Cardivas In
Cardivas In Uses, Dosage, Side Effects, Food Interaction and all others data.
(Carvedilol) is a cardiovascular drug whose main pharmacological action is non-selective antagonism of β-adrenergic receptors but which also possesses appreciable α-adrenergic antagonistic activity. It also has antiproliferative properties and is a scavenger of reactive free oxidant radicals. It is used in the treatment of hypertension, angina pectoris and congestive heart failure.
Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism. It has a long duration of action as it is generally taken once daily and has a broad therapeutic index as patients generally take 10-80mg daily. Patients taking carvedilol should not abruptly stop taking this medication as this may exacerbate coronary artery disease.
Ivabradine is a pure heart rate lowering agent. It acts by selective and specific inhibition of the cardiac pacemaker I f current that controls the spontaneous diastolic depolarization in the sinus node and regulates heart rate. By decreasing heart rate, Ivabradine decreases the cardiac workload and therefore oxygen consumption. Concomitantly, Ivabradine prolongs diastole allowing increased perfusion of coronary arteries and increased oxygen supply to the heart. The cardiac effects are specific to the sinus node with no effect on intra-atrial, atrioventricular or intraventricular conduction times, nor on myocardial contractility or ventricular repolarization.
The funny channels (If) open during repolarization and close during depolarization, making ivabradine's activity dependent on heart rate or the closing and opening of the channels. Therefore ivabradine exhibits use-dependence and is more pharmacologically active at higher heart rates. Ivabradine exhibits a linear dose-dependent heart-rate lowering activity (bradycardic effect) until a maximum dose of 30-40mg. At higher doses, the concentration of ivabradine tends to plateau, reducing risk of serious sinus bradycardia. It has been shown that the metabolite of ivabradine lowers heart rate as well, contributing to ivabradine's overall effect.
| Trade Name | Cardivas In |
| Generic | Carvedilol + Ivabradine |
| Weight | 12.5mg, 6.25mg, 3.125mg |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Sun Pharma |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
(Carvedilol) is used for the treatment of mild or moderate {NYHA (New York Heart Association) class II or III} heart failure of ischemic or cardiomyopathic origin, in conjunction with digitalis, diuretics and ACE inhibitor, to reduce the progression of disease as evidenced by cardiovascular death, cardiovascular hospitalization, or the need to adjust other heart failure medications. Carvista (Carvedilol) may be used in patients unable to tolerate an ACE inhibitor. Carvista (Carvedilol) may be used in patients who are not receiving digitalis, hydralazine or nitrate therapy.
Symptomatic treatment of chronic stable angina pectoris in coronary artery disease patients with normal sinus rhythm. Ivabradine is used for:
- In patients unable to tolerate or with a contra-indication to the use of beta-blockers or
- In combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is > 60 bpm.
Cardivas In is also used to associated treatment for these conditions: Atrial Fibrillation, Chronic Stable Angina Pectoris, High Blood Pressure (Hypertension), LVEF ≤40% Left ventricular dysfunction, NYHA Class I or II heart failure, Chronic heart failure with reduced ejection fraction (NYHA Class III), Chronic heart failure with reduced ejection fraction (NYHA Class IV)Chronic Heart Failure (CHF), Chronic Stable Angina Pectoris, Left Ventricular Dysfunction, Chronic, stable, symptomatic Heart Failure
How Cardivas In works
Carvedilol inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors. Carvedilol's action on alpha-1 adrenergic receptors relaxes smooth muscle in vasculature, leading to reduced peripheral vascular resistance and an overall reduction in blood pressure. At higher doses, calcium channel blocking and antioxidant activity can also be seen. The antioxidant activity of carvedilol prevents oxidation of low density lipoprotein and its uptake into coronary circulation.
Ivabradine lowers heart rate by selectively inhibiting If channels ("funny channels") in the heart in a concentration-dependent manner without affecting any other cardiac ionic channels (including calcium or potassium). Ivabradine binds by entering and attaching to a site on the channel pore from the intracellular side and disrupts If ion current flow, which prolongs diastolic depolarization, lowering heart rate. The If currents are located in the sinoatrial node and are the home of all cardiac pacemaker activity. Ivabradine therefore lowers the pacemaker firing rate, consequently lowering heart rate and reducing myocardial oxygen demand. This allows for an improved oxygen supply and therefore mitigation of ischemia, allowing for a higher exercise capacity and reduction in angina episodes.
