Piramil, tablets 10 mg 28 pcs

A ACE inhibitor. Ramipril is rapidly absorbed in the gastrointestinal tract and is hydrolyzed in the liver to form the active metabolite ramiprilat. Ramiprilat is a long-acting inhibitor of ACE, the enzyme catalyzing the conversion of angiotensin I to angiotensin II.

Ramipril causes decreased plasma levels of angiotensin II, increased renin activity and decreased aldosterone release. It suppresses kinase II levels, interferes with the breakdown of bradykinin, increases the synthesis of prostaglandins. Under the action of ramipril, peripheral vessels are dilated and the RPS is reduced.

Arterial hypertension

It has a hypotensive effect in the lying and standing position of the patient. Reduces RPS (post-load), congestion pressure in the pulmonary capillaries without a compensatory increase in HR. Increases coronary and renal blood flow without affecting glomerular filtration rate.

The onset of hypotensive action is 1-2 hours after ingestion, the maximum effect develops 3-6 hours after ingestion. The action lasts for at least 24 hours.

Chronic heart failure and heart failure due to acute myocardial infarction

Ramipril reduces PPS and eventually BP. It increases cardiac output and exercise tolerance. With long-term use promotes inverse development of myocardial hypertrophy in patients with stage I and II heart failure; improves blood supply to ischemic myocardium.

Ramipril improves survival of patients with symptoms of transient or chronic heart failure after myocardial infarction. The effect occurs as early as one month after the beginning of using the drug and persists for 2 years after the end of therapy. It has cardioprotective effect, prevents coronary ischemic episodes, reduces the probability of myocardial infarction and decreases the duration of hospitalization.

Nephropathy

In patients with diabetic nephropathy, ramipril reduces albuminuria. In nephropathy of other etiology, ramipril slows the progression of renal failure. In insulin-dependent diabetes mellitus and severe diabetic nephropathy, ramipril reduces the severity of proteinuria. In presence of diabetes and at least one risk factor (microalbuminuria, hypertension, elevated total cholesterol, low HDL cholesterol, smoking) ramipril reduces the severity of complications of diabetes.

Pharmacokinetics

Intake

Ramipril is rapidly absorbed in the GI tract after oral administration. Absorption is not dependent on food intake. After absorption, ramipril is rapidly and almost completely converted to the active metabolite ramiprilate by the liver esterase enzyme. Ramiprilat is about 6 times more potent inhibitor of ACE than ramipril. Other pharmacologically inactive metabolites have also been found.

The C_max of ramipril in plasma is reached within 1 h after administration, the C_max of ramiprilat within 2-4 h after drug administration. Bioavailability of ramipril is 60%.

Distribution

The plasma protein binding reaches 73% for ramipril and 56% for ramiprilat.

Elevation

The T_1/2 of ramiprilat in long-term use at a dose of 5-10 mg once daily is 13-17 hours.

After administration of 5 mg, the renal clearance of ramiprilat is 10-55 ml/min, and the extrarenal clearance reaches 750 ml/min. For ramiprilat, these values are 70-120 ml/min and about 140 ml/min, respectively. Ramipril and ramiprilat are mainly excreted by the kidneys (40-60%).

Pharmacokinetics in special clinical cases

In patients with impaired renal function, the conversion of ramipril to ramiprilat is delayed due to the relatively short esterase action period, so plasma levels of ramipril in these patients are elevated.

In impaired renal function, their excretion is delayed.

Indications

Active ingredient

Composition

Associates:

Microcrystalline cellulose,

Pregelatinized starch,

silicon dioxide precipitated,

glycine hydrochloride,

glyceryl dibegenate.

How to take, the dosage

The drug is taken orally, regardless of meals, without chewing, with water.

Hypertension

The recommended starting dose for patients without heart failure who are not taking diuretics is 2.5 mg/day. The dose may be gradually increased every 2-3 weeks depending on effect and tolerability. The maximum dose is 10 mg once daily. The maintenance dose is usually 2.5-5 mg once daily. If there is no satisfactory therapeutic effect with 10 mg/day, it is recommended to prescribe a combination drug therapy.

If a patient is taking diuretics, their use should be stopped or their dose reduced 2 to 3 days before starting Piramil treatment. For these patients, the recommended starting dose is 1.25 mg once daily.

Chronic heart failure

The recommended starting dose of Piramil is 1.25 mg once daily.

