MODURETIC ® is a drug based on amiloride hydrochloride + hydrochlorothiazide
THERAPEUTIC GROUP: diuretics / thiazide diuretics in combination with potassium sparing
Indications MODURETIC ® Amiloride + hydrochlorothiazide
MODURETIC ® is used in the treatment of edematous situations due to heart and liver diseases.
MODURETIC ® is also used successfully in antihypertensive therapy.
Mechanism of action MODURETIC ® Amiloride + hydrochlorothiazide
MODURETIC ® taken orally, has a good absorption profile, with a maximum plasma peak of both active ingredients (amiloride and hydrochlorothiazide) between the fourth and sixth hour. The beginning of the diuretic action is observed already around the second hour, when the biological effect of the two active principles begins to take place. The first, belonging to the category of thiazide diuretics, guarantees an inhibition of the sodium / chlorine cotransporter on the apical surface. of the cells of the distal convoluted tubule of the nephron, increasing the urinary excretion of water, sodium and chlorine (and subsequently also of potassium and magnesium), with an important diuretic effect.
Amiloride, on the other hand, is able to inhibit the ATP dependent sodium / potassium transporter expressed on the surface of the cells of the distal tubule, guaranteeing at the same time a reduction in sodium reabsorption and an inhibition of active potassium excretion.
This combination is very important, not only to enhance the modest diuretic effects of amiloride, but above all to combine the marked saluretic and diuretic action of hydrochlorothiazide with a sparing action on potassium excretion. In fact, it is known that most of the side effects related to the intake of diuretics are linked to the symptoms associated with hypokalaemia, which is decidedly reduced thanks to the contextual presence of amiloride.
The effect of the drug is prolonged on average between 9 and 12 hours, following which the unchanged urinary excretion of both active ingredients of MODURETIC ® begins.
Studies carried out and clinical efficacy
1. HYDROCHLOROTHIAZIDE / AMYLORIDE IN PRESSURE CONTROL
Clin Exp Hypertens. 2008 Oct; 30: 553-64.
Blood pressure-lowering efficacy of amiloride versus enalapril as add-on drugs in patients with uncontrolled blood pressure receiving hydrochlorothiazide.
Guerrero P, Fuchs FD, Moreira LM, Martins VM, Bertoluci C, Fuchs SC, Gus M.
The concomitant administration of amiloride and hydrochlorothiazide was tested in 82 patients with hypertension, with blood pressure levels above 140/90 mmHg. The data reported in this study show how the addition of between 2.5 and 5 mg / day of amiloride to 25 mg of hydrochlorothiazide, guaranteed a further drop in blood pressure values of about 2mmHg. Despite the positivity of this combination, the combination of hydrochlorothiazide with enalapril appears to be even more effective.
2. AMYLORIDE / HYDROCHLOROTHIAZIDE AND FIBRINOLYSIS.
Anadolu Kardiyol Derg. 2006 Jun; 6: 143-7.
The effects of thiazide and thiazide-potassium sparing diuretics on fibrinolytic system parameters.
Kaşifoğlu T, Yalçin AU.
This study, conducted on 28 hypertensive patients, shows how the therapy with hydrochlorothiazide at 50 mg + amiloride at 5 mg, although it can guarantee a significant decrease in blood pressure levels, also does not guarantee the reduction of fibrinolytic effects (potentially dangerous for the hypertensive patient), such as instead observed in the combination hydrochlorothiazide - spironolactone.
3. AMYLORIDE / HYDROCHLOROTHIAZIDE AND DOPING
acta Med Scand. 1975 May; 197: 415-9.
The effect of hydrochlorothiazide and amiloride administered together on muscle electrolytes in normal subjects.
Bergström J.
Study dated 1975, which shows how the administration of amiloride and hydrochlorothiazide at high doses (15 mg - 150 mg / day), therefore potentially dangerous, in 10 normal subjects, guaranteed a reduction in body weight of about 1.9 kg, while preserving levels muscle intracellular calcium and magnesium, and causing an increase in blood pH. Despite this effect, it is necessary to remember that the use, indeed the abuse of the drug in normal subjects, is potentially dangerous, especially when used in high doses, as well as illegal.
Method of use and dosage
MODURETIC ® tablets of 5mg of amiloride + 50mg of hydrochlorothiazide: it is generally recommended to take one or 2 tablets a day, taking into account that the maximum dose allowed should never exceed 4 tablets per day. It should be remembered that taking of MODURETIC ® must be carried out under strict medical supervision, and that the dosage may vary according to the physio-pathological conditions of the patient and the severity of the pathology.