Dosage
Cardivas In dosage
In heart failure, initially 3.125 mg twice daily (with food) may be given, dose may be increased at intervals of at least 2 weeks to 6.25 mg twice daily, then to 12.5 mg twice daily, then to 25 mg twice daily. The dose may be increased to highest dose tolerated, maximum 25 mg twice daily in patients less than 85 kg body-weight and 50 mg twice daily in patients over 85 kg.In hypertension initially 12.5 mg once daily, increased after 2 days to usual dose of 25 mg once daily; if necessary the dose may be further increased at intervals of at least 2 weeks to maximum 50 mg daily in single or divided doses.In elderly patients the initial dose of 12.5 mg daily may provide satisfactory control.In angina pectoris the recommended dose for initiation of therapy is 12.5 mg twice daily for the first 2 days. Thereafter, the recommended dosage is 25 mg twice daily. For elderly patients, the maximum daily dose is 50 mg daily in divided doses.
Adult: The usual recommended starting dose of Ivabradine is 5 mg twice daily which may be increased after 3-4 weeks of treatment to 7.5 mg twice daily, depending on therapeutic response. Usual dose is 1 tablet in the morning and 1 tablet in the evening during meals.
If the heart rate decreases persistently below 50 bpm at rest or if symptoms related to bradycardia, the dose must be adjusted downwards to 2.5 mg twice daily (one half of the 5 mg tablet twice daily). Treatment must be discontinued if heart rate remains below 50 bpm or symptoms of bradycardia persist.
Elderly: Consider a lower starting dose (2.5 mg twice daily i.e. one half 5 mg tablet twice daily).
Children and adolescents: Not recommended.
Side Effects
Postural hypotension, dizziness, headache, fatigue, gastro-intestinal disturbances, bradycardia; occasionally diminished peripheral circulation, peripheral oedema and painful extremities, dry mouth, dry eyes, eye irritation or disturbed vision, impotence, disturbances of micturition, influenza-like symptoms, rarely angina, AV block, exacerbation of intermittent claudication or Raynaud's phenomenon, allergic skin reactions, exacerbation of psoriasis, nasal stuffiness, wheezing, depressed mood, sleep disturbances, paresthesia, heart failure, changes in liver enzymes, thrombocytopenia, leukopenia are also reported.
Visual symptoms, blurred vision, bradycardia, 1st degree AV block, ventricular extrasystoles, headaches, and dizziness.
Toxicity
Patients experiencing an overdose may present with hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest. Patients should remain in a supine position and may be given atropine for bradycardia and glucagon followed by sympathomimetics to support cardiovascular function.
Ivabradine may cause fetal toxicity when administered to pregnant women. Animal studies in pregnant rats have shown embryo-fetal toxicity and cardiac teratogenic effects. Effective contraception in women is recommended while using ivabradine.
Precaution
Take caution in hepatic impairment and in heart failure monitor clinical status for 2-3 hours after initiation and after increasing each dose. Before increasing dose ensure that the renal function and heart failure are not deteriorating.
Mild to moderate hypotension, atrial fibrillation, patients with congenital QT syndrome or treated with QT wave prolonging medicinal products, Moderate hepatic insufficiency, severe renal insufficiency.
Interaction
Drug interactions have been seen with co-administration of carvedilol and digoxin, resulting in an increased bioavailability of digoxin. This increase is not clinically significant and does not correlate with pharmacologic response. Pharmacokinetics studies demonstrated a lack of drug interaction between carvedilol and hydrochlorothiazide, cimetidine, torsemide and warfarin
QT wave prolonging medicinal products is not recommended. Cardiovascular QT wave prolonging medicinal products (e.g. quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone). Non cardiovascular QT wave prolonging medicinal products (e.g. pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin).
