Possible side effects of Pritor:
Common side effects (may affect up to 1 in 10 people):
Low blood pressure (hypotension) in patients treated for the reduction of cardiovascular events. Uncommon side effects (may affect up to 1 in 100 people): Urinary tract infections, upper respiratory tract infections (e.g. sore throat, sinusitis, common cold), reduced red blood cells (anemia), high blood potassium in the blood, difficulty falling asleep, feeling sad (depression), fainting (syncope), feeling spinning (dizziness), slow heartbeat (bradycardia), low blood pressure (hypotension) in patients treated for high blood pressure feeling unsteady on standing up (orthostatic hypotension), shortness of breath, cough, abdominal pain, diarrhea, abdominal discomfort, swelling, vomiting, itching, increased sweating, drug rash, back pain, muscle cramps, muscle pain (myalgia), renal impairment including acute renal failure and chest pain, feeling of weakness, increased blood creatinine levels gue.
Rare side effects (may affect up to 1 in 1,000 people):
Sepsis * (often called "blood infection" is a severe infection with a whole body inflammatory response that can lead to death), increase in some white blood cells (eosinophilia), low platelet count (thrombocytopenia), severe allergic reaction (anaphylactic reaction ), allergic reaction (e.g. rash (rash), itching, difficulty in breathing, wheezing, swelling of the face or low blood pressure), low blood sugar levels (in diabetic patients), feeling anxious, sleepy, abnormal vision, rapid heartbeat (tachycardia), dry mouth, stomach upset, altered taste (dysgeusia), impaired liver (liver) function (Japanese patients are more prone to this side effect), rapid swelling of the skin and mucosal which can also lead to death (angioedema including fatal outcome), eczema (skin disorder), redness of the skin (hives), severe rash d o medication, joint pain (arthralgia), pain in extremity, tendon pain, flu-like illness, decrease in hemoglobin (a blood protein), increase in uric acid levels, increase in liver enzymes or creatine phosphokinase in the blood .
Very rare side effects (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease) **.
* The event may have occurred by chance or could be related to a mechanism currently unknown.
** There have been reports of progressive scarring of lung tissue while taking telmisartan. However, it is not known whether telmisartan was the cause.
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 listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
This medicinal product does not require any special storage temperatures. Store in the original package in order to protect from moisture. Take your Pritor tablet out of the blister only immediately before taking.
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 Pritor contains
The active substance is telmisartan. Each tablet contains 20 mg of telmisartan.
The other ingredients are povidone, meglumine, sodium hydroxide, sorbitol (E420) and magnesium stearate.
What Pritor looks like and contents of the pack
Pritor 20 mg tablets are white, round, imprinted with the company logo and the code 50H.
Pritor is available in blisters containing 14, 28, 30, 56, 90 or 98 tablets.
Not all pack sizes may be marketed.
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
PRITOR 20 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 20 mg telmisartan.
Excipients with known effects:
Each tablet contains 84 mg of sorbitol (E420).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets
White, round tablets of 2.5 mm, debossed with the code "50H" on one side and the company logo on the other side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hypertension
Treatment of essential hypertension in adults.
Cardiovascular prevention
Reduction of cardiovascular morbidity in adults with:
• manifest atherothrombotic cardiovascular disease (history of coronary artery disease, stroke or peripheral arterial disease) or
• type 2 diabetes mellitus with documented target organ damage.
04.2 Posology and method of administration
Dosage
Treatment of essential hypertension
The generally effective dose is 40 mg once a day. Some patients may already benefit from the 20 mg once daily dose. In cases where blood pressure control is not achieved, the dose of telmisartan can be increased to a maximum of 80 mg once daily. Alternatively, telmisartan can be used in combination with thiazide diuretics, such as hydrochlorothiazide, which has been shown to have an additive blood pressure lowering effect, in combination with telmisartan. When considering a dose increase, it should be borne in mind that the maximum antihypertensive effect is generally achieved four to eight weeks after initiation of treatment (see section 5.1).
Cardiovascular prevention
The recommended dose is 80 mg once a day. It is not known whether telmisartan doses below 80 mg are effective in reducing cardiovascular morbidity.
