Teldipin: composition and form
One tablet contains 40 mg or 80 mg of telmisartan and 5 mg or 10 mg of amlodipine as the besylate. The four dose combinations are not there for variety: the medicine replaces two drugs the patient already takes separately, and the tablet is chosen so that the doses of both substances match the previous ones.
It can be taken regardless of meals, and the tablet is washed down with water. The composition includes lactose and sorbitol, and the 80 mg + 5 mg and 80 mg + 10 mg tablets contain 293.08 mg of sorbitol each, which matters in hereditary fructose intolerance. There is less than 1 mmol of sodium per tablet, so the medicine counts as "sodium-free".
How Teldipin works
Telmisartan is a selective antagonist of the angiotensin II receptor of the AT1 subtype, active when taken by mouth. Thanks to a very high affinity it displaces angiotensin II from binding to that receptor and shows not even partial agonist activity; the binding is long-lasting, and it has no affinity for other receptors. Telmisartan lowers the concentration of aldosterone but does not suppress plasma renin activity and does not block ion channels. What it does not do stands apart: it does not inhibit angiotensin-converting enzyme, the same kininase II that breaks down bradykinin — so the adverse effects tied to bradykinin are not to be expected. A dose of 80 mg almost completely suppresses the rise in blood pressure caused by angiotensin II, the effect lasts the full 24 hours and remains measurable up to 48.
The other half of the combination, amlodipine, belongs to the calcium antagonists, that is the calcium channel blockers; the product information calls it that outright, and in overdose intravenous calcium gluconate is given to reverse the blockade of those channels. The consequence of pairing them is that blood pressure falls by two independent routes — through the angiotensin receptor and through the vessel wall — and the effects add up.
Indications
The indication is worded unusually narrowly: the medicine is used as substitution therapy for essential arterial hypertension in patients whose blood pressure is already adequately controlled by taking telmisartan and amlodipine together at the same doses as in the combined product. It is therefore not a means of starting treatment but a way of reducing two tablets to one in someone for whom both already work.
Hence the rule the product information repeats under dosing as well: the combined product is not used at the start of treatment. Blood pressure is first brought under control with two separate medicines, and only then is the patient moved to the ready-made combination. The safety and efficacy of the combination in children and adolescents under 18 have not been established.
Administration and dosage
The recommended dose is 1 tablet a day, and it is determined not by the severity of the hypertension but by the doses of the individual substances the patient was taking at the moment of switching. The maximum daily dose of amlodipine is 10 mg and of telmisartan 80 mg. In older patients no dose adjustment is needed, but it should be raised with caution.
The organ-based limits are asymmetric. In mild and moderate renal impairment the dose does not change; on severe impairment and on dialysis there is little data — all the more so because neither amlodipine nor telmisartan is removed by dialysis. With the liver it is stricter: in severe impairment the medicine is contraindicated, and for mild and moderate impairment there are no dosing recommendations at all, so it is used with caution and with a ceiling — the telmisartan dose here must not exceed 40 mg once a day. The reason lies in the routes of elimination: telmisartan is excreted mainly in the bile, and with a diseased liver the half-life of amlodipine lengthens and the area under the curve grows.
Contraindications
The list is short, and half of it concerns not the heart but the flow of bile and the state of the liver: obstruction of the biliary tract and severe hepatic impairment. The logic is the same as under dosing: telmisartan is excreted in the bile, and with cholestasis its hepatic clearance falls. Hypersensitivity to the active substances or excipients belongs here too.
The other half is haemodynamic. The medicine is not given in severe hypotension or shock, cardiogenic shock included, in obstruction of the outflow from the left ventricle — a high-grade aortic stenosis, for instance — or in haemodynamically unstable heart failure after an acute infarction. Listed separately are pregnancy in the second and third trimesters, and aliskiren: combining them is contraindicated in diabetes or with a glomerular filtration rate below 60 ml/min/1.73 m².
