Composition, form of production and packaging
The solution for infusions is transparent, yellowish in color.
1 ml of 1 fl.
nifedipine 100 Ојg 5 mg
Excipients: ethanol 96% - 7.5 g, macrogol 400 - 7.5 g, sodium hydroxide 0.1N (up to pH 4.5-7.5), water d / and - 34.995 g.
50 ml - bottles of dark glass (1) - packs of cardboard complete with disposable syringe and connecting tube for infusions - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Nifedipine is a selective blocker of slow calcium channels, a derivative of 1,4-dihydropyridine. Has antianginal and hypotensive effect. Reduces the flow of calcium ions through slow calcium channels into cells, mainly inside cardiomyocytes, smooth muscle cells of coronary and peripheral arteries, while decreasing peripheral vascular resistance and dilating coronary arteries, especially large blood supply vessels, and even intact segment walls of partially stenosed vessels. In addition, nifedipine lowers the tone of the smooth muscles of the coronary arteries, thereby preventing angiospasm, increasing blood flow in the poststenotic sections of the vessels and increasing the delivery of oxygen to the myocardium; decreases myocardial oxygen demand by decreasing peripheral vascular resistance (afterload), and with prolonged admission it is able to prevent the development of new atherosclerotic lesions in the coronary arteries.
Nifedipine reduces the tone of the smooth muscles of the arterioles, thereby reducing the increased peripheral vascular resistance and, consequently, blood pressure. At the beginning of Adalat treatment, there may be a temporary reflex increase in heart rate and, as a consequence, cardiac output. However, this increase is not so significant as to compensate for the dilatation of blood vessels. In addition, nifedipine for short-term and long-term use increases the excretion of sodium and water from the body. The hypotensive effect of nifedipine is especially pronounced in patients suffering from hypertension.
After intravenous administration, nifedipine is rapidly distributed in the body; 50% of the administered dose is distributed in the body after 5-6 minutes. It binds to plasma proteins (albumin) by 95%.
After parenteral administration, nifedipine is almost completely metabolized in the liver to inactive metabolites.
It is excreted mainly by the kidneys in the form of inactive metabolites, to a lesser extent (5-15%) - with bile. In urine, only traces (less than 1%) of unchanged active substance are found.
T 1/2 nifedipine after parenteral administration is 1.7 hours. In patients with impaired renal function, the pharmacokinetics of nifedipine does not change significantly.
In liver failure, there is a significant elongation of T 1/2 of the drug and a decrease in its overall clearance, which may require a dose reduction. Penetrates through the placental barrier, excreted in breast milk. Hemodialysis and peritoneal dialysis does not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its elimination.
- Prinzmetal angina;
- hypertensive crisis.
50 ml of Adalat В® solution is administered intravenously infusion over about 4-8 hours (at a rate of 6.3-12.5 ml / h, corresponding to 0.63-1.25 mg of nifedipine / h).
The maximum dose of the drug administered within 24 hours should not exceed 150-300 ml (corresponding to 15-30 mg of nifedipine / 24 hours).
Infusion therapy can be performed continuously for 3 days. Then, switching to oral therapy with nifedipine is recommended.
The safety and effectiveness of Adalat В® in children and adolescents under the age of 18 years is not established.
In elderly patients , a reduction in maintenance dose may be required due to pharmacokinetics disorders (compared to younger patients).
In patients with impaired liver function, the drug is used with caution under the control of liver function, with severe violations of liver function, it is necessary to reduce the dose.
In patients with impaired renal function, dose adjustment is not required.
When nifedipine was used, side effects were evaluated in placebo-controlled studies. The following side effects were classified as follows: often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10 000, <1/1000). The degree of incidence of adverse reactions was "often" estimated to be less than 3%, except for edema (9.9%) and headache (3.9%). Side effects, which were noted only during post-marketing observations, and whose frequency was not assessed, are indicated "in some cases".
