Lisinoratio 20: composition and form
One tablet contains 5 mg, 10 mg or 20 mg of lisinopril; this pack holds the twenty-milligram strength. Three strengths are not a formality: in almost every indication lisinopril is started at a small dose and raised in steps, so treatment moves from one tablet to another along the way.
Food does not affect the absorption of lisinopril, so it can be taken regardless of meals. It is taken once a day, every day at the same time — the fixed hour matters, because the dose is adjusted by the blood pressure measured immediately before the next tablet.
How Lisinoratio 20 works
Lisinopril is an angiotensin-converting enzyme inhibitor, but within the group it stands apart: it is not a prodrug, undergoes no biotransformation in the liver and is water-soluble, which is why it is assigned a class of its own, the third. The mechanism is the inhibition of the renin-angiotensin-aldosterone system by blocking the enzyme that converts angiotensin I into the vasoconstricting angiotensin II. The consequences are several: the concentration of angiotensin II falls in tissues and plasma, aldosterone release by the adrenals decreases, and plasma renin activity drops.
The second, less obvious effect runs through the kallikrein-kinin system. The converting enzyme resembles kininase II, which breaks down bradykinin, so lisinopril raises the concentration of vasodilating bradykinin, and that in turn boosts the conversion of arachidonic acid into the vasodilating prostaglandins PGI2 and PGE2. There is a third side to the matter: angiotensin II is not only vasoconstrictive but also mitogenic — it speeds up the synthesis of type I and III collagen, that is, fibrosis, and increases the release of endothelin. Suppressing the system therefore prevents hypertrophy of the heart muscle and fibrosis of the vessel wall. In practice blood pressure falls both lying and standing, without reflex tachycardia, resistance in the renal arteries drops without affecting glomerular filtration, and a short break in treatment produces no rebound effect.
Indications
There are four indications, and they form a sequence running from blood pressure to its consequences. The first is essential and renovascular arterial hypertension, as monotherapy or together with other blood-pressure-lowering medicines. The second is heart failure, alone or together with diuretics and in some cases with digitalis preparations. The third is haemodynamically stable patients in the early phase, within 24 hours, of myocardial infarction, and the aim here is preventive: to keep left ventricular dysfunction and heart failure from developing.
The fourth indication speaks not of the heart but of the kidneys: treatment of patients with hypertension, type 2 diabetes and incipient nephropathy. It rests on the nephroprotective properties of the class — slowing renal failure by reducing proteinuria, limiting excessive filtration in healthy nephrons and restraining proliferative processes in the glomeruli. In patients in the early phase of infarction lisinopril additionally reduces left ventricular hypertrophy and improves survival, especially together with nitrates.
Administration and dosage
In essential hypertension in a patient not on diuretics, treatment starts with 10 mg, and the usual maintenance dose is 20-40 mg once a day. The expected fall in blood pressure appears in some people only after 2-4 weeks, and the highest dose studied, 80 mg a day, added no efficacy. If the patient is already taking a diuretic, it is withdrawn where possible 2-3 days before the start, and if it cannot be withdrawn, treatment begins with 5 mg under close medical supervision. In renovascular hypertension the starting dose is smaller still, 2.5 or 5 mg. Children aged 6 to 16 are given 2.5 mg a day at a body weight of 20 to 50 kg and 5 mg at 50 kg and above; below the age of 6 it is not given.
In heart failure the morning starting dose is 2.5 mg and the maintenance dose usually 5-20 mg; the dose was raised no more often than every 4 weeks and by no more than 10 mg per step. With hyponatraemia below 130 mEq/l or creatinine clearance below 30 ml/min, treatment starts at 2.5 mg under supervision; the greatest fall in blood pressure comes 6-8 hours after the first dose. In the early phase of infarction the schedule is written out by the hour: 5 mg on the first day, another 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once a day for six weeks, together with anticoagulants, antiplatelet agents and beta-blockers; with a systolic pressure of 120 mmHg or below, 2.5 mg is given for the first three days. In diabetic nephropathy treatment starts at 10 mg and is raised if needed to 20 mg. In renal failure the dose is calculated from creatinine clearance, at most 40 mg a day, and patients on dialysis are given the dose after the session.
