Adipine MR 10 mg modified-release tablets - Summary of Product Characteristics (SmPC) (2023)

Adypina MR 10

One modified-release tablet contains 10 mg of nifedipine.

Excipient with known effect: lactose monohydrate 39 mg

For the full list of excipients, see section 6.1.

Modified release pills for oral use.

Round, slightly biconvex, pink film-coated tablets with a smooth surface.

Hypertension

Prevention of chronic stable angina pectoris

Dose

The recommended starting dose of Adipine MR is 10 mg every 12 hours, swallowed with water, then increased based on response. Adipine MR is a titrated starting dose that can be titrated to 40 mg every 12 hours up to a maximum daily dose of 80 mg.

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).

Application Method

Oral administration.

As a general rule, the tablets are swallowed whole with a small amount of liquid, regardless of food.

Adipine MR should not be taken with grapefruit juice (see section 4.5).

Treatment duration

Treatment can be continued indefinitely.

Additional information on special populations

Elderly (> 65 years)

Nifedipine pharmacokinetics are altered in the elderly, therefore lower maintenance doses of nifedipine may be required compared to younger patients.

Patients with liver damage.

Nifedipine is mainly metabolized in the liver, therefore patients with liver damage should be carefully monitored and, in severe cases, a dose reduction may be necessary.

Patients with kidney damage.

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

Pediatric population

The safety and efficacy of nifedipine in children under 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.

Adipine MR is not a beta-blocker and therefore offers no protection against the dangers of abruptly stopping beta-blockers; any such interruption should involve a gradual reduction in the beta-blocker dose, preferably over 8 to 10 days.

Adipine MR can be used in combination with beta-blockers and other antihypertensives; however, the possibility of additive effects leading to orthostatic hypotension should be considered. Adipine MR will not prevent possible rebound effects after discontinuation of other antihypertensive drugs.

Caution is required in patients with very low blood pressure (severe hypotension with systolic blood pressure less than 90 mmHg), severe heart failure, and severe aortic stenosis.

Adipine MR should not be used during pregnancy unless the clinical condition of the woman requires treatment with nifedipine. The use of Adipine MR should be reserved for women with severe hypertension unresponsive to standard therapy (see section 4.6).

During intravenous administration of nifedipine, it is necessary to carefully monitor blood pressure. magnesium sulfate because it can cause an excessive drop in blood pressure, which can harm both the mother and the fetus. For additional information on use during pregnancy, see section 4.6.

The use of Adipine MR is not recommended during lactation, as nifedipine has been reported to pass into breast milk and the effects of small amounts of oral nifedipine absorbed by the nursing infant are unknown (see section 4.6).

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

Adipine MR should be used with caution in patients with reduced cardiac reserve.

Occasionally exacerbation of heart failure has been observed with the use of nifedipine.

Diabetics may need to adjust their control when using Adipine MR.

In patients with malignant hypertension and hypovolemia on dialysis, a significant drop in blood pressure may occur.

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

Medicinal products known to be inhibitors of the cytochrome P450 3A4 system and therefore may increase the plasma concentration of nifedipine are, for example,

• macrolide antibiotics (eg erythromycin)

• HIV protease inhibitors (for example, ritonavir)

• azole antifungals (eg ketoconazole)

• antidepressants, nefazodone and fluoxetine

• chinuprystyna/dalfopristyna

• valproic acid

• cimetidine

When used simultaneously with these drugs, it is necessary to monitor blood pressure and, if necessary, consider reducing the dose of nifedipine.

As this medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, Lappish lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

For use in special populations, see section 4.2.

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:

Ryfampicyna: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 the following weak or moderate inhibitors of the cytochrome P450 system 3A4 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.

Macrolide antibiotics (eg, erythromycin)

No interaction studies between nifedipine and macrolide antibiotics have been performed. Some macrolide antibiotics are known to inhibit cytochrome P450 3A4-mediated metabolism of other drugs. Therefore, the possibility of an increased nifedipine plasma concentration when the two drugs are administered concurrently cannot be excluded (see section 4.4).

Azithromycin, although structurally related to the macrolide class of antibiotics, does not inhibit CYP3A4.

HIV protease inhibitors (for example, ritonavir)

A clinical study evaluating the potential for interactions between nifedipine and certain HIV protease inhibitors has not yet been performed. Drugs in this class are known to inhibit the cytochrome P450 3A4 system. In addition, drugs in this class have been shown to inhibit cytochrome P450 3A4-mediated metabolism of nifedipine in vitro. With simultaneous use with nifedipine, a significant increase in nifedipine plasma concentration as a result of reduced first-pass metabolism and reduced elimination cannot be excluded (see section 4.4).

