Ampril HD: composition and dosage form
One tablet contains 2.5 mg or 5 mg of ramipril and 12.5 mg or 25 mg of hydrochlorothiazide. The ratio between the components is fixed in the tablet and one of them can no longer be adjusted separately from the other — that is the defining feature of any fixed combination and the reason one does not arrive at it straight away.
The medicine is taken once a day, every day at the same time, preferably in the morning. Food does not change the bioavailability, so the tablet may be taken before, during or after a meal, but it must be swallowed whole with liquid: it is neither chewed nor crushed. The tablets contain lactose, so the medicine is unsuitable for patients with the rare hereditary galactose intolerance, with Lapp lactase deficiency, or with glucose-galactose malabsorption syndrome.
How Ampril HD works
Ramipril is inactive in itself — the work is done by its metabolite ramiprilat, which blocks angiotensin-converting enzyme. That enzyme does two things at once: it turns angiotensin I into the vasoconstrictor angiotensin II, and it breaks down bradykinin, which dilates vessels. Blocking it strikes both sides at the same time, so the vessels widen, and along with the fall in angiotensin II the secretion of aldosterone drops as well.
Hydrochlorothiazide works differently: it inhibits the reabsorption of sodium and chloride in the distal tubule of the kidney, water follows the ions out, plasma and extracellular fluid volume fall, renal vascular resistance changes, and the response to noradrenaline and angiotensin II weakens. The two substances have one unobvious point in common — potassium — and they act on it in opposite directions: the thiazide increases the excretion of potassium and magnesium, while the ACE inhibitor, on the contrary, retains potassium. It is precisely that mutual cancelling-out that makes the combination sensible, but it does not remove the need for a test: there is no guarantee it will work in a given patient.
Indications
There is only one indication here, and it is worded with a caveat that explains the whole logic of the medicine: the treatment of arterial hypertension in patients whose blood pressure is not adequately controlled by ramipril alone or by hydrochlorothiazide alone.
That is, Ampril HD is not a starting medicine. It appears at the second step, once monotherapy has been tried and turned out to be insufficient.
Method of administration and dosage
The dose is fitted individually to the patient's profile and to how well the blood pressure is controlled. The general rule runs like this: the fixed combination of ramipril with hydrochlorothiazide is normally given after the dose of each component has been chosen separately. One begins with the smallest available dose and, if needed, raises it gradually until the target blood pressure is reached.
| Situation | Maximum daily dose | Condition |
| The ordinary case | 10 mg of ramipril and 25 mg of hydrochlorothiazide | this is the upper limit for the combination as a whole |
| Creatinine clearance 30-60 ml/min | 5 mg of ramipril and 25 mg of hydrochlorothiazide | only the smallest dose of the combination is used, and only after a period of ramipril monotherapy |
| Mild and moderate hepatic impairment | 5 mg of ramipril and 12.5 mg of hydrochlorothiazide | treatment is begun solely under close medical supervision |
| Creatinine clearance below 30 ml/min in non-dialysed patients | the medicine is not used | the limit comes from the hydrochlorothiazide and is written into the contraindications |
| Severe hepatic impairment and hepatic encephalopathy | the medicine is not used | the electrolyte shifts caused by the diuretic can themselves bring on encephalopathy |
| The patient is already taking a diuretic | start with 1.25 mg of ramipril as a separate medicine | because of the risk of a sharp fall in blood pressure; the move to the combination no higher than 2.5 mg and 12.5 mg |
Older patients need a smaller starting dose, and it should be raised more slowly. Children and adolescents under 18 are not recommended the medicine: the data on safety and efficacy is insufficient.
Contraindications
The first group is reactions and history: hypersensitivity to ramipril, to any other ACE inhibitor, to hydrochlorothiazide, to other thiazide diuretics, to sulfonamides or to the excipients, and also angioedema in the past — hereditary, idiopathic, or related to earlier treatment with ACE inhibitors or angiotensin II receptor blockers.
The second group is conditions and procedures: significant bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney; severe renal impairment with a creatinine clearance below 30 ml/min in non-dialysed patients; severe hepatic impairment and hepatic encephalopathy; clinically significant electrolyte disturbances that treatment could worsen; the second and third trimesters of pregnancy and the breastfeeding period. Named separately are extracorporeal treatments in which blood comes into contact with negatively charged surfaces, and the ban on combining the medicine with aliskiren in patients with diabetes or with a glomerular filtration rate below 60 ml/min/1.73 m².
Special warnings and precautions
The most dangerous moment is the start of treatment and the first dose increase. In patients with a strongly activated renin-angiotensin-aldosterone system, blood pressure can fall sharply and kidney function can worsen; this can be predicted in advance from severe hypertension, decompensated heart failure, aortic or mitral valve stenosis, unilateral renal artery stenosis with the other kidney working, cirrhosis with ascites, a deficit of fluid and salt, and the taking of diuretics.
