CORDAFLEKS RD TAB. P/P/O MODIF.HIGH. 40MG No. 30
Interaction
Pharmacokinetic interactions • Drugs that affect the metabolism of nifedipine. Nifedipine is metabolized by CYP3A4/5 isoenzymes, which are found in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may affect the first pass effect through the liver (after oral administration) or the clearance of nifedipine.
Inducers of the CYP3A4 isoenzyme
Rifampicin
Rifampicin is a powerful inducer of the CYP3A4 isoenzyme. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.
Antiepileptic drugs that induce the CYP3A4 isoenzyme (for example, phenytoin, carbamazepine, phenobarbital) Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine decreases and its effectiveness decreases. When using this combination simultaneously, it is necessary to monitor the clinical response to nifedipine therapy and, if necessary, increase its dose. If the dose of nifedipine is increased with simultaneous use of both drugs, the dose of nifedipine should be reduced after discontinuation of phenytoin. Clinical studies examining the potential interaction between nifedipine and carbamazepine or phenobarbital have not been conducted. Since both drugs reduce the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness cannot be excluded.
CYP3A4 isoenzyme inhibitors
Macrolide antibiotics (for example, erythromycin) Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. It is known that some macrolides inhibit the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and macrolide antibiotics. Azithromycin, which belongs to the macrolide group of antibiotics, does not inhibit the CYP3A4 isoenzyme.
HIV protease inhibitors (eg, ritonavir)
Clinical studies examining the interaction of nifedipine and HIV protease inhibitors have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. In addition, it has been shown that drugs of this class suppress the metabolism of nifedipine mediated by the CYP3A4 isoenzyme in vitro. When used simultaneously with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma cannot be ruled out due to a decrease in the effect of “first pass” through the liver and slower elimination.
Azole antifungals (for example, ketoconazole) Clinical studies examining the interaction of nifedipine and azole antifungals have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When used simultaneously with nifedipine, a significant increase in the systemic bioavailability of nifedipine is possible by reducing the effect of “first pass” through the liver.
Cimetidine and ranitidine
It has been established that cimetidine and ranitidine inhibit the CYP3A4 isoenzyme and cause an increase in the concentration of nifedipine in the blood plasma (by 80% and 70%, respectively), thereby enhancing its antihypertensive effect.
Diltiazem
Diltiazem reduces the clearance of nifedipine. This combination should be used with caution. A dose reduction of nifedipine may be required.
Fluoxetine
Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro suppresses the metabolism of nifedipine, mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and fluoxetine.
Nefazodone
Clinical studies examining the interaction between nifedipine and nefazodone have not been conducted. Nefazodone is known to suppress the metabolism of other drugs mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and nefazodone.
Quinidine
Increased plasma concentrations of nifedipine have been reported when administered concomitantly with quinidine. Therefore, when using quinidine and nifedipine simultaneously, careful monitoring of blood pressure is necessary. If necessary, the dose of nifedipine should be reduced.
Quinupristin/dalfopristin Concomitant use of quinupristin/dalfopristin may lead to increased plasma concentrations of nifedipine.
Valproic acid
Clinical studies examining the interaction of nifedipine and valproic acid have not been conducted. Since valproic acid increases the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of increasing the concentration of nifedipine in the blood plasma and enhancing its effectiveness cannot be excluded.
Grapefruit juice
Grapefruit juice inhibits the CYP3A4 isoenzyme and suppresses the metabolism of nifedipine. The simultaneous use of nifedipine with grapefruit juice leads to an increase in the concentration of nifedipine in the blood plasma and a prolongation of its action due to a decrease in the effect of “primary passage” through the liver and a decrease in clearance. This may enhance the antihypertensive effect of nifedipine. With regular consumption of grapefruit juice, this effect can last for 3 days after the last consumption of the juice. The consumption of grapefruit/grapefruit juice during treatment with nifedipine is contraindicated (see section Contraindications).
Substrates of the CYP3A4 isoenzyme
CYP3A4 isoenzyme substrates (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, can act as CYP3A4 inhibitors and increase the concentration of nifedipine in the blood plasma.
Cisapride
Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.
• Effect of nifedipine on other drugs
Quinidine
Nifedipine causes a decrease in the concentration of quinidine in the blood plasma. After discontinuation of nifedipine, a sharp increase in the concentration of quinidine in the blood plasma may occur. Therefore, when using nifedipine as additional therapy or discontinuing nifedipine, the concentration of quinidine in the blood plasma should be monitored and, if necessary, its dose should be adjusted.
Digoxin. The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, consequently, to an increase in the concentration of digoxin in the blood plasma. The patient should be carefully monitored for symptoms of glycoside overdose and, if necessary, reduce the dose of digoxin, taking into account its concentration in the blood plasma.