When initiating therapy with telmisartan for the reduction of cardiovascular morbidity, careful monitoring of blood pressure is recommended and, if appropriate, adjustment of the dose of blood pressure lowering medicinal products may be necessary.
Special populations
Patients with renal insufficiency
Experience in patients with severe renal impairment or on hemodialysis is limited. A lower starting dose of 20 mg is recommended in these patients (see section 4.4). No dosage adjustment is required for patients with mild or moderate renal impairment. .
Patients with hepatic insufficiency
Pritor is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild or moderate hepatic impairment the dose should not exceed 40 mg once daily (see section 4.4).
Elderly patients
There is no need to adjust the dose in elderly patients.
Pediatric population
The safety and efficacy of Pritor in children and adolescents below 18 years of age have not been established.
Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.
Method of administration
Telmisartan tablets are for oral, once-daily administration and should be taken with liquid, with or without food.
Precautions to be taken before handling or administering the medicinal product
Telmisartan tablets should be stored in the sealed blister due to their hygroscopic characteristics. They must be removed from the blister just before administration (see section 6.6).
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
• Second and third trimester of pregnancy (see sections 4.4 and 4.6)
• Obstruction of the biliary tract
• Severe hepatic insufficiency
The concomitant use of Pritor with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR 2) (see sections 4.5 and 5.1).
04.4 Special warnings and appropriate precautions for use
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 AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Hepatic insufficiency
Pritor must not be given to patients with cholestasis, biliary obstruction or severe hepatic insufficiency (see section 4.3) as telmisartan is mainly eliminated in the bile. For these patients, reduced hepatic clearance is expected for telmisartan. Pritor should only be used with caution in patients with mild to moderate hepatic impairment.
Renovascular hypertension
In patients with bilateral renal artery stenosis or renal artery stenosis afferent to a single functioning kidney, treated with a drug that affects the renin-angiotensin-aldosterone system, there is an increased risk of severe hypotension and renal failure.
Renal failure and renal transplant
When Pritor is used in patients with renal dysfunction, periodic monitoring of serum potassium and creatinine levels is recommended. There are no data regarding the administration of Pritor in patients who have recently undergone kidney transplantation.
Intravascular hypovolemia
In patients with sodium depletion and / or hypovolaemia caused by high doses of diuretics, salt restricted diets, diarrhea or vomiting, symptomatic hypotension may occur, especially after the first dose of Pritor. These conditions must be corrected before starting treatment with Pritor. Sodium depletion and / or hypovolaemia must be corrected before starting treatment with Pritor.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual block therapy is considered absolutely necessary, this should only be done under the supervision of a specialist and with close and frequent monitoring of kidney function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function are primarily dependent on the activity of the renin-angiotensin-aldosterone system (eg patients with severe congestive heart failure or with kidney disease, including renal artery stenosis), treatment with medicinal products affecting this system, such as telmisartan, has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure (see section 4.8).
Primary aldosteronism
Patients with primary aldosteronism generally do not respond to antihypertensive medicinal products which act by inhibiting the renin-angiotensin system. Therefore, the use of telmisartan is not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, particular caution is advised in patients with aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.
Diabetic patients treated with insulin or antidiabetics
Hypoglycaemia may occur in these patients during treatment with telmisartan. Therefore, appropriate blood glucose monitoring should be considered in these patients; dose adjustment of insulin or antidiabetics may be required, where indicated.
Hyperkalemia
The use of medicinal products that affect the renin-angiotensin-aldosterone system can cause hyperkalaemia.
In elderly patients, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicinal products that can increase potassium levels and / or in patients with intercurrent events, hyperkalaemia can be fatal.
Before considering the concomitant use of medicinal products that affect the renin-angiotensin-aldosterone system, the risk / benefit ratio should be considered.
The main risk factors that must be considered for hyperkalemia are:
- Diabetes mellitus, renal impairment, age (> 70 years)
- Combination with one or more medicinal products affecting the renin-angiotensin-aldosterone system and / or potassium supplements. Medicines or therapeutic classes of medicines that can cause hyperkalaemia are: potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin , immunosuppressants (cyclosporine or tacrolimus) and trimethoprim.
