Vivace: composition and pharmaceutical form
One tablet contains 2.5 mg, 5 mg or 10 mg of ramipril. The composition includes lactose monohydrate, so the medicine is not used in rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
The tablet is swallowed whole and washed down with liquid. Food does not affect bioavailability, so the medicine may be taken before, during or after a meal, but preferably every day at the same time.
How Vivace works
Ramipril is a prodrug: the work is done by its active metabolite ramiprilat. It inhibits dipeptidyl carboxypeptidase I, also known as angiotensin-converting enzyme and kininase II: in plasma and tissues this enzyme converts angiotensin I into the powerfully vasoconstrictive angiotensin II and at the same time breaks down bradykinin, which dilates the vessels.
Hence the double result: less angiotensin II is formed, bradykinin is destroyed more slowly, and the vessels relax. Since angiotensin II stimulates the release of aldosterone, ramiprilat also reduces its secretion. The average response to monotherapy with ACE inhibitors is smaller in black patients than in other races: hypertension with low plasma renin activity is more common in that population.
Indications
The first indication is arterial hypertension. The second is prevention of cardiovascular disease: reduction of cardiovascular morbidity and mortality in patients with manifest disease of atherosclerotic origin (coronary heart disease, stroke or peripheral vascular disease in the history) or with diabetes and at least one risk factor.
The renal indications and two cardiological situations with strict prescribing rules are set out separately.
- the early stage of diabetic glomerular nephropathy, established by microalbuminuria;
- manifest nephropathy established by proteinuria: diabetic — in patients with at least one cardiovascular risk factor; non-diabetic glomerular — with proteinuria of at least 3 g per day;
- symptomatic heart failure and secondary prevention after myocardial infarction — reduction of mortality in the acute phase in patients with signs of heart failure; the medicine is added later than 48 hours from the onset of infarction, from the third day.
Method of use and dosage
The dose is chosen individually according to the patient's profile and blood pressure; the medicine is used as monotherapy or together with antihypertensives from other groups, with the dose raised gradually, usually by doubling. For cardiovascular prevention treatment starts at 2.5 mg daily, is doubled after 1–2 weeks and after a further 2–3 weeks reaches the maintenance dose of 10 mg.
| Situation | Regimen |
| Arterial hypertension | start 2.5 mg daily; doubling every 2–4 weeks to the target pressure, maximum 10 mg, usually as a single dose |
| Strong activation of the system or use of diuretics | start at 1.25 mg under supervision: an excessive fall in blood pressure is possible after the first dose; the diuretic is withdrawn 2–3 days earlier where possible, otherwise renal function and potassium are monitored |
| Nephropathy: diabetes with microalbuminuria or non-diabetic nephropathy / diabetes with a risk factor | 1.25 mg, after two weeks 2.5 mg, after another two weeks 5 mg / 2.5 mg, after 1–2 weeks 5 mg, after a further 2–3 weeks the target 10 mg |
| Symptomatic heart failure | in patients stabilised on a diuretic, 1.25 mg daily; doubling every 1–2 weeks to a maximum of 10 mg, preferably in two divided doses |
| After acute myocardial infarction | in a stable patient after 48 hours — 2.5 mg twice daily for three days; if poorly tolerated, 1.25 mg twice daily for two days, then 2.5 and 5 mg; the target is 5 mg twice daily, and if 2.5 mg twice daily cannot be reached, treatment is stopped |
| Renal impairment by creatinine clearance | 60 ml/min and above — start 2.5 mg, maximum 10 mg daily; 30–60 — start 2.5 mg, maximum 5 mg; 10–30 — start 1.25 mg, maximum 5 mg; on haemodialysis 1.25 mg and a maximum of 5 mg a few hours after the session |
In hepatic impairment treatment is started only under close medical supervision, with a maximum of 2.5 mg daily. In older people the starting doses are lower and the increase more gradual: in the very old and frail a start at 1.25 mg is considered. Efficacy and safety in children have not been established, and the data on NYHA class IV immediately after infarction are likewise insufficient.