Contraindications
The list is short, and almost every item on it concerns previous experience with this same class of medicines. It is not given in hypersensitivity to lisinopril dihydrate, to other angiotensin-converting enzyme inhibitors or to the excipients. Listed separately is angioedema that followed the use of inhibitors of this enzyme, as well as idiopathic or hereditary angioedema — having occurred once, it closes the door to the whole class.
The second part of the prohibitions is anatomical. The medicine is contraindicated in haemodynamically significant obstruction of the outflow of blood from the left ventricle, in bilateral renal artery stenosis and in unilateral stenosis if the kidney is solitary: where flow is already mechanically limited, removing vasoconstrictor tone does not improve matters. Pregnancy closes the list.
Special warnings and precautions
The main theme of the section is an excessive fall in blood pressure after the first dose and after every increase in the dose of lisinopril or of the diuretic. In uncomplicated hypertension this is rare, but the likelihood grows past the age of 70, in severe hypertension, with hyponatraemia below 140 mmol/l, hypovolaemia, severe heart failure, kidney disease and marked narrowing of the cerebral arteries. If pressure has fallen, the patient is laid flat with the legs raised, blood volume is replaced with saline, and atropine is given for bradycardia; such an episode does not call for withdrawing the medicine.
| Situation | What the doctor does |
| Starting treatment in a patient at risk | starts in hospital at 2.5 mg a day and observes for no less than 8 hours after the first dose |
| Renal artery stenosis or renovascular hypertension | starts in hospital at 2.5 mg, withdraws diuretics and monitors renal function in the first weeks |
| Early phase of infarction, systolic pressure below 100 mmHg | lowers the dose to 5 mg, if needed to 2.5 mg; if it stays below 90 for over an hour, withdraws the medicine |
| Proteinuria above 1 g a day | continues treatment only after weighing benefit against risk to the kidney, with regular monitoring |
| Swelling of the tongue, pharynx or larynx | 0.3-0.5 ml of 0.1% adrenaline subcutaneously or 0.1 mg slowly intravenously under ECG control, then corticosteroids and antihistamines; observation for 12-24 hours |
| Haemodialysis on high-flux membranes, LDL apheresis, desensitisation to wasp and bee venom | changes the membrane type or replaces the medicine in advance with another antihypertensive |
The remaining warnings are shorter but numerous. Neutropenia and agranulocytosis with fever, sore throat and enlarged lymph nodes are rarely possible: in kidney disease, systemic connective tissue disease and while taking allopurinol or corticosteroids, the white cell count is checked regularly. With jaundice or a rise in liver enzymes the medicine is withdrawn, and before general anaesthesia blood volume is increased in advance. Potassium may rise, so potassium-sparing diuretics and potassium preparations are not recommended in renal and cardiac failure. In primary hyperaldosteronism the medicine is not recommended because of low efficacy, and after a kidney transplant and on dialysis treatment starts at 2.5 mg with the blood count watched: anaemia may develop after 1-6 months.
Interactions with other medicines
Part of the interactions strengthen the main effect and therefore threaten hypotension. Other blood-pressure-lowering medicines, above all diuretics, and also hypnotics, narcotic analgesics, anaesthetics, amifostine and baclofen enhance the action of lisinopril; the enzyme inhibitors in turn enhance the effect of alcohol, and alcohol enhances theirs. In the opposite direction work the non-steroidal anti-inflammatory drugs such as acetylsalicylic acid and indometacin: they weaken the effect and can worsen renal function. It is also weakened by sympathomimetics — salbutamol, fenoterol — and by table salt; antacids reduce bioavailability.