Furthermore, in the case of prolonged therapies, it is recommended to use lower maintenance dosages, which however allow to obtain an adequate diuresis.
IN ANY CASE, BEFORE TAKING MODURETIC ® Amiloride + hydrochlorothiazide - YOU MUST BE PRESCRIBED AND CHECKED BY YOUR DOCTOR.
MODURETIC ® Amiloride + hydrochlorothiazide warnings
Before the administration of MODURETIC ® the plasma levels of electrolytes should be carefully evaluated in order to avoid hydro-saline decompensation potentially dangerous for the patient's health. These checks must be even more stringent in subjects with a manifest risk of alteration of the electrolyte balance, suffering from cirrhosis, cardiopulmonary diseases, advanced age or hospitalized. In this case, frequent checks not only serve to detect any episodes of hyponatremia, but also to avoid the possibility of hyperkalaemia, particularly evident in diabetic patients.
The use of thiazide diuretics exposes the diabetic patient to potential hyperglycaemia, for which an adjustment of hypoglycemic therapy may be necessary, while gouty episodes may become more frequent in hyperuremic patients.
MODURETIC ® could cause an increase in plasma calcium levels, altering the results of any tests on parathyroid function.
Although there are no known direct effects of the drug in altering the normal ability to drive and use machines, it must be considered that electrolyte imbalances, potentially verifiable in case of MODURETIC ® could cause a decrease in the patient's normal perceptive and reactive abilities. .
PREGNANCY AND BREASTFEEDING
The use of MODURETIC ® during pregnancy is not recommended. In fact it is known that amiloride can easily cross the placental barrier and reach the fetal blood, resulting in fetal jaundice or typical side effects of diuretics. Furthermore, the haemodynamic action of diuretics on maternal blood could lead to an impairment of the normal haemodynamic supply of organs important for fetal development, compromising growth.
Since both active ingredients of MODURETIC ® are found intact in breast milk, it is advisable to stop breastfeeding during drug therapy.
Interactions
The simultaneous administration of other diuretics and antihypertensive agents could increase the hypotensive effect of MODURETIC ® with consequent appearance of the relative side effects.
Furthermore, the effects of MODURETIC ® could be exasperated by the concomitant administration of alcohol, barbiturates and narcotics of various kinds.
The toxicity of lithium and the biological action of curare derivatives could increase if administered concomitantly with hydrochlorothiazide and amiloride, while the risk of an electrolyte alteration could increase in case of concomitant intake of corticosteroids and ACTH.
Contraindications MODURETIC ® Amiloride + hydrochlorothiazide
MODURETIC ® should not be taken in case of hyperkalaemia or concomitant administration of other potassium-sparing diuretics, in case of reduced or impaired hepatic and renal function with anuria, in diabetic patients with relative nephropathy, hyperuremic or with high plasma levels of nitrogen and creatinine .
Of course, the drug is strictly not recommended in case of hypersensitivity to one of its components.
Undesirable Effects - Side Effects
The synergy between amiloride and hydrochlorothiazide, present in MODURETIC ® seems to be well tolerated by patients undergoing drug therapy, with the absence of clinically relevant side effects and characterized mostly by gastro-intestinal effects such as thirst, nausea, vomiting, loss of appetite, accompanied in severe cases by dizziness, drowsiness, nervousness, general malaise.
In patients suffering from hyperuricemia it is possible to find an increase in gouty episodes, probably due to the phenomenon of haemoconcentration that accompanies therapy with MODURETIC ®, while in diabetic patients the episodes of hyperglycaemia are quite frequent for which an adjustment of the therapy is often made. hypoglycemic.
Naturally, the typical side effects of the drug are added all those due to hypersensitivity to one of its components, which include dermatological phenomena such as skin rashes and urticaria, systemic and respiratory.
Note
MODURETIC ® can only be sold under medical prescription.
The use of MODURETIC ® should always take place after consulting your doctor.
The indiscriminate use of MODURETIC ® among athletes and non-athletes, to search for the loss of a few kilos, exposes the body to serious side effects. Furthermore, it is always advisable to reiterate that weight loss is dictated by the elimination of liquids and salts and not by a real slimming effect, intended as a loss of fat mass.
Therefore it is classified among the DOPING substances.
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