Corinfar Retard, 20 mg 50 pcs

Indications

Active ingredient

Composition

How to take, the dosage

Overly after a meal, without chewing and with plenty of liquid.

The dose of the drug is adjusted by the physician individually according to the severity of the disease and the patient’s sensitivity to the drug. For patients with concomitant severe cerebrovascular disease and in elderly patients, the dose should be reduced.

Concomitant ingestion delays, but does not decrease, absorption of the active ingredient from the gastrointestinal tract.

The recommended dosing regimen for adults:

Stable angina and vasospastic angina (Prinzmetal angina, variant angina)

The drug is prescribed at 20 mg (1 tablet) 2 times daily. If the clinical effect is not sufficiently pronounced, the dose is gradually increased to 40 mg (2 tablets) 2 times a day. The maximum daily dose is 80 mg (4 tablets daily).

Arterial hypertension

The drug is prescribed 20 mg (1 tablet) 2 times a day. If the clinical effect is not sufficiently pronounced, the dose of the drug is gradually increased to 40 mg (2 tablets) 2 times a day. The maximum daily dose is 80 mg (4 tablets daily).

If 2-times a day the interval between doses should be on average 12 hours. The minimum interval between doses is at least 4 hours.

The duration of treatment is determined by the physician.

In cases where the drug is taken in high doses and/or for a long time, treatment should be stopped gradually to avoid withdrawal syndrome.

Some patients may require higher doses of nifedipine. Increasing the daily dose of nifedipine above 120 mg is not recommended.

When a daily dose of nifedipine in excess of 40 mg is required for the treatment of arterial hypertension or angina pectoris, administration of nifedipine preparations in the form of sustained release tablets in doses of 40 mg or 60 mg is recommended.

Patient special groups

Elderly patients

The pharmacokinetics of nifedipine are altered in elderly patients (over 65 years of age); therefore, the maintenance dose of the drug may be reduced compared with younger patients.

Patients with hepatic impairment

In patients with mild hepatic impairment, the dose of nifedipine should be reduced. In patients with moderate to severe hepatic impairment (Child-Pugh grades B and C) the use of the drug is contraindicated.

Patients with impaired renal function

In patients with impaired renal function no dose adjustment of nifedipine is required.

Interaction

Pharmacokinetic interactions

Drugs affecting the metabolism of nifedipine

Nifedipine is metabolized by CYP3A4/5 isoenzymes, which are located in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may affect the effect

“primary passage” through the liver (after ingestion) or clearance of nifedipine.

Inductors of CYP3A4 isoenzyme Rifampicin

Special Instructions

Cardiovascular disease

Arterial hypotension

Nifedipine dilates the peripheral arteries, reduces blood pressure and may in some cases cause severe arterial hypotension. It is necessary to use the drug with caution in patients who are prone to arterial hypotension, especially in patients with coronary heart disease or with cerebrovascular diseases in whom excessive reduction of BP may lead to myocardial infarction or stroke. In case of severe arterial hypotension, the dose should be reduced or nifedipine should be temporarily stopped.

The risk of arterial hypotension is higher in patients taking beta-adrenoblockers. Concomitant use of nifedipine and beta-adrenoblockers should be performed under close medical supervision, as it may cause excessive BP reduction and in some cases aggravation of chronic heart failure symptoms.

Severe arterial hypotension and/or high need for fluid replacement have been noted in patients treated with nifedipine and beta-adrenoblockers during aortocoronary bypass surgery under general anesthesia with high-dose fentanyl. If the patient requires surgery under general anesthesia during therapy, it is necessary to inform the anesthesiologist about the nature of the therapy. If surgery under general anesthesia with high doses of fentanyl is planned, it is recommended to discontinue Corinfar® retard at least 36 hours prior to surgery.

Arterial hypertension

There is no clinical experience with the use of nifedipine in malignant arterial hypertension.

The drug Corinfar® retard should not be used to lower blood pressure in a hypertensive crisis.

Chronic Coronary Heart Disease

The Corinfar® retard drug retard should not be used to relieve angina attacks and for secondary prevention of cardiovascular complications in patients who have had a myocardial infarction.

Unstable angina and/or myocardial infarction

.In rare cases, patients with coronary artery disease (especially those with severe obstructive coronary artery disease) have reported increased frequency, duration and/or severity of angina attacks and, in isolated cases, the development of myocardial infarction after initiation of BMCCs (including nifedipine) or after increasing their dosage. The mechanism of this phenomenon is not known.

Nifedipine in immediate-release tablet form is contraindicated in acute myocardial infarction.

