|Composition||OLMESARTAN 20mg + METOPROLOL 25 mg & OLMESARTAN 20mg + METOPROLOL 50 mg|
|Indication||For management of Hypertension|
|Mechanism of Action||
Olmesartan is a selective and competitive angiotensin II Type 1 (AT1) receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. As a result, Olmesartan relaxes blood vessels, hence lowering BP and increases blood supply and oxygen to the heart.
Metoprolol selectively inhibits β1-adrenergic receptors but has little or no effect on β2-receptors except in high doses. It does not exhibit membrane stabilising or intrinsic sympathomimetic activity.
Absorption: Bioavailability: Approx. 26%. Time to peak plasma concentration: Approx. 1-2 hr.
Distribution: Volume of distribution: 17 L. Plasma protein binding: ≤99%.
Metabolism: Olmesartan medoxomil undergoes ester hydrolysis in the GI tract to active form Olmesartan.
Excretion: Via faeces (50-65%) and urine (35-50%) both as Olmesartan. Terminal half-life: Approx. 10-15 hr.
Onset: 1-2 hr (oral); 20 min, when infused over 10 min (IV).
Duration: Oral: Approx 3-6 hr (immediate release); approx 24 hr (extended release). IV: 5-8 hr.
Absorption: Absorbed readily and completely from the GI tract. Bioavailability increased by food. Bioavailability: Approx 50%. Time to peak plasma concentration: Approx 1.5-2 hr (oral).
Distribution: Widely distributed, enters breast milk, crosses the placenta and blood-brain barrier. Volume of distribution: 3.2-5.6 L/kg. Plasma protein binding: Approx 12%.
Metabolism: Extensively hepatic via CYP2D6 isoenzyme and undergoes oxidative deamination, O-dealkylation followed by oxidation and aliphatic hydroxylation.
Excretion: Via urine (as metabolites and unchanged drug). Elimination half-life: 3-4 hr (fast hydroxylators); approx 7 hr (poor hydroxylators).
Potentially Fatal: Acute renal failure. May cause sprue-like enteropathy (Symptoms: Severe, chronic diarrhoea with substantial wt. loss). Dizziness, headache, abdominal pain, dyspepsia, diarrhoea, gastroenteritis, nausea, bronchitis, pharyngitis, rhinitis, arthritis, back pain, skeletal pain, fatigue, flu-like symptoms, angioedema, peripheral oedema, haematuria, UTI, hyperkalaemia, hypertriglyceridemia, hyperuricaemia, hyperglycaemia, elevated liver enzymes.
Dizziness, insomnia, tiredness, headache, vertigo, confusion, bradycardia, shortness of breath, hypotension, Raynaud's phenomenon, CHF, peripheral oedema, cold extremities, syncope, chest pain, palpitations, gangrene, claudication, hallucinations, nightmares, visual disturbances; diarrhoea, constipation, flatulence, GI pain, heartburn, nausea, hiccups, xerostomia; bronchoconstriction, wheezing, dyspnoea; dry skin, maculopapular, psoriasiform, pruritus, worsening of psoriasis, urticarial rash. Rarely, Peyronie's disease, tinnitus, restless legs, musculoskeletal pain, a polymyalgia-like syndrome, decreased libido, blurred vision, dry mucous membranes, sweating; reversible alopecia, thrombocytopenia, agranulocytosis, retroperitoneal fibrosis, wt gain, arthritis, dry eyes.
Patients with aortic or mitral valve stenosis, renal artery stenosis; at risk for hypotension (e.g. patients with volume or salt depletion); history of angioedema; at risk for hyperkalaemia (e.g. patients w/ DM). Severe renal and hepatic impairment. Lactation. Monitoring Parameters Monitor BP, serum creatinine and K levels periodically.
Patients with myasthenia gravis, well-compensated heart failure, bronchospastic disease, AV conduction disorders, substantial cardiomegaly. May mask signs and symptoms of hyperthyroidism and hypoglycaemia. Patients with history of cardiac failure or those with minimal cardiac reserve. Patients undergoing major surgery involving general anaesthesia. Avoid abrupt withdrawal as it may precipitate thyroid storm or MI, and may exacerbate angina and ventricular arrhythmias. Hepatic impairment. Pregnancy and lactation. Patient Counselling May affect ability to drive or operate machinery. Monitoring Parameters Monitor BP, ECG and heart rate.
Adult: Initial: 10-20 mg once daily may then be increased up to max 40 mg once daily if needed.
Child: 6-16 yr. 35 kg: 10 mg once daily; ≥35 kg: 20 mg once daily. Doses may be doubled once if necessary after 2 wk.
Elderly: No dosage adjustment needed.
Renal impairment: Mild to moderate (Circle: 20-60 mL/min): Max: 20 mg once daily.
Moderate: Initial: 10 mg once daily may increase up to max 20 mg once daily.
Adult: Conventional tab: Initially, 100 mg/day in single or 2 divided doses, may increase wkly to 400 mg/day depending on response. Maintenance: 100-200 mg/day. Extended-release tab: Initially, 25-100 mg once daily.
Renal impairment: No dosage adjustment needed.
Hepatic impairment: Reduce dose.