- Intercurrent events, in particular dehydration, acute heart failure, metabolic acidosis, worsening of kidney function, sudden worsening of kidney conditions (such as infections), cell lysis (such as acute limb ischemia, rhabdomyolysis, extensive trauma).
Close monitoring of serum potassium is recommended in patients at risk (see section 4.5).
Sorbitol
This medicine contains sorbitol (E420). Patients with rare hereditary fructose intolerance problems should not take Pritor.
Ethnic differences
As observed for angiotensin converting enzyme inhibitors, telmisartan and other angiotensin II receptor antagonists are apparently less effective in lowering blood pressure in black patients than in other patients, possibly due to the higher prevalence of states characterized by a low level of renin in the black population with hypertension.
Other
As with any antihypertensive agent, an excessive decrease in blood pressure in patients with ischemic heart disease or ischemic cardiovascular disease could cause myocardial infarction or stroke.
04.5 Interactions with other medicinal products and other forms of interaction
Digoxin
When telmisartan was co-administered with digoxin, mean increases in peak plasma concentration (49%) and trough concentration (20%) of digoxin were observed. If telmisartan treatment is initiated, modified and discontinued, digoxin levels should be monitored to keep them within the therapeutic range.
Like other medicinal products that affect the renin-angiotensin-aldosterone system, telmisartan can induce hyperkalaemia (see section 4.4). The risk may be increased when combined with other medicinal products which may also induce hyperkalaemia (potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including COX-inhibitors) 2 selective), heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim).
The onset of hyperkalaemia depends on the association of risk factors. The risk increases in the case of combination of the treatments listed above. The risk is particularly high when combined with potassium-sparing diuretics and when combined with potassium-containing salt substitutes. The combination, for example, with ACE inhibitors or NSAIDs presents a lower risk as long as the precautions for use are strictly observed.
Concomitant use not recommended
Potassium-sparing diuretics or potassium supplements
Angiotensin II receptor antagonists such as telmisartan attenuate diuretic-induced potassium loss. Potassium-sparing diuretics such as spironolactone, eplerenone, triamterene or amiloride, potassium supplements or potassium-containing salt substitutes may lead to a significant increase in serum potassium If concomitant use is indicated due to documented hypokalaemia, they should be administered with caution and serum potassium levels should be monitored frequently.
Lithium
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists, including telmisartan. combination proves necessary, careful monitoring of serum lithium levels is recommended.
Concomitant use requiring caution
Non-steroidal anti-inflammatory drugs
NSAIDs (ie, anti-inflammatory dosage acetylsalicylic acid, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with impaired renal function (eg dehydrated patients or elderly patients with impaired renal function) the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase may lead to further deterioration of renal function , including possible acute renal failure which is usually reversible. Therefore, co-administration should be undertaken with caution, especially to the elderly. Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and therefore periodically.
In one study, co-administration of telmisartan and ramipril resulted in an up to 2.5-fold increase in ramipril and ramiprilat AUC0-24 and Cmax. The clinical relevance of this observation is unknown.
Diuretics (thiazide or loop diuretics)
Previous treatment with high-dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may lead to fluid depletion and a risk of hypotension when initiating therapy with telmisartan.
To be taken into consideration in case of concomitant use
Other antihypertensive agents
The hypotensive effect of telmisartan may be enhanced by the concomitant use of other antihypertensive medicinal products.
Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events. such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single agent active on the RAAS system (see sections 4.3, 4.4 and 5.1).
Based on their pharmacological characteristics the following medicinal products can be expected to potentiate the hypotensive effects of all antihypertensive agents including telmisartan: baclofen, amifostine. In addition, orthostatic hypotension can be aggravated by alcohol, barbiturates, narcotics, or antidepressants.
Corticosteroids (systemically)
Reduction of the antihypertensive effect.
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).
There are insufficient data on the use of Pritor in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).
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 controlled epidemiological data on risk with angiotensin II receptor antagonists (AIIRAs) are not available, a similar risk may also exist for this class of medicinal products.For patients planning pregnancy, alternative antihypertensive treatment with a proven safety profile for use in pregnancy should be used unless continued AIIRA therapy 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 (reduced renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) in women. (See paragraph 5.3).
