Zanidip

The joint Italian-Irish company Recordati Industria Himica e Farmasevtica SpA has launched the drug Lercanidipine (this is the international name of the drug) - a calcium channel blocker - on the pharmacological market. In our pharmacies it can be found under the name Zanidip. It is known to doctors as an excellent antihypertensive drug.

This material is for informational purposes only and should not be used as a self-medication guide. Any medication must be prescribed by a doctor based on the clinical picture of the disease. Zanidip is an effective antihypertensive drug, but it should only be taken as prescribed and under the constant supervision of a specialist doctor.

Indications Zanidipa

This is a targeted drug. Therefore, the indications for the use of Zanidip are not as extensive as many other pharmacological drugs, but this in no way diminishes its effectiveness.

The main and only indication for the use of Zanidip is essential hypertension, the severity of which can be described as mild or moderate (average).

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Release form

The active ingredient of Zanidip is lercanidipine hydrochloride, auxiliary chemical compounds include: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, povidone K30 and magnesium stearate.

The release form is tablets, which are covered with a thin layer of shell. The pharmacy market offers blisters with different numbers of pieces (7,14,15,25,28,30 pieces respectively).

The tablets are light yellow and have a dosage of the active chemical compound lercanidipine hydrochloride - 10 mg, tablets of a shade from pink to dark pink - 20 mg of the active substance. The quantitative composition of auxiliary elements, respectively, in pink tablets is twice as concentrated.

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Pharmacodynamics

The active ingredient of Zanidip is lercanidipine, which is a fairly strong calcium antagonist belonging to the dihydropyridine group of chemical compounds. Lercanidipine inhibits the intermembrane transport of this chemical element into the internal area of cardiomyocytes and smooth muscle vascular cells.

Pharmacodynamics Zanidip with its active substance lercanidipine is characterized by a direct targeted relaxing effect on the smooth muscles of blood vessels, which makes it possible to reduce the total peripheral vascular resistance (TPVR). The drug begins to work within five to seven hours after administration of the drug, the positive therapeutic effect lasts for the next day (24 hours).

High vascular selectivity (selectivity) of the drug allows adequately affecting the entire cardiovascular system of a person, without creating a negative inotropic lesion. Zanidip (in contrast to the small T½ in the blood serum), due to its high membrane distribution coefficient, is able to provide a prolonged effect on the antihypertensive characteristic of the patient's body. Lercanidipine gradually affects the vasodilation process, which allows avoiding sudden severe attacks of hypertension (arterial hypotension) with reflex tachycardia.

The results of laboratory and clinical observations showed that after the introduction of the drug Zanidip, 40% of patients with acute arterial hypotension had normalized blood pressure (the drug was prescribed to patients once a day at a dosage of 20 mg). When taking 10 mg of lercanidipine twice a day, this percentage was higher - 56% of patients.

During the course of the duplicated, blinded, randomized monitoring study, results were obtained of an effective reduction in systolic blood pressure (BP) from 172.6±5.6 to 140.2±8.7 mm Hg.

Lercanidipine acts selectively in blocking the flow of calcium ions that are transported between cell membranes. This feature allows it to control the flow of internal calcium penetration into cardiac and vascular cell walls, as well as into smooth muscle cells.

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Pharmacokinetics

Absorption. Due to its biochemical characteristics, the pharmacokinetics of Zanidip allows for the full absorption of the active substance from the gastrointestinal tract into the human bloodstream. In blood plasma, the peak amount of lercanidipine is observed after one and a half to three hours after administration and shows figures of 3.3 ng/ml (if the patient took 10 mg twice during the day) and 7.66 ng/ml (after a single administration of 20 mg of Zanidip).

Distribution. Metabolism of lercanidipine in all systems, organs and tissues of the patient from the blood is quite mobile. The active substance shows a high percentage of interaction (more than 98%) in the process of binding to plasma proteins. If the drug was taken after meals, the bioavailability of the active component is determined to be 10%, while in the case of administration of the drug no later than two hours after a very high-fat meal, bioavailability increases fourfold. Based on this, it follows that in order to achieve a greater effect, the drug Zanidip must be used with food (that is, during or immediately after a meal). When administered repeatedly, it does not accumulate in the body. The active substance is metabolized quite easily through the liver, biotransforming a certain number of metabolites that do not have high pharmacological activity.

Excretion. After biotransformation, lercanidipine metabolites are excreted from the patient's body through the kidneys via urine and intestines along with feces. There are two stages of excretion:

• Early elimination phase. The half-life of Zanidip is two to five hours.
• Terminal elimination phase. The half-life of Zanidip is eight to ten hours.

Clinical analyses show that the drug in its original form is practically not present in either urine or feces.

It has been clinically established that the pharmacokinetics of Zanidip are virtually identical in their manifestations in individuals with a history of liver and kidney disease and in elderly patients.

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Dosing and administration

Most often, the method of administration and dosage of the drug Zanidip are unambiguous. The drug is taken orally with plenty of liquid. The tablet should not be chewed.

The starting daily dosage of the drug is 10 mg and is taken once 15 minutes before meals. If the therapeutic effect does not occur within two weeks, the daily dose can be increased to 20 mg, taken once or divided into two doses.

There is no need to adjust the dosage for elderly patients, but it is necessary to constantly monitor the patient's general well-being and, if necessary, stop or adjust the administration of Zanidip.

If the patient's medical history shows mild or moderate liver and/or kidney dysfunction, there is no need to adjust the dosage of the drug; in acute cases, this medication is not recommended. The starting dose in this case is 10 mg, subsequently it is very carefully increased to 20 mg.

