Normodipine 5mg Gedeon tablets treat hypertension, stable angina (3 blisters x 10 tablets)

Amlodipine is a calcium ionic inhibitor of the dihydropyridine group (slow ion antagonist or a slow calcium channel blocker), it inhibits the calcium ionic current through the cell membrane into the blood vessel and heart muscle.

Amlodipine's anti -hypertension mechanism is due to the direct effect on blood vessel plain relaxation. Amlodipine's exact anti -angina mechanism has not been fully determined, but Amlodipine reduces ischemic anemia in the following two effects:

In patients with angina, one -time dosage mode increases the total time of exertion, extending the distance between angina and reducing the frequency of the difference to 1 mm on the heart, reducing the frequency of angina attacks and reducing the need to use glyceryl trinitrate.

amlodipine is not related to adverse effects on metabolism or changes in lipid concentration in plasma, so it can be used in patients with bronchial asthma, diabetes and gout.

On patients with coronary artery disease (CAD)

On patients with heart failure

Studies on hemodynamic and clinical trials with control exertion conducted on patients with heart failure level II - IV according to the NYHA classification ladder shows that Amlodipine does not worsen clinical condition when measured by the possibility of patients with tolerance when exertion, with left ventricular blood loss and clinical symptoms.

A restorative study with placebo (Praise research) is designed to evaluate patients with heart failure III - IV Nyha in using digoxin, diuretics and angiotensin transferring inhibitors have shown that amlodipine does not increase the risk of death or combination of death and heart failure. A long-term monitoring study, with a fatality (Praise-2 research) assesses the use of amlodipine on heart failure III and IV NYHA (no clinical symptoms of ischemia, signs of hint of ischemia or are undergoing ischemic disease; stabilizing the Angiotensin, digitalis, and diuretic inhibitors Cardiovascular trying. On this patient population itself, Amlodipine is associated with an increase in reports on pulmonary edema.

Research on anti -hypertension treatment and blood lipid lowering to prevent heart attacks (Allhat)

A random study, double the mortality rate - the incidence called "Research on anti -hypertension treatment and blood lipid lowering to prevent angina" (Allhat research) with the results shows that there is no significant difference in the main evaluation criteria of the study when comparing the amlodipine usage regimen and the chlorthalidon usage regimen: RR 0.98; RR 0.98; 95%confidence interval: 0.90 -1.07; P = 0.65.

Children (children over 6 years old and adolescents)

In a study conducted over 268 children aged 6-17 with secondary hypertension; Compare the effectiveness of 2.5 mg of amlodipine and 5.0 mg of amlodipine with placebo, showing both doses are significant to lower the systolic blood pressure compared to placebo. The difference in effectiveness between two dose is not statistically significant.

Amlodipine's long -term influence on growth, puberty and general development of children have not been studied.

Amlodipine's long -term efficiency on children's regimens to reduce cardiovascular disease incidence and cardiovascular mortality when adults have not been set up.

pharmacokinetics

absorption, distribution and ratio of cohesion to plasma proteins

After drinking with treatment dose, Amlodipine is absorbed well and reaches blood peak concentration after about 6 - 12 hours. Absolute bioavailability is about 64 - 80%. The distribution volume is approximately 21 liters/ kg. In vitro studies show that about 97.5% of the drug circulated with plasma proteins.

Birth of amlodipine is not affected by food.

Biometric/ excretion

Half of life eliminates plasma about 35 - 50 hours, corresponding to the dosage mode 1 time/ day. Amlodipine is strongly metabolized through the liver into non -active metabolites; With 10% of the parent and 60% of metabolites are excreted into the urine.

Hepatic failure: There is very little clinical data on the use of amlodipine in patients with liver failure. In patients with liver failure, Amlodipine clearance decreases, increasing the increase in the selling time and AUC increases by about 40-60%.

Elderly: Amlodipine's plasma peak time is similar to the elderly and young people. In elderly patients, Amlodipine clearance tends to decrease leading to an increase in AUC and increase the sale time. Increasing AUC and increasing waste time in patients with congestion heart failure are as expected for the age group.