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
As no data are available regarding the use of Pritor during lactation, Pritor is not recommended and alternative treatments with a proven safety profile for use during lactation are preferred, especially when nursing a newborn or preterm infant.
Fertility
In preclinical studies, no effect of Pritor on male and female fertility was observed.
04.7 Effects on ability to drive and use machines
When driving vehicles or operating machines, it should be taken into account that somnolence and dizziness may occasionally occur with antihypertensive therapy, such as Pritor.
04.8 Undesirable effects
Summary of the safety profile
Serious adverse drug reactions include anaphylactic reaction and angioedema which may occur rarely (≥1 / 10,000,
The overall incidence of adverse reactions reported with telmisartan was usually comparable to that reported with placebo (41.4% versus 43.9%) in controlled clinical trials in patients treated for hypertension. The incidence of adverse reactions was not dose related and was not related to the sex, age or race of the patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular morbidity was consistent with that in patients treated for hypertension.
The following adverse reactions were collected from controlled clinical trials performed in patients treated for hypertension and from post-marketing reports. The list also includes serious adverse reactions and treatment discontinuation adverse reactions reported in three clinical studies long-term which included 21,642 patients treated for up to six years with telmisartan for the reduction of cardiovascular morbidity.
Summary table of adverse reactions
Adverse reactions have been ranked by frequency using the following convention: very common (≥1 / 10); common (≥1 / 100,
Within each frequency grouping, adverse reactions are listed in order of decreasing severity.
1,2,3,4: for further descriptions, see subsection "Description of selected adverse reactions "
Description of selected adverse reactions
Sepsis
An "increased incidence of sepsis with telmisartan compared to placebo" was observed in the PRoFESS study. The event may be a random result or may be related to a mechanism currently unknown (see also section 5.1).
Hypotension
This adverse reaction was reported as common in patients with controlled blood pressure who were treated with telmisartan for the reduction of cardiovascular morbidity in addition to standard therapy.
Impaired liver function / liver disorder
Most post-marketing cases of impaired liver function / liver disorder occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions.
Interstitial lung disease
Cases of interstitial lung disease have been reported post-marketing in temporal association with the intake of telmisartan. However, a causal relationship has not been established.
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.
04.9 Overdose
There is limited information available regarding overdose in humans.
Symptoms: The most relevant manifestations related to telmisartan overdose were hypotension and tachycardia; Bradycardia, dizziness, increased serum creatinine and acute renal failure have also been reported.
Treatment: Telmisartan is not removed by hemodialysis. The patient should be closely monitored and treatment should be symptomatic and supportive. Treatment depends on the time since ingestion and the severity of symptoms. Suggested measures include induction of emesis and / or gastric lavage. Activated charcoal can be useful in the treatment of overdose. Serum electrolyte and creatinine levels should be checked frequently. In the event of hypotension, the patient should be placed in the supine position and salts and fluids should be rapidly replenished.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Angiotensin II antagonists, unassociated, ATC code C09CA07.
Mechanism of action
Telmisartan is a specific and effective orally effective angiotensin II receptor antagonist (type AT1). Telmisartan displaces angiotensin II with a "high affinity" from its binding site to the AT1 receptor subtype, responsible for the well-known effects of " angiotensin II. Telmisartan does not exhibit any partial agonist activity for the AT1 receptor. Telmisartan selectively binds to the AT1 receptor. This bond is long-lasting. Telmisartan does not show significant affinity for other receptors, including AT2 and other less characterized AT receptors. The functional role of these receptors and the effect of their possible overstimulation by angiotensin II, whose levels are increased, are unknown. from telmisartan. Telmisartan causes a decrease in plasma aldosterone levels. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit the angiotensin converting enzyme (kininase II), which also degrades bradykinin. potentiation of bradykinin-mediated adverse events is not expected.
In "humans, an 80 mg dose of telmisartan results in" almost complete inhibition of the "blood pressure increase induced by" angiotensin II. The inhibitory effect lasts for 24 hours and is still measurable for up to 48 hours.