Azolni antifungals (for example, ketoconazole)

A formal interaction study evaluating the potential for interaction between nifedipine and some azole antifungals has not yet been performed. Drugs in this class are known to inhibit the cytochrome P450 3A4 system. When administered orally with nifedipine, a significant increase in the systemic bioavailability of nifedipine as a result of reduced first-pass metabolism cannot be excluded (see section 4.4).

fluoxetine

No clinical study has yet been performed to evaluate the possibility of interaction between nifedipine and fluoxetine. Fluoxetine has been shown to inhibit cytochrome P450 3A4-mediated metabolism of nifedipine in vitro. Therefore, an increase in nifedipine plasma concentrations cannot be excluded when the two drugs are administered concomitantly (see section 4.4).

nefazodon

No clinical study has yet been performed to assess the possibility of interaction between nifedipine and nefazodone. Nefazodone is known to inhibit the cytochrome P450 3A4-mediated metabolism of other drugs. Therefore, an increase in nifedipine plasma concentrations cannot be excluded when the two drugs are administered concomitantly (see section 4.4).

Chinuprystyna / Dalfoprystyna

Co-administration of quinupristin/dalfopristin and nifedipine may result in increased nifedipine plasma concentrations (see section 4.4).

Valproic acid

No formal studies have been performed to investigate the possible interaction between nifedipine and valproic acid. Since valproic acid has been shown to increase the plasma concentration of the structurally similar calcium channel blocker nimodipine by inhibiting the enzyme, an increase in the plasma concentration of nifedipine and thus an increase in its efficacy cannot be excluded. (see section 4.4).

Cimetidine

Due to the inhibition of cytochrome P450 3A4, cimetidine increases the plasma concentration of nifedipine and may potentiate the antihypertensive effect (see section 4.4).

more research

cizaprida

Concomitant use of cisapride and nifedipine may cause an increase in nifedipine plasma concentration.

Cytochrome P450 3A4 system for the induction of antiepileptic drugs such as phenytoin, carbamazepine, and phenobarbitone.

Phenytoin induces the cytochrome P450 3A4 system. When used concurrently with phenytoin, the bioavailability of nifedipine and therefore its efficacy is reduced. If both drugs are administered concurrently, the clinical response to nifedipine should be monitored and, if necessary, an increase in the nifedipine dose should be considered. If the nifedipine dose is increased during concomitant administration of both drugs, consideration should be given to reducing the nifedipine dose after stopping phenytoin treatment.

No formal studies have been performed to investigate the possible interaction between nifedipine and carbamazepine or phenobarbitone. Since both drugs have been shown to reduce plasma concentrations of the structurally similar calcium channel blocker nimodipine by enzyme induction, a reduction in nifedipine plasma concentration and therefore a reduction in its efficacy cannot be excluded.

Effect of nifedipine on other drugs.

Medicines to lower blood pressure.

Nifedipine may potentiate the blood pressure-lowering effect of concomitantly administered antihypertensive drugs, such as:

• diuretics,

• β-blocking,

• ACE inhibitors,

• angiotensin 1 (AT1) receptor antagonists,

• other calcium antagonists,

• alpha-adrenergic blockers,

• PDE5 inhibitors,

• α-methylodopa

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 examined as a precautionary measure for signs of digoxin overdose and, if necessary, the dose of the glycoside should be reduced, taking into account digoxin plasma concentrations.

Quinidine

During simultaneous administration of nifedipine and quinidine, in isolated cases, reduced quinidine concentrations or a marked increase in plasma quinidine concentration were observed after discontinuation of nifedipine. For this reason, when adding or discontinuing nifedipine, it is recommended to monitor the quinidine plasma concentration and, if necessary, adjust the quinidine dose. Some authors reported an increase in nifedipine plasma concentrations after simultaneous administration of both drugs, while others observed no changes in nifedipine pharmacokinetics.

Therefore, blood pressure should be carefully monitored if quinidine is added to existing nifedipine therapy. The dose of nifedipine should be reduced if necessary.

tacrolimus

Tacrolimus has been shown to be metabolised via the cytochrome P450 3A4 system. Recently published data show that the dose of tacrolimus when used concomitantly with nifedipine can be reduced in individual cases. When both drugs are co-administered, tacrolimus plasma concentrations should be monitored and, if necessary, a reduction in the tacrolimus dose should be considered.