Contraindications
Hypersensitivity to ramipril, to any excipient or to another ACE inhibitor. Angioedema in the history — hereditary, idiopathic or previously caused by ACE inhibitors or angiotensin II receptor antagonists. Significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. The second and third trimesters of pregnancy.
The medicine is not used in hypotension or in haemodynamically unstable patients, nor during therapeutic procedures in which blood contacts negatively charged surfaces. Combination with medicines containing aliskiren is contraindicated in diabetes or renal impairment with a glomerular filtration rate below 60 ml/min/1.73 m².
Special warnings and precautions
With increased activation of the renin-angiotensin-aldosterone system the risk of a marked fall in blood pressure and of deteriorating renal function is higher, especially at the first administration of the inhibitor or the diuretic and at the first dose increase. It is suspected in severe hypertension, decompensated heart failure, haemodynamically significant obstruction to inflow or outflow from the left ventricle, unilateral renal artery stenosis with a second functioning kidney, dehydration and cirrhosis with ascites.
- dehydration, hypovolaemia and sodium deficiency are corrected before treatment starts, though in heart failure the risk of volume overload is weighed up; the medicine is withdrawn where possible the day before surgery, and renal function is assessed before and during treatment, especially in the first weeks;
- angioedema requires immediate withdrawal and emergency measures: the patient is observed for 12–24 hours and discharged only after the symptoms have gone; intestinal angioedema has also been described, presenting with abdominal pain;
- hyperkalaemia occurs more often in renal failure, over the age of 70, with poorly controlled diabetes, dehydration, acidosis and with medicines that raise potassium: it is then monitored regularly;
- neutropenia and agranulocytosis, thrombocytopenia and anaemia were reported rarely, and bone marrow suppression has been described, so the white cell count is monitored — more often at the start of treatment and in kidney disease and collagen disorders.
The likelihood and severity of anaphylactic reactions to insect venom and other allergens increase under ACE inhibition, so temporary withdrawal is considered before desensitisation. The cough here is characteristically non-productive and persistent, resolves after withdrawal and is taken into account in the differential diagnosis. Dizziness from a fall in blood pressure impairs concentration: for several hours after the first dose or an increase in it, driving is not recommended.
Interaction with other medicines
Contraindicated are procedures in which blood contacts negatively charged surfaces: haemodialysis or haemofiltration with highly permeable membranes such as polyacrylonitrile, and low-density lipoprotein apheresis with dextran sulfate, because of the risk of severe anaphylactoid reactions. If the procedure is necessary, another type of dialyser or antihypertensives of a different class are chosen.
- dual blockade of the system by combining an ACE inhibitor, an angiotensin II receptor antagonist or aliskiren produced in a clinical trial more hypotension, hyperkalaemia and renal impairment, including acute renal failure, than monotherapy;
- potassium salts, heparin, potassium-sparing diuretics and other substances that raise potassium, including angiotensin II antagonists, tacrolimus and ciclosporin, may cause hyperkalaemia, so potassium is monitored; the same was reported with co-trimoxazole, and the risk of angioedema is higher with mTOR inhibitors — temsirolimus, everolimus, sirolimus;
- substances that lower blood pressure — diuretics, nitrates, tricyclic antidepressants, anaesthetics, alcohol, alpha-blockers — increase the risk of hypotension, while sympathomimetics such as dopamine and epinephrine, on the contrary, weaken the antihypertensive effect;
- allopurinol, immunosuppressants, corticosteroids and cytostatics raise the risk of haematological reactions, and ACE inhibitors reduce the excretion of lithium; non-steroidal anti-inflammatory drugs and acetylsalicylic acid weaken the antihypertensive effect and increase the risk of worsening renal function and rising potassium, while hypoglycaemia is possible with insulin.
The risk here gathers around three parameters: potassium, blood pressure and renal function — and the control of combinations is built around them. That is why, when any new medicine is added, from a painkiller to a salt substitute, the doctor needs the full list of what the patient takes.