Clinical efficacy and safety
Treatment of essential hypertension
The antihypertensive activity begins to manifest gradually within 3 hours of the administration of the first dose of telmisartan. The maximum reduction in blood pressure is generally achieved 4 to 8 weeks after the start of treatment and is maintained over the course of long-term therapy.
The antihypertensive effect continues consistently for 24 hours after administration and includes the last 4 hours before the next administration, as demonstrated by continuous 24 hour blood pressure measurements. This is confirmed by the fact that the relationship between minimum and maximum concentrations of telmisartan in placebo-controlled clinical trials remained consistently above 80% after a dose of 40 mg and 80 mg. C "is an apparent trend for a relationship between dose and time to return to baseline systolic blood pressure (PAS). From this point of view, the data regarding diastolic blood pressure (PAD) are not consistent.
In hypertensive patients, telmisartan reduces both systolic and diastolic blood pressure without affecting heart rate. The contribution of the diuretic and natriuretic effect of the medicinal product to its hypotensive efficacy has not yet been established. The antihypertensive efficacy of telmisartan is comparable to that of medicinal products representative of other classes of antihypertensive agents (demonstrated in clinical trials comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril).
After abrupt discontinuation of telmisartan treatment, blood pressure gradually returns to pre-existing values over a period of several days, without resulting in a rebound effect.
In clinical trials directly comparing the two antihypertensive treatments, the incidence of dry cough was significantly lower in patients treated with telmisartan than in those treated with angiotensin converting enzyme inhibitors.
Cardiovascular prevention
ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) compared the effects of telmisartan, ramipril and the combination of telmisartan and ramipril on cardiovascular outcomes in 25,620 patients at least 55 years of age with a history of coronary heart disease, stroke, TIA , peripheral arterial disease or type 2 diabetes mellitus associated with evidence of target organ damage (e.g. retinopathy, left ventricular hypertrophy, macro- or microalbuminuria) representing a population at risk for cardiovascular events.
Patients were randomized to one of the following three treatment groups: telmisartan 80 mg (n = 8,542), ramipril 10 mg (n = 8,576) or the combination of telmisartan 80 mg plus ramipril 10 mg (n = 8,502) and followed for an average observation period of 4.5 years.
Telmisartan has shown similar efficacy to ramipril in reducing the primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for congestive heart failure. The incidence of the primary endpoint was similar in the telmisartan (16.7%) and ramipril (16.5%) treatment arms. The "hazard ratio for telmisartan versus ramipril was 1.01 (97.5% CI 0.93 - 1.10, p (non-inferiority) = 0.0019 with a margin of 1.13). L" the incidence of all-cause mortality was 11.6% and 11.8%, respectively, in patients treated with telmisartan and ramipril.
Telmisartan was found to be as effective as ramipril in the pre-specified secondary endpoints of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke [0.99 (97.5% CI 0.90 - 1.08, p (non-inferiority ) = 0.0004], primary endpoint in the reference study HOPE (The HeartOutcomes Prevention Evaluation Study) which evaluated the efficacy of ramipril versus placebo.
TRASCEND randomized ACE inhibitor intolerant patients with similar inclusion criteria as ONTARGET to receive either telmisartan 80 mg (n = 2,954) or placebo (n = 2,972), both given on top of standard therapy. The mean duration of the follow-up period was 4 years and 8 months. There was no statistically significant difference in the incidence of the composite primary endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for congestive heart failure) (15.7% in the telmisartan group and 17, 0% in the placebo group with a hazard ratio of 0.92 (95% CI 0.81 - 1.05, p = 0.22)]. & EACUTE; the advantage of telmisartan over placebo in the secondary endpoint was shown of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke [0.87 (95% CI 0.76 - 1.00, p = 0.048)]. There was no evidence of benefit on cardiovascular mortality (hazard ratio 1.03, 95% CI 0.85 - 1.24).
Cough and angioedema were reported less frequently in patients treated with telmisartan than in patients treated with ramipril, while hypotension was reported more frequently with telmisartan.