There is no clinical experience with nifedipine in sustained release tablet form in acute myocardial infarction and unstable angina pectoris; therefore, their use is contraindicated in these diseases.

Chronic Heart Failure (CHF)

BMCs (including nifedipine) should be used with extreme caution in patients with CHF. In decompensated CHF the use of Corinfar® retard is not recommended.

Withdrawal syndrome of beta-adrenoblockers

.In patients with angina pectoris, discontinuation of beta-adrenoblockers may lead to development of withdrawal syndrome (increased frequency, duration and/or severity of angina attacks), possibly due to hypersensitivity to catecholamines. Administration of nifedipine does not prevent the development of “withdrawal” syndrome of beta-adrenoblockers, and may even lead to its enhancement due to reflex release of catecholamines in response to peripheral vasodilation.

Nifedipine has no antiarrhythmic effect and does not prevent the occurrence of cardiac rhythm disturbances during abrupt withdrawal of beta-adrenoblockers. If therapy with a beta-adrenoblocker needs to be discontinued, the dose should be gradually reduced until nifedipine is prescribed.

Aortic stenosis/ mitral stenosis/hypertrophic obstructive cardiomyopathy

As with all drugs with vasodilatory effects, nifedipine should be used with caution in patients with aortic stenosis, mitral stenosis or hypertrophic obstructive cardiomyopathy. In patients with hemodynamically significant left ventricular outflow tract obstruction (e.g., severe aortic stenosis) the drug is contraindicated.

In patients with obstructive cardiomyopathy there is a risk of increased frequency, severity and duration of angina attacks after nifedipine administration. In this case, withdrawal of the drug is necessary.

Peripheral edema

Slight to moderate peripheral edema associated with peripheral arterial dilatation has been reported with nifedipine. Swelling is usually localized in the lower extremities, sometimes reduced with the use of diuretics. In patients with concomitant chronic heart failure, peripheral edema associated with nifedipine use should be carefully differentiated from symptoms of progressive left ventricular dysfunction.

Diabetes

In patients with diabetes, plasma glucose concentration monitoring may be required when using nifedipine preparations.

Liver function impairment

In rare cases, when using nifedipine preparations, increased activity of some enzymes, such as: alkaline phosphatase, creatine phosphokinase, lactate dehydrogenase, aspartate aminotransferase (ACT) and alanine aminotransferase (AJIT) – which are usually transient but can sometimes be significantly pronounced. The causal relationship with nifedipine intake is uncertain in most cases, but in some cases it is very likely. These changes in laboratory parameters are rarely accompanied by clinical symptomatology. However, cases of cholestasis with or without jaundice have been described, as well as rare cases of autoimmune hepatitis.

Patients with impaired liver function are closely monitored, and if necessary, the drug dose is reduced and/or other dosage forms of nifedipine are used.

In patients with impaired renal function

The use of nifedipine in patients with impaired renal function is safe; no dose adjustment of nifedipine is required. In some cases, transient increase in serum urea nitrogen and creatinine concentrations has been observed in patients with chronic renal insufficiency. Causal relationship with nifedipine intake is uncertain in most cases, but in some cases it is very probable.

In patients with malignant hypertension on hemodialysis, hypovolemia (decreased circulating blood volume) after dialysis procedure may enhance antihypertensive effect of nifedipine and lead to a sharp decrease of BP. In such patients Corinfar® retard should be used with extreme caution, if necessary, the drug dose should be reduced.

Drug interactions

Nifedipine is metabolized by CYP3A4 isoenzyme. Drugs that inhibit or induce CYP3A4 may affect the effect

The “primary passage” through the liver or clearance of nifedipine.

Drugs that are mild to moderate inhibitors of the CYP3A4 isoenzyme that increase plasma concentrations of nifedipine include:

When nifedipine and the above drugs are used concomitantly, BP should be monitored and the dose of nifedipine should be adjusted if necessary. Surgical interventions/general anesthesia

Inhalational anesthetics may increase BP reduction. If a patient requires surgery under general anesthesia during therapy, it is necessary to inform the anesthesiologist that the patient is taking nifedipine.

Diagnostic tests

At the time of treatment, positive results are possible with direct Coombs reaction (with or without hemolytic anemia) and laboratory tests for antinuclear antibodies.

Nifedipine, like other DMARDs, inhibits platelet aggregation under in vitro conditions. A small number of clinical studies support data on statistically significant decrease in platelet aggregation and increase in bleeding time.

Presumably, the cause of these changes is blockade of calcium transport across the platelet membrane. The clinical significance of this effect is unknown.

