Cardil

Cardil is a drug from the subgroup of substances that block the action of Ca channels and has antihypertensive, antiarrhythmic and antianginal effects.

The active element of the drug is diltiazem, a benzodiazepine substance that prevents the passage of Ca into the cells of cardiomyocytes, as well as the cells of the smooth muscles of the vessels. When the flow of calcium ions decreases, the smooth muscles of the vascular membrane relax, which allows for an increase in the vascular lumen, stabilization of microcirculation within ischemic areas and a decrease in the systemic resistance of peripheral vessels. All this helps to reduce blood pressure. [ 1 ]

Indications Cardil

It is used for angina (including its variant and stable varieties). The drug is not used to eliminate acute angina attacks.

It can be used in cases of increased blood pressure – for example, in situations where substances that block the activity of β-adrenergic receptors cannot be used. Cardil is administered both in monotherapy and in combination therapy.

It is also prescribed in case of arrhythmia – for example, to reduce the rhythm of the ventricles of the heart in atrial fibrillation.

Release form

The drug is released in the form of tablets - 30 or 100 pieces in a bottle. There is 1 such bottle in a box.

Pharmacodynamics

The antianginal properties of the drug develop after coronary vasodilation and reduction of afterload. In case of stable angina, individuals using the drug showed objective (prolongation of the period during which there was no ST-segment depression during physical exertion) and subjective (reduction in the number of angina episodes requiring the use of nitrates) improvement in the condition. The severity of the effect of Cardil in people with unstable angina is on average similar to the effect of nifedipine or verapamil, while the frequency of adverse effects when using diltiazem is less than when administering the above drugs.

The antihypertensive effect of the drug develops with a decrease in increased blood pressure (diastolic and systolic); at normal blood pressure values, diltiazem does not change it. The use of the drug in people with hypertension did not lead to the appearance of reflex tachycardia as a reaction to a decrease in blood pressure. [ 2 ]

The drug has a weak negative inotropic effect, but its administration does not reduce stroke volume or left ventricular ejection fraction. In people with left ventricular hypertrophy, long-term use of diltiazem leads to regression of the disorder. [ 3 ]

In people with supraventricular arrhythmias, the drug suppresses the movement of calcium ions inside the cells of the sinus and AV nodes, thereby stabilizing the heart rhythm.

Cardil can be used in monotherapy or in combination with other antihypertensive drugs (including diuretics and ACE inhibitors). The medication is prescribed to people who cannot use drugs that block the effect of β-adrenergic receptors - with peripheral angiopathies or bronchial asthma, as well as diabetics.

The drug does not have a negative effect on the lipid structure of the blood.

Pharmacokinetics

After oral administration, the drug is fully absorbed in the gastrointestinal tract. It participates in the 1st intrahepatic passage (with the absolute bioavailability level equal to 40% in the range of personal variability, which is 24-74%). Bioavailability indicators are not tied to the portion size and do not change when using different dosage forms in the spectrum of clinical dosages. Serum values of Cmax of diltiazem are noted after 3-4 hours and are equal to 39-120 ng / ml after a single use of 60 mg of the drug.

About 80% of the administered portion of diltiazem is involved in serum protein synthesis (approximately 40% with albumin). The drug easily penetrates into tissues; the distribution volume is about 5 l/kg.

Equilibrium serum values of diltiazem in case of regular use of 60 mg of the drug 3 times a day are noted by the 3-4th day of treatment. In case of use of daily portions in the range of 0.12-0.3 g, stable serum values of the substance are equal to 20-200 ng/ml (minimum therapeutic level is in the range of 70-100 ng/ml).

Intrahepatic exchange processes of drugs occur with the help of CYP3 A4; the drug is a substrate of P-glycoprotein. After the introduction of diltiazem, the effect of hemoprotein CYP3 A4 decreases.

During the first stage of metabolism, deacetylation processes as well as O- and N-demethylation occur. The main metabolic component is deacetyldiltiazem (its serum level is approximately 15-35% of the values of unchanged diltiazem), which has a similar medicinal activity to the active ingredient, but it is slightly weaker (approximately 40-50% of the effect of diltiazem).

