Zofenil 7.5: composition and presentation
Zofenil comes as tablets in two strengths: one tablet contains either 7.5 mg or 30 mg of zofenopril calcium, equivalent to 7.2 mg or 28.7 mg of zofenopril. The figure in the name refers to the smaller strength. The tablet may be taken before, during or after a meal — food has no bearing on it.
The two strengths here are not simply "the weak one and the strong one": both are needed at once. In acute myocardial infarction the schedule starts at 7.5 mg and reaches 30 mg within five days, so in the course of a single treatment the patient takes each in turn. That is why the description notes separately that 15 mg is either two 7.5 mg tablets or half a 30 mg tablet.
How Zofenil 7.5 works
The benefit of the medicine in arterial hypertension and in acute myocardial infarction rests chiefly on inhibition of the renin-angiotensin-aldosterone system in the plasma. Suppressing the activity of the angiotensin-converting enzyme lowers the concentration of angiotensin II and with it its ability to contract the muscular layer of the vessels; in parallel, the secretion of aldosterone is held back.
That second effect is comparatively weak, but it may lead to a slight rise in serum potassium along with a loss of sodium and water — hence the attention paid to potassium in the interactions section. The fall in angiotensin II breaks the negative feedback on renin, so plasma renin activity rises. The description gives the depth of the block in figures: 24 hours after oral doses of 30 mg and 60 mg of zofenopril calcium, enzyme activity is inhibited by 53.4% and 74.4% respectively.
Indications
There are two indications and they concern different situations. The first is treatment of mild and moderate essential arterial hypertension, that is, chronic treatment measured in months and years. The second is treatment of the early phase of acute myocardial infarction, with or without signs of heart failure.
The second indication carries hard conditions written into the text itself: treatment begins within the first 24 hours of symptom onset, in haemodynamically stable patients who have not received thrombolytic treatment. Each condition narrows the circle: the medicine cannot be started "a few days after the infarction", it is not given to an unstable patient, and it is not used together with thrombolysis. All of that happens in hospital, not at home.
Method of use and dosage
In hypertension the dose is set from blood pressure readings taken immediately before the next dose, and at least four weeks are allowed between changes. Without fluid or sodium depletion, treatment starts at 15 mg a day as a single dose and is raised to optimal blood pressure control; the effective dose is usually 30 mg a day and the maximum 60 mg, as one dose or two divided ones. Where the effect is insufficient, an antihypertensive from another group is added, a diuretic for instance. If fluid or sodium depletion is suspected, the order differs: those deficits are corrected first, diuretics are stopped 2 to 3 days before starting and treatment begins at 15 mg; if diuretics cannot be stopped, at 7.5 mg a day. Patients at high risk of severe acute hypotension are watched especially closely, preferably in hospital.
| Day from the start of infarction treatment | Dose every 12 hours |
| Days 1 and 2 | 7.5 mg — one 7.5 mg tablet |
| Days 3 and 4 | 15 mg — two 7.5 mg tablets or half a 30 mg tablet |
| from day 5 onwards | 30 mg — one 30 mg tablet |
Treatment of the infarction begins within 24 hours of symptom onset and continues for six weeks, and the dose increases in this table are tied to blood pressure. If at the start of treatment, or during the following three days, systolic pressure is low — 120 mm Hg or below — the daily dose is not raised. With hypotension of 100 mm Hg or below, the previously well tolerated dose is continued. In severe hypotension, that is, systolic pressure below 90 mm Hg on two consecutive readings at least an hour apart, the medicine is stopped. After six weeks the patient is reassessed: with no signs of left ventricular dysfunction or heart failure, treatment is stopped; where they are present, it continues. The dose is also adjusted to organ function: with a creatinine clearance above 45 ml/min the schedule is the usual one, below 45 ml/min the dose is halved, and in dialysis patients it is cut to a quarter. In mild and moderate hepatic impairment the starting dose in hypertension is halved; in severe impairment the medicine is contraindicated. Children are not given it: safety and efficacy have not been established.
