Nifedipine 60 mg prolonged-release tablets - Summary of Product Characteristics (SmPC) (2023)

Nidef prolonged release tablets 60 mg

Nifedipine Morningside 60 mg extended-release tablets

One prolonged-release tablet contains 60 mg nifedipine.

To comply with label claims, each tablet contains 10% excess nifedipine.

For the full list of excipients, see section 6.1.

extended release tablets

Pink, round, biconvex, film-coated tablet with a hole on one side and plain on the other, debossed with "X" on one side.

For treatment of hypertension of all degrees.

For the prophylaxis of chronic stable angina pectoris, alone or in combination with a beta-blocker.

Dose

For mild to moderate hypertension, the recommended starting dose is one 20 mg tablet once daily. For severe hypertension, the recommended starting dose is one 30 mg tablet once daily. If necessary, the dose can be increased according to individual needs up to a maximum of 90 mg once daily.

For the prophylaxis of angina pectoris, the recommended starting dose is one 30 mg tablet once daily. The dose can be increased according to individual needs up to a maximum of 90 mg once daily.

Patients whose symptoms of hypertension or angina are controlled with nifedipine capsules or nifedipine extended-release tablets can safely switch to nifedipine extended-release tablets.

Prophylactic antianginal efficacy is maintained after switching from other calcium channel blockers, such as diltiazem or verapamil, to nifedipine extended-release tablets.

Patients switching from other calcium channel blockers should begin treatment with the recommended starting dose of 30 mg nifedipine prolonged-release tablets. once a day. A subsequent dose increase may be initiated as clinically warranted.

Concomitant use with CYP 3A4 inhibitors or inducers of CYP 3A4 may result in a recommendation for dose adjustment of nifedipine or complete discontinuation of nifedipine treatment (see section 4.5).

Treatment duration

Treatment can be continued indefinitely.

Additional information on special populations

Pediatric population

The safety and efficacy of Nidef/Nifedipine prolonged-release tablets in children below 18 years of age have not been established. Currently available data on the use of nifedipine in the treatment of hypertension are described in section 5.1.

Old people

Based on the pharmacokinetic data of nifedipine, no dose adjustment is necessary in patients older than 65 years.

kidney damage

Based on pharmacokinetic data, no dose adjustment is necessary in patients with renal impairment (see section 5.2).

Application Method

oral administration.

The tablets should be swallowed whole with a glass of water, regardless of meals. The tablets should be taken approximately 24 hours apart, ie at the same time every day, preferably in the morning. Nidef/Nifedipine extended-release tablets should be swallowed whole; under no circumstances should they be bitten, chewed or broken.

Nidef/Nifedipine prolonged-release tablets should not be taken with grapefruit juice (see section 4.5).

Nidef/Nifedipine extended-release tablets are contraindicated in patients with a known hypersensitivity to nifedipine or other dihydropyridines due to the theoretical risk of cross-reactions. They should also not be used in case of known hypersensitivity to any of the excipients listed in sections 4.4 and 6.1.

They should not be used in lactating women or in women who are pregnant or may become pregnant (see section 4.6).

Nidef/Nifedipine extended-release should not be used in clinically significant aortic stenosis, unstable angina, or during or within one month after a myocardial infarction. They should not be used in patients with cardiogenic shock.

Nidef/Nifedipine prolonged-release tablet should not be used for the treatment of acute attacks of angina or in patients who have experienced ischemic pain after previous administration.

The safety of Nidef/Nifedipine prolonged-release tablets for the treatment of malignant hypertension has not been established.

Nidef/Nifedipine extended release should not be used for the secondary prevention of myocardial infarction.

The use of prolonged-release Nidef/Nifedipine should be contraindicated in patients with acute porphyria.

Nidef/nifedipine extended release should not be used in patients with Kock syndrome (ileostomy after proctocolectomy).

Nidef/Nifedipine prolonged-release tablets should not be co-administered with rifampicin as effective nifedipine plasma concentrations can be achieved by enzyme induction (see section 4.5)..

Since Nidef/Nifedipine prolonged-release tablets are long-acting, they should not be administered to patients with hepatic impairment (see section 4.5).

Nifedipine should be used with caution in patients with hypotension as there is a risk of further lowering of blood pressure. Caution is required in patients with very low blood pressure (severe hypotension with systolic blood pressure less than 90 mm Hg).

The use of nifedipine in diabetic patients may require adjustment of the antidiabetic treatment.