- potassium is measured during the first week of treatment and any hypokalaemia found is corrected;
- the opposite shift — hyperkalaemia — is brought by the ramipril, and its likelihood rises if the kidneys are working poorly, if the patient is past seventy, if the diabetes is not compensated, or if the regimen includes potassium preparations and potassium-sparing diuretics;
- sodium is monitored regularly: dilutional hyponatraemia is symptomless at first, and in older people and in cirrhosis the tests are done more often; the syndrome of inappropriate antidiuretic hormone secretion has also been described;
- creatinine is looked at not as a one-off certificate but as a series: before the start, then in the first weeks and later during treatment, and the dose is reviewed by exactly that series;
- angioedema requires the medicine to be withdrawn at once, emergency treatment to be started and the patient to be observed for at least 12-24 hours; the risk is higher where mTOR inhibitors or vildagliptin are taken at the same time;
- hydrochlorothiazide, being a sulfonamide, can cause acute transient myopia and angle-closure glaucoma in the first hours or weeks of treatment: a sudden worsening of vision or eye pain calls for immediate withdrawal;
There are metabolic consequences as well, worth knowing about in advance. The thiazide worsens glucose tolerance, so in diabetes the dose of insulin or tablets may need revising, and a latent diabetes can come to light; cholesterol and triglycerides rise; uric acid goes up and gout can flare. On the ramipril side a dry, persistent cough is characteristic, which passes after withdrawal and which it is important not to confuse with other causes of coughing. Dual blockade of the renin-angiotensin system — combining it with angiotensin II receptor blockers or with aliskiren — is not recommended because of the increased risk of hypotension, hyperkalaemia and renal failure, and in diabetic nephropathy such a combination is not used at all.
Interaction with other medicines
The interactions divide according to which of the two components produces them. From ramipril comes everything to do with potassium and the kidneys: potassium salts, heparin, potassium-sparing diuretics, tacrolimus and ciclosporin raise potassium, and it has to be measured regularly; the same applies to trimethoprim and co-trimoxazole. Non-steroidal anti-inflammatory drugs and acetylsalicylic acid weaken the blood-pressure-lowering effect and, together with an ACE inhibitor, increase the risk of worsening kidney function and rising potassium. Lithium salts are a story of their own: the ACE inhibitor reduces the elimination of lithium, the thiazide strengthens that effect, and combining the medicine with lithium is not recommended.
From hydrochlorothiazide other lines run. Corticosteroids, ACTH, amphotericin B, carbenoxolone, large amounts of liquorice preparations and long-used laxatives intensify the loss of potassium. Antidiabetic medicines can be weakened by the thiazide, so at the start of taking them together blood glucose is monitored with particular care.
Pregnancy and breastfeeding
In the first trimester the medicine is not recommended; in the second and third it is contraindicated. The epidemiological data on the teratogenicity of ACE inhibitors with exposure in the first trimester is not conclusive, but a small rise in risk cannot be ruled out. Women planning a pregnancy have their treatment changed to another antihypertensive with an established safety profile, and once a pregnancy is confirmed the medicine is stopped immediately.
From the second trimester, toxicity to the fetus is established: impaired kidney function, oligohydramnios, delayed ossification of the skull — and toxicity in the newborn in the form of renal failure, hypotension and hyperkalaemia. Hydrochlorothiazide adds risks of its own: it crosses the placenta, with prolonged exposure in the second and third trimesters it can cause fetoplacental ischaemia with delayed fetal growth, and with exposure around the time of birth rare cases of hypoglycaemia and thrombocytopenia in newborns have been described. Breastfeeding while taking the medicine is contraindicated: both substances pass into milk.
Adverse effects
The adverse reaction profile of the combination is made up of three sources. The first is the fall in blood pressure and the loss of fluid volume from increased urine output. The second is ramipril with its persistent dry cough. The third is hydrochlorothiazide, which worsens the metabolism of glucose, lipids and uric acid. Common are headache and dizziness, inadequate control of diabetes and reduced glucose tolerance, a rise in blood glucose and uric acid, worsening of gout, and raised cholesterol and triglycerides.
Uncommon reactions include a fall in the count of white cells and red cells and in haemoglobin, haemolytic anaemia and thrombocytopenia, hypokalaemia, increased thirst and reduced appetite. The most severe reactions the product information lists separately: angioedema and anaphylactic reactions, impaired kidney or liver function, pancreatitis, severe skin reactions and neutropenia extending to agranulocytosis. With unknown frequency, bone marrow failure, pancytopenia, hyponatraemia, hypomagnesaemia and hypercalcaemia, dehydration, confusion, and also cerebral ischaemia including stroke and transient ischaemic attack, and angle-closure glaucoma have been described.
Overdose
An overdose is made up of two pictures. From the ACE inhibitor — excessive dilation of the peripheral vessels with marked hypotension extending to shock, bradycardia, electrolyte disturbance, renal failure, cardiac rhythm disturbance, disturbed consciousness up to coma, convulsions of cerebral origin, pareses and paralytic ileus. From hydrochlorothiazide — acute urinary retention in predisposed patients, for example those with prostatic enlargement.
Treatment is symptomatic and supportive, with careful observation. Detoxification comes first — gastric lavage and adsorbents — along with restoring haemodynamic stability, giving α1-adrenergic receptor agonists or angiotensin II if needed. Ramiprilat is poorly removed by haemodialysis.
How to get a prescription for Ampril HD online
The combination tablet is the second step of treatment, not the first: the product information says plainly that it is prescribed to those whose blood pressure was held neither by ramipril nor by hydrochlorothiazide separately, and usually after the dose of each component has been chosen. What matters to the doctor is therefore not only the blood pressure figures but also what you have already taken and at what dose. 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 your treatment history: which blood pressure medicines you have taken, at what doses, what helped and what did not, and whether you are taking a diuretic now — the starting dose depends on that. Give recent test results with their dates: creatinine with clearance, potassium, sodium, glucose and uric acid. Report separately any angioedema in the past, including on other blood pressure medicines — that is an outright contraindication, as are severe kidney and liver impairment. Name your other conditions: diabetes, gout, glaucoma, sulfonamide allergy, liver disease. List your other medicines, above all lithium, potassium-sparing diuretics and potassium preparations, non-steroidal anti-inflammatory drugs, antidiabetic medicines and anything belonging to the angiotensin II receptor blockers or to aliskiren. Women of childbearing age need to state their method of contraception and their plans regarding pregnancy.