The dose can be gradually increased depending on effect and tolerability, doubling every 1 to 2 weeks. Doses of 2.5 mg/day and above may be taken in 1-2 doses. The maximum dose is 10 mg once daily.

For patients taking high doses of diuretics, their doses should be reduced before starting Piramil treatment to minimize the risk of symptomatic arterial hypotension.

Heart failure due to acute myocardial infarction

The treatment is started 3-10 days after acute myocardial infarction. The initial dose is 2.5 mg 2 times/day, after 2 days the dose is increased to 5 mg 2 times/day. If the initial dose of 2.5 mg twice daily is not well tolerated, a dose of 1.25 mg twice daily should be prescribed for 2 days, then increasing the dose to 2.5 mg and 5 mg twice daily. The maintenance dose is 2.5-5 mg 2 times/day. The maximum daily dose is 10 mg.

Nephropathy

The recommended starting dose is 1.25 mg once daily. Depending on tolerance, the dose may be doubled at 2-3 week intervals to a maximum dose of 5 mg/day.

If the patient is taking diuretics, the dose should be stopped or reduced 2 to 3 days before starting Piramil, in which case the recommended starting dose of Piramil is 1.25 mg once daily.

People with special patient groups

For patients with impaired renal function (CKR 0.3-0.8 ml/sec/1.73 m2), the recommended starting dose of Pyramil is 1.25 mg 1 time/day and the maximum dose should not exceed 5 mg/day. In severe renal impairment (CKR less than 0.3 ml/sec/1.73 m2), the recommended starting dose of Pyramil is 1.25 mg once daily, and the dose may be increased to 2.5 mg/day if necessary.

In patients with impaired liver function, both enhancement and weakening of the therapeutic effect of Piramil may be observed. Treatment should be started under a physician’s supervision with a prescribed dose of 1.25 mg. The maximum dose should not exceed 2.5 mg/day.

Caution should be exercised when prescribing ramipril in elderly patients with renal or hepatic impairment as well as in patients with heart failure and concomitant use of diuretics. The dose should be adjusted individually depending on the target BP.

Interaction

Hypotensive drugs, diuretics, nitrates, tricyclic antidepressants, neuroleptics, sleeping pills, opioid analgesics, general anesthetic agents increase the hypotensive effect of ramipril.

Piramil® increases the hypoglycemic effect of sulfonylurea derivatives and insulin.

NSAIDs may decrease the antihypertensive effect of ramipril and may also cause impairment of renal function, sometimes leading to renal failure.

Baking salt may weaken the effect of ramipril.

Potassium preparations, potassium-saving diuretics, potassium-containing salt substitutes, heparin increase the risk of hyperkalemia when used concomitantly with ramipril.

Concomitant use with lithium preparations increases their concentration in blood, which leads to increased neurotoxic and cardiotoxic effects of lithium preparations.

The concomitant administration of ramipril with corticosteroids is not recommended.

Sympathomimetics may weaken the hypotensive effect of ramipril.

It increases the risk of leukopenia when used concomitantly with allopurinol, cytostatic drugs, immunosuppressants, procainamide.

Do not drink alcohol during treatment with ramipril (the CNS depressant effect of ethanol is increased).

Estrogens weaken the hypotensive effect (fluid retention) of ramipril.

Special Instructions

After the first dose and when increasing the dose of the diuretic and/or Piramil, patients should be under medical supervision for 8 hours because of the possibility of orthostatic hypotension.

Transient arterial hypotension is not a contraindication for continuation of therapy with Piramil, because once the RBC is restored and the BP is normalized, administration of subsequent doses of the drug usually does not cause symptomatic arterial hypotension. If severe arterial hypotension occurs again, the dose should be reduced or the drug should be discontinued. Patients with malignant arterial hypertension or concomitant chronic heart failure in the decompensation stage should start treatment under hospital conditions.

Before and during Piramil treatment renal function (creatinine, urea), plasma potassium levels, blood count, hemoglobin, liver function tests should be monitored regularly.

If cholestatic jaundice or marked elevation of liver enzymes develops, the ACE inhibitors should be discontinued.

The risk group for hyperkalemia includes patients with renal impairment, diabetics, and those taking potassium-saving diuretics, potassium supplements or potassium-containing salt substitutes, and medications that increase serum potassium levels (such as heparin).