The second part concerns laboratory shifts. Taking potassium preparations, potassium-sparing diuretics — spironolactone, amiloride, triamterene — and other medicines that raise potassium, heparin for instance, alongside it can lead to hyperkalaemia, especially in renal failure. The enzyme inhibitors can strengthen the glucose-lowering action of sulfonylureas, biguanides and insulin. Serum lithium concentration may rise. And a separate risk group on the blood side: taking allopurinol, procainamide, antineoplastic agents or systemic corticosteroids at the same time increases the likelihood of leucopenia.
Pregnancy and breastfeeding
Here the product information is extremely terse: the medicine is not used during pregnancy or breastfeeding. Pregnancy is moreover listed among the contraindications — this is not a warning the doctor weighs up, but a direct ban. Neither study data nor a description of the mechanism appears in this section.
The practical conclusion is simple. A woman planning a pregnancy should discuss changing the medicine with her doctor in advance. If pregnancy has occurred during treatment, the doctor is told at once: what to replace lisinopril with, and how quickly, is for them to decide. In the questionnaire before a prescription, pregnancy and breastfeeding are stated without fail.
Adverse reactions
The section opens with a statement unusual for a medicine with such a wide dose range: the frequency and severity of adverse reactions do not depend on the dose. Most often it is a fall in blood pressure or orthostatic hypotension, usually after the first dose and after every increase in the dose of lisinopril or of the diuretic. In isolated cases tachycardia, rhythm disturbances, chest pain, an angina attack, infarction and stroke have been described. In patients in the early phase of infarction, second- and third-degree atrioventricular block, severe hypotension and impaired renal function were seen sporadically, usually on the first day, and rarely cardiogenic shock.
The best-known consequence of treatment is a dry, persistent cough that worsens at night; it occurs more often in women, in non-smokers and when lying down, and passes after withdrawal. Less often there are sore throat, hoarseness and bronchitis, and less often still breathlessness, sinusitis, rhinitis, bronchospasm and pulmonary infiltrates. On the renal side, as a consequence of suppressing the renin-angiotensin-aldosterone system, disturbances of function may appear or worsen; in severe congestive heart failure oliguria, a rise in urea and isolated cases of acute renal failure have been described. On the digestive side nausea, upper abdominal pain and dyspepsia arise sporadically, and less often vomiting, diarrhoea and constipation; isolated cases of cholestatic jaundice and fulminant hepatitis have been described. Skin reactions are rash and, less often, urticaria, itching and angioedema of the lips and face; among the severe ones pemphigus, erythema multiforme and Stevens-Johnson and Lyell's syndromes have been reported. On the nervous side headache and fatigue are possible, and less often dizziness, depression, sleep disturbance, impotence, paraesthesia, muscle cramps and a metallic taste in the mouth.
Overdose
The picture of overdose directly continues the main action of the medicine and depends on its degree. Severe hypotension up to shock, bradycardia, electrolyte disturbances and renal failure are possible. The product information names no specific antidote: treatment is symptomatic and, if required, giving catecholamines and angiotensin II — substances acting in the opposite direction — is considered.
The second way of helping is to remove lisinopril from the blood, and for this molecule that is available: the medicine is cleared by dialysis. But with a caveat repeated in the warnings as well: high-flux polyacrylonitrile membranes must not be used. Dialysis on them can by itself provoke an anaphylactoid reaction — facial swelling, flushing, a fall in blood pressure and breathlessness within minutes of the session starting.
How to get a prescription for Lisinoratio 20 online
Lisinopril is almost never prescribed "just for blood pressure": it has four different indications, and which of them is yours determines both the starting dose and how fast it is raised. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will dispense the tablets.
In the questionnaire state exactly what you are treating: hypertension, heart failure, the state after an infarction or diabetic nephropathy, and give your usual blood pressure readings and the dose you take now. Be sure to report kidney disease, renal artery stenosis, dialysis or a kidney transplant, diabetes, and whether you take diuretics. List the medicines separately — potassium preparations and potassium-sparing diuretics, non-steroidal painkillers, lithium, insulin, allopurinol, corticosteroids. And be sure to write it down if, after an inhibitor of this enzyme, you ever had swelling of the face, lips or tongue, or a dry cough appeared: the first closes the door to the whole class, the second is often the reason for a change.
