Lisinoratio 20 — (IR): composition and dosage form
One tablet contains 20 mg of lisinopril. The medicine is taken once a day, every day at the same time, and that requirement is stricter than it looks: the hypotensive effect weakens as the next dose approaches, and scatter in the time of dosing shifts that point.
Food does not affect the bioavailability of lisinopril, so there is no need to tie it to meals. Salt does affect it: excessive intake can weaken the medicine's antihypertensive action.
How Lisinoratio 20 — (IR) works
Lisinopril is a synthetic peptide compound taken by mouth that inhibits the activity of the angiotensin-converting enzyme. That enzyme converts angiotensin I into angiotensin II, a substance with a strong vasoconstrictor action that raises blood pressure. Angiotensin II additionally increases the secretion of aldosterone by the adrenal cortex. By inhibiting the enzyme, the medicine lowers the plasma concentration of angiotensin II and the secretion of aldosterone, and that in turn may slightly raise serum potassium.
How slightly has been measured. In patients with hypertension and normal kidney function treated with lisinopril alone for 24 weeks, the mean rise in potassium was less than 0.1 mEq/l. But the mean hides the spread: in about 10% of patients potassium rose by more than 0.5 mEq/l, and in almost 6% it fell by as much. In those who took lisinopril together with a thiazide diuretic, on the other hand, no significant changes in potassium were seen at all — the diuretic and the ACE inhibitor balance each other out.
Indications
There are four indications and they cover almost the whole field of ACE inhibitor use. The first is the treatment of arterial hypertension, essential and renovascular, as monotherapy or with other blood-pressure-lowering medicines. The second is the treatment of heart failure, again as monotherapy or together with diuretics and, in certain cases, with digitalis preparations.
The third indication differs in its timing: the treatment of haemodynamically stable patients in the early phase of myocardial infarction, within the first 24 hours, to prevent left ventricular dysfunction and heart failure. The fourth concerns the kidneys: patients with hypertension and type 2 diabetes with renal complications and microalbuminuria. Each indication has its own dosing schedule, and they differ not by percentages but by multiples.
Method of administration and dosage
The general principle is one: start low and adjust to the blood pressure measured right before the next dose. The rest depends on what the medicine was prescribed for.
- essential hypertension without diuretics: starting dose 10 mg, maintenance usually 20–40 mg once a day; in some patients the expected fall in blood pressure comes only after 2–4 weeks, and 80 mg a day added no efficacy in long-term studies;
- hypertension on a background of diuretics: the diuretic is stopped 2–3 days before starting; if it cannot be stopped, treatment begins under close supervision with 5 mg and blood pressure is watched until the expected fall and for an hour beyond it;
- renovascular hypertension: treatment starts at 2.5 or 5 mg, because with bilateral renal artery stenosis or stenosis of the artery of a single kidney the pressure may fall excessively;
- heart failure: 2.5 mg as a single morning dose, maintenance 5–20 mg; the dose is raised no more often than every 4 weeks and by no more than 10 mg a step, and the greatest fall in pressure comes about 6–8 hours after the starting dose;
- early phase of infarction: 5 mg in the first 24 hours, another 5 mg after a day, 10 mg after two, then 10 mg once a day for 6 weeks; with a systolic pressure of 120 mm Hg or below, 2.5 mg is given for the first three days, and if it falls below 90 mm Hg for longer than an hour the medicine is withdrawn;
- diabetic nephropathy: 10 mg once a day and 20 mg if needed, the target being a diastolic pressure below 90 mm Hg seated; children aged 6–16 with hypertension are given 2.5 mg at a body weight of 20 to 50 kg and 5 mg from 50 kg, with a maximum of 20 and 40 mg a day respectively.