Special warnings and precautions
The first theme is dual blockade of the renin-angiotensin-aldosterone system. Using angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren together raises the risk of hypotension, hyperkalaemia and renal failure, so it is not recommended; if it is unavoidable, it is done under a specialist's supervision, and in diabetic nephropathy combining an enzyme inhibitor with a receptor antagonist is not allowed at all. The second theme is potassium. Hyperkalaemia in older patients, in renal failure and in diabetes may end in death; the main risk factors are diabetes, kidney disease and age above 70, and potassium is raised by potassium-containing salt substitutes, potassium-sparing diuretics, enzyme inhibitors, non-steroidal anti-inflammatory drugs, heparin, ciclosporin, tacrolimus and trimethoprim. Dangerous too are dehydration, decompensation of heart failure, metabolic acidosis and cell lysis in rhabdomyolysis or trauma.
The third theme is the situations in which the fall in blood pressure turns out to be excessive. With a reduced intravascular volume or a low sodium — from intensive diuretic treatment, a low-salt diet, diarrhoea or vomiting — symptomatic hypotension is possible, particularly after the first dose, and these disturbances are corrected before treatment begins. In patients whose vascular tone and renal function depend on the activity of this system — severe heart failure or renal artery stenosis — acute hypotension, hyperazotaemia, oliguria and rarely acute renal failure have been described. Caution is needed with aortic or mitral valve stenosis, with hypertrophic cardiomyopathy and in heart failure: in a long placebo-controlled study in patients of NYHA class III-IV, pulmonary oedema occurred more often in the amlodipine group than on placebo. In primary hyperaldosteronism the medicine is not recommended, because such patients usually do not respond to suppression of this system, and in patients of black ethnicity telmisartan lowers blood pressure noticeably less. Hypoglycaemia is possible: blood glucose is monitored, and the insulin dose sometimes has to be changed.
Interactions with other medicines
On the telmisartan side the main threads are potassium, lithium and the kidneys. Potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes can raise serum potassium considerably, and that is the riskiest of the combinations; with enzyme inhibitors the risk is lower, but the precautions still hold. The lithium concentration rises transiently along with its toxicity, so it is checked often. Non-steroidal anti-inflammatory drugs weaken the antihypertensive effect and, in dehydrated and older patients with impaired renal function, can lead to acute, usually reversible renal failure. Digoxin deserves separate attention: the median of its peak concentration rose by 49% and of its trough by 20%, so when telmisartan is started, adjusted or stopped, digoxin is checked. Giving ramipril alongside increased the area under the curve of ramipril and ramiprilat up to 2.5-fold.
On the amlodipine side everything is decided by the CYP3A4 isoenzyme. Its strong and moderate inhibitors — protease inhibitors, azole antifungals, macrolides, verapamil, diltiazem — markedly increase exposure to amlodipine and the risk of hypotension, especially in older people. Inducers, above all rifampicin and St John's wort, conversely change its concentration, so blood pressure is monitored both during such treatment and after it. Grapefruit and grapefruit juice should not be combined with amlodipine. Amlodipine itself is a weak CYP3A inhibitor: it raises the concentration of tacrolimus and of mTOR inhibitors and, after a kidney transplant, lifts the trough concentration of ciclosporin by an average of 0-40%. With simvastatin the figure is exact: 10 mg of amlodipine increased its exposure by 77%, so the simvastatin dose is reduced to 20 mg a day. On atorvastatin, digoxin and warfarin amlodipine had no effect. And one more ban: in people susceptible to malignant hyperthermia calcium antagonists are avoided.
Pregnancy and breastfeeding
In the first trimester the medicine is not recommended, and in the second and third it is contraindicated — because of the telmisartan. There are no data on its use in pregnant women, and animal studies showed reproductive toxicity. Epidemiological data on the teratogenicity of enzyme inhibitors in the first trimester are inconclusive, but a small increase in risk cannot be ruled out, and a similar risk may apply to receptor antagonists. Women planning a pregnancy are given a different antihypertensive, and once pregnancy is confirmed the medicine is withdrawn at once. Use in the second and third trimesters is toxic to the fetus — impaired renal function, oligohydramnios, delayed skull ossification — and to the newborn: renal failure, hypotension, hyperkalaemia. If exposure fell in the second trimester or later, an ultrasound of the fetal skull and renal function is performed.