From the cardiovascular system: often - peripheral edema, symptoms of vasodilation (redness of the face, heat sensation); infrequently - tachycardia, palpitations, lowering blood pressure, fainting; in some cases - chest pain (angina pectoris).
From the side of the central nervous system: often - a headache; infrequently - dizziness, migraine, tremor, vertigo, anxiety, sleep disturbances, rarely - paresthesia, dysesthesia; in some cases - hypoesthesia, drowsiness.
On the part of the digestive system: often - constipation, infrequent gastrointestinal and abdominal pain (pain in the stomach and intestines), nausea, dyspepsia, flatulence, dryness of the oral mucosa, transient increase in liver transaminases; rarely - gingival hyperplasia; in some cases - vomiting, insufficiency of the cardiac sphincter, jaundice.
On the part of the respiratory system: infrequently - epistaxis, nasal congestion; in some cases - dyspnea.
From the musculoskeletal system: infrequently - muscle cramps, swelling of the joints; in some cases - arthralgia, myalgia.
From the urinary system: infrequently - polyuria, dysuria.
From the immune system: infrequently - allergic reactions in the form of allergic / angioedema (including potentially life-threatening laryngeal edema); rarely - skin itching, rash, urticaria; in some cases - anaphylactic / anaphylactoid reactions.
From the skin and subcutaneous fat: infrequently - erythema; in some cases - toxic epidermal necrolysis, photosensitivity, allergic reactions, purpura.
From the side of the organ of vision: infrequent - impaired vision; in some cases, pain in the eyes.
From the side of the reproductive system: infrequently - erectile dysfunction.
From the hematopoietic system: in some cases - agranulocytosis, leukopenia.
Metabolic disorders: in some cases - hyperglycemia.
Local reactions: infrequently - reactions at the injection site (including thrombophlebitis).
Other: often - poor health; infrequently - nonspecific pain syndrome, chills.
In patients with malignant hypertension and hypovolemia and those on dialysis, a drop in blood pressure may be due to vasodilation.
- Pregnancy (up to 20 weeks);
- the period of breastfeeding;
- cardiogenic shock;
- unstable angina;
- Acute myocardial infarction (in the first 4 weeks after myocardial infarction);
- simultaneous administration with rifampicin;
- age under 18 years (safety and efficacy not established);
- hypersensitivity to nifedipine or any other component of the drug.
With caution: acute heart failure, chronic heart failure of III-IV functional class according to NYHA classification, severe aortic stenosis, severe bradycardia (heart rate less than 50 beats per minute), liver failure, severe arterial hypotension (systolic blood pressure less than 90 mm Hg .), in patients with malignant arterial hypertension and hypovolemia, on hemodialysis, pregnancy (after 20 weeks).
PREGNANCY AND LACTATION
The use of Adalat В® is contraindicated in pregnancy up to 20 weeks.
Controlled clinical studies of the use of Adalat В® in pregnant women have not been conducted; accordingly, the data of controlled clinical studies on the safety and efficacy of the drug Adalat В® in pregnant women are absent.
Tests in animals showed the presence of embryotoxicity, placental toxicity, fetotoxicity and teratogenicity when taking nifedipine during and after the organogenesis period.According to available clinical data, it is not possible to evaluate specific prenatal risk. At the same time, there are data on the increase in the probability of perinatal asphyxia, cesarean section, premature birth and intrauterine growth retardation. It is unclear whether these cases are the result of a major disease (arterial hypertension), treatment or a specific effect of Adalat В® . The information available is insufficient to exclude the possibility of side effects, which are dangerous for the fetus and the newborn. Therefore, the use of Adalat В® after the 20th week of pregnancy requires a careful individual assessment of the risk-benefit ratio for the patient, fetus and / or newborn and can only be considered if other methods of therapy are contraindicated or ineffective.