The kidneys set a scale of their own, since lisinopril is excreted in the urine. At a creatinine clearance of 30 to 70 ml/min the starting daily dose is 5–10 mg, at a clearance of 10 to 30 ml/min it is 2.5–5 mg, and below 10 ml/min, including patients on dialysis, 2.5 mg; the maximum maintenance dose in renal failure is 40 mg. Lisinopril is removed from the plasma during haemodialysis, so dialysis patients are given the daily dose after the session. In the elderly the dose is raised very cautiously: the strength of action is the same as in younger patients, but the maximum serum concentration proved about twice as high.
Contraindications
The first three prohibitions concern oedema: hypersensitivity to lisinopril or to the excipients, angioedema caused in the past by treatment with an ACE inhibitor, and congenital, idiopathic angioedema. Then come pregnancy and breastfeeding.
The remaining two contraindications are drug-related. Simultaneous use with products containing aliskiren is forbidden in patients with diabetes or with renal impairment at a glomerular filtration rate below 60 ml/min/1.73 m2. And the combination with a neprilysin inhibitor, sacubitril for example, is forbidden outright: the medicine must not be given within 36 hours before or after sacubitril with valsartan.
Special warnings and precautions
The main warning is angioedema of the face, limbs, lips, tongue, glottis and larynx: in patients receiving ACE inhibitors it was seen rarely, but it can cost a life. With swelling of the tongue, glottis or larynx airway obstruction is likely, especially if the patient has had airway surgery in the past. In black patients such oedema on ACE inhibitors occurs more often.
- symptomatic hypotension is more likely with water and electrolyte imbalance from diuretics, a low-sodium diet, dialysis, diarrhoea or vomiting, and also in severe renin-dependent hypertension;
- in patients simultaneously undergoing desensitisation with hymenoptera venom, life-threatening anaphylactoid reactions occur occasionally;
- the risk factors for hyperkalaemia are renal failure, diabetes and concurrent use of potassium-sparing diuretics;
- neutropenia and agranulocytosis have been described, more often with impaired kidney function or with vascular collagen diseases, and occasionally a syndrome develops that begins with cholestatic jaundice and passes into life-threatening fulminant hepatitis;
- like other vasodilators, ACE inhibitors are used with caution in obstruction of the left ventricular outflow tract.
The cough stands apart — the best-known feature of this class. With ACE inhibitors a dry chronic cough may appear that worsens at night; it goes away once the medicine is stopped. It is worth knowing in advance: a cough on lisinopril calls not for a lung investigation but for a conversation with the doctor about changing the medicine.
Interaction with other medicines
Lisinopril's interactions are easier to sort by what they lead to than by drug group. There are three outcomes: an excessive fall in blood pressure, a rise in potassium and worsening kidney function, and most combinations lead to one of them. The worst case is when all three arrive together, and that happens when several medicines acting on the same system are taken at once: a clinical trial showed that combining an ACE inhibitor with an angiotensin II receptor antagonist or with aliskiren produces more adverse events, acute renal failure included, than any of them on its own.
| With what | What happens | What to do |
| Diuretics | enhancement of the antihypertensive effect and, with potassium-losing ones, prevention of the hypokalaemia they cause | stop the diuretic 2–3 days before starting treatment |
| NSAIDs, including selective COX-2 inhibitors | weakening of the hypotensive effect and, with impaired kidney function, in the elderly and in dehydration, worsening of renal disturbance up to probable acute renal failure, usually reversible | caution in combined treatment |
| Angiotensin II receptor antagonists or aliskiren | dual blockade of the same system instead of single blockade worsens all three outcomes named above at once | do not use dual blockade |
| Lithium salts | lisinopril may slow the excretion of lithium | monitor lithium regularly and lower its dose if necessary |
| Potassium supplements, potassium-sparing diuretics, potassium salt substitutes | a rise in serum potassium, especially with impaired kidney function | caution and frequent potassium monitoring |
| Insulin and oral antidiabetic medicines | possible enhancement of the hypoglycaemic effect, more likely in the first weeks of treatment and with impaired kidney function | monitor blood glucose closely in the first month |
Three further interactions share one outcome — angioedema, the risk of which rises when mTOR inhibitors such as temsirolimus, sirolimus and everolimus, neprilysin inhibitors of the sacubitril type, and vildagliptin are taken at the same time. General anaesthetics enhance the antihypertensive effect to the point of hypotension, cytotoxic medicines and systemic glucocorticoids increase the risk of leucopenia, and in patients receiving injectable gold salts, reactions resembling those of nitrates have rarely been described: facial flushing, nausea, vomiting and hypotension. With nitrates, propranolol, digoxin and hydrochlorothiazide no significant interactions were found.