Excretion occurs mainly as derivatives via the kidneys; systemic clearance is 0.7-1.3 L/kg/h. Five unconjugated derivatives of diltiazem are excreted in urine, some of which also exist in conjugated form. Elimination has single-stage kinetics. According to the 3-chamber model, the half-life is 0.1, 2.1, and 9.8 hours during the initial, middle, and final stages of elimination. The overall half-life is in the range of 4-7 hours.

Dosing and administration

The medicine should be taken orally, without crushing the tablets before use. The dosage size is calculated so that it corresponds to the volume of the substance inside 1 tablet. The administration mode and portion sizes are selected by the doctor, taking into account the severity and course of the disease, the weight and age of the patient, as well as concomitant treatment.

On average, 0.18-0.24 g of the drug should be used per day; if necessary, an increase to the maximum daily dose of 0.48 g is allowed. If negative symptoms develop during an increase in the dose, the volume of diltiazem should be reduced. If the required control over the blood pressure level is not established when administering the maximum daily dose of the drug (0.48 g), but this dose is well tolerated, other antihypertensive agents should be additionally used (for example, diuretics or ACE inhibitors).

The initial daily dose of the drug should be 60 mg, administered 3-4 times. Later, taking into account the therapeutic effectiveness and the overall clinical picture, it can be increased or decreased. For most patients, 3-time administration of 0.12 g per day is sufficient to control blood pressure and prevent angina attacks.

Elderly people should initially take 30 mg of the substance 3-4 times. The dose for this group of patients can be increased only under the supervision of a doctor and in the absence of complications from the administration of diltiazem.

People with liver dysfunction should use Cardil very carefully - they undergo more careful monitoring of blood pressure levels and ECG readings, and at the same time a lower initial dosage is prescribed (3-4 times a day, 30 mg).

• Application for children

The use of the medication in pediatrics is prohibited.

Use Cardil during pregnancy

The drug is not used during pregnancy. When planning or conception while using diltiazem, you should consult with your doctor regarding the selection of alternative treatment.

If it is necessary to use Cardil during breastfeeding, you should stop breastfeeding before starting to administer the drug.

Contraindications

Contraindicated for use in case of intolerance to diltiazem or additional components of the drug.

It should not be used in cases of cardiac conduction disorders, including AV block (stages 2-3; except for situations when the patient has a pacemaker) and SSSU.

It is prohibited to prescribe the drug to people with low blood pressure (with systolic marks below 90 mm Hg), severe bradycardia (heart rate less than 50 beats/minute) and decompensated heart failure.

In addition, it is not used in the active phase of myocardial infarction (with complications), WPW syndrome and cardiogenic shock associated with poisoning with digitalis substances.

Side effects Cardil

Possible side effects include:

• problems with the activity of the cardiovascular system: bradycardia, sinus or AV block (stage 1; more rarely - 2-3), CHF, decreased blood pressure, suppression of the sinus node activity and paradoxical worsening of angina, as well as tachycardia and palpitations, arrhythmia, syncope, extrasystole, facial hyperemia, loss of consciousness and peripheral edema;
• gastrointestinal dysfunction: nausea, weight gain, loss of appetite, xerostomia, vomiting, bowel disorders, dyspeptic symptoms, gingivitis and hyperplasia in the gum area;
• lesions of the subcutaneous layer and epidermis: SJS, urticaria, itching, lupus erythematosus, TEN, exanthema and petechiae, as well as Quincke's edema, vasculitis, exfoliative dermatitis and photosensitivity;
• disorders of hepatobiliary function: hyperglycemia, increased activity of intrahepatic enzymes and granulomatous hepatitis;
• problems with the blood system: thrombocytopenia or leukopenia, as well as prolongation of the bleeding period;
• CNS dysfunction: confusion, personality changes, amnesia, depression, paresthesia and hallucinations, as well as drowsiness, tremor, tinnitus, sleep disorders, gait disturbances and drowsiness;
• others: myalgia, eosinophilia, dyspnea, lymphadenopathy, taste and smell disturbances, ocular irritation or amblyopia, nasal congestion or bleeding, polyuria, pain affecting bones or joints, nocturia, gynecomastia, erectile dysfunction and increased creatine kinase values.

