Cordaflex® RD
Pharmacokinetic interactions
Medicines that affect 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 first pass effect through the liver (after oral administration) or the clearance of nifedipine.
Inducers of the CYP3A4 isoenzyme
Rifampicin
Rifampin is a potent 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 CYP3A4 (eg, phenytoin, carbamazepine, phenobarbital)
Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine is reduced and its effectiveness is reduced. 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. Some macrolides are known to 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, a macrolide antibiotic, 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, drugs of this class have been shown to 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 (eg, 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.
Fluoxetia
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 inhibit the metabolism of other drugs mediated by 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).
CYP3A4 isoenzyme substrates
Substrates of the CYP3A4 isoenzyme (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, may 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
BMCCs 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 magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which is dangerous for 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®
From the point of view of enhancing the antihypertensive and antianginal effect, the combination of Cordaflex with beta-blockers, diuretics, ACE inhibitors, and nitrates is rational. All of the above combinations are safe and effective in most clinical situations, since they lead to summation or potentiation of effects, however, in some cases there is a risk of a pronounced decrease in blood pressure and increased symptoms of heart failure.
The combination of Cordaflex with clonidine, methyldopa, octadine, prazosin is possible according to indications, but can cause severe orthostatic hypotension.
An increase in the hypotensive effect is also observed with combination therapy with cimetidine, ranitidine and tricyclic antidepressants.
Nifedipine increases the concentration of digoxin and theophylline in the blood plasma, and therefore the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.
Procaine, quinidine and other drugs that cause QT prolongation enhance the negative inotropic effect and increase the risk of QT prolongation. Under the influence of nifedipine, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. When nifedipine is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. Caution should be exercised when using such combinations, especially in patients with impaired left ventricular function.
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - derivatives of coumarin and indanedione, NSAIDs), as a result of which their concentrations in the blood plasma may increase.
When administered simultaneously with rifampicin, phenytoin and calcium preparations, the effect of nifedipine is weakened.
Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.
Diltiazem inhibits the metabolism of nifedipine in the body; if necessary, reduce the dose of nifedipine.
Grapefruit juice, erythromycin and azole antifungals (fluconazole, intraconazole, ketoconazole) may inhibit the metabolism of nifedipine and therefore enhance its effects.
Similarly, the simultaneous use of Cordaflex and cimetidine increases the concentration of nifedipine in the blood plasma and enhances its effects; however, simultaneous use with ranitidine does not lead to a significant increase in the concentration of nifedipine in the blood plasma.
Since nifedipine is metabolized by the CYP3A4 isoenzyme, any inhibitor or inducer of this enzyme may affect the metabolism of nifedipine. Cyclosporine is also a CYP3A4 substrate; therefore, when cyclosporine and nifedipine are used together, each may increase the duration of the effect of the other.
Cordaflex RD tablets with controlled release 40 mg No. 30
Compound
Active substance: nifedipine 40 mg.
Excipients: microcrystalline cellulose, cellulose*, lactose monohydrate*, hypromellose 4000, magnesium stearate, colloidal anhydrous silicon dioxide, film shell [hypromellose 15 (mPa.s)**, macrogol 6000, macrogol 400**, red iron oxide** , titanium dioxide**, talc**].
* 10 mg of cellulose and 30 mg of lactose monohydrate can be replaced with the commercially available Cellactose® product containing cellulose and lactose monohydrate of Euro quality. Pharm. ** Instead of these ingredients, Opadry® red 04B0003 can be used. The composition of the substance Opadry® red 04B0003 is qualitatively and quantitatively identical to the shell. Macrogol 6000 is used after the coating process as a polishing agent and is therefore not included in Opadry® Red 04B0003.
Pharmacokinetics
Absorption
Nifedipine is rapidly and almost completely (90%) absorbed from the gastrointestinal tract after oral administration. The duration of the effect after a single oral dose exceeds 24 hours. When developing the active substance of the drug Cordaflex® RD, zero-order release kinetics was chosen in order to ensure a constant release rate. The relative bioavailability of the drug is about 60%. The maximum concentration (Cmax) in blood plasma is 29.4 ± 12.0 mg/ml (x ± SD); the concentration of the drug in the blood plasma reaches a plateau 7.4 ± 6.4 hours after taking each dose. Maximum levels of the drug in blood plasma are achieved when it is taken in combination with food. However, at the end of the dosing interval, the concentration of the drug in the blood plasma does not change.