Careful blood pressure control should be performed in pregnant women with Adalat В® simultaneously with iv magnesium sulfate due to the possibility of excessive blood pressure lowering, which is dangerous for both the mother and the fetus and / or the newborn.
Nifedipine is excreted in breast milk, so if Adalat В® is needed during lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with renal insufficiency, dose adjustments are not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with impaired liver function when Adalat В® is administered require careful monitoring, and in some cases a reduction in the dose of the drug
APPLICATION FOR CHILDREN
Efficacy and safety of use under the age of 18 years are not established.
APPLICATION IN ELDERLY PATIENTS
With caution appoint elderly patients.
The dose of Adalat В® should be selected individually, taking into account the severity of the disease and the patient's response to ongoing treatment, as well as strictly monitor blood pressure and heart rate.
It is not recommended simultaneous use of the drug Adalat В® and beta-adrenoblockers because of the risk of a pronounced decrease in blood pressure, and in some cases, worsening of the course of chronic heart failure. If simultaneous use of nifedipine with beta-blockers is necessary, follow-up of the patient is necessary.
The drug Adalat В® should not be used in patients who are supposed to have an association of ischemic pain with previous therapy with nifedipine.
As with the use of other vasodilators, with the use of the preparation Adalat В® very rarely there can be angina attacks, as well as aggravation of angina with weighting, lengthening and the increase in angina attacks, especially at the very beginning of treatment.
In some cases, the development of myocardial infarction has been documented, but it is not possible to establish a cause-and-effect relationship of the disease with nifedipine, since myocardial infarction can arise as a result of the natural course of IHD.
Patients with a dysfunction of the liver with the introduction of the drug Adalat В® require careful observation; in severe cases, a reduction in the dose of Adalat В® is necessary.
Nifedipine is metabolized by the CYP3A4 isoenzyme. Thus, drugs - inhibitors or inducers of the CYP3A4 isoenzyme can influence metabolism during the "first passage" of nifedipine through the liver and its clearance in a joint application. In the case of combined use of nifedipine and drugs - weak or moderate inhibitors of the isoenzyme CYP3A4 listed below, an increase in the concentration of nifedipine in the blood plasma is possible, and therefore careful monitoring of blood pressure and, if necessary, a reduction in the dose of nifedipine: antibiotics of the macrolide group (eg erythromycin ), HIV protease inhibitors (eg ritonavir), antifungals from the azole group (eg, ketoconazole), antidepressants (nefazodone and fluoxetine), quinupristine / delfopristin. valproic acid, cimetidine.
The Adalat В® preparation contains 18% by volume of ethyl alcohol, which corresponds to 45 g of ethanol per day of the drug. This need to be taken into account when used in patients with alcoholism or having metabolic disorders of ethanol, as well as in pregnant and lactating women, children, as well as in patients at high risk (with liver disease or epilepsy).
In isolated cases, when performing in vitro fertilization with the use of slow calcium channel blockers dihydropyridine series, reversible biochemical changes in the head of spermatozoa were noted, which led to a disruption of the sperm function. With unsuccessful attempts of in vitro fertilization and with the exclusion of other causes of infertility, one should take into account the probability of the influence of slow calcium channel blockers dihydropyridine line on sperm, provided they are taken.
Nifedipine causes a false positive increase in the concentration of vanillylmandelic acid in the urine as determined by the spectrophotometric method and does not affect the result of this reaction when using the high performance liquid chromatography (HPLC) method.
The Adalat В® preparation in a vial provided with a plastic light-shielding coating remains stable in daylight for 1 hour, and under artificial illumination - for 6 hours.
Impact on the ability to drive vehicles and manage mechanisms
Ethanol contained in the formulation Adalat В® , can affect the effects of other drugs. applied simultaneously with the preparation Adalat В® , and can disrupt the ability to drive vehicles and work with the required mechanisms of attention.
Symptoms: loss of consciousness right up to coma, lowering blood pressure, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock accompanied by pulmonary edema.