Epidermal manifestations caused by the introduction of diltiazem disappear on their own, without discontinuing the use of the drug. However, if epidermal disorders continue to persist for a long time, the option of discontinuing the use of Cardil should be considered.

Overdose

When administering excessively large doses of the drug, the intensity of negative symptoms characteristic of diltiazem may be potentiated. Moderate or severe poisoning is observed after administering 900-1800 mg of the drug. Severe poisoning occurs with a single administration of 2600 mg of the drug in elderly people and 5900 mg in younger adults. The use of 10.8 g of Cardil caused extremely severe poisoning.

Signs of intoxication appear on average 8 hours after the drug is administered. The main manifestations include irritability, AV block, hypothermia and drowsiness, as well as decreased blood pressure, hyperglycemia, bradycardia, nausea and cardiac arrest.

There is no antidote. In case of intoxication, it is necessary to perform gastric lavage and take enterosorbents, as well as perform symptomatic and supportive actions. It is necessary to regularly monitor respiratory function, acid-base and electrolyte parameters, as well as hemodynamic values.

In case of a decrease in blood pressure, dopamine or CaCl is administered intravenously. If bradycardia or, in some situations, AV block due to drug overdose is observed, intravenous injection of atropine or the use of an electrical stimulator is used (if drug therapy does not produce results).

Interactions with other drugs

The medication potentiates the properties of other antihypertensive substances.

Use with digoxin, amiodarone or β-blockers leads to potentiation of AV conduction and an increased risk of developing bradycardia.

The suppressive effect of isoflurane and halothane on the myocardium is potentiated when used in combination with diltiazem.

In case of intravenous administration of parenteral Ca drugs, the therapeutic effect of Cardil is weakened.

Primary metabolic processes of drugs are realized with the help of CYP3 A4. Substances that slow down the action of this enzyme (including cimetidine), when combined with the drug, can lead to an increase in diltiazem indices in plasma. The activity of the substance can also be enhanced when combined with macrolides, nifedipine, antimycotics, as well as with azole derivatives, tamoxifen, fluoxetine and agents that slow down HIV protease.

Medicines that induce the effect of CYP3 A4 weaken the effect of the drug. For example, a decrease in effectiveness is noted when combined with rifampicin, carbamazepine or phenobarbital.

Cardil weakens metabolic processes caused by the activity of CYP3 A4 and P-glycoprotein. It is necessary to combine the drug very carefully with substances whose metabolism is realized with the help of the specified isoenzyme - for example, with cyclosporine, methylprednisolone, phenytoin, theophylline and sirolimus, as well as with digitoxin and digoxin.

The combination of the drug and substances that inhibit the activity of HMG-CoA reductase, whose metabolism processes are carried out using CYP3 A4 (this includes simvastatin and atorvastatin with lovastatin) is used with extreme caution. The combined use of these drugs may require a reduction in the dose of anticholesterolemic drugs (due to an increased likelihood of hepatotoxicity and rhabdomyolysis). The drug does not change the pharmacokinetics of pravastatin with fluvastatin.

Cardil is capable of increasing serum levels of such drugs as buspirone, propranolol, alfentanil with nifedipine, alprazolam and sildenafil with imipramine, diazepam and metoprolol with cisapride, as well as midazolam and portriptyline.

In case of combination of the drug with lithium substances, the risk of neurotoxic activity increases. Serum lithium values should be closely monitored when using such a drug combination.

Storage conditions

Cardil should be stored in a place closed to small children. Temperature values are in the range of 15-25°C.

Shelf life

Cardil is permitted to be used within a 36-month period from the date of sale of the pharmaceutical substance.

Analogues

Analogues of the drug are the medications Blokaltsin, Dilcem with Diltiazem, Tiakem and Cortiazem, as well as Zilden with Altiyazem RR, Dilren with Diacordin and Dilkardia.