Nifedipine can cause false increases in urinary concentrations of vanillylmindalic acid when determined by spectrophotometric method, but does not affect the results of measurements when using high performance liquid chromatography (HPLC).

Alcohol

Alcoholic beverages are not recommended during treatment because of the risk of excessive lowering of blood pressure.

The use in elderly patients

Cautious use of nifedipine in elderly patients must be observed because of the high likelihood of age-related renal dysfunction.

Cessation of therapy

Cessation of nifedipine should be done gradually (there is a risk of withdrawal).

Influence on ability to drive vehicles, mechanisms

In some patients, especially at the beginning of treatment, nifedipine may cause dizziness, which reduces the ability to drive vehicles or other mechanisms. Thereafter, the degree of restriction depends on the individual tolerability of nifedipine.

At the time of treatment, especially at the beginning of treatment or when changing the dose, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

With caution

Arterial hypotension, malignant arterial hypertension (no experience in clinical use), coronary heart disease (especially with severe obstructive coronary artery disease) or cerebrovascular disease, chronic heart failure; concomitant use with beta-adrenoblockers and other hypotensive drugs; concomitant use with cardiac glycosides; aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy; diabetes mellitus; mild hepatic impairment (class A according to Child-Pugh classification); hemodialysis in patients with malignant hypertension (risk of severe arterial hypotension); concomitant use with CYP3A4 isoenzyme inhibitors and/or inducers (e.g., phenytoin, carbamazepine, phenobarbital, macrolide antibiotics, HIV protease inhibitors, ketoconazole, antidepressants, fluoxetine, valproic acid, etc.

Pregnancy of more than 20 weeks (the drug may be used as “backup therapy”); older age.

Side effects

Unwanted reactions are systematized relative to each of the organ systems according to frequency of occurrence using the World Health Organization (WHO) classification as follows: Very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10000, < 1/1000); very rare (< 1/10000); frequency unknown (cannot be determined from available data).

Blood and lymphatic system disorders: rare – thrombocytopenia, thrombocytopenic purpura; very rare – anemia; frequency unknown – leukopenia, agranulocytosis.

Disorders of the immune system: infrequent – allergic reactions, edema due to the development of an allergic reaction/angioedema (Quincke’s edema) (including laryngeal edema*); rare – skin itching, skin rash, urticaria; very rare – autoimmune hepatitis, photodermatitis; frequency unknown – anaphylactic/anaphylactoid reactions.

Disorders of metabolism and nutrition: very rare – hyperglycemia, weight gain.

Mental disorders: infrequent – anxiety, sleep disorders.

Nervous system disorders: frequently – headache, weakness; infrequently – migraine, dizziness; rarely – paresthesia, dysesthesia; frequency unknown – hypoesthesia, increased fatigue, drowsiness. When taking the drug in high doses for a long time – paresthesia of extremities, anxiety, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, tremor of hands and fingers, difficulty in swallowing), depression.

Visual disorders: infrequent – visual impairment (including transient loss of vision at maximum plasma concentration of nifedipine); frequency unknown – eye pain.

Chronic disorders: infrequent – tachycardia, palpitations; rare – in some patients, especially at the beginning of treatment or when increasing the dose, angina attacks may occur, and in single cases – development of myocardial infarction, which requires stopping the drug; frequency is unknown – arrhythmia, chest pain.

vascular disorders: often – peripheral edema, manifestations of excessive vasodilation (asymptomatic BP decrease, development or aggravation of the course of heart failure (often aggravation of already existing), “rushes” of blood to the face, facial skin hyperemia, feeling of heat); infrequent – pronounced BP decrease, fainting.

Relatory system, chest and mediastinum disorders: infrequent – nasal bleeding, stuffy nose; rare – difficulty in breathing, cough; very rare – bronchospasm; frequency unknown – shortness of breath, pulmonary edema**.

Gastrointestinal tract disorders: Frequent – constipation; infrequent – astrointestinal and abdominal pain, dyspepsia (nausea, diarrhea or constipation), dry mouth mucosa, flatulence; rare – gum hyperplasia (bleeding, painfulness, swelling); frequency unknown – vomiting, gastroesophageal sphincter failure, increased appetite.

Hepatic and biliary tract disorders: infrequent – increased activity of “hepatic” transaminases; rarely – in long-term use – hepatic dysfunction (intrahepatic cholestasis).

Dermatological and subcutaneous tissue disorders: infrequent erythema; rare – exfoliative dermatitis, photodermatitis; frequency unknown – toxic epidermal necrolysis (Lyell’s syndrome), purpura.