Theophylline. Nifedipine increases plasma concentrations of theophylline, and therefore the concentration of theophylline in blood plasma should be monitored. The clinical effect of both drugs when used together does not change.
Tacrolimus. Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of increased tacrolimus concentrations in selected cases when administered concomitantly with nifedipine. When using tacrolimus and nifedipine simultaneously, the concentration of tacrolimus in the blood plasma should be monitored and, if necessary, its dose should be reduced.
Vincristine. Nifedipine slows down the elimination of vincristine from the body and may cause increased side effects of vincristine. If simultaneous use is necessary, reduce the dose of vincristine.
Drugs that bind to blood proteins
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), quinine, salicylates, sulfinpyrazone), as a result of which their concentration may increase in blood plasma.
Cephalosporins. With the simultaneous administration of cephalosporins (for example, cefixime) and nifedipine in probands, the bioavailability of the cephalosporin increased by 70%.
Pharmacodynamic interactions
Medicines that lower blood pressure. The antihypertensive effect of nifedipine may be enhanced when used simultaneously with antihypertensive drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARA II), other BMCCs, alpha-blockers, phosphodiesterase-5 inhibitors, methyldopa. When using nifedipine and beta-blockers simultaneously, it is necessary to carefully monitor the patient's condition, since in some cases the course of CHF may worsen. The severity of the decrease in blood pressure increases with the simultaneous use of inhalational anesthetics and tricyclic antidepressants.
Nitrates. When used simultaneously with nitrates, tachycardia increases. Antiarrhythmic drugs BMCC can enhance the negative inotropic effect of antiarrhythmic drugs such as amiodarone and quinidine. Nifedipine should be co-administered with disopyramide and flecainide with caution due to a possible increase in negative inotropic effect.
Magnesium sulfate It is necessary to carefully monitor blood pressure in pregnant women while using nifedipine with intravenous administration of magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which poses a danger to both the mother and the fetus.
Fentanyl. The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension. If possible, it is recommended that nifedipine be discontinued at least 36 hours before fentanyl-based anesthesia. Calcium preparations Reduced effectiveness of nifedipine. NSAIDs NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandin synthesis, sodium and fluid retention in the body. Sympathomimetics Sympathomimetics reduce the antihypertensive effect of nifedipine.
Estrogens. Estrogens reduce the antihypertensive effect of nifedipine due to fluid retention in the body.
Lithium preparations. When BMCC is used together with lithium drugs, it is possible to increase the manifestation of the neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Cordaflex 20 mg 30 pcs. extended-release film-coated tablets
pharmachologic effect
Antianginal, hypotensive.
Composition and release form Cordaflex 20 mg 30 pcs. extended-release film-coated tablets
Tablet - 1 tablet:
- Nifedipine 20 mg;
- Excipients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hydroxypropylcellulose, polyvinylbutyral B 30 T, talc, magnesium stearate;
- shell composition: hypromellose, titanium dioxide, red iron oxide, magnesium stearate.
Extended-release, film-coated tablets. 30 pcs. packaged.
Directions for use and doses
Adults Cordaflex 10 mg are prescribed 1 tablet. 3-4 times/day. If necessary, the dose is gradually increased to 20 mg 2 times / day. The maximum daily dose is 40 mg.
When carrying out a course of therapy, it is recommended to use a prolonged form of the drug - Cordaflex Retard 20 mg. The drug is prescribed 20-40 mg 2 times a day.
For elderly people, the initial dose of the drug is reduced by half.
Indications for use Cordaflex 20 mg 30 pcs. extended-release film-coated tablets
Coronary heart disease: for the prevention (in some cases, relief) of attacks in various forms of angina, incl. angiospastic (Prinzmetal's angina); arterial hypertension of various origins; Raynaud's syndrome.
Contraindications
Cardiogenic shock; severe arterial hypotension (systolic blood pressure below 90 mm Hg); severe aortic stenosis, idiopathic hypertrophic subaortic stenosis; I trimester of pregnancy; severe heart failure; hypersensitivity to nifedipine.
Application of Cordaflex 20 mg 30 pcs. extended-release film-coated tablets during pregnancy and lactation
Cordaflex is contraindicated for use in the first trimester of pregnancy.
The use of Cordaflex in pregnant women is indicated only in cases where normalization of blood pressure is impossible with the use of other antihypertensive drugs.
Since nifedipine is excreted in breast milk, you should avoid using Cordaflex during lactation or stop breastfeeding during treatment with the drug.
Children under 18 years of age.
special instructions
The antihypertensive effect of Cordaflex is enhanced by hypovolemia. A decrease in pulmonary artery pressure and hypovolemia after dialysis may also enhance the effects of the drug, and therefore a dose reduction is recommended.
