Besipine

Besipine Uses, Dosage, Side Effects, Food Interaction and all others data.

Besipine is a Dihydropyridine Calcium antagonist that inhibits the transmembrane influx of Calcium ions into cardiac and vascular smooth muscle. It has greater affinity towards vascular smooth muscle than on cardiac muscle. Besipine is peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and thereby reduces blood pressure. Besipine reduces tone, decreases coronary vasoreactivity and lowers cardiac oxygen demand by reducing after load.

General pharmacodynamic effects

Besipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen , .

Hemodynamic effects

Trade Name Besipine
Availability Prescription only
Generic Amlodipine
Amlodipine Other Names Amlodipine, Amlodipino, Amlodipinum
Related Drugs aspirin, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, propranolol, Xarelto, spironolactone
Weight 5mg
Type Tablet
Formula C20H25ClN2O5
Weight Average: 408.876
Monoisotopic: 408.145199627
Protein binding

About 98% , .

Groups Approved
Therapeutic Class Calcium-channel blockers
Manufacturer Csh Pharmaceuticals-north (pvt) Ltd
Available Country Pakistan
Last Updated: September 19, 2023 at 7:00 am
Besipine
Besipine

Uses

Patients with mild to moderate hypertension (alone or in combination with other antihypertensives).

The treatment of chronic stable and vasospastic angina.

Raynaud\'s disease.

Besipine is also used to associated treatment for these conditions: Anginal Pain, Cardiovascular Events, Chronic Stable Angina Pectoris, Coronary Artery Disease (CAD), High Blood Pressure (Hypertension), Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Mixed Dyslipidemias, Primary Hypercholesterolemia, Vasospastic Angina

How Besipine works

Mechanism of action on blood pressure

Besipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Besipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Besipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure .

Mechanism of action in angina

The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:

Besipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .

Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .

Dosage

Besipine dosage

For treatment of both hypertension and angina pectoris, the usual initial dose is 5 mg once daily. If the desired therapeutic effect cannot be achieved within 2-4 weeks, the dose may be increased to a maximum dose of 10 mg once daily. Besipine 10 mg once daily provides symptomatic improvement in patients with Raynaud's disease.

Use in children: Use of Besipine in children (under 12 years of age) is not recommended.

Side Effects

Besipine is generally well tolerated. The most commonly observed side effects are headache, peripheral oedema, palpitations, flushing, dizziness, nausea, abdominal pain.

Toxicity

Acute oral toxicity (LD50): 37 mg/kg (mouse) .

Overdose

An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported .

Carcinogenesis, mutagenesis, impairment of fertility

Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose .

Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects .

There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) .

Use in pregnancy

The safety of amlodipine in human pregnancy or lactation has not been proven. Besipine is therefore considered a pregnancy category C drug . Use amlodipine only if the potential benefit justifies the potential risk .

Use in nursing

Discontinue when administering amlodipine .

Precaution

Hypotension: Since the vasodilUse in renal failure

Although Besipine is excreted primarily via kidney, mild renal impairment does not appear to have an effect on the plasma concentrations. Severe renal impairment may however require a dosage reduction. Besipine is not dialyzable.

Use in patients with impaired hepatic function

Besipine half-life is prolonged in patient with impaired hepatic function. Besipine should therefore be administered at lower (5mg) initial dose in these patients.

Use in heart failure

An increased number of pulmonary oedema has been reported.atation induced by Besipine is gradual in onset, acute hypotension has rarely been reported after oral administration of Besipine. Nonetheless, caution should be exercised when administering the drug with any other peripheral vasodilator particularly in patients with severe aortic stenosis.

Cardiac failure: Patients with heart failure should be treated with caution. Calcium channel blockers, including Besipine, should be usedwith caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

Beta blocker withdrawal: Besipine gives no protection against the danger of abrupt beta blocker withdrawal; any such withdrawal should be gradualreduction of the dose of beta blocker.

Hepatic failure: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function. Besipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.

Interaction

Use of Besipine together with thiazide diuretics or angiotensin-converting-enzyme inhibitors in the treatment of hypertension is additive. There are no hazardous interaction of Besipine with Digoxin, Cimetidine, Warfarin and food.

Food Interaction

  • Avoid grapefruit products.
  • Avoid natural licorice.
  • Take with or without food. The absorption is unaffected by food.

[Minor] The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine.

The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

Data have been conflicting and the clinical significance is unknown.

Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

Besipine multivitamins interaction

[Moderate] Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium.

Calcium chloride has been used to manage acute severe verapamil toxicity.

Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

Volume of Distribution

21 L/kg , .

Elimination Route

Besipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food .

Half Life

The terminal elimination half-life of about 30–50 hours .

Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment .

Clearance

Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers , .

Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required .

Elimination Route

Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing . Besipine is 10% excreted as unchanged drug in the urine. Besipine can be initiated at normal doses in patients diagnosed with renal failure , .

Pregnancy & Breastfeeding use

Pregnancy: Safety in pregnancy has not been established.

Lactation: It is not known whether Besipine is excreted in breast milk. It is advised to stop breastfeeding during treatment with Besipine.

Contraindication

Besipine is contraindicated in patients with-

  • Hypersensitivity to amlodipine, dihydropyridine derivatives or any of the excipients
  • Shock (including cardiogenic shock)
  • Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
  • Unstable angina
  • Hemodynamically unstable heart failure after acute myocardial infarction (during the first 28 days)
  • Severe hypotension

Special Warning

Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.

Children under 6 years old: The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.

Elderly: Besipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.

Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Besipine is not dialysable.

Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Besipine have not been studied in severe hepatic impairment. Besipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.

Acute Overdose

There is no well documented experience with Besipine overdosage. In case of clinically significant hypotension due to Besipine over dosage, calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. Since Besipine is highly protein-bound, dialysis is unlikely to be of benefit.

Storage Condition

Keep out of the reach of children. Store below 30° C. Keep in the original package in a cool & dry place in order to protect from light and moisture.

Innovators Monograph

You find simplified version here Besipine

Besipine contains Amlodipine see full prescribing information from innovator Besipine Monograph, Besipine MSDS, Besipine FDA label

FAQ

What is Besipine used for?

Besipine is a medicine used to treat high blood pressure (hypertension).Besipine is also used to prevent chest pain caused by heart disease. 

How safe is Besipine?

Besipine is generally a safe and effective drug, but it may cause side effects in some people.

How does Besipine work?

Besipine works in high blood pressure by relaxing and widening blood vessels.

What are the common side effects of Besipine?

The most common side effects include headache, flushing, feeling tired and swollen ankles.

Is Besipine safe during pregnancy?

early pregnancy does not appear to be associated with an increased rate of fetal malformations compared with other antihypertensive medications or maternal hypertension without treatment.

Is Besipine safe during breastfeeding?

Besipine use of Besipine during breastfeeding has not caused any adverse effects in breastfed infants. If Besipine is required by the mother, it is not a reason to discontinue breastfeeding.

Can I drink alcohol with Besipine?

Yes, you can drink alcohol with Besipine.But drinking alcohol can increase the blood pressure-lowering effect of Besipine, which can make you feel sleepy, dizzy or bring on a headache. If this happens to you, it's best to stop drinking alcohol while you're taking Besipine.

Can I drive after taking Besipine ?

If the tablets make you feel sick, dizzy or tired, or give you a headache, do not drive or use machines and contact your doctor immediately.

When is the best time to take Besipine?

It does not matter what time of day you take Besipine morning or evening, but it is best to take it at the same time every day,

How long does Besipine take to work?

Besipine starts to work on the day you start taking it, but it may take a couple of weeks for full effect. If you're taking Besipine for high blood pressure, you may not have any symptoms.

How long does Besipine stay in my system?

Besipine will stay in your system for about 10 days after your last dose.

Can I take Besipine for a long time?

Besipine is generally safe to take for a long time. In fact, it works best when you take it for a long time.

Can Besipine cause kidney damage?

Besipine should not cause kidney damage and in fact are used to treat high blood pressure and slow the progression of chronic kidney disease.

When should I stop taking Besipine?

If you have been using Besipine regularly for several weeks, do not suddenly stop using it.

Is Besipine bad for my liver?

Liver injury due to Besipine have not been reported.

Does Besipine affect heart rate?

Besipine has little or no effect on your heart rate.

Can Besipine cause depression?

Mood changes such as depression or anxiety may occurs.

Can Besipine cause a cough?

No, you probably won't have a cough when taking Besipine.

What happens if I overdose of Besipine?

If you take too much Besipine by accident, contact your doctor or go to your nearest hospital straight away. An overdose of Besipine can cause dizziness and sleepiness.

What happens if I miss a dose of Besipine?

If you forget to take a dose of Besipine, take it as soon as you remember that day and then carry on as normal. If you forget to take the dose for the whole day, skip the missed dose and carry on as normal the next day. Do not take a double dose to make up for a forgotten one.

*** Taking medicines without doctor's advice can cause long-term problems.
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