Treatment: emergency interventions for overdose should first of all be aimed at removing nifedipine from the body and restoring stable hemodynamics. With bradycardia -? -sympatomimetics, with life-threatening bradycardia - implantation of a temporary artificial pacemaker, with a pronounced decrease in blood pressure, a slow intravenous administration of 10-20 ml of 10% calcium gluconate solution is permissible (repeated administration is permissible), with ineffectiveness prescribed vasoconstrictive sympathomimetics (dopamine or norepinephrine). Doses of these drugs are selected depending on the therapeutic effect obtained. The introduction of fluid should be limited in connection with the risk of cardiac overload.
Carrying out of a hemodialysis is inexpedient, as nifedipine is not deduced or removed at a dialysis; it is recommended to conduct plasmapheresis.
Drugs affecting the metabolism of nifedipine
Nifedipine is metabolized by the CYP3A4 isoenzyme localized in the liver and intestinal mucosa. Consequently, drugs that inhibit or induce this enzyme system can affect the effect of "first passage" through the liver of nifedipine (when ingesting it) and clearance. Nifedipine is a drug with high clearance. Since hepatic clearance is mainly determined by the volume of hepatic blood flow, the possible interactions listed below, which may affect the pharmacokinetic performance of nifedipine when administered concomitantly, can not be compared with interactions with nifedipine in the form of a solution for infusions.
Rifampicin is a powerful inducer of the isoenzyme CYP3A4. When combined with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness decreases. The use of nifedipine in conjunction with rifampicin is contraindicated.
Simultaneous reception of nifedipine with mild and moderate inhibitors of the CYP3A4 isoenzyme requires regular monitoring of blood pressure and, if necessary, a reduction in the dose of nifedipine. These drugs include:
Antibiotics of the macrolide group (eg, erythromycin)
Clinical studies of the interaction of nifedipine with macrolides were not conducted. It is known that some macrolides are inhibitors of the CYP3A4 isoenzyme. As a result, the possibility of increasing the concentration of nifedipine in blood plasma can not be ruled out when these drugs are used together.
Azithromycin, belonging to the macrolide group, is not an inhibitor of the CYP3A4 isoenzyme.
HIV protease inhibitors (eg ritonavir)
Clinical studies of the interaction of nifedipine with HIV protease inhibitors have not been conducted. It is known that preparations of this group are inhibitors of the isoenzyme CYP3A4. These drugs inhibit the isoenzyme CYP3A4 metabolism of nifedipine in vitro. In the case of combined use with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma due to delayed metabolism during the "first passage" through the liver and delayed excretion.
Antifungal agents from the group of azoles (e.g., ketoconazole)
Clinical studies nifedipine interactions with drugs in this group were not conducted. It is known that drugs of this group are inhibitors isoenzyme CYP3A4. In the case of joint use with nifedipine can not be excluded marked increase nifedipine concentrations in plasma due to slow metabolism in the "first pass" through the liver.
Clinical interaction studies have not been conducted with fluoxetine nifedipine. It is known that fluoxetine is an inhibitor of isozyme CYP3A4. Fluoxetine inhibits the isoenzyme CYP3A4 metabolism caused by nifedipine in vitro. In the case of joint use with nifedipine may significantly increase concentrations of nifedipine in blood plasma.
Clinical interaction studies have not been conducted with nifedipine nefazodone. It is known that nefazodone is an inhibitor of isozyme CYP3A4. In the case of joint use with nifedipine may significantly increase concentrations of nifedipine in blood plasma.
Quinupristin / dalfopristin
Due isoenzyme CYP3A4 inhibition combined use with nifedipine may lead to increased concentrations of nifedipine in the blood plasma.