In rare cases, at the beginning of a course of treatment with Cordaflex or when its dose is increased, chest pain (angina due to paradoxical ischemia) may occur soon after taking the drug. If a causal relationship is found between taking the drug and angina pectoris, treatment should be discontinued.
In case of arterial hypertension or coronary vascular disease, abrupt withdrawal of nifedipine can cause a hypertensive crisis or myocardial ischemia (the “rebound” phenomenon).
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the Cordaflex therapy being performed.
Elderly patients are more likely to have decreased cerebral blood flow due to acute peripheral vasodilation.
During a course of treatment with Cordaflex, the consumption of alcoholic beverages is not recommended due to the risk of an excessive decrease in blood pressure.
Use in pediatrics:
Due to the lack of sufficient clinical data, the drug is not recommended for use in children and adolescents under 18 years of age.
Impact on the ability to drive vehicles and operate machinery:
During the initial, individually determined period of use of Cordaflex, driving vehicles and engaging in other potentially hazardous activities that require rapid psychomotor reactions are not allowed. In the process of further treatment, the degree of restrictions is determined depending on the patient’s individual response to the drug.
Overdose
Symptoms: severe arterial hypotension, headache, collapse, tachycardia, depression of the sinus node, bradycardia, arrhythmia.
Treatment: given the lack of a specific antidote, in cases of early detoxification, gastric lavage is performed with the administration of activated charcoal. 10% solutions of calcium gluconate or calcium chloride are administered intravenously and then, as indicated, as a long-term infusion. With a sharp decrease in blood pressure, intravenous infusion of norepinephrine is indicated, and with the development of heart failure - glycosides.
Side effects Cordaflex 20 mg 30 pcs. extended-release film-coated tablets
From the cardiovascular system: facial skin flushing, severe arterial hypotension, peripheral edema, tachycardia; rarely - increased angina attacks (drug discontinuation required), increased heart failure, fainting.
From the central nervous system and peripheral nervous system: headache, dizziness, increased fatigue, sleep disturbances (drowsiness or insomnia); in isolated cases - mood lability, visual impairment; with long-term use in high doses - paresthesia in the limbs, tremor.
From the digestive system: diarrhea, constipation, nausea, heartburn; rarely (with long-term use of the drug) - dry mouth, flatulence, intrahepatic cholestasis, increased activity of liver transaminases; in some cases - gum hyperplasia, gingivitis, anorexia.
From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; in some cases - anemia.
From the urinary system: increased daily diuresis; rarely - deterioration of renal function in patients with chronic renal failure.
From the musculoskeletal system: myalgia; in isolated cases - arthritis.
From the endocrine system: in isolated cases - gynecomastia, hyperglycemia (completely disappear after discontinuation of the drug), changes in body weight, galactorrhea.
Allergic reactions: rarely - urticaria, exanthema, itching; in some cases - autoimmune hepatitis.
Other: feeling of heat; in isolated cases - weakness, sweating, fever, chills, photodermatitis.
Drug interactions
The combined use of nitrates with Cordaflex significantly enhances the antianginal effect.
The simultaneous use of Cordaflex and beta-blockers is effective and safe in most clinical situations, as it leads to the summation of the antianginal and antihypertensive effects of the drugs, however, in some cases, severe arterial hypotension and heart failure may develop.
The combination of Cordaflex with clonidine (clonidine), alpha-methyldopa (dopegite), diuretics, captopril, octadine, prazosin, reserpine is considered rational, from the point of view of enhancing the hypotensive effect; Do not use Cordaflex with apressin.
With the simultaneous use of Cordaflex and calcium preparations, the effect of nifedipine is reduced due to an antagonistic interaction caused by an increase in the concentration of calcium ions in the extracellular space.
The hypotensive effect of Cordaflex when used simultaneously with cimetidine is significantly enhanced due to an increase in the concentration of nifedipine in the blood plasma, which requires dose adjustment of the drugs.
Under the influence of Cordaflex, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in the bioavailability of quinidine, the induction of enzymes that inactivate it, an increase in blood flow in the liver and kidneys, an increase in the volume of distribution of the drug, as well as changes in hemodynamics. When Cordaflex is discontinued after its simultaneous use with quinidine, a transient increase in the concentration (approximately 2 times) of the latter in the serum is observed, which reaches a maximum level on the 3-4th day after discontinuation, as well as a prolongation of the QT interval on the ECG. Thus, when using a combination of quinidine with Cordaflex, caution should be exercised, especially in patients with depressed left ventricular function.
When administered simultaneously with rifampicin, a weakening of the effect of Cordaflex will be observed.