Pregnancy and breastfeeding
Pregnancy and breastfeeding stand directly on the list of contraindications — this is not a recommendation but a prohibition. The reason lies in the mechanism: the medicine acts on the renin-angiotensin system, and in the fetus that system governs the development of the kidneys and the volume of amniotic fluid.
The practical conclusion for women of childbearing age is simple: the doctor must be told about a planned pregnancy in advance, so that there is time to choose another blood pressure medicine. If a pregnancy comes to light during treatment, lisinopril is withdrawn.
Adverse effects
Commonly there are dizziness and headache, orthostatic phenomena with a fall in blood pressure, cough, diarrhoea and vomiting, and impaired kidney function. Uncommonly recorded are mood changes, paraesthesia, disturbances of taste and sleep, palpitations, tachycardia, Raynaud's phenomenon, rhinitis, nausea, abdominal pain, dyspepsia, rash, itching, impotence, tiredness and weakness. On a line of their own stand myocardial infarction and a cerebrovascular event, probably secondary to an excessive fall in blood pressure in high-risk patients — a reminder of why the dosage section is so full of caveats about gradualness.
The rare and very rare reactions affect mainly the blood, the skin and the liver. Rarely: a fall in haemoglobin and haematocrit, disorientation, dryness of the oral mucosa, urticaria, alopecia, angioedema, uraemia, acute renal failure, gynaecomastia. Very rarely: bone marrow depression, anaemia, thrombocytopenia, leucopenia, agranulocytosis, haemolytic anaemia, enlarged lymph nodes, autoimmune diseases, hypoglycaemia, bronchospasm, pancreatitis, intestinal angioedema, hepatitis and liver failure with jaundice, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, oliguria or anuria. With unknown frequency, the syndrome of inappropriate antidiuretic hormone secretion, gout, depression, stroke, angina pectoris and cardiac rhythm disturbances have been described.
Overdose
The section is short because the mechanism of overdose follows directly from the mechanism of action: the most likely manifestation is an excessive fall in blood pressure and the disturbances it causes.
The treatment matches the cause. If the pressure falls, 0.9% sodium chloride solution is given by intravenous infusion; the use of angiotensin II may prove helpful. And there is one option many medicines do not offer: lisinopril can be removed from the blood by haemodialysis — the same property because of which dialysis patients are given the daily dose after the session.
How to get a prescription for Lisinoratio 20 — (IR) online
Lisinopril is one of those medicines where the dose says more about the diagnosis than the name does: 10 mg in ordinary hypertension, 2.5 mg in heart failure or renovascular hypertension, 5 mg on the first day of an infarction. What matters to the doctor, therefore, is not that you need "something for blood pressure" but what exactly for. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with the indication: hypertension, heart failure, the state after an infarction, or diabetic nephropathy — the whole schedule depends on it. Give your latest blood pressure readings and your creatinine or creatinine clearance: the renal scale here is a separate one, and below a clearance of 10 ml/min the dose falls to 2.5 mg. Be sure to report whether you have ever had angioedema — especially on ACE inhibitors — and whether congenital angioedema runs in your family: that is a direct contraindication. Name separately any diuretics, potassium supplements and salt substitutes, lithium, regular NSAIDs, and also aliskiren and sacubitril with valsartan, which are incompatible with lisinopril. If you have diabetes, say what you are treated with: hypoglycaemia may be intensified in the first month. And say whether you are pregnant or planning a pregnancy — in pregnancy the medicine is forbidden.
