Ramipril

Ramipril is a drug from the group of so-called angiotensin-conversion enzyme inhibitors (ACE inhibitors) with the molecular formula: C23H32N2O5 Its average half-life is about 15.0 h. ACE inhibitors inhibit the angiotensin converting enzyme inhibitor (ACE), a peptidase involved in the conversion of angiotensin-I to angiotensin-II. Angiotensin-II is an endogenous substance that binds to the receptors of the blood vessels and thus leads to vasoconstriction. The result is an increase in blood pressure. Ramipril prevents the formation of angiotensin-II and thus causes the blood vessels to relax and blood pressure to drop. In addition, it develops effects on the heart which lead to an economisation of the heart's work.

Ramipril is a so-called prodrug, which develops its effect by converting into the active form, ramiprilat. Ramiprilat is produced by esterification of ramiprilpril in the liver and binds with high affinity to ACE. Although ramipril is metabolized via the liver and kidney to both a glucuronate conjugate and a diketopiperazine derivative, much of the drug is excreted in urine as ramiprilate and as a glucuronate conjugate of ramiprilate. Elimination from the body is characterised by a relatively rapid initial phase with a half-life of 7 hours and a late phase with a half-life of about 120 hours.

Ramipril is used for:

non organ-related hypertension (essential hypertension)

mild to moderate heart failure (NYHA II to III) after acute (2 to 9 days old) heart attack,

Patients with non-diabetic glomerular nephropathy (creatinine clearance < 70 ml/min/1.73 m2 , protein excretion in urine > 1 g/day) - especially if arterial hypertension is present at the same time.

kidney diseases associated with diabetes (glomerular diabetic nephropathy with microalbuminuria or macroproteinemia)

following a heart attack (myocardial infarction) with consecutive heart failure

Patients with an increased cardiovascular risk, e.g. manifest coronary heart disease), diabetes mellitus with at least one additional risk factor, circulatory disorders of the limbs (peripheral arterial occlusive disease) or a history of stroke.

It is advisable to start the therapy with ramipril with small doses at first and then increase these over several weeks until the desired maintenance dose is reached. This is easy for the patient to handle, as the tablets are available in different concentrations (e.g. 2.5 mg, 5 mg, 7.5 mg and 10 mg, with break notches for a slight halving of the dose). Ramipril can be taken independently of meals as food intake does not affect bioavailability. However, it is important that the tablets are always taken at the same time of day to maintain a constant level of active ingredients in the body over time. After about four days of taking the tablets, this level has usually reached a stable level. Depending on the indication, different dosages are recommended:

• Treatment of hypertension: The usual initial dose is 1.25 mg or 2.5 mg once a day.
• Patients treated with diuretics: Dose adjustment necessary.
• For reduction of risk of heart attack or stroke: The usual initial dose is 2.5 mg once a day.
• Treatment to reduce the risk or slow the progression of renal dysfunction: Initial dose is either 1.25 mg or 2.5 mg once daily.
• Treatment of heart failure: The usual starting dose is 1.25 mg once daily.
• Treatment after heart attack: The usual starting dose is 1.25 mg once a day to 2.5 mg twice a day.

Ramipril shows the usual side effects of ACE inhibitors(see there).

Furthermore it was reported about:

• triggering of pityriasis rubra pilaris (Bell SL et al. 2014)
• Release of a Lichen planus pemphigoides (Ogg GS et al. 1997)
• Triggering of generalised pustular psoriasis (Thakor P et al. 2010)

Ramipril should not be combined with AT1 receptor antagonists or the direct renin inhibitor aliskiren, as this promotes the occurrence of potassium deficiency, a drop in blood pressure and a decrease in renal function.

Non-steroidal anti-inflammatory drugs such as ibuprofen, diclofenac, acetylsalicylic acid and naproxen can reduce the antihypertensive effect of Ramipril. A blood pressure control should therefore be carried out regularly when administered at the same time.

Spironolactone, amiloride and triamterene in combination with ramipril can lead to an increase in potassium levels.

If ramipril is combined with immunosuppressants, allopurinol, glucocorticoids or procainamide, the risk of blood count changes increases. If these combinations are unavoidable, regular blood count checks should be carried out.

As ramipril can promote the occurrence of allergic reactions, hyposensitisation (immunotherapy) should not be carried out while taking it.

Ramipril may delay the excretion of lithium (dose adjustment)

Allergies to ramipril, another ACE inhibitor

for angioneurotic edema in the medical history

Dialysis Patients

Renal artery stenosis

during the last 6 months of pregnancy

with simultaneous intake of aliskiren

1. Bell SL et al (2014) Consider triggers for pityriasis rubra pilaris. Clin Exp Dermatol 39:403-405.
2. Ogg GS et al (1997) Ramipril-associated lichen planus pemphigoides. Br J Dermatol 136:412-414.
3. Thakor P et al (2010) Ramipril-induced generalized pustular psoriasis: case report and literature review. On J Ther 17:92-95.