If the antihypertensive effect is too pronounced, the amount of medication taken should be reduced.

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Use Zanidipa during pregnancy

Since there is no data at all regarding the use of Zanidip during pregnancy and breastfeeding, it is not recommended to use this drug during this period.

There are data from animal testing of other dihydropyridines. The results show that drugs of this group can have a destructive effect on the fetus in the womb, subsequently manifesting themselves in all sorts of defects and deformities (teratogenic effect). Therefore, if possible, women should not use them not only during pregnancy and lactation, but also during the period when it is planned.

Due to the high degree of lipophilicity of the active substance Zanidip, there is a high probability of its getting into breast milk. Therefore, you should not take the drug during this period, and in case of medical necessity of taking it, you should stop breastfeeding the newborn.

Contraindications

Based on the pharmacokinetics and pharmacodynamics of lercanidipine, contraindications for the use of Zanidip are quite extensive:

• Unstable angina.
• Chronic heart failure at the stage of decompensation.
• Impaired renal function. Glomerular filtration is reduced and is less than 39 ml/min.
• If less than a month has passed since the myocardial infarction occurred.
• Acute liver failure.
• Pathology of the left ventricle of the heart and associated vascular obstruction.
• The safety of the drug for children and adolescents has not been established. Age limit: up to 18 years.
• Pregnancy and lactation.
• Deficiency in the body or complete intolerance of such an enzyme as lactose.
• Zanidip is contraindicated for use in combination with strong inhibitors (such as erythromycin, itraconazole, cyclosporine, ketoconazole). Do not drink grapefruit juice while taking the medication.
• Individual intolerance to lercanidipine or other components of the drug.
• Representatives of the fair sex of childbearing age who are planning to become pregnant in the near future.
• Chronic heart failure.
• Zanidip should be taken with great caution in combination with digoxin and beta-blockers.
• While undergoing treatment, it is necessary to be especially careful when driving a vehicle and operating moving machinery.

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Side effects Zanidipa

Despite its high efficiency, there are also side effects of Zanidip:

• Dizziness and headaches.
• Increased sensitivity.
• Drowsiness.
• Nausea with vomiting.
• Myocardial infarction.
• Skin rash.
• Tachycardia and angina are sometimes observed.
• Diarrhea.
• Blood rush to the facial epidermis.
• Although quite rare, fainting and chest pain still occur.
• Drop in blood pressure.
• Myalgia is muscle pain.
• Polyuria is increased urine production.
• Increased fatigue.

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Overdose

Considering the pharmacokinetics and pharmacodynamics of lercanidipine and referring to clinical monitoring of the treatment of essential hypertension, it can be stated that an overdose of Zanidip is accompanied by the following symptoms:

• Peripheral vasodilation.
• reflex tachycardia.
• Drop in blood pressure.
• Increase in the duration and frequency of angina attacks.
• Myocardial infarction.

When these deviations appear, the attending physician prescribes medications that can relieve the identified symptoms.

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Interactions with other drugs

Only an experienced doctor can correctly prescribe the drug and select the dosage. It is especially necessary to be careful when using drugs in combination, because the interactions of Zanidip with other drugs are not always fully understood.

For example, it would seem that elementary grapefruit juice in combination with Zanidip stimulates the growth of the quantitative component of lercanidipine in the blood. For the same reason, you should not take this drug with inhibitors such as itraconazole, erythromycin and others. The combined use of cyclosporine with Zanidip provokes a surge in the concentration of both drugs in the plasma.

Care should be taken when co-administering with drugs such as quinidine, amiodarone, astemizole, and terfenadine.

The level of lercanidipine may decrease when taken in tandem with anticonvulsant medications (carbamazepine, phenytoin, rifamycin are among these). This is due to the fact that the antihypertensive effectiveness of the active substance of Zanidip is reduced.

Concomitant administration of lercanidipine with midazolam in an elderly person can cause an increase in the volume of absorbed lercanidipine, while the clearance of absorption decreases. If there is a medical need for simultaneous administration with digoxin, it is necessary to continuously monitor the patient's condition for signs of intoxication with the latter.

The bioavailability of the active substance Zanidip is reduced by half when working in tandem with metoprolol, while its characteristics remain unchanged. Such consequences can occur due to beta-blockers, which are capable of blocking or partially blocking the blood flow through the liver. A similar situation can arise when "cooperating" with other dosage forms of this group.

Complex paired administration with such drugs as fluoxetine or warfarin does not have a significant effect on the pharmacokinetics of lercanidipine. If cimetidine is administered to a patient in doses not exceeding the daily threshold of 800 mg, then no significant changes in the clinical process are observed. While at higher doses of the drug, the antihypertensive effect of lercanidipine can increase.

It is better to take Zanidip in the morning, and simvastatin in the evening. This will be enough to minimize the mutual negative impact. If necessary, ethanol can enhance the effect of the drug in question.

During treatment with Zanidip, it is necessary to minimize the intake of any type of alcohol. Otherwise, it may negatively affect the pharmacodynamics of the drug, increasing the vasodilator effect.

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Storage conditions

The temperature of the room where Zanidip will be stored should not exceed 25 °C - 30 °C. The location should be chosen so that it is inaccessible to small children. The storage conditions for Zanidip are quite simple and do not require much effort.

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Shelf life

The expiration date of the drug Zanidip in question is three years. The expiration date is indicated on the packaging and should not be exceeded. If the expiration date has expired, further use of this drug is not recommended.

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