Distribution
The connection with blood plasma proteins (albumin) is 94-97%. Studies with labeled nifedipine in animals have shown that unbound nifedipine is distributed in all organs and tissues. Nifedipine concentrations were found to be higher in the myocardium than in skeletal muscles. There is no cumulative effect.
Metabolism
Nifedipine is mainly metabolized in the liver to inactive metabolites.
Removal
60-80% of the drug dose taken orally is excreted in the urine in the form of inactive metabolites, the remaining part is excreted in bile and feces. The half-life of nifedipine from blood plasma is approximately 2 hours. However, the release of the drug Cordaflex® RD is longer - up to 14.9 ± 6.0 hours in the equilibrium concentration phase.
The concentration of the drug in the blood plasma reaches a minimum of 12.0±6.5 mg/ml 24 hours after administration, which is twice the concentration achieved after taking 20 mg of nifedipine 2 times a day.
If renal function is impaired, the pharmacokinetics of nifedipine does not change (nifedipine is excreted in the urine in small quantities). With a significant decrease in liver function, the clearance of nifedipine is reduced, so it is not recommended to exceed the daily dose.
Indications for use
- Arterial hypertension
- Stable angina (angina pectoris), post-infarction angina, as well as vasospastic angina (Prinzmetal angina).
Contraindications
- Hypersensitivity to nifedipine or any other component of the drug, other 1,4-dihydropyridine derivatives.
- Severe arterial hypotension with a risk of collapse in cardiovascular shock with respiratory manifestations.
- Unstable angina.
- Myocardial infarction with left ventricular failure.
With caution: Severe aortic stenosis, acute myocardial infarction (within the first 4 weeks), severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, chronic heart failure, severe cerebrovascular accidents, age up to 18 years (efficacy and safety have not been established), elderly age, renal and liver failure (especially patients on hemodialysis - high risk of excessive and unpredictable decrease in blood pressure).
Directions for use and doses
Cordaflex® RD 40 mg should be taken in the morning, during a meal (for example, breakfast), not chewed and washed down with a sufficient amount of water.
The dose should be selected individually, depending on the severity of the patient's condition and response to therapy. The following doses can be recommended:
Arterial hypertension
1 tablet of Cordaflex® RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex® RD 40 mg in one or two doses). Increasing the dose above 80 mg is not recommended.
Cardiac ischemia
1 tablet of Cordaflex® RD 40 mg 1 time per day.
If necessary, the dose can be increased to 80 mg (2 tablets of Cordaflex® RD 40 mg in one or two doses). Doses above 80 mg can be given in exceptional cases under medical supervision. The daily dose should not exceed 120 mg.
Dosage for decreased renal or hepatic function
It is recommended to use with caution the same doses as for normal renal or hepatic function (tolerance may develop). If there is a significant decrease in liver function, it is not recommended to exceed the daily dose of 40 mg.
Storage conditions
At a temperature not exceeding 30 ° C, in a place protected from direct sunlight. Keep out of reach of children.
Best before date
5 years. Do not use after the date indicated on the package.
special instructions
After myocardial infarction, the drug should be started only after stabilization of hemodynamic parameters.
Patients with acute myocardial infarction and for 30 days after it should not use short-acting calcium channel blockers such as 1,4-dihydropyridine. When treating such patients with controlled-release BMCCs such as 1,4-dihydropyridine, careful monitoring is necessary. It is more advisable to prescribe in the absence of a tendency to tachycardia, as well as in patients in whom beta-blockers are ineffective or have contraindications to their use.
In cases of insufficient effectiveness of monotherapy with Cordaflex® RD 40 mg, it is advisable to continue treatment using effective combinations with other drugs (see Interactions with other drugs).
