|Composition||Benidipine Hydrochloride 4 mg + Telmisartan 40 mg + Chlorthalidone 12.5 /6.25 mg tablets|
|Indication||Resistant Hypertension with dual therapy|
|Mechanism of Action||
Benidipine: The vasorelaxant effect of benidipine is due to its affinity towards dihydropyridine binding sites in calcium channels. Binding of benidipine with calcium channels inhibits calcium current.
The onset of action is slow, which results in minimal tachycardia or palpitation Chlortalidone is an oral, long acting antihypertensive/diuretic. It is a monosulfamyl diuretic that acts by enhancing the excretion of sodium and chloride ions, and water by interfering with the transport of sodium ions across the renal tubular epithelium. Their primary site of action appears to be at the cortical diluting segment in the nephron of the loop of Henle.
Telmisartan: is a nonpeptide AT1 angiotensin II receptor antagonist. It exerts antihypertensive activity by preventing angiotensin II from binding to AT1 receptors thus inhibiting the vasoconstricting and aldosterone-secreting effects of angiotensin II.
Benidipine: Rapid absorption. Cmax within 2 h. Highest level in the liver and also distribution in the kidneys, plasma, and other tissues. No tissue showed a particularly high accumulation of the drug following repeated oral administrations. Protein binding 98% The percentage urinary excretion of benidipine following an oral dose is about 36%
Chlortalidone: Onset: 2 hr.
Duration: 48-72 hr.
Absorption: Erratic absorption from the GI tract (oral).
Distribution: Binds to red blood cells; crosses the placenta and enters breast milk. Protein-binding: Weak.
Excretion: Urine (as unchanged drug); 40-60 hr (elimination half-life).
Telmisartan: Onset: 1-2 hr.
Duration: Up to 24 hr.
Absorption: Rapidly absorbed from the GI tract. Food may slightly decrease the bioavailability. Absolute bioavailability: Dose-dependent (approx 42% after 40-mg dose; 58% after 160-mg dose). Time to peak plasma concentration: Approx 0.5-1 hr.
Distribution: Volume of distribution: 500 L. Plasma protein binding: >99%. Metabolism: Undergoes conjugation w/ glucuronic acid to form inactive metabolites.
Excretion: Via faeces (97%, as unchanged drug). Terminal elimination half-life: Approx 24 hr.
Benidipine: Palpitation, facial flushing, hot flushes, chest pressure sensation, headache, dizziness, sleepiness, constipation, nausea, abdominal discomfort, oedema, malaise, tinnitus, redness and warm feeling in the fingers, shoulder stiffness, increased frequency of micturition. Hypersensitive reactions e.g. Rash and itching. Elevation of SGOT, SGPT, alkaline phosphatase, total bilirubin, creatinine and uric acid.
Chlortalidone : Dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, oliguria, hypotension, fatigue, muscle cramps and GI disturbances, nausea, vomiting, constipation, diarrhoea, anorexia. Diabetes and gout may be precipitated. Impotence. Raised blood levels of glucose, urates, lipids and calcium. Reduced levels of K and magnesium. Raised CPK levels. Potentially Fatal: Rare. Severe hyponatraemia and idiosyncratic hypersensitivity.
Telmisartan: Dizziness, fatigue, headache, sinusitis, upper resp tract infection, pharyngitis, UTI, back pain, myalgia, diarrhoea, abdominal pain, dyspepsia, nausea.
Potentially Fatal: Intermittent claudication and skin ulcer.
Benidipine Elderly. In case of dizziness or lightheadedness, advise patients against handling of heavy machines or working at elevated spots. Reduce dosage gradually while withdrawing drug. Liver function tests.
Chlortalidone: Existing fluid and electrolyte disturbances, hepatic cirrhosis, severe heart failure, hyperuricaemia, mild to moderate renal impairment. Elderly. Monitor fluid and electrolyte balance. Kidney or liver disease; diabetes; gout; hyperlipidaemia and ventricular extra systoles.
Telmisartan: Volume- or salt-depleted patients including patients on prolonged diuretic therapy. Patients w/ renal artery stenosis, aortic or mitral stenosis, obstructive biliary disease. Renal and mild to moderate hepatic impairment. Lactation. Monitoring Parameters Monitor BP, electrolytes and serum creatinine levels.
Benidipine: Adult: PO HTN 2-4 mg once daily, up to 8 mg once daily if needed. Angina pectoris 4 mg twice daily.
Chlortalidone: Adult: PO HTN 25 mg/day, up to 50 mg/day. Oedema Initial: 25-50 mg/day up to 100-200 mg/day in severe cases. Maintenance: 25-50 mg/day or on alternate days. Diabetes insipidus Initial: 100 mg twice daily. Maintenance: 50 mg/day.
Telmisartan: Adult: PO HTN Initial: 40 mg once daily, may be adjusted to 20-80 mg once daily. CV risk reduction 80 mg once daily.