The combination of telmisartan and ramipril did not add any benefit over ramipril or telmisartan alone. Cardiovascular mortality and all cause mortality were numerically superior with the combination. In addition, there was a significantly higher incidence of hyperkalaemia, renal failure, hypotension and syncope in the combination arm. Therefore, the use of a combination of telmisartan and ramipril is not recommended in this patient population.
In the study "Prevention Regimen For Effectively avoiding Second Strokes" (PRoFESS) in patients aged at least 50 who had recently had a stroke, an "increased incidence of sepsis was observed with telmisartan compared to placebo, 0.70% versus 0.49% [RR 1.43 (95% confidence interval 1.00 - 2.06)]; the incidence of fatal cases of sepsis was increased for patients treated with telmisartan (0.33%) compared to patients treated with placebo (0.16%) [RR 2.07 (95% confidence interval 1.14 - 3.76)]. The increased incidence of sepsis observed in association with the use of telmisartan may be a random result or related to a currently unknown mechanism.
Two large randomized controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA Nephron-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE inhibitor with an antagonist of the angiotensin II receptor.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus associated with evidence of organ damage. For more detailed information see above under "Cardiovascular Prevention".
VA NEPHRON-D was a study conducted in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies did not demonstrate any significant beneficial effect on renal and / or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute renal injury and / or hypotension was observed compared to monotherapy. These results are also relevant for other ACE inhibitors and angiotensin II receptor antagonists, given their similar pharmacodynamic properties.
ACE inhibitors and angiotensin II receptor antagonists should therefore not be used simultaneously in patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study aimed at verifying the advantage of adding aliskiren to standard therapy of an ACE inhibitor or angiotensin II receptor antagonist in patients with diabetes mellitus. type 2 and chronic kidney disease, cardiovascular disease, or both. The study was terminated early due to an increased risk of adverse events. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group, and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were reported more frequently in the aliskiren group than in the placebo group.
Pediatric population
The safety and efficacy of Pritor in children and adolescents below 18 years of age have not been established.
The hypotensive effects of two doses of telmisartan were evaluated in 76 hypertensive patients, largely overweight, aged 6 to body weight ≥ 20 kg and ≥ 120 kg, mean 74.6 kg), after taking telmisartan 1 mg / kg (n = 29 treated) or 2 mg / kg (n = 31 treated) during a four-week treatment period. At the time of inclusion the presence of secondary hypertension was not investigated. In some of the patients studied the doses used were higher than those recommended in the treatment of hypertension in the adult population, reaching a daily dose comparable to 160 mg, which was been studied in adults. After adjustment for age-related effects in the group, mean changes in systolic blood pressure (PAS) from baseline (primary endpoint) were -14.5 mm Hg in the telmisartan 2 mg / kg group, -9 , 7 mm Hg in the telmisartan 1 mg / kg group and -6.0 in the placebo group. Adjusted changes from baseline in diastolic blood pressure (PAD) were -8.4 mm Hg, - 4.5 mm Hg and -3.5 mm Hg, respectively. The variation was dose-dependent. The safety data from this study in patients aged 6 to
An increase in eosinophils reported in this patient population was not seen in adults. Its clinical significance and relevance are unknown.
These clinical data do not allow conclusions to be drawn on the efficacy and safety of telmisartan in the pediatric hypertensive population.
05.2 Pharmacokinetic properties
Absorption
Absorption of telmisartan is rapid, although the absorbed fraction is variable. The absolute bioavailability of telmisartan averages approximately 50%.
When telmisartan is taken with food, the reduction in the area under the plasma concentration / time curve (AUC0-∞) of telmisartan ranges from approximately 6% (40 mg dose) to approximately 19% (160 mg dose) Plasma concentrations are similar 3 hours after administration whether telmisartan is taken on an empty stomach or with a meal.
Linearity / non-linearity
The slight decrease in AUC is not believed to cause a reduction in therapeutic efficacy.
There is no linear relationship between doses and plasma levels. Cmax and, to a lesser extent, AUC increase disproportionately at doses above 40 mg.
Distribution
Telmisartan is highly bound to plasma proteins (> 99.5%), particularly albumin and alpha-1 acid glycoprotein. The mean apparent volume of distribution at steady state (Vdss) is approximately 500 liters.