The concomitant use of cardiovascular and non cardiovascular QT wave prolonging medicinal products with ivabradine should be avoided since QT wave prolongation may be exacerbated by heart rate reduction. If the combination appears necessary, close cardiac monitoring is needed.
Volume of Distribution
Carvedilol has a volume of distribution of 1.5-2L/kg or 115L.
~100 L.
Elimination Route
Carvedilol has a bioavailability of 25-35%. Carvedilol has a Tmax of 1 to 2 hours. Taking carvedilol with a meal increases Tmax without increasing AUC. Carvedilol doses of 50mg lead to a Cmax of 122-262µg/L and an AUC of 717-1600µg/L*h. Carvedilol doses of 25mg lead to a Cmax of 24-151µg/L and an AUC of 272-947µg/L*h. Carvedilol doses of 12.5mg lead to a Cmax of 58-69µg/L and an AUC of 208-225µg/L*h.
It is recommended to take ivabradine with food to reduce variability in systemic exposure. Administration with food slows absorption by 1 hour, but increases systemic absorption by 20-30%. Ivabradine's oral bioavailability is about 40%.
Half Life
The half life of carvedilol is between 7-10 hours, though significantly shorter half lives have also been reported.
2 hours.
Clearance
The plasma clearance of carvedilol has been reported as 0.52L/kg or 500-700mL/min.
Total clearance is about 400ml/min; renal clearance about 70ml/min. About 4% is excreted unchanged in urine.
Elimination Route
16% of carvedilol is excreted in the urine with 4 Carvedilol is primarily excreted in the bile and feces.
Metabolites are equally excreted in feces and urine.
Pregnancy & Breastfeeding use
Carvedilol should not be used during breast-feeding, since no studies have been performed in lactating women and animal studies have shown that carvedilol is excreted in breast milk. Safety and efficacy in children have not been established with carvedilol. Carvedilol should not be used during pregnancy as no studies have been performed in this group. Animal studies have shown that carvedilol crosses the placental barrier. No information is available on safety and efficacy of Carvedilol use in neonates.
Fertility: Studies in rats have shown no effect on fertility in males and females
Pregnancy: There are no or limited amount of data from the use of ivabradine in pregnant women. Therefore, ivabradine is contra indicated during pregnancy.
Breast-feeding: Animal studies indicate that ivabradine is excreted in milk. Therefore, ivabradine is contra-indicated during breast-feeding.
Contraindication
Carvedilol is contraindicated in patients with severe chronic cardiac failure requiring intravenous inotropic therapy, bronchial asthma or related bronchospastic conditions, second or third-degree AV block, sick sinus syndrome (unless a permanent pacemaker is in place), cardiogenic shock, or severe bradycardia. Use of carvedilol in patients with clinically manifested hepatic impairment is not recommended. Carvedilol is contraindicated in patients with hypersensitivity to the drug.
History of hypersensitivity to Ivabradine or any of the excipients, resting heart rate below 60 bpm before treatment, cardiogenic shock, acute myocardial infarction, severe hypotension (< 90/50 mmHg), severe hepatic insufficiency, sick sinus syndrome, sino- atrial block, heart failure, pacemaker dependent, unstable angina, 3 rd degree AV block, combination with strong cytochrome P-450 3A4 inhibitors (such as azole antifungals, macrolide antibiotics, HIV protease inhibitors).
Special Warning
The safety and efficacy of carvedilol in paediatric patients have not been established.
Renal insufficiency: Use with caution in patients with creatinine clearance
Hepatic impairment: Use with caution in patients with moderate hepatic impairment; Contraindicated in severe hepatic impairment.
Acute Overdose
Symptoms: Severe hypotension, bradycardia, heart failure, cardiogenic shock and cardiac arrest. Resp problems, bronchospasms, vomiting, lapses of consciousness and generalised seizures.
Management: Symptomatic and supportive treatment. Consider use of atropine for excessive bradycardia, IV glucagon or sympathomimetics to support ventricular function. Consider using norfenephrine or noradrenaline if vasodilation dominates the intoxication profile and IV inj of diazepam or clonazepam for seizures.
Storage Condition
Store in a cool and dry place. Protect from light and moisture.
Store at cool and dry place, protect from light and moisture.
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