Contraindications
The medicine is not used in hypersensitivity to zofenopril calcium, to other ACE inhibitors or to any excipient; in angioedema linked to past treatment with an ACE inhibitor, and in hereditary or idiopathic angioedema; in severe hepatic impairment; in bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.
A separate block concerns pregnancy. The second and third trimesters appear among the contraindications directly, but beside them stands an entry seen less often: the medicine is contraindicated in women of childbearing age who are not using effective contraception. Finally, taking preparations containing aliskiren at the same time is contraindicated in patients with diabetes or renal impairment where the glomerular filtration rate is below 60 ml/min/1.73 m² — a particular case of the general rule about dual blockade of the renin-angiotensin system.
Special warnings and precautions
The main theme of the section is a fall in blood pressure, especially after the first dose. In uncomplicated hypertension symptomatic hypotension is rare, but it becomes likelier with dehydration and electrolyte depletion from diuretics, salt restriction, dialysis, diarrhoea or vomiting, and in severe renin-dependent hypertension. In heart failure hypotension occurs more often, and the more so the more severe the failure — as high doses of loop diuretics, hyponatraemia or impaired renal function indirectly indicate. In at-risk groups treatment is started under close medical supervision, preferably in hospital, at a low dose, and diuretics are temporarily withdrawn where possible. The same applies to patients with angina and cerebrovascular disease: in them a sudden fall in pressure may cause a heart attack or a stroke. If hypotension develops, the patient is laid on their back and, if necessary, given intravenous saline. An important qualification: hypotension after the first dose does not close the door on careful further dose increases once its causes have been dealt with.
In the acute phase of infarction treatment is not started where there is a heightened risk of severe haemodynamic disturbance in response to a vasodilator: at a systolic pressure below 100 mm Hg or in cardiogenic shock. If hypotension drags on — systolic pressure staying below 90 mm Hg for more than an hour — the medicine is stopped. In renovascular hypertension and renal artery stenosis, ACE inhibitors raise the risk of severe hypotension and renal failure, and that risk grows with concurrent diuretics; treatment is begun in hospital at a low dose and renal function is monitored in the first weeks. Situations carrying a risk of anaphylactoid reactions are named separately: haemodialysis through high-flux polyacrylonitrile membranes such as AN 69, LDL apheresis with dextran sulfate, and desensitisation, for instance to hymenoptera venom. In the first two, membranes of another type or an antihypertensive from another group are advised; in the third, temporary withdrawal of the ACE inhibitor.
Interactions with other medicines
Concurrent use is discouraged above all with anything that raises potassium. ACE inhibitors reduce the potassium loss caused by diuretics, so potassium-sparing diuretics — spironolactone, triamterene, amiloride, eplerenone — potassium preparations and potassium-containing salt substitutes may raise serum potassium considerably; where such a combination is needed because of hypokalaemia, potassium and the ECG are monitored. The second undesirable combination is dual blockade of the renin-angiotensin-aldosterone system: pairing an ACE inhibitor with an angiotensin II receptor antagonist or with aliskiren was associated in a clinical study with more frequent hypotension, hyperkalaemia and renal impairment up to acute failure. Combination with lithium is not recommended either: a reversible rise in its serum concentration and toxicity have been described, and thiazide diuretics compound that risk.
A wider circle calls for caution. Previous treatment with high doses of diuretics reduces intravascular volume and creates a risk of hypotension at the start of treatment; withdrawing the diuretic, increasing fluid or salt, or starting at a low dose softens it. Anaesthetics, opioids, tricyclic antidepressants, antipsychotics and barbiturates strengthen the hypotensive effect or bring on orthostatic hypotension; the same goes for other antihypertensives, nitrates and vasodilators. Cimetidine raises the risk of a hypotensive effect, ciclosporin the risk of renal failure, and allopurinol, procainamide, cytostatics and immunosuppressants the risk of hypersensitivity reactions and, on data for other ACE inhibitors, of leukopenia. In diabetes ACE inhibitors rarely strengthen the glucose-lowering effect of insulin and other medicines. A separate and vivid reaction is described for injectable gold preparations: in people taking ACE inhibitors a nitrate-like reaction occurs more often, with facial flushing, nausea, dizziness and sometimes severe hypotension.