Food-Drug Interactions

Grapefruit juice slows you down

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 of nifedipine may be potentiated. With regular consumption of grapefruit juice, this effect can last for at least three 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.

Nifedipine should not be used during pregnancy unless the clinical condition of the woman requires treatment with nifedipine. Nifedipine should be reserved for women with severe hypertension unresponsive to standard therapy (see section 4.4).

There are no adequate and well-controlled studies in pregnant women.

Available data are insufficient to exclude harmful effects to the fetus and newborn. Therefore, any use during pregnancy requires a very careful individual risk-benefit assessment and should only be considered when other treatment options are not recommended or have failed.

Nifedipine has been shown to cause embryotoxicity, foetotoxicity and teratogenicity in animal studies (see section 5.3).

Based on the available clinical evidence, no specific prenatal risk has been identified. Although an increased incidence of perinatal asphyxia, cesarean delivery, prematurity, and intrauterine growth retardation has been reported. It is not clear whether these reports are due to the underlying disease, the treatment of hypertension, or the effect of a specific drug.

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 passes into breast milk. The concentration of nifedipine in breast milk is almost comparable to that in maternal serum. For immediate-release formulations, it is suggested to delay breastfeeding or expressing milk for 3 to 4 hours after administration to reduce the exposure of the infant to nifedipine (see section 4.4).

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. For those men who have repeatedly failed to conceive a child.in vitroconception, and if no other explanation can be found, calcium antagonists such as nifedipine should be considered as a possible cause.

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%).

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'.

¹can have life-threatening consequences

²Cases of use of tocolytics 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 via the yellow card system at www.mhra.gov.uk/yellow.

Symptoms

In case of severe nifedipine poisoning, the following symptoms are observed:

Altered consciousness up to coma, hypotension, tachycardia/bradycardia, arrhythmias, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema.

Management

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

After oral administration, a thorough gastric lavage is indicated, if necessary in combination with small intestinal lavage.

Especially in the case of poisoning by nifedipine in slow-release forms, the elimination should be as complete as possible, including the small intestine, in order to avoid the inevitable subsequent absorption of the active substance.

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

Hypotension resulting from cardiogenic shock and arterial vasodilation can be treated with calcium (10-20 mL of 10% calcium gluconate solution given slowly intravenously and repeated if necessary). As a result, serum calcium levels can vary from the upper normal range to slightly elevated levels. If a sufficient increase in blood pressure is not achieved with the use of calcium, it is necessary to use vasoconstrictor sympathomimetics such as dopamine or norepinephrine. The dose of these drugs should be based on the patient's response.

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

Additional fluid or volume should be administered with caution due to the risk of cardiac overload.

Pharmacotherapeutic group:Dihydropyridine derivatives

Kod ATC: C08CA05

Nifedipine is a specific and potent 1,4-dihydropyridine calcium antagonist. Calcium antagonists reduce the transmembrane entry of calcium ions through the slow calcium channel into the cell. Nifedipine acts specifically on myocardial cells and smooth muscle cells of coronary arteries and peripheral resistance vessels.

In hypertension, the main effect of nifedipine is peripheral vasodilation, which reduces peripheral resistance.

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.

Nifedipine administered twice daily provides control of elevated blood pressure for 24 hours. Nifedipine lowers blood pressure to such an extent that the percentage reduction is directly related to its baseline value. In normotensive people, nifedipine has little or no effect on blood pressure.

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.

Absorption

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

reproductive toxicology

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 if a sufficiently high systemic exposure is achieved; however, all doses associated with teratogenic, embryotoxic or foetotoxic effects in animals were maternally toxic, many times the highest recommended human dose (see section 4.6).

2 cans

Do not use the medicine after the expiration date printed on it.

Protect from light. Store at a temperature of up to 25°C.

Note: The active substance nifedipine is sensitive to light and is protected by special packaging. Once modified-release tablets are removed, they should not be unnecessarily exposed to bright light for prolonged periods.

The modified-release tablets are packed in aluminum blisters and PVC foil. The blister packs are packaged together with the medication instructions in a folding cardboard box.

The package contains 10 modified-release tablets.

The package contains 20 modified-release tablets.

The pack contains 30 modified-release tablets.

The pack contains 50 modified-release tablets.

Pack of 56 personalized release tablets.

The pack contains 60 modified-release tablets.

The pack contains 100 modified-release tablets.

Not all pack sizes may be commercially available.

Thornton & Ross Ltd. (trading as "STADA")

Linthwaite'a,

Huddersfield,

hd7 5qh,

Britain