In patients with malignant hypertension and irreversible hypovolemic renal failure on dialysis, a significant drop in blood pressure may occur due to the vasodilatory effect of nifedipine.

Nifedipine should be used with caution in patients with reduced cardiac reserve; in patients with heart failure or significantly weakened left ventricular function. Occasionally exacerbation of heart failure has been observed with the use of nifedipine.

In patients with liver damage, careful monitoring may be necessary and, in severe cases, a dose reduction may be necessary.

Excessive drops in blood pressure can lead to temporary blindness. If these symptoms occur, do not try to drive or use machines (see section 4.8).

Although the steal effect has not been demonstrated, patients experiencing this effect should discontinue nifedipine treatment.

Because nifedipine does not have a beta-blocker effect, it does not protect against the dangers of abruptly stopping beta-blockers. Withdrawal of previously prescribed beta-blockers should be gradual, preferably over 8 to 10 days.

Nifedipine can be used in combination with beta-blockers and other antihypertensives, but the possibility of an additive effect leading to orthostatic hypotension should be considered.

Nifedipine will not prevent possible rebound effects after discontinuation of other antihypertensive drugs.

Nifedipine is metabolized by the cytochrome P450 3A4 system. Therefore, drugs that inhibit or induce this enzyme system may alter the first pass or elimination of nifedipine.(see section 4.5).

Drugs that are inhibitors of the cytochrome P450 3A4 system and therefore increase the plasma concentration of nifedipine are eg.

- macrolide antibiotics (for example, erythromycin),

- HIV protease inhibitors (for example, ritonavir),

- azole antifungals (for example, ketoconazole),

- antidepressant nefazodon and fluoksetin,

- chinuprystyna/dalfopristyna,

- valproic acid,

- cimetidine.

Blood pressure should be monitored when these medicinal products are used concomitantly and a dose reduction of nifedipine should be considered if necessary (see section 4.5).

This medicine contains less than 1 mmol sodium (23 mg) per tablet, which means that it is essentially "sodium-free".

Drugs that affect nifedipine:

Nifedipine is metabolized by the cytochrome P450 3A4 system, which is found both in the intestinal mucosa and in the liver. Therefore, drugs that inhibit or induce this enzyme system may alter the first pass (oral) or clearance of nifedipine (see section 4.4).

When nifedipine is used with the following medications, the extent and duration of the interaction should be taken into account:

Rifampicin:Rifampin strongly induces the cytochrome P450 3A4 system. When used concurrently with rifampicin, the bioavailability of nifedipine is significantly reduced and therefore its efficacy. Therefore, the use of nifedipine in combination with rifampicin is contraindicated (see section 4.3).

Blood pressure should be monitored during co-administration of known inhibitors of the cytochrome P450 3A4 system and, if necessary, a dose reduction of nifedipine should be considered (see sections 4.2 and 4.4)..In most of these cases, formal studies on interactions between nifedipine and the mentioned drugs have not been performed to date.

Drugs that increase exposure to nifedipine:

-macrolide antibiotics (for example, erythromycin)

-HIV protease inhibitors (for example, ritonavir)

-azolni antifungals (for example, ketoconazole)

-fluoxetine

-nefazodon

-chinuprystyna/dalfopristyna

-cyzapryd

-valproic acid

-h₂- receptor antagonist (especially cimetidine)

-Other calcium channel blockers (especially diltiazem)

When inducers of the cytochrome P450 3A4 system are co-administered, the clinical response to nifedipine should be monitored and, if necessary, an increase in nifedipine dose should be considered. If the nifedipine dose is increased during concurrent use of both drugs, consideration should be given to reducing the nifedipine dose after stopping treatment.

Elevated concentrations of nifedipine in plasma were recorded with the simultaneous use of alcohol, cyclosporine, ginkgo biloba, and ginseng.

Potentiated hypotensive effects of nifedipine may occur with: aldesleukin, alprostadil, anesthetics, antipsychotics, diuretics, phenothiazides, prazosin, and intravenous x-ray ion contrast agents. Cases of profound hypotension have been reported with the use of nifedipine and intravenous magnesium sulphate in the treatment of pre-eclampsia.

Drugs that reduce exposure to nifedipine:

- rifampicin (see above)

- kao phenytoin

- carbamazepine

- phenobarbital

During concomitant administration of St. John's wort, reduced concentrations of nifedipine in plasma were recorded.

Effect of nifedipine on other drugs.

Nifedipine may potentiate the blood pressure lowering effect of concomitantly administered antihypertensive drugs.