Children and adolescents: A pharmacokinetics study conducted on 74 children with hypertension aged 1-17 (with 34 children from 6-12 years old and 28 children from 13-17 years old) using Amlodpine in the dose of 1.25 - 20 mg used once or 2 times/ day. Over the age of 6 - 12 years old and adolescence 13-17 years old, the typical clearance of oral medication (Cl/ F) corresponds to 22.5 and 27.4 liters/ hour for men and corresponding to 10.4 and 21.3 liters/ hour for women. The big difference in exposure of drugs between individuals has been recorded. The reporting data on the use of amlodipine for children under 6 years of age is limited.

Summary of drug safety records

The adverse reactions during treatment are often reported most of the drowsiness, dizziness, headache, chest drum, redness, abdominal pain, nausea, swollen ankles, edema and fatigue.

Table of adverse reactions

In each frequency group, the adverse reactions are presented in the order of severity.

Precautions when used

Safety and effectiveness of amlodipine in unpretated acute hypertension.

heart failure

Be careful when using amlodipine for patients with heart failure.

In a long -term study, with a placebo, a placebo on patients with severe heart failure (level III and IV according to NYHA classification scale), amlodipine treatment group has a higher rate of lung edema records than a placebo group (see the pharmacological section). Caution should be used when using calcium channel blockers, including amlodipine, in patients with congestive heart failure because these drugs may increase the risk of cardiovascular events and death.

Hepatic failure

Amlodipine's waste time is prolonged and higher AUC value in patients with liver failure; The recommended dose of amlodipine on this object has not been set. Therefore, amlodipine should be started in patients with liver failure at low doses in the dose range and need to be cautious at the beginning of treatment and when increasing the dose. In patients with severe liver failure, the adjustment of the dose should be done slowly and under close supervision.

Elderly

In elderly patients, the increase in the dose should be done carefully (see the dose and use and pharmacokinetic section).

kidney failure

In patients with renal impairment, Amlodipine can be used in normal doses. There is no correlation between changes in plasma amlodipine levels and renal failure. Amlodipine is not separated.

The ability to drive and operate machinery

Amlodipine can affect the average level of moderate to the ability to drive and operate the machine. If the patient uses amlodipine dizziness, headache, fatigue or nausea, the reaction ability may decrease. Precautions especially when starting treatment.

pregnancy

Amlodipine safety in pregnant women has not been set.

Animal studies show that toxicity on reproduction in high doses.

Use during pregnancy is only recommended in the event that there is no other safer option and the disease is higher for the mother and the fetus.

The period of breastfeeding

Amlodipine is determined to be present in the mother's infant's infant to be treated with amlodipine. The median concentration ratio of amlodipine in milk/ plasma in 31 women who are breastfeeding has hypertension due to pregnancy is 0.85 after using amlodipine at the starting dose of 5mg/ time/ day and is adjusted if needed (average daily dose and daily dose in respect of 6 mg and 98.7 mcg/ kg). The estimated daily dose of Amlodipine that babies receive through breast milk is 4.17 mcg/ kg. The influence of amlodipine on infants is not known. It is necessary to consider the benefits of breastfeeding and the benefits of using amlodipine to treat the mother when making a decision to continue/ stop breastfeeding or continue/ stop using amlodipine.

fertility

Biochemical changes can recover at the sperm head on some patients treated with calcium channel blockers that have been recorded. The existing clinical data on the influence of amlodipine on fertility is limited. A study conducted on rats showed that Amlodipine causes adverse effects on the fertility of male mice.

Drug interaction

Amlodipin has been shown to be safe to use with thiazide diuretics, alpha receptor inhibitors, beta receptor inhibitors, angiotensin transferring enzymes (ACEI), prolonged nitrates, nitroglycerin under the tongue, non -steroid anti -inflammatory drugs and oral hypoglycemic drugs.

In vitro data from plasma studies has shown that amlodipine does not affect the cohesion with the blood protein of research drugs (digoxin, phenytoin, warfarin or indomethacin).

The effect of other drugs on amlodipine

CYP3A4 inhibitors

Simultaneously use 180 mg of diltiazem daily dose with 5 mg of amlodipine for the elderly (69 - 87 years old) with hypertension increases 57% of the system exposure rate with amlodipine. Simultaneously used with erythromycin on healthy volunteers (18 - 43 years old) does not significantly change the exposure rate of system infection with amlodipine (up 22% under the curve under the curve of blood concentration of blood drugs over time [AUC]). Although clinically related to these studies are not sure, pharmacokinetic changes can be notified more in elderly patients.