During treatment, drinking alcohol is not recommended due to the risk of excessively lowering blood pressure.
In patients with heart failure, appropriate therapy with digitalis preparations is recommended before starting treatment with Cordaflex® RD 40 mg.
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the therapy being performed.
Caution should be exercised in elderly patients due to the greater likelihood of age-related impairment of renal and hepatic function.
Description
Blocker of “slow” calcium channels.
Pharmacodynamics
The active ingredient of the drug Cordaflex® RD is nifedipine. Nifedipine is a selective blocker of “slow” calcium channels, a 1,4-dihydropyridine derivative. Has antihypertensive and antianginal effects. Reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. In therapeutic doses, it normalizes the transmembrane current of calcium ions, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces total peripheral resistance, reduces afterload and myocardial oxygen demand. At the same time, it improves blood supply to ischemic areas of the myocardium without developing the “steal” syndrome, and also activates the functioning of collaterals. It has virtually no effect on the sinoatrial and atrioventricular nodes and does not have either pro- or antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing moderate natriuresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels without affecting the time of their activation, inactivation and recovery.
Side effects
In the vast majority of cases, Cordaflex® RD 40 mg is well tolerated by patients.
In some cases, especially in the initial period of treatment, the following transient adverse events may occur:
Cardiovascular system: at the beginning of treatment - facial skin flushing, marked decrease in blood pressure, tachycardia; peripheral edema (ankles, feet, legs); rarely - the appearance of angina attacks (which is also typical for other vasodilators and requires discontinuation of the drug), heart failure.
Central nervous system: headache, dizziness, fatigue, drowsiness. With long-term use in high doses - paresthesia in the limbs, tremor. Digestive system: nausea, heartburn, diarrhea or constipation; rarely with long-term use of the drug - intrahepatic cholestasis, increased activity of “liver” enzymes, which disappear after discontinuation of the drug; very rarely - gingival hyperplasia.
Hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, leukopenia; very rarely - anemia.
Urinary system: increased daily diuresis; rarely - deterioration of renal function (in patients with renal failure).
Musculoskeletal system: myalgia; very rarely - arthritis, arthralgia.
Allergic reactions: rarely - urticaria, exanthema, itching; very rarely - photodermatitis.
Other: very rarely - visual impairment, gynecomastia, hyperglycemia, which completely disappear after discontinuation of the drug; change in body weight, galactorrhea.
Use during pregnancy and breastfeeding
The use of nifedipine in pregnant women is recommended if it is impossible to use other drugs without restrictions.
Since nifedipine is excreted in breast milk, you should refrain from prescribing the drug during lactation, or stop breastfeeding during treatment.
Interaction
The drug Cordaflex® RD 40 mg with controlled release of the active substance has wide possibilities for highly effective combination therapy.
Rational from the point of view of antihypertensive and antianginal effects is the combination of Cordaflex® RD 40 mg with beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors, and nitrates. The combined use of Cordaflex® RD 40 mg with beta-blockers is safe and effective in most clinical situations, as it leads to summation and potentiation of effects; however, in some cases there is a risk of arterial hypotension and increased symptoms of heart failure.
An increase in the hypotensive effect is also observed with combination therapy with cimetidine, ranitidine and tricyclic antidepressants.
Cordaflex® RD 40 mg does not reduce its effectiveness during treatment with steroidal and non-steroidal anti-inflammatory drugs.
Nifedipine increases the concentration of digoxin and theophylline, and therefore the clinical effect and/or the content of digoxin and theophylline in the blood plasma should be monitored.
When administered simultaneously with rifampicin and calcium preparations, the effect of nifedipine is weakened.
Procaine, quinidine and other drugs that cause QT prolongation enhance the negative inotropic effect and increase the risk of QT prolongation. Under the influence of nifedipine, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in its bioavailability, as well as the induction of enzymes that inactivate quinidine. When nifedipine is discontinued, a transient increase in quinidine concentration is observed (approximately 2 times), which reaches a maximum level on days 3-4. Caution should be exercised when using such combinations, especially in patients with impaired left ventricular function.