Muscular and connective tissue disorders: infrequent – muscle cramps, joint swelling; rare – arthralgia, myalgia; frequency unknown – arthritis.

Kidney and urinary tract disorders: infrequent – polyuria, dysuria; frequency unknown – worsening of renal function (in patients with renal failure).

Gender and mammary gland disorders: infrequent – erectile dysfunction; very rare – gynecomastia (in elderly patients, disappearing completely after discontinuation of the drug), galactorrhea.

General disorders and disorders at the site of administration: often – asthenia, weakness; infrequently – nonspecific pain, chills.

* may lead to a life-threatening condition

** cases have been reported when used as a tocolytic agent during pregnancy (see Use in pregnancy and during breastfeeding)

In patients on hemodialysis, with malignant arterial hypertension, or with reduced circulating blood volume, a marked decrease in BP may occur as a result of vasodilation.

Overdose

Symptoms

Nifedipine causes peripheral vasodilation with severe and possibly prolonged systemic arterial hypotension: headache, facial hyperemia, prolonged marked BP decrease, sinus node suppression, bradycardia and/or tachycardia, bradyarrhythmia. In severe poisoning – loss of consciousness, coma.

Treatment

The treatment of overdose consists of standard procedures for eliminating the drug from the body. Administration of activated charcoal, gastric lavage (if necessary – small bowel lavage), restoration of stable hemodynamic parameters is indicated.

In case of overdose with prolonged nifedipine it is necessary to ensure the most complete elimination of the drug from the body, if possible – small intestine lavage in order to prevent further absorption of the active substance. When using laxatives it should be taken into account that PBMC may cause decrease of intestinal muscle tone up to intestinal atony.

The antidote for nifedipine is calcium preparations. Intravenous injection of 10-20 ml of 10% solution of calcium chloride or calcium gluconate is indicated, followed by switching to prolonged infusion. If the administration of calcium preparations failed to achieve a sufficient rise in BP, alpha-adrenomimetics (dopamine, norepinephrine) may be used.

In bradyarrhythmia – IV administration of atropine, beta-adrenomimetics. In life-threatening bradyarrhythmias, placement of a temporary pacemaker is recommended. In the development of heart failure – intravenous infusion of strophantine. Infusion therapy is recommended with caution due to the risk of volume overload of the heart.

Careful monitoring of the heart, lungs and excretory system is necessary. It is recommended to monitor glucose concentrations (insulin release may decrease) and electrolytes (potassium, calcium) in the blood.

Hemodialysis is ineffective due to the high degree of binding to plasma proteins and relatively small volume of distribution. Plasmapheresis is possible.

Pregnancy use

Pregnancy

The use of nifedipine in pregnancy below 20 weeks is contraindicated. The use of nifedipine at more than 20 weeks’ gestation is possible as a “backup therapy” for severe arterial hypertension in cases where the expected benefit to the mother exceeds the possible risk to the fetus.

There have been no adequately controlled studies involving pregnant women. The available information is insufficient to rule out the possibility of side effects that pose a risk to the fetus and the newborn.

In animal studies, nifedipine has been shown to be embryotoxic, fetotoxic, and teratogenic. No specific prenatal risk has been identified based on clinical data. However, there has been an increased incidence of perinatal asphyxia, cesarean section, as well as preterm birth and intrauterine fetal delay. The relationship of these reports to existing arterial hypertension, its treatment, or the specific effect of the drug is unclear.

In the use of PBMCs, including nifedipine, as a tocolytic agent during pregnancy, especially multiple pregnancies (twins or more), cases of acute pulmonary edema have been observed with intravenous administration of the drug and/or with concurrent use of beta2-adrenomimetics.

Nifedipine should not be used during pregnancy unless the woman’s clinical condition requires treatment with nifedipine. Nifedipine may be considered as a “backup therapy” for women with severe arterial hypertension who do not respond to standard therapy.

Period of breastfeeding

Nifedipine is excreted in breast milk. The concentration of nifedipine in breast milk is comparable to its concentration in the blood serum of the mother. The effect of the drug excreted with breast milk on the child is unknown. Therefore, if it is necessary to use nifedipine during lactation, it is recommended to stop breastfeeding.

Fertility

In single cases in in vitro fertilization, the use of PBMCs, including nifedipine, has been associated with reversible biochemical changes in the sperm head, which could lead to impaired sperm function. If in vitro fertilization attempts are unsuccessful and other causes of infertility are excluded, the possibility of effects of BMCCs, including nifedipine, on sperm function should be considered.

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