Pregnancy and breastfeeding
The medicine is not recommended in the first trimester and is contraindicated in the second and third. There are no conclusive epidemiological data on the teratogenic effect of ACE inhibitors in the first trimester, but a small increase in risk cannot be excluded. If continuation of treatment is not considered essential, women planning a pregnancy are advised to switch to treatment with confirmed safety in pregnancy; once pregnancy is established, the medicine is stopped immediately.
Treatment with ACE inhibitors or angiotensin II receptor antagonists in the second and third trimesters is toxic to the fetus — impaired renal function, oligohydramnios, delayed ossification of the skull bones — and to the newborn: renal failure, hypotension, hyperkalaemia. With exposure from the second trimester onwards, ultrasound monitoring of renal function and the skull is recommended, and newborns are watched for hypotension, oliguria and hyperkalaemia. The data on ramipril during breastfeeding are insufficient, so it is not recommended, especially where the child is a newborn or premature.
Adverse reactions
The safety profile of ramipril is defined by a persistent dry cough and reactions caused by the fall in blood pressure. Serious events include angioedema, hyperkalaemia, impaired renal or hepatic function, pancreatitis, severe skin reactions and neutropenia with agranulocytosis.
- common: headache and dizziness, raised blood potassium, hypotension, orthostatic hypotension and fainting, non-productive cough, bronchitis, sinusitis, breathlessness, dyspepsia, diarrhoea, nausea and vomiting, rash, muscle cramps, chest pain, fatigue;
- uncommon: eosinophilia, reduced appetite, depressed mood, sleep disturbances, paraesthesia, myocardial ischaemia up to angina and infarction, tachycardia, arrhythmias, oedema, bronchospasm, pancreatitis, raised transaminases, angioedema, impaired renal function;
- rare: leukopenia with neutropenia and agranulocytosis, reduced red cells and platelets, disturbances of consciousness, tremor, conjunctivitis, hearing impairment, vasculitis, cholestatic jaundice, urticaria, asthenia;
- frequency not known: bone marrow aplasia, pancytopenia, haemolytic anaemia, anaphylactic reactions, ischaemia of the central nervous system, acute liver failure, toxic epidermal necrolysis, Stevens — Johnson syndrome.
Safety was followed in two studies involving 325 children and adolescents aged 2 to 16. The nature of the events is the same as in adults, but the frequency of some is higher: tachycardia, nasal congestion and inflammation of the nasal mucosa were common in children against uncommon, conjunctivitis common against rare, and tremor and urticaria uncommon against rare.
Overdose
The symptoms of overdose with ACE inhibitors include excessive dilation of the peripheral vascular bed with a marked fall in blood pressure and shock, bradycardia, electrolyte disturbances and renal failure. The patient stays under close observation and treatment is symptomatic and supportive.
The recommended methods include removal of the active substance — gastric lavage and adsorbents — and techniques that secure haemodynamic stability, including the administration of α1-adrenergic receptor agonists or angiotensin II. Ramiprilat is removed from the circulation by haemodialysis only to a small extent.
How to get a prescription for Vivace online
The medicine is prescription-only, and the conversation with the doctor begins with what ramipril is being prescribed for: blood pressure, prevention of cardiovascular events, nephropathy, heart failure or a recent infarction. Both the starting dose and the pace of its increase depend on the indication.
It is worth mentioning in advance any angioedema in the history and intolerance of other ACE inhibitors, pregnancy or plans for it, renal artery stenosis, kidney disease with test results and liver disease, diabetes and low blood pressure, and — because of the lactose in the composition — galactose intolerance. The medicines being taken are listed separately: diuretics, potassium and salt substitutes, angiotensin II receptor antagonists and aliskiren, lithium, painkillers from the non-steroidal anti-inflammatory group, insulin. The doctor will assess these circumstances during the online consultation and, if there are no contraindications, will issue an electronic prescription.
