Amlessa: composition and dosage form
One tablet contains 4 mg or 8 mg of perindopril with tert-butylamine, corresponding to 3.34 mg or 6.68 mg of perindopril, and 5 mg or 10 mg of amlodipine as the besilate. There are therefore four combinations, and the choice between them is made not by the severity of the hypertension but by which doses of the two separate medicines the patient is already taking.
One tablet is taken a day, preferably in the morning, before a meal. That is the only regimen: this medicine has no other dosing and can have none, because the tablet is not designed for adjusting the dose.
How Amlessa works
Perindopril inhibits the enzyme that converts angiotensin I into the vasoconstrictor angiotensin II; it acts through its active metabolite perindoprilat, while the other metabolites do not inhibit the enzyme. The same enzyme breaks down bradykinin, which dilates vessels, so blocking it not only lowers the level of angiotensin II and the secretion of aldosterone but also intensifies the work of the kallikrein-kinin system. Part of the effect is attributed to that side consequence — and along with it part of the adverse reactions, the cough above all.
Amlodipine works in a completely different way: it is a calcium antagonist, it inhibits the entry of calcium ions into the cells of the heart muscle and the vessels, and it lowers blood pressure by relaxing the smooth muscle of the vessel wall directly. The two substances thus reach the same goal from different sides — one switches off the hormonal signal, the other the mechanics of contraction. That is what the idea of the combination rests on: the effects add up and the points of action do not overlap.
Indications
The wording of the indication is unusual here and is worth reading in full: the medicine is used in essential arterial hypertension and/or stable coronary artery disease as substitution therapy in patients whose symptoms are controlled by taking perindopril and amlodipine together at the same doses as those contained in the tablet.
That is, the medicine is not prescribed to someone whose treatment is only beginning. It is prescribed to someone whose treatment is already chosen and working, and the only thing that changes is the number of tablets. There is neither a new illness nor a new dose in that switch.
Method of administration and dosage
The dosage section is short for this medicine, because there is nothing here to dose. The product information says so plainly: the combination product is not suitable for initial treatment, and if the dose needs changing it should be changed through the doses of the individual components. This is to be taken literally — the tablet has no titration step of its own. Any correction means a temporary return to the two medicines, adjusting on them and, if the new pairing coincides with one of the four available combinations, moving back to a single tablet.
The organ limits follow from the same thing. The medicine may be used at a creatinine clearance of 60 ml/min and above, and below 60 it is unsuitable — not because it is dangerous but because separate dose setting is needed there: in older people and in renal impairment the elimination of perindopril is reduced, so the usual medical monitoring includes creatinine and potassium. The concentration of amlodipine, by contrast, does not depend on the state of the kidneys. In hepatic impairment no dosing scheme has been established at all, while amlodipine's half-life is prolonged and its exposure higher — hence the requirement for caution. Children and adolescents are not prescribed the medicine: the efficacy and tolerance of perindopril have not been established in them either separately or in combination with amlodipine.
Contraindications
The most convenient way through them is by source, because each component brings its own set, and all of them pass to the combination in full.
| Prohibition | Component | Why this one |
| Intolerance of the class | perindopril | the ban extends to any ACE inhibitor and not only to the substance itself, so swapping within the group resolves nothing |
| Angioedema in the past | perindopril | any such episode counts: hereditary, without apparent cause, or arising on an earlier ACE inhibitor; recurrence is likely and can close off the airway |
| Pregnancy from the second trimester | perindopril | a damaging effect on the fetal kidneys and on the condition of the newborn is confirmed |
| Very low blood pressure and shock | amlodipine | cardiogenic shock belongs here too; the medicine dilates vessels, that is, it adds another fall to an already low blood pressure |
| Obstruction to left ventricular outflow | amlodipine | the typical example is severe aortic stenosis: the heart cannot raise its output in response to the widening of the vascular bed |
| Unstable state after a heart attack | amlodipine | this means heart failure that is not yet holding the circulation; extra vasodilation is poorly tolerated at such a moment |
To this are added hypersensitivity to dihydropyridines and to any excipient, and a prohibition belonging to the combination itself: concurrent use with medicines containing aliskiren is contraindicated in patients with diabetes or with impaired kidney function where the glomerular filtration rate is below 60 ml/min/1.73 m².
Special warnings and precautions
Part of the warnings concerns situations where blood pressure may fall too far: in coronary artery disease and in cerebrovascular disease an excessive fall can end in a heart attack or a stroke, so in such cases blood pressure, kidney function and potassium are watched closely. Before major surgery or anaesthesia with agents that lower blood pressure, treatment is stopped a day beforehand.
- a syndrome has been described that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis: if jaundice appears or liver enzymes rise substantially, the ACE inhibitor is stopped at once and medical help is sought;
- in patients with diabetes treated with tablets or insulin, blood glucose is monitored carefully throughout the first month of taking the ACE inhibitor;
- in low-density lipoprotein apheresis with dextran sulfate, life-threatening anaphylactoid reactions have been described — temporary withdrawal of the medicine before each session prevents them;
- the same applies to desensitisation treatment, for example for allergy to hymenoptera venom: with the medicine withdrawn for the course the reactions did not occur, and on accidental intake they returned;
- in people taking ACE inhibitors, neutropenia, agranulocytosis, thrombocytopenia and anaemia have been described; with normal kidney function and no other risk factors neutropenia is rare, but in collagen diseases and on immunosuppressants particular caution is needed;
- a dry, persistent cough that passes after withdrawal is a typical reaction to an ACE inhibitor, and it is worth keeping in mind when the causes of a cough are being worked through;
Hepatic impairment stands apart. There amlodipine's half-life lengthens, the area under the curve grows, and no dosing recommendations exist, so in such cases amlodipine is begun at the smallest dose and taken forward carefully. For the combination tablet this means something simple: the smallest dose cannot be chosen inside it, so with appreciable liver damage it is more sensible to stay on the two separate medicines.