Biotransformation
Telmisartan is metabolised by conjugation of the parent substance to the glucuronide. No pharmacological activity has been demonstrated for the conjugate.
Elimination
Telmisartan exhibits bi-exponential decay kinetics with a terminal elimination half-life greater than 20 hours. The maximum plasma concentration, (Cmax), and, to a lesser extent, the area under the plasma concentration / time curve (AUC), increase to an extent not proportional to the dose. There is no clinically relevant accumulation when telmisartan is taken at recommended doses. Plasma concentrations are higher in women than in men, but this does not significantly affect efficacy.
Following oral (and intravenous) administration, telmisartan is almost exclusively excreted in the faeces, mainly in unchanged form. Cumulative urinary excretion is hepatic plasma (approx. 1,500 ml / min).
Special populations
Pediatric population
Two-dose pharmacokinetics of telmisartan were evaluated as a secondary endpoint in hypertensive patients (n = 57) aged 6 to
Type
Differences in plasma concentrations were observed between the sexes, in women Cmax and AUC were respectively 3 and 2 times higher than in men.
Senior citizens
The pharmacokinetics of telmisartan do not differ between elderly patients and those under the age of 65.
Kidney dysfunction
A doubling of plasma concentrations was observed in patients with mild to moderate and severe renal dysfunction. However, lower plasma concentrations were observed in patients with renal insufficiency on dialysis. In patients with renal insufficiency, telmisartan is highly bound to plasma proteins and cannot be eliminated by dialysis. The elimination half-life does not vary in patients with renal dysfunction.
Liver dysfunctions
An increase in absolute bioavailability up to almost 100% was observed in pharmacokinetic studies in patients with hepatic insufficiency. The elimination half-life does not vary in patients with hepatic dysfunction.
05.3 Preclinical safety data
In preclinical safety studies, doses such as to determine an exposure comparable to that of the range of doses to be used in clinical therapy caused a reduction in erythrocyte parameters (erythrocytes, hemoglobin, hematocrit), alterations in renal haemodynamics (increased azotemia and creatininemia) as well as an increase in potassium in normotensive animals. Renal tubule dilation and atrophy were observed in dogs. In addition, lesions of the gastric mucosa (erosions, ulcers or inflammation) were observed in rats and dogs. These pharmacologically mediated undesirable effects, as evidenced by preclinical studies with both angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists, can be prevented by administering oral saline supplements.
In both species, increased plasma renin activity and hypertrophy / hyperplasia of renal juxtaglomerular cells were observed. These changes, also an effect of the whole class of angiotensin converting enzyme inhibitors and other antagonists of receptor angiotensin II, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however effects on the postnatal development of the offspring such as lower body weight and delayed eye opening were observed at toxic doses of telmisartan.
There was no evidence of mutagenesis or relevant clastogenic activity in the studies in vitro nor of carcinogenicity in rats and mice.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Povidone (K25)
Meglumine
Sodium hydroxide
Sorbitol (E420)
Magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years
06.4 Special precautions for storage
This medicinal product does not require any special storage temperatures. Store in the original package to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / aluminum blisters (PA / Al / PVC / Al or PA / PA / Al / PVC / Al). One blister contains 7 or 10 tablets.
Pack sizes: Blisters with 14, 28, 30, 56, 90 or 98 tablets.
Not all pack sizes may be marketed
06.6 Instructions for use and handling
Telmisartan must be kept in the sealed blister due to the hygroscopic characteristics of the tablets. The tablets should be removed from the blister just before administration.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer Pharma AG
13342 Berlin
Germany
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/98/089/011 (14 tablets) AIC 034326114 / E
EU / 1/98/089/012 (28 tablets) AIC 034326126 / E
EU / 1/98/089/020 (30 tablets)
EU / 1/98/089/013 (56 tablets) AIC 034326138 / E
EU / 1/98/089/019 (90 tablets)
EU / 1/98/089/014 (98 tablets) AIC 034326140 / E
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 11 December 1998
Date of last renewal: 11 December 2008
10.0 DATE OF REVISION OF THE TEXT
09/2014
