BENIDIN M
Composition BENIDIPINE 4 mg + Metoprolol succinate (SR) 50/25 mg tablets
Indication Hypertension, STABLE ANGINA
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

Metoprolol: 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).

Pharmacokinetic's

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%

Metoprolol: 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.

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).

Side effects

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.

Metoprolol :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.

Precaution

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.

Metoprolol: Patients w/ myasthenia gravis, well-compensated heart failure, bronchospastic disease, AV conduction disorders, substantial cardiomegaly. May mask signs and symptoms of hyperthyroidism and hypoglycaemia. Patients w/ history of cardiac failure or those w/ minimal cardiac reserve. Patients undergoing major surgery involving general anaesth. 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.

Dosage

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.

Metoprolol: Hypertension

Adult: Conventional tablet: 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 tablet: Initially, 25-100 mg once daily.

Angina pectoris Adult: Conventional tablet: 50-100 mg Twice a day or Thrice a day. Extended release tablet: 100 mg once daily. Max: 200 mg once daily.

Renal impairment: No dosage adjustment needed. Hepatic impairment: Reduce dose.