OLMEHEART 40

Indications

• Hypertension
• Heart failure
• Chronic kidney disease

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Medoxomil is converted to its active metabolite, which selectively blocks the angiotensin II receptor subtype 1 (AT1). This inhibition prevents angiotensin II from exerting its vasoconstrictor effects, leading to vasodilation and a reduction in blood pressure. By blocking the effects of angiotensin II, medoxomil also reduces aldosterone secretion, promoting natriuresis and diuresis.

Pharmacodynamics

The active form of medoxomil exhibits dose-dependent antihypertensive effects, contributing to improved cardiovascular outcomes. It has been shown to reduce systemic vascular resistance and improve endothelial function. The onset of action typically occurs within a few hours of administration, with peak effects seen within 24 hours.

Pharmacokinetics

Medoxomil is well absorbed after oral administration and undergoes extensive first-pass metabolism to its active form. The half-life of the active metabolite allows for once-daily dosing. It is primarily excreted via the kidneys, with both renal and hepatic pathways involved in its elimination.

Contra-indications

• Hypersensitivity to medoxomil or any component of the formulation
• Severe renal impairment
• Pregnancy

Adverse effects

• Headache
• Dizziness
• Fatigue
• Hypotension
• Nausea
• Diarrhea
• Cough

Interactions

• Caution with concomitant use of other antihypertensive agents
• Possible interaction with diuretics leading to additive hypotensive effects
• Use with caution in patients taking medications that affect renal function

Precautions

• Monitor renal function prior to and during treatment
• Use with caution in patients with a history of angioedema
• Assess risk of hypotension in patients with volume depletion

Pregnancy

Medoxomil is contraindicated in pregnancy due to potential risks to the fetus. Consult healthcare providers for alternatives.

Breast-feeding

It is unknown whether medoxomil is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct light. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Indications

• Hypertension
• Heart failure
• Chronic kidney disease with hypertension

Dosage

Children: For children aged 6 years and older, the dosage is based on body weight and should be determined according to the BNF for Children. Generally, the initial dose is 0.3 mg/kg once daily, not exceeding 20 mg.

Adults: The typical adult dose for hypertension is 20 mg once daily, which may be increased to a maximum of 40 mg once daily if necessary.

Mechanism of action

Olmesartan selectively binds to the angiotensin receptor 1 (AT1), inhibiting the action of angiotensin II, a potent vasoconstrictor. By blocking angiotensin II from binding to its receptor, olmesartan prevents vasoconstriction, reduces aldosterone secretion, and promotes renal sodium excretion, leading to lower blood pressure and reduced cardiac workload. Its action is independent of the synthesis pathways of angiotensin II.

Pharmacodynamics

The pharmacodynamic effects of olmesartan include reduced blood pressure, decreased aldosterone levels, and increased sodium excretion. In patients with volume or salt depletion, there may be a risk of symptomatic hypotension upon initiation of therapy. The drug also alters renal function due to its effects on the renin-angiotensin-aldosterone system (RAAS), and caution is advised in patients with renal impairment.

Pharmacokinetics

Olmesartan is absorbed well orally, with peak plasma concentrations occurring within 1 to 2 hours after administration. It has a half-life of approximately 13 hours, allowing for once-daily dosing. The drug is primarily eliminated through the bile and feces, with minimal renal excretion. The pharmacokinetics can be affected by hepatic function, and dose adjustments may be required in patients with liver impairment.

Contra-indications

• Hypersensitivity to olmesartan or any of its components
• Pregnancy
• Severe hepatic impairment
• Bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney

Adverse effects

• Dizziness
• Hypotension
• Hyperkalemia
• Renal impairment
• Angioedema
• Diarrhea
• Fatigue

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of olmesartan
• Dual blockade of the renin-angiotensin system (e.g., combination with another ARB or ACE inhibitor) increases the risk of renal impairment, hypotension, and hyperkalemia

Precautions

• Monitor blood pressure and renal function regularly during treatment
• Use with caution in patients with volume depletion or heart failure
• Caution in patients with aortic stenosis due to potential risk of decreased coronary perfusion
• Consider potential hypotensive effects in patients on diuretics or with renal impairment

Pregnancy

Olmesartan is contraindicated during pregnancy due to the risk of fetal harm, particularly in the second and third trimesters.

Breast-feeding

It is not known whether olmesartan is excreted in human milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Olmesartan medoxomil 5 mg, 20 mg, 40 mg tablets

Mechanism of action

Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includes [telmisartan], [candesartan], [losartan], [valsartan], and [irbesartan]. ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein angiotensin II from binding and exerting its hypertensive effects. As the principal pressor agent of the renin-angiotensin system, Angiotensin II causes vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. Olmesartan also effects on the renin-angiotensin aldosterone system (RAAS) plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling. Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney and converts angiotensin (Ang) II to Ang-(1-7), a renoprotective peptide. Urinary ACE2 has been shown to be elevated in patients with chronic kidney disease. However, the effects of antihypertensive agents on urinary ACE2 remain unclear. METHODS: Of participants in the Tanno-Sobetsu cohort study in 2011 (n = 617), subjects on no medication (n = 101) and hypertensive patients treated with antihypertensive agents, including the calcium channel blockers amlodipine and long-acting nifedipine; the ACE inhibitor enalapril; and the Ang II receptor blockers losartan, candesartan, valsartan, telmisartan, and olmesartan, for more than 1 year (n = 100) were enrolled, and urinary ACE2 level was measured. Glucose and hemoglobin A1c were significantly higher in patients treated with enalapril, telmisartan or olmesartan than in the control subjects. Urinary albumin-to-creatinine ratio (UACR) was significantly higher in patients treated with enalapril than in the control subjects. Urinary ACE2 level was higher in the olmesartan-treated group, but not the other treatment groups, than in the control group. Urinary ACE2 level was positively correlated with systolic blood pressure (r = 0.211; P = 0.003), UACR (r = 0.367; P < 0.001), and estimated salt intake (r = 0.260; P < 0.001). Multivariable regression analysis after adjustment of age, sex, and the correlated indices showed that the use of olmesartan was an independent predictor of urinary ACE2 level. In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor in vascular smooth muscle. Its action is, therefore, independent

Pharmacodynamics

Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. **Hypotension in Volume- or Salt-Depleted Patients** In patients with an activated renin-angiotensin aldosterone system, such as volume-and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may be anticipated after initiation of treatment with olmesartan. Initiate treatment under close medical supervision. If hypotension does occur, place the patient in the supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized. Valvular Stenosis: there is concern on theoretical grounds that patients with aortic stenosis might be at a particular risk of decreased coronary perfusion, because they do not develop as much afterload reduction. **Impaired Renal Function** As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with olmesartan. In patients whose renal function may depend upon the activity of the renin-angiotensin- aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. Similar results may be anticipated in patients treated with olmesartan. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected. **Sprue-like Enteropathy** Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies. Consider discontinuation of olmesartan medoxomil in cases where no other etiology is identified. **Electrolyte Imbalances** Olmesartan medoxomil contains olmesartan, a drug that inhibits the renin-angiotensin system (RAS). Drugs that inhibit the RAS can cause hyperkalemia. Monitor serum electrolytes periodically.