In case of simultaneous use of nifedipine and beta-blockers, the patient should be carefully monitored, since worsening of heart failure is also known in isolated cases.

digoxin:Simultaneous use of nifedipine and digoxin may result in decreased digoxin clearance and therefore increased plasma digoxin concentration. Therefore, the patient should be monitored prophylactically for signs of digoxin overdose and, if necessary, the glycoside dose reduced.

Quinidine:Concomitant use of nifedipine with quinidine may result in decreased quinidine plasma concentration and, in isolated cases, a significant increase in quinidine plasma concentration may be observed after discontinuation of nifedipine treatment. Therefore, when nifedipine is added or discontinued, it is recommended to monitor the plasma concentration of quinidine and, if necessary, adjust the quinidine dose.

It is necessary to carefully monitor blood pressure and, if necessary, reduce the dose of nifedipine.

Tacrolimus:Tacrolimus is metabolized by the cytochrome P450 3A4 system. The publications show that in individual cases the dose of tacrolimus administered simultaneously with nifedipine can be reduced. When both drugs are co-administered, tacrolimus plasma concentrations should be monitored and, if necessary, a reduction in the tacrolimus dose should be considered.

Plasma concentrations of phenytoin, theophylline, and nondepolarizing muscle relaxants (eg, tubocurarine) are increased when used in combination with nifedipine.

The risk of excessive hypotension, bradycardia, and heart failure is increased with the use of beta-blockers.

Nifedipine may cause increased mizolastine levels due to CYP3A4 inhibition.

Nifedipine may potentiate the neuromuscular blocking effect of vecuronium.

Drug Interactions with Food:

Grapefruit juice inhibits the cytochrome P450 3A4 system. Therefore, co-administration of nifedipine with grapefruit juice results in increased nifedipine plasma concentrations and prolonged effects of nifedipine due to reduced first-pass metabolism or reduced elimination. As a consequence, the blood pressure lowering effect may be potentiated. If grapefruit juice is consumed regularly, this effect can last for at least 3 days after the last consumption of grapefruit juice. Therefore, consumption of grapefruit/grapefruit juice should be avoided while taking nifedipine (see section 4.2).

Other forms of interaction:

Nifedipine may falsely increase the spectrophotometric values ​​of vanillylmandelic acid in urine. However, this does not affect HPLC measurements.

The pregnancy

As animal studies have shown embryotoxicity and teratogenicity, nifedipine is contraindicated during pregnancy (see section 4.3). Embryotoxicity was observed with 6 to 20 times the recommended dose of nifedipine in rats, mice, and rabbits, and teratogenicity in rabbits with 20 times the recommended dose of nifedipine. There are no adequate and well-controlled studies in pregnant women.

Increased rates of perinatal asphyxia, cesarean delivery, and intrauterine growth retardation and prematurity have been reported, but it is unclear whether these reports are due to essential hypertension, its treatment, or a specific drug effect.

Acute pulmonary edema has been observed with calcium channel blockers, including nifedipine as a tocolytic during pregnancy (see section 4.8), especially in multiple pregnancies (twins or multiples), administered intravenously and/or with concomitant beta-2 agonists. .

Breast-feeding

Nifedipine is excreted in breast milk, therefore Nidef/Nifedipine prolonged release is not recommended during lactation (see section 4.3).

Fertility

In individual casesin vitroFertilization Calcium antagonists, such as nifedipine, are associated with reversible biochemical changes in the sperm head that can cause sperm dysfunction. Nifedipine should be considered as a possible cause. if there is no other explanation for the failed paternity.

Reactions to medicinal products, the intensity of which varies from person to person, may affect the ability to drive and use machines (see section 4.8). This applies especially at the start of treatment, change of medication and combination with alcohol.

Possible side effects include dizziness and lethargy. If these symptoms occur, do not try to drive or use machines (see section 4.8).

Excessive drops in blood pressure can lead to temporary blindness. If these symptoms occur, do not try to drive or use machines (see section 4.8).

Adverse Drug Reactions (ADRs) Based on Placebo-Controlled Studies of Nifedipine, Ranked by CIOMS Frequency Category III (Clinical Trials Database: Nifedipine n=2661; Placebo n=1486; Accessed February 22, 2006, and ACTION study: nifedipine n=3825; placebo n=3840) are listed below:

Side effects listed under "common" were seen in less than 3%, with the exception of edema (9.9%) and headache (3.9%). Most of the side effects are due to the vasodilator effect of nifedipine.