Strong CYP3P4 inhibitors (such as ketoconazole, otraconazole, ritovanir) may increase the concentration of amlodipine in the blood larger than the diltiazem. Should be cautious when using amlodipine along with CYP3A4 inhibitors.

Clarithromycin

Clarithromycin is a CYP3A4 inhibitor. There is an increase in the risk of hypotension in patients with amlodipine common with clarithromycin. Recommendations for monitoring patients when taking amlodipine with clarithromycin.

CYP3A4 induction

There is no data on the effects of CYP3A4 induction on Amlodipine. The simultaneous use of CYP3A4 induction (such as rifampicin, holy grass John [Hypericum Perforatum]) can reduce serum amlodipine concentration. Caution should be careful when using Amlodipine and the CYP3A4 touch substances.

Grapefruit/ grapefruit juice

Self -use 240 ml of grapefruit juice with a single dose of 10 mg of amlodipine in 20 healthy volunteers does not significantly affect the pharmacokinetics of Amlodipine. This research does not allow the test of the influence of the genetic form of CYP3A4, the main enzyme is responsible for transforming amlodipine; Therefore, it is recommended not to use simultaneously amlodipine and grapefruit or grapefruit juice because it can increase the bioavailability of the drug in some patients, leading to increased hypotension.

cimetidine

Simultaneous use of amlodipine and cimetidine does not change the pharmacokinetics of amlodipine.

Aluminum/ Magnesi salt (antacids)

Concomitance of antacids is aluminum salt and magnesium salt with a single dose of amlodipine does not significantly affect the pharmacokinetics of Amlodipine.

Sidenafil

Use a single dose of 100 mg of Sildenafil in objects with idiopathic hypertension does not affect the pharmacokinetic parameters of Amlodipine. When using a combination of amlodipine and sildenafil, each drug has its own antihypertensive effect.

Dantrolen (Translation)

In animals, ventricular vibration and cardiovascular collapse lead to death due to hyperkalemia after use simultaneously Verapamil and Vetrolen intravenously have been recorded. Due to the risk of hyperkalemia, avoiding simultaneous use of calcium channel blockers such as amlodipine in patients susceptible to malignant high fever and in the treatment of malignant high fever.

The effect of amlodipine on other drugs

Amlodipine's hypotension effect will match the hypotension effect of other anti -hypertension drugs.

atorvastatin

Soonered with 10 mg of amlodipine with 80 mg atorvastatin does not significantly change the pharmacokinetic parameters of Atorvastatin in a stable concentration state in plasma.

digoxin

Simultaneous use of amlodipine with digoxin does not change the concentration of digoxin in plasma or the renal clearance of digoxin in healthy volunteers.

warfarin

Simultaneous use amlodipine with warfarin does not change the time of prothrombin inhibitors of warfarin.

Ethanol (alcohol)

Use single -dose or multi -dose 10 mg of amlodipine does not significantly affect the pharmacokinetics of ethanol.

tacrolimus

Coordination with Amlodipine is at risk of increasing the concentration of Tacrolimus, but the pharmacokinetic mechanism of this interaction has not been fully understood. To avoid Tacrolimus poisoning, when using Amlodipine combination in patients who are being treated with Tacrolimus, the blood concentration of Tacrolimus should be monitored and adjust the dose of Tacrolimus if necessary.

Mechanical goals of Rapamicin inhibitors (MTOR)

MTor inhibitors, such as Siromilus, Temsirolimus and Everolimus are the substrate of CYP3A4, Amlodipine are a weak CYP3A4 inhibitor. When used simultaneously with MTOR inhibitors, Amlodipine can increase the exposure of MTOR inhibitors. Cyclosporin currently has no studies have conducted an assessment of interactions between cyclosporin and amlodipine on healthy volunteers or on other patients, except for kidney transplant patients - in these patients the base concentration of Cyclosporin increases with a large range of fluctuations (average 0% - 40%). Cyclosporin concentration should be considered in kidney transplant patients using amlodipine and reducing cyclosporine dose if needed.

Simvastatin simultaneously repeated 10 mg of Amlodipine and 80 mg of simvastatin, increasing the exposure of Simvastatin 77% compared to the unique simvastatin. Therefore, the dosage of simvastatin in patients who are using amlodipine is limited to 20 mg/ day.