In patients with increased risk of neutropenia (with renal dysfunction, systemic connective tissue diseases) it is necessary to monitor blood counts once/month during the first 3-6 months of therapy and also during the first signs of infection. If neutropenia is confirmed (neutrophil count is less than 2000/μL), therapy with ACE inhibitors should be stopped.

In rare cases during treatment with ACE inhibitors, including ramipril, angioedema of the face, extremities, lips, tongue, larynx and/or pharynx have been observed. If edema develops suddenly, at any time during treatment, the drug should be stopped immediately, emergency medical measures should be taken and the patient should be closely monitored until complete and sustained disappearance of the symptoms.

The use of dialysis membranes AN69 in combination with ACE inhibitors is not recommended (because of the possibility of patients developing anaphylactoid reactions). In rare cases, LDL apheresis with dextran sulfate and concomitant use of ACE inhibitors may result in anaphylactoid reactions, which can be avoided by discontinuing the ACE inhibitors prior to each apheresis session and resuming at the end of the session.

Antihypertensive agents that inhibit the renin-angiotensin system are usually ineffective in patients with primary hyperaldosteronism, so the use of ramipril is not recommended.

Impact on driving and operating machinery

Caution should be exercised when driving vehicles and performing other work requiring increased attention, especially when taking the initial dose, changing to another drug, or taking diuretics concomitantly.

Contraindications

Side effects

The incidence of adverse events was classified as follows: very frequently (≥1/10), frequently (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), very rarely (<1/10 000).

Cardiovascular system disorders: frequently – significant decrease of BP; infrequently – orthostatic hypotension, orthostatic collapse, angina pectoris, myocardial infarction or cerebrovascular disorders (due to sharp decrease of BP in risk patients), tachycardia, arrhythmia, Raynaud’s syndrome.

Allergic reactions: infrequent – skin rash, pruritus, rarely – urticaria, photosensitization, angioedema of the face, lips, tongue, throat, extremities; very rare – myalgia, myositis, arthralgia/arthritis, erythema multiforme (including erythema multiforme exudative).Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), pemphigus, vasculitis, serositis, eosinophilia.

Gastrointestinal system disorders: infrequent – dry mouth, nausea, vomiting, abdominal pain, dyspepsia, decreased appetite, diarrhea, increased liver enzymes activity; very rarely – pancreatitis, hepatitis, cholestatic jaundice, liver dysfunction, stomatitis, glossitis.

CNS disorders: often – weakness, headache; infrequent – mood swings, paresthesia, dizziness, sleep disorders; rarely (with high doses) – confusion, depression, anxiety, impaired cerebral circulation.

The respiratory system: often – dry cough; infrequently – shortness of breath, rhinitis, bronchitis; very rarely – bronchospasm, sinusitis, allergic alveolitis, eosinophilic pneumonia.

Urogenital system disorders: often – renal dysfunction; rarely – sexual dysfunction, proteinuria; very rarely – oliguria or anuria.

Hematopoietic organs: rare – decreased concentration of hemoglobin and hematocrit; very rare – anemia, thrombocytopenia, hemolytic anemia, neutropenia, agranulocytosis, pancytopenia, suppression of bone marrow function, lymphadenopathy. Neutropenia and agranulocytosis are reversible and disappear when ACE inhibitors are discontinued.

Others: infrequent – asthenia, fever, alopecia, impaired taste, smell, gynecomastia, decreased potency, tinnitus; very rare – hypoglycemia, hearing and vision disorders, muscle cramps.

Laboratory parameters: infrequent – increase in urea, creatinine, hyperkalemia; rarely – hyperbilirubinemia, hyponatremia, appearance of antinuclear antibodies.

Overdose

Symptoms: marked BP decrease, impaired water-electrolyte balance, shock, acute renal failure, stupor.

Treatment: in mild cases of overdose – gastric lavage, administration of adsorbents, sodium sulfate (preferably within 30 minutes after ingestion). The function of vital organs should be monitored. In severe arterial hypotension, if necessary, catecholamines, angiotensin II should be administered, IV (intravenous) injection of physiological saline solution. There is no experience of using forced diuresis, change of urine pH, hemofiltration or dialysis for accelerated elimination of ramipril from the body. Hemodialysis is indicated in cases of development of renal failure.

Pregnancy use

Pregnancy and lactation

The drug is contraindicated in pregnancy and during breast-feeding.

Perinent use in children

The drug is contraindicated in children and adolescents under 18 years of age.

Similarities