Frequencies of adverse reactions reported with nifedipine-containing products are summarized in the table below. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), and rare (≥1/10,000 to <1/1000). Side effects that have been identified only during continuous post-marketing surveillance and whose frequency could not be estimated are listed under 'Unknown'.

¹= can cause life-threatening effects

²= Myocardial infarction has been reported, although it is not possible to distinguish such an event from the natural course of ischemic heart disease.

^**= Cases of tocolytic use during pregnancy have been reported (see section 4.6)

In patients with malignant hypertension and hypovolemia on dialysis, a pronounced fall in blood pressure may occur as a consequence of vasodilatation.

Report suspected side effects

It is important to report suspected side effects after the drug has been approved. It allows continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are requested to report any suspected side effects through the Yellow Card Scheme at: www.mhra.gov.uk/amarillocard or by searching for MHRA Yellow Card on Google Play or the Apple App Store.

Symptoms

Reports of nifedipine overdose are limited and symptoms are not necessarily dose related. The most likely symptoms of an overdose are severe hypotension due to vasodilation, tachycardia, and bradycardia.

Metabolic abnormalities include hyperglycemia, metabolic acidosis, and hypo- or hyperkalemia.

Cardiac effects may include heart block, atrioventricular dissociation and asystole, and cardiogenic shock with pulmonary edema.

Other toxic effects include nausea, vomiting, drowsiness, dizziness, disorientation, lethargy, flushing, hypoxia, and unconsciousness up to coma.

Treatment

In treatment, the priority is the elimination of nifedipine and the establishment of a stable cardiovascular condition.

After oral administration, gastric lavage is indicated, if necessary in combination with small bowel lavage. Ipecacuanha should be given to children.

Elimination should be as complete as possible, including the small intestine, to avoid inevitable subsequent absorption of the active substance.

The benefits of gastric decontamination are uncertain.

1. Consider the use of activated charcoal (50 g for adults, 1 g/kg for children) if the patient develops a potentially toxic amount within 1 hour of ingestion.

Although it may seem reasonable to assume that delayed application of activated charcoal could be beneficial for sustained release (SR, MR) formulations, there is no evidence for this.

2. Alternatively, consider gastric lavage in adults within 1 hour of a life-threatening overdose.

3. Additional doses of activated charcoal should be considered every 4 hours if a clinically significant amount of an extended-release preparation is ingested with a single dose of an osmotic laxative (eg, sorbitol, lactulose, or magnesium sulfate).

4. Asymptomatic patients should be observed for at least 4 hours after ingestion and 12 hours when a sustained release preparation is used.

Hemodialysis is not helpful because nifedipine cannot be dialyzed, but plasmapheresis (high plasma protein binding, relatively small volume of distribution) is recommended.

Activated charcoal should be administered in doses every 4 hours of 25 g for adults and 10 g for children.

It is necessary to monitor blood pressure, ECG, central arterial pressure, pulmonary wedge pressure, urea and electrolytes.

Hypotension due to cardiogenic shock and arterial vasodilation should be treated by elevating the feet and using plasma dilators. If these measures are not effective, hypotension can be treated with 10-20 ml of 10% calcium gluconate intravenously over 5-10 minutes. Symptoms are insufficient, treatment can be continued with ECG monitoring. In addition, beta-sympathomimetics can be used, for example, isoprenaline 0.2 mg slowly i.v. or as a continuous infusion of 5 μg/min. If administration of calcium and isoprenaline does not produce an adequate increase in blood pressure, additional vasoconstrictor sympathomimetics such as dopamine or norepinephrine are given. The dose of these drugs should be based on the patient's response.

If necessary, bradycardia can be treated with atropine, beta-sympathomimetics, or a temporary pacemaker.

Additional fluids must be administered carefully to avoid stress on the heart.

Pharmacotherapeutic group: Selective calcium channel blockers, mainly vascular, dihydropyridine derivatives, ATK code: C08CA05

Nifedipine is a calcium antagonist of the 1,4-dihydropyridine type. Calcium antagonists reduce the transmembrane entry of calcium ions through the slow calcium channel into the cell. As a specific and potent calcium antagonist, nifedipine acts especially on myocardial cells and smooth muscle cells of coronary arteries and peripheral resistance vessels. The main effect of nifedipine is the relaxation of the smooth muscle of the arteries, both in the coronary and peripheral circulation. Nidef/Nifedipine extended-release tablets have been developed to achieve controlled delivery of nifedipine in a release profile sufficient for once-daily dosing to be effective in clinical use.

