Felopress 5/5


Pharmaceutical Form
film-coated tablets

Felodipine  5mg
Ramipril     5mg

Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.
Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril. It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.

Felodipine :

The bioavailability is approximately 15% and is not influenced by concomitant intake of food. The peak plasma concentration is reached after 3 to 5 hours. Binding to plasma proteins is more than 99%. The distribution volume at steady state is 10 l/kg. The half-life for felodipine in the elimination phase is approximately 25 hours and steady state is reached after 5 days. There is no risk of accumulation during long-term treatment. Mean clearance is 1200 ml/min. Decreased clearance in older people leads to higher plasma concentrations of felodipine.

Age only partly explains the interindividual variation in plasma concentration, however.

Felodipine is metabolised in the liver and all identified metabolites are devoid of vasodilating properties. Approximately 70% of a given dose is excreted as metabolites in the urine and about 10% with the faeces. Less than 0.5% of the dose is excreted unchanged in the urine. Impaired renal function does not influence the plasma concentration of felodipine.


The pharmacokinetic parameters of ramiprilat are calculated after intravenous administration of ramipril.

Ramipril is metabolised in the liver, and aside from the active metabolite ramiprilat, pharmacologically inactive metabolites have been identified. The formation of active ramiprilat may be decreased in patients with impaired liver function. The metabolites are excreted mainly via the kidneys. The bioavailability of ramiprilat is approximately 28% after oral administration of ramipril. After intravenous administration of 2.5 mg ramipril, approximately 53% of the dose is converted to ramiprilat. A maximum serum concentration of ramiprilat is achieved after 2 to 4 hours. Absorption and bioavailability are not influenced by concomitant intake of food.

The protein binding of ramiprilat is approximately 55%. The distribution volume is approximately 500 litres. The effective half-life, after repeated daily dosage of 5 to 10 mg, is 13 to 17 hours. Steady-state is achieved after approximately 4 days. Renal clearance is 70 to 100 ml/min and total clearance is approximately 380 ml/min. Impaired renal function delays the elimination of ramiprilat and excretion in the urine is reduced.

Characteristics of the combination product

In Felopress  the pharmacokinetics of ramipril, ramiprilat and felodipine are essentially unaltered compared to the mono products, felodipine  tablets and ramipril tablets.

Felodipine does not influence the ACE inhibition caused by ramiprilat. The fixed combination tablets are thus regarded as bioequivalent to the free combination.

Felopress used for treatment of essential hypertension.
Felopress fixed dose combination is indicated in patients whose blood pressure is not adequately controlled on felodipine or ramipril alone.

Use in adults, including older people:

One tablet Felopress once daily.

should be swallowed whole with a sufficient amount of liquid. The tablets must not be divided, crushed or chewed. The tablet can be administered without food or following a light meal not rich in fat or carbohydrate.