Less is known about amlodipine: the safety of its use in human pregnancy has not been established, and in animals high doses were toxic to reproduction. Breastfeeding on this medicine is not recommended — medicines with a better safety profile are preferable, especially where the child is a newborn or premature. On telmisartan during lactation there is no information, while amlodipine does pass into milk: the share of the dose the infant receives lies between 3 and 7%, with a maximum of 15%. On fertility: preclinical studies of telmisartan showed no effect, while with calcium antagonists reversible biochemical changes in the heads of sperm have been described.
Adverse reactions
About telmisartan the product information speaks first of the rare but serious: anaphylactic reaction and angioedema, both at a frequency of between 1 case in 10 000 and 1 in 1000, and acute renal failure. In controlled trials the overall frequency of adverse reactions was comparable with placebo: 41.4% against 43.9%. It did not depend on the dose and was not linked to sex, age or race; the safety profile was confirmed by three long-term studies covering 21 642 patients for up to six years.
With amlodipine the picture is different: there are many common reactions but few serious ones among them. Most often reported are drowsiness, dizziness, headache, palpitations, flushing of the face, abdominal pain, nausea, ankle swelling and fatigue — with oedema classed as very common. Commonly there are also visual disturbances, breathlessness, altered bowel habit, dyspepsia and muscle cramps. Uncommonly: depression, insomnia, tremor, taste disturbance, fainting, bradycardia and rhythm disturbances up to ventricular tachycardia, hypotension, rhinitis, cough, vomiting, dry mouth, urticaria, hair loss, itching, muscle and joint pain, frequent urination, impotence and gynaecomastia. Very rarely: thrombocytopenia, leucopenia, hyperglycaemia, peripheral neuropathy, myocardial infarction, vasculitis, pancreatitis, gum hyperplasia, hepatitis, jaundice and severe skin reactions including Stevens-Johnson syndrome and angioedema.
Overdose
There is little data on overdose in humans. For telmisartan the most significant features are hypotension and tachycardia; bradycardia, dizziness, a rise in creatinine and acute renal failure have also been described. A substantial overdose of amlodipine causes excessive peripheral vasodilatation and reflex tachycardia; prolonged systemic hypotension up to fatal shock has been reported. Non-cardiogenic pulmonary oedema was recorded rarely — with a delay of 24 to 48 hours and requiring respiratory support; early resuscitation with fluid overload may predispose to it.
What is done depends on how much time has passed and how severe the symptoms are. Inducing vomiting and gastric lavage are recommended, activated charcoal may help with both substances, and electrolytes and creatinine are checked often. For hypotension the patient is laid on their back and water and electrolyte losses are replaced quickly; a vasoconstrictor restores vascular tone, and intravenous calcium gluconate reverses the effects of calcium channel blockade. Haemodialysis is useless for both components: amlodipine binds firmly to plasma proteins, and telmisartan is not removed by dialysis.
How to get a prescription for Teldipin online
This medicine has a particular prescribing scenario: it is not for starting treatment but for continuing what has already been settled with two tablets. So the doctor's first question is what exactly you take now and at what doses. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will dispense the tablets.
In the questionnaire name both medicines with their doses — telmisartan 40 or 80 mg and amlodipine 5 or 10 mg — and give your usual blood pressure readings on that regimen. Report liver and biliary disease, kidney disease, dialysis or a kidney transplant, renal artery stenosis, diabetes, heart failure and any past infarction, pregnancy and breastfeeding. List the medicines separately: potassium preparations and potassium-sparing diuretics, ACE inhibitors and aliskiren, lithium, non-steroidal painkillers, digoxin, simvastatin, ciclosporin, antifungals and macrolides. And mention hereditary fructose intolerance, because of the sorbitol in the tablet.