Pregnancy and breastfeeding
The second and third trimesters of pregnancy are named directly among the contraindications, and beside them stands the requirement of effective contraception for women of childbearing age. That wording means the question is settled before the medicine is prescribed, not after a pregnancy comes to light.
The reason for such strictness lies in the mechanism of action. In the second half of pregnancy ACE inhibitors act on the foetal kidneys, on whose work the volume of amniotic fluid depends, and after oligohydramnios the development of the lungs and the skull bones suffers. In practice that means a woman planning a pregnancy while being treated for hypertension discusses a change of medicine in advance, and a pregnancy already confirmed is reported to the doctor at once: another regimen can usually be found quickly.
Adverse reactions
The medicine's own list is short. Common effects are dizziness and headache, cough, nausea or vomiting and fatigue; uncommon ones are rash, muscle cramps and weakness; rare is angioedema. The dry cough here, as across the whole class, comes from the accumulation of bradykinin and passes once the medicine is stopped.
The second part of the section covers effects recorded with ACE inhibitors in general. In the blood, agranulocytosis and pancytopenia are possible in some patients, and there are reports of haemolytic anaemia in glucose-6-phosphate dehydrogenase deficiency. Hypoglycaemia has been described very rarely; rarely depression, mood changes, sleep disturbance and confusion, blurred vision and tinnitus; sometimes paraesthesia and disturbances of taste and balance. In the heart, isolated cases of tachycardia, palpitations, arrhythmia, angina and myocardial infarction combined with hypotension have been described. A severe fall in blood pressure at the start of treatment or after a dose increase is singled out: it shows itself as dizziness, weakness, visual disturbance and rarely loss of consciousness; occasionally there is sudden flushing of the face.
Overdose
The features of overdose are severe hypotension, shock, stupor, bradycardia, electrolyte disturbance and renal failure. The patient is observed in hospital, preferably in an intensive care unit, with frequent measurement of plasma electrolytes and creatinine, and treatment is matched to the nature and severity of the symptoms.
If the medicine was taken recently, measures limiting absorption are used: gastric lavage, adsorbents and sodium sulfate. If blood pressure falls, the patient is laid on their back with the legs raised, circulating volume is increased and administration of angiotensin II is considered. Bradycardia and other signs of excessive vagal stimulation are treated with atropine, and cardiac pacing is used if needed. ACE inhibitors are removed during haemodialysis, but high-flux polyacrylonitrile membranes should be avoided in it — for the same reason described in the warnings.
How to get a Zofenil 7.5 prescription online
The two indications of the medicine fare quite differently in the remote format. Treatment of an infarction begins in hospital and within the first day, so an online prescription has no bearing on that situation. Continuing treatment of hypertension that has already been settled on, however, is the typical case for e-zdrowie.com: you fill in a medical questionnaire, the doctor reviews the answers and issues an electronic prescription; the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
In the questionnaire state who prescribed the medicine and when, which strength you take — 7.5 mg or 30 mg — and how many times a day, and for what reason: for blood pressure or after an infarction. Recent blood pressure readings will be useful, as will fresh test results: creatinine, potassium and, if needed, the calculated clearance. Be sure to report a pregnancy or plans for one, liver and kidney disease, dialysis, and the use of diuretics, potassium preparations, lithium, sartans or aliskiren. And separately, any episode of swelling of the face, lips or tongue on an ACE inhibitor in the past: that is a contraindication to the whole class, without exception.