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, non-steroidal anti-inflammatory drugs), as a result of which their concentration in the blood plasma may increase.
Since it has been shown that carbamazepine and phenobarbital, by activating liver enzymes, reduce the plasma concentrations of other slow calcium channel blockers (SCBCs), a similar decrease in the plasma concentrations of nifedipine cannot be excluded. Valproic acid, inhibiting the activity of enzymes, led to an increase in the concentration in the blood plasma of other blockers of “slow” calcium channels, so an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously with valproic acid.
Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.
Diltiazem inhibits the metabolism of nifedipine in the body; careful monitoring is necessary; if necessary, reduce the dose of nifedipine.
Grapefruit juice inhibits the metabolism of nifedipine in the body, and therefore it is not recommended to use it with nifedipine.
Overdose
Symptoms
In case of acute overdose, headache, a pronounced decrease in blood pressure, as well as a violation of the energy supply of the myocardium (an attack of angina) occur.
Treatment
In the early stages after an overdose is detected, first aid can be to rinse the stomach and give activated charcoal. If necessary, small intestinal lavage can be done, which is especially useful in cases of overdose of controlled-release drugs.
Since nifedipine is highly bound to plasma proteins, hemodialysis is ineffective, but plasmapheresis may be effective.
Symptoms of cardiac arrhythmias with bradycardia can be eliminated by administering beta sympathomimetics. For life-threatening bradycardia, an artificial pacemaker should be used.
If there is a significant decrease in blood pressure, an infusion of usual doses of norepinephrine (norepinephrine) is indicated. If symptoms of heart failure develop, intravenous administration of fast-acting digitalis glycosides is recommended.
Due to the lack of a specific antidote, symptomatic therapy is indicated. Dopamine, isoprenaline and 10% calcium gluconate solution (10 - 20 ml IV) can be used as antidotes.
Impact on the ability to drive vehicles and operate machinery
During the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require rapid psychomotor reactions. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerability of the drug.
Cordaflex, 60 pcs., 20 mg, extended-release film-coated tablets
Inside.
Film-coated tablets, 10 mg
should be swallowed whole before meals, without chewing, with a small amount of water.
The dosage regimen is set individually, depending on the severity of the disease and the patient’s response to the therapy. The initial dose is 1 tablet. (10 mg) 3 times a day. If necessary, the dose can be increased to 2 tablets. (20 mg) - 1-2 times a day. At least 2 hours should pass between two doses of the drug. The maximum daily dose is 40 mg.
If it is necessary to increase the dose to 80–120 mg for the treatment of angina pectoris or arterial hypertension, it is recommended to transfer the patient to Cordaflex® extended-release film-coated tablets, 20 mg.
To speed up the action of the drug at the beginning of an attack of angina or hypertensive crisis, the tablet should be chewed, held in the mouth for some time, and then swallowed with a small amount of water.
In elderly patients, the pharmacokinetics of nifedipine changes, and therefore lower doses may be required to maintain sufficient therapeutic effect.
If renal or hepatic function decreases, it is recommended to use with caution the same doses as for normal renal or hepatic function (tolerance may develop). If there is a significant decrease in liver function, it is not recommended to take a dose of more than 40 mg per day.
Extended-release film-coated tablets, 20 mg
should be swallowed whole, without chewing, with a small amount of water.
The recommended starting dose is 1 tablet. 2 times a day (2 × 20 mg). If necessary, the daily dose can be increased up to 2 times 2 tablets. The maximum daily dose of nifedipine should not exceed 120 mg. It is recommended to divide the daily dose into 2 doses at 12-hour intervals.
In patients with impaired liver function, the drug is used with caution under the monitoring of liver function; in case of severe impairment of liver function, the dose must be reduced. In patients with impaired renal function, no dose adjustment is required.
In elderly patients, the metabolism of nifedipine during the initial passage through the liver is reduced, and there is also a higher likelihood of deterioration of cerebral blood flow due to possible sharp peripheral vasodilation, therefore, at the beginning of treatment, the dose of Cordaflex® is reduced by approximately 2 times.
The drug should be discontinued gradually, especially after taking high doses.
