Active ingredients: Telmisartan
Micardis 20 mg tablets
Micardis package inserts are available for pack sizes:- Micardis 20 mg tablets
- Micardis 40 mg tablets
Indications Why is Micardis used? What is it for?
Micardis 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. Micardis blocks the effect of angiotensin II, causing the blood vessels to relax and thus lowering blood pressure.
Micardis 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.
Micardis 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 Micardis should not be used
Do not take Micardis
- 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 Micardis 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 Micardis.
Precautions for use What you need to know before taking Micardis
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 Micardis:
- 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 Micardis".
- 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). Micardis 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 Micardis.
Micardis may be less effective in lowering blood pressure in ethnic African patients.
Children and adolescents
The use of Micardis is not recommended in children and adolescents up to 18 years.
Interactions Which drugs or foods can change the effect of Micardis
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 Micardis:
- 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 Micardis, 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 Micardis" and "Warnings and precautions").
- Digoxin.
The effect of Micardis may be reduced when taking NSAIDs (non-steroidal anti-inflammatory medicines, eg aspirin or ibuprofen) or corticosteroids.
Micardis 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 can 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 Micardis.
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 Micardis before becoming pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Micardis. Micardis is not recommended for use 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. Micardis 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 Micardis. If these effects occur, do not drive or use machines.
Micardis contains sorbitol.
If you are intolerant to any sugars, consult your doctor before taking Micardis
Dosage and method of use How to use Micardis: Dosage
Always take Micardis exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose of Micardis is one tablet per day. Try to take the tablet at the same time each day.
You can take Micardis with or without food. The tablets should be swallowed with some water or another non-alcoholic drink. It is important to take Micardis every day until your doctor tells you otherwise. If you have the impression that the effect of Micardis is too strong or too weak, consult your doctor or pharmacist.
For the treatment of high blood pressure, the recommended dose of Micardis 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. Micardis can also be used in combination with diuretics such as hydrochlorothiazide, which have been shown to have an additive effect with the combination with Micardis in terms of blood pressure reduction.
For the reduction of cardiovascular events, the usual dose of Micardis is one 80 mg tablet once daily. At the start of preventive therapy with Micardis 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 Micardis
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 Micardis
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 Micardis
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 Micardis:
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 levels, difficulty falling asleep, feeling sad (depression), fainting (syncope), spinning sensation (vertigo), slow heart rate (bradycardia), low blood pressure (hypotension) in patients treated for high blood pressure, feeling unsteady on standing up (orthostatic hypotension), breathing shortness of breath, cough, abdominal pain, diarrhea, abdominal discomfort, bloating, vomiting, itching, sweating increased, drug-induced rash, back pain, muscle cramps, muscle pain (myalgia), renal impairment including acute kidney failure, chest pain feeling weak, increased blood creatinine levels.
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 skin rash drug addiction, 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. Remove the Micardis tablet from 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.
Contents of the pack and other information
What Micardis contains
The active substance is telmisartan. Each tablet contains 40 mg of telmisartan.
The other ingredients are povidone, meglumine, sodium hydroxide, sorbitol (E420) and magnesium stearate.
What Micardis looks like and contents of the pack
Micardis 40 mg tablets are white, oblong, embossed with the company logo and the code "51H".
Micardis is available in blisters containing 14, 28, 56, 84 or 98 tablets, in perforated unit dose blisters containing 28 x 1, 30 x 1 or 90 x 1 tablets or in multipacks containing 360 tablets (4 packs of 90 x 1 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
MICARDIS 40 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 40 mg telmisartan.
Excipients with known effects:
Each tablet contains 169 mg of sorbitol (E420).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets
White, oblong 3.8 mm tablets with the code "51H" debossed on one side and the company logo debossed on the other.
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 damage of the target organs.
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 8 weeks after initiation of treatment (see section 5.1).
Prevention of cardiovascular morbidity and mortality:
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:
Micardis 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 Micardis in children and adolescents below 18 years of age have not been established. There are no data available.
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
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:
Micardis 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. Micardis 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 Micardis 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 Micardis 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 Micardis. These conditions must be corrected before starting treatment with Micardis. Sodium depletion and / or hypovolaemia should be corrected before starting treatment with Micardis.
Dual blockade of the renin-angiotensin-aldosterone system:
As a consequence of the inhibition of the renin-angiotensin-aldosterone system, hypotension, syncope, hyperkalaemia and alterations in renal function (including acute renal failure) have been reported in susceptible individuals, especially when combined with medicinal products affecting this system. Blockade of the renin-angiotensin-aldosterone system (eg by administration of telmisartan with other blockers of the renin-angiotensin-aldosterone system) is therefore not recommended. If co-administration is considered necessary, close monitoring of renal function is advised.
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, special 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. Medicinal products 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 Micardis.
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
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 also may induce potassium-containing salt substitute hyperkalaemia, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including COX-2 inhibitors 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. association 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 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 thereafter 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.
Based on their pharmacological characteristics the following medicinal products can be expected to potentiate the hypotensive effects of all antihypertensive agents including telmisartan: baclofenac, 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 Micardis 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 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 (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 Micardis during lactation, Micardis 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 Micardis 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 Micardis.
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.
04.9 Overdose
There is limited information available regarding overdose in humans.
Symptoms:
The most prominent 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 the 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 case of hypotension, the patient should be placed in the supine position and salts and fluids should be quickly 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:
Antihypertensive activity begins within 3 hours of administration of the first dose of telmisartan. Maximum reduction in blood pressure is generally achieved 4 to 8 weeks after initiation of treatment and is maintained throughout 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 Heart Outcomes Prevention Evaluation Study) which evaluated the effect 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). The advantage of telmisartan over placebo was shown in the pre-specified secondary endpoint 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.
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 (AUC0-24) 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 steady-state volume of distribution (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 (AUC0-24) , increase disproportionately 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
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 studies of tolerability and safety, 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 (increase in BUN and creatinine) 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, but 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
4 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 blister (PA / Al / PVC / Al or PA / PA / Al / PVC / Al). One blister contains 7 or 10 tablets.
Pack sizes: Blisters with 14, 28, 56, 84 or 98 tablets or perforated unit dose blisters with 28 x 1, 30 x 1 or 90 x 1 tablets; multipacks containing 360 tablets (4 packs of 90 x 1 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
Boehringer Ingelheim International GmbH - Binger Str. 173, D-55216 Ingelheim am Rhein - Germany
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/98/090/001 (14 tablets) - AIC: 034328017
EU / 1/98/090/002 (28 tablets) - AIC: 034328029
EU / 1/98/090/003 (56 tablets) - AIC: 034328031
EU / 1/98/090/004 (98 tablets) - AIC: 034328043
EU / 1/98/090/013 (28 x 1 tablets)
EU / 1/98/090/015 (84 tablets)
EU / 1/98/090/017 (30 x 1 tablets)
EU / 1/98/090/019 (90 x 1 tablets)
EU / 1/98/090/021 (4 x (90 x 1) tablets)
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 16 December 1998
Date of last renewal: December 16, 2008
10.0 DATE OF REVISION OF THE TEXT
25/05/2012