Interaction with other medicines
On the amlodipine side the main thing is cytochrome CYP3A4, which processes it. Strong and moderate inhibitors of that enzyme — protease inhibitors, antifungal azoles, macrolides such as erythromycin and clarithromycin, verapamil and diltiazem — raise its concentration noticeably and with it the risk of an excessive fall in blood pressure; inducers, conversely, call for the dose to be reviewed. Grapefruit and grapefruit juice are not recommended for the same reason. There is a reverse influence too: amlodipine 10 mg together with simvastatin 80 mg raised exposure to simvastatin by 77%, so when they are taken together the simvastatin dose is limited to 20 mg a day. The concentration of tacrolimus also rises on amlodipine and has to be monitored.
On the perindopril side the lines are different and familiar across the whole class. Lithium: a reversible rise in its concentration with serious neurotoxic effect has been described, and concurrent use is not recommended. Non-steroidal anti-inflammatory drugs, including acetylsalicylic acid at doses from 3 g a day, weaken the blood-pressure-lowering effect and raise the risk of worsening kidney function. Everything that raises potassium calls for it to be measured often. And estramustine increases the likelihood of angioedema.
Pregnancy and breastfeeding
In the second and third trimesters the medicine is contraindicated; in the first it is not recommended. The reason is the perindopril: exposure to ACE inhibitors from the second trimester produces toxicity to the fetus — impaired kidney function, oligohydramnios, delayed ossification of the skull — and to the newborn in the form of renal failure, hypotension and hyperkalaemia.
Women planning a pregnancy have their treatment changed in advance to another antihypertensive with an established safety profile; once a pregnancy is confirmed the medicine is stopped immediately. Breastfeeding while taking it is not recommended. It is worth remembering a feature of this dosage form here: withdrawing one component while keeping the other is impossible in a combination tablet, so both planning a pregnancy and becoming pregnant mean changing the whole regimen.
Adverse effects
The reactions divide conveniently by component, because they differ. Amlodipine is recognised by its vascular manifestations: drowsiness, dizziness and headache are common, especially at the start of treatment, as are palpitations, sudden flushing of the face, breathlessness, abdominal pain, nausea, dyspepsia and a change in bowel habit. Uncommon are insomnia, mood changes, depression, tremor, reduced sensation and paraesthesia, fainting, disturbances of heart rhythm, a fall in blood pressure, inflammation of the nasal mucosa and cough, vomiting and dry mouth.
Perindopril adds its own: cough, electrolyte disturbance, an effect on kidney function. The rare and very rare reactions of both components deserve attention of their own, because they do not look like the side effects of a blood pressure tablet: from the blood these are leucopenia, neutropenia and thrombocytopenia; from metabolism, hyperglycaemia; from the nervous system, confusion, peripheral neuropathy and extrapyramidal manifestations; from the heart, an episode of angina and, very rarely, a myocardial infarction, probably secondary to an excessive fall in blood pressure in high-risk patients. Vasculitis has been described as well.
Overdose
There is no data on overdose of the combination itself in humans, so the picture is put together from two parts. An overdose of amlodipine produces excessive dilation of the peripheral vessels with marked and probably prolonged hypotension; such a state is managed in a cardiac intensive care unit. A vasoconstrictor helps if there are no contraindications to it, and intravenous calcium gluconate can reverse the calcium channel blockade. Amlodipine is not removed by dialysis.
An overdose of perindopril shows itself as hypotension, shock, electrolyte disturbance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, restlessness and cough. Treatment begins with an intravenous infusion of 0.9% sodium chloride solution; where there is hypotension the patient is placed in the anti-shock position; where possible, intravenous angiotensin II or catecholamines are considered, and for resistant bradycardia a pacemaker is fitted. Unlike amlodipine, perindopril is removed by haemodialysis. Throughout, vital signs, electrolytes and creatinine are monitored.
How to get a prescription for Amlessa online
This tablet treats nothing new — it replaces two tablets with one in someone who already takes perindopril and amlodipine and whose blood pressure holds on them. What the doctor mainly needs is therefore not your symptoms but the exact names and doses of what you take now: the dose in the combination must match yours, or the medicine does not fit. 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 current regimen: how many milligrams of perindopril and how many of amlodipine you take, for how long, and whether your blood pressure holds on those doses — attach several recent readings. Then the kidneys: creatinine with clearance and the date of the test are needed, because below 60 ml/min the combination tablet is not used and treatment stays separate. Report liver disease: there the amlodipine dose needs an adjustment this form does not allow. State separately any angioedema in the past, including on other blood pressure medicines, severe aortic stenosis and a previous heart attack. List your other medicines, above all antifungals, macrolides, HIV medicines, verapamil and diltiazem, simvastatin, tacrolimus, lithium, painkillers from the non-steroidal anti-inflammatory group, and anything containing aliskiren. Women of childbearing age need to state their method of contraception and their plans regarding pregnancy.