Clinical studies of the interaction is not performed nifedipine with valproic acid. Since it has been shown that valproic acid increases the concentration in plasma is structurally similar to nifedipine, a calcium channel blocker nimodipine slow due to the inhibition of microsomal liver enzymes, it is impossible to exclude the possibility of increasing concentrations of nifedipine in the blood plasma.
Due isoenzyme CYP3A4 inhibition combined use with nifedipine may lead to increased concentrations of nifedipine in the blood plasma.
The combined use of cisapride and nifedipine may lead to increased concentrations of nifedipine in blood plasma, which requires regular monitoring of blood pressure and, if necessary, reduce the dose of nifedipine.
Antiepileptics isoenzyme inducers of CYP3A4 (phenytoin, carbamazepine, phenobarbital)
Phenytoin induces CYP3A4 isozyme and reduces the bioavailability of nifedipine and, as a consequence, reduces its effectiveness, which requires clinical observation and, if necessary, to increase its dosage. If nifedipine dose was increased during co-administration, after discontinuation of nifedipine phenytoin dose should be reduced to the initial value.
Clinical studies of the interaction of nifedipine with carbamazepine and phenobarbital is not carried out. Since it has been shown that both drugs decrease the concentration in plasma is structurally similar to the slow calcium blocker nifedipine, nimodipine ropes by induction of hepatic microsomal enzymes, it is impossible to exclude the possibility of lowering plasma concentrations of nifedipine and consequently reducing its efficiency.
Effect of nifedipine on other drugs
Nifedipine may enhance the antihypertensive effect when combined with other antihypertensive agents such as diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, other calcium blockers slow ropes, alpha-blockers, PDE5 inhibitors, methyldopa.
With simultaneous application of nifedipine with beta-blockers is necessary to monitor the patient, since in some cases it is possible worsening of chronic heart failure.
Nifedipine reduces the clearance of digoxin, which leads to an increase in the concentration of digoxin in the blood plasma. Therefore, patients should establish a thorough clinical and ECG monitoring for early detection of digoxin overdose; if necessary digoxin dose should be reduced by taking into account its concentration in plasma.
In some cases, concomitant use of nifedipine and quinidine observed reduction of quinidine concentration in blood plasma, as well as a marked increase of quinidine concentration in blood plasma after cancellation quinidine. Therefore, in the case of joint use of nifedipine as an additional means, any failure should be controlled from nifedipine concentrations in plasma quinidine and optionally required correction of quinidine doses. In some cases, the combined use of nifedipine and quinidine may increase concentrations of nifedipine in blood plasma. Because BP is necessary to monitor and if necessary reduction of the dose of nifedipine.
Tacrolimus is metabolized isoenzyme CYP3A4. In some cases, may increase tacrolimus plasma concentrations when combined with nifedipine. Therefore, in the case of combined use is necessary to control the concentration of tacrolimus in the blood plasma, and if necessary to reduce the dose of tacrolimus.
No effect on the pharmacokinetics of nifedipine following medicines: ajmaline, benazepril, debrizohin, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone, talinolol, triamterene / hydrochlorothiazide, acetylsalicylic acid and candesartan.
The combined use of nifedipine and acetylsalicylic acid 100 mg did not affect the pharmacokinetics of nifedipine; nifedipine, in turn, does not change the antiplatelet properties of acetylsalicylic acid, 100 mg (platelet aggregation, and bleeding time).
Combined use of nifedipine and candesartan no effect on the pharmacokinetics of both drugs.
drug Adalat В® contains 18% by volume of ethanol that must be considered in combination with drugs that are incompatible with ethanol.
drug Adalat В® is compatible with the following solutions: 0.9% sodium chloride solution, 5% dextrose (glucose) solution, 5% fructose solution.
Infusion rate for the drug Adalat В® is 10 ml / hr, and in combination with compatible solutions - 40 ml / h. Combination with other infusion solutions is not recommended.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The temperature is not above 25 В° C, protected from light and the reach of children.
Shelf life - 2 years. Do not use after the expiration date printed on the package.