In hypertension, the main effect of nifedipine is peripheral vasodilation, which reduces peripheral resistance. Once daily, nifedipine provides 24-hour control of high blood pressure. Nifedipine lowers blood pressure in such a way that the percentage reduction is proportional to its initial level. In normotensive people, nifedipine has little or no effect on blood pressure.

In angina pectoris, nifedipine reduces peripheral and coronary vascular resistance, leading to increased coronary blood flow, cardiac output, and stroke volume, while reducing afterload. In addition, submaximal nifedipine dilates clear and atherosclerotic coronary arteries, thus protecting the heart from coronary artery spasm and improving perfusion of the ischemic myocardium. Nifedipine reduces the frequency of painful attacks and ischemic ECG changes, regardless of the relative contribution of coronary artery spasm or atherosclerosis.

In an international prospective, randomized, double-blind study in 6321 hypertensive patients with at least one additional risk factor, followed for 3 to 4.8 years, nifedipine 30 and 60 (nifedipine GITS) were shown to reduce blood pressure compared to a standard combination. of diuretics.

Pediatric population

Limited information is available comparing nifedipine with other antihypertensive agents for acute and long-term hypertension, for different formulations and at different doses. Nifedipine has been shown to have an antihypertensive effect, but dosing recommendations, long-term safety, and impact on cardiovascular outcomes have not yet been established. There is no pharmaceutical form for children.

General characteristics:

Nidef/Nifedipine Extended-Release Tablets are an extended-release form of nifedipine designed to provide fewer fluctuations and a longer duration of nifedipine blood concentration compared to standard immediate-release formulations.

Nifedipine is highly protein bound. In the liver, it is oxidized to inactive metabolites, which are excreted in the urine (80%) and feces (20%).

Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity and carcinogenic potential.

Following acute oral and intravenous administration of nifedipine in different animal species, the following LD50 values ​​(mg/kg) were obtained:

*95% confidence interval.

In subacute and subchronic toxicity studies in rats and dogs, nifedipine was tolerated without impairment at doses up to 50 mg/kg (rats) and 100 mg/kg (dogs) orally. thirteen and four weeks respectively. Following intravenous administration, dogs tolerated nifedipine up to 0.1 mg/kg for six days without injury. Rats tolerated daily intravenous administration of 2.5 mg/kg nifedipine for three weeks without injury.

In chronic toxicity studies in dogs treated for up to one year, nifedipine was tolerated without deterioration at doses up to 100 mg/kg orally. In rats, toxicity occurred at concentrations greater than 100 ppm in food (approximately 5-7 mg/kg body weight).

In a rat carcinogenicity study (two years) there was no evidence of carcinogenicity of nifedipine.

Nifedipine has been shown to cause teratogenic effects in rats, mice, and rabbits, including digit abnormalities, limb malformations, cleft palate, cleft sternum, and rib malformations.

The digit abnormalities and limb malformations are probably the result of impaired blood flow in utero, but were also observed in animals treated with nifedipine only after the end of the period of organogenesis.

The use of nifedipine has been associated with a variety of embryotoxic, placental, and fetotoxic effects, including fetal stunting (rats, mice, rabbits), small placentas and underdeveloped chorionic villi (monkeys), embryofoetal death (rats, mice, rabbits). and prolonged pregnancy. /decreased neonatal survival (rats; not evaluated in other species). A risk to humans cannot be excluded with a sufficiently high systemic exposure; however, all doses associated with teratogenic, embryotoxic, or fetotoxic effects in animals were maternally toxic, many times the highest recommended human dose.

Nifedipine has not been shown to be mutagenic in in vitro and in vivo studies.

center

polyethylene oxide

Hydroxypropylmethylcellulose (E464)

Sodium chloride

polyethylene oxide

iron oxide (E172)

Magnesium Stearate (E572)

sealing coating

Hypromellose (E464)

Cellulose acetate coating

Cellulose acetate

Polyethylene glycol (E1521)

dichloromethane

methanol

film coating

Hydroxypropylcellulose (E463)

Hypromellose (E464)

Titanium dioxide (E171)

Razgovor (E553b)

red iron oxide (E172)

printing ink

The Winds (E904)

black iron oxide (E172)

Propylene glycol (E1520)

PVC/PE/PVDC aluminum blister. Blisters with 10, 14, 15, 28, 30, 56, 60, 90 and 112 prolonged-release tablets.

Not all pack sizes may be commercially available.

Morningside Healthcare Ltd.

Jedinica C, Harcourt Way

leicester

LE19 1WP

Britain