Vasolexin

Uses

(Vasolexin) 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 (Vasolexin) may be used in patients unable to tolerate an ACE inhibitor. Carvista (Vasolexin) may be used in patients who are not receiving digitalis, hydralazine or nitrate therapy.

Vasolexin 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)

How Vasolexin works

Vasolexin inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors. Vasolexin'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.

Dosage

Vasolexin 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.

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.

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.

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.

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

Food Interaction

• Take with food. Food slows the absorption and reduces the incidence of adverse effects.

Vasolexin Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Vasolexin Cholesterol interaction

[Moderate] Beta-adrenergic receptor blocking agents (aka beta-blockers) may alter serum lipid profiles.

Increases in serum VLDL and LDL cholesterol and triglycerides, as well as decreases in HDL cholesterol, have been reported with some beta-blockers.

Patients with preexisting hyperlipidemia may require closer monitoring during beta-blocker therapy, and adjustments made accordingly in their lipid-lowering regimen.

Vasolexin multivitamins interaction

[Moderate] ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers.

The exact mechanism of interaction is unknown.

In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively.

The elimination half-life increased by 44%.

Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone.

However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments.

The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours.

Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

Vasolexin Drug Interaction

Moderate: furosemide, furosemideMinor: aspirin, aspirin, aspirin, aspirinUnknown: apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Vasolexin Disease Interaction

Major: bradyarrhythmia/AV block, cardiogenic shock/hypotension, hemodialysis, hypersensitivity, ischemic heart disease, PVD, CHF, liver disease, peripheral vascular disease, severe hepatic impairment, asthma/COPDModerate: cerebrovascular insufficiency, glaucoma, hyperlipidemia, hyperthyroidism, myasthenia gravis, pheochromocytoma, psoriasis, tachycardia, renal dysfunction, Prinzmetal's variant angina

Volume of Distribution

Vasolexin has a volume of distribution of 1.5-2L/kg or 115L.

Elimination Route

Vasolexin has a bioavailability of 25-35%. Vasolexin has a T_max of 1 to 2 hours. Taking carvedilol with a meal increases T_max without increasing AUC. Vasolexin doses of 50mg lead to a C_max of 122-262µg/L and an AUC of 717-1600µg/L*h. Vasolexin doses of 25mg lead to a C_max of 24-151µg/L and an AUC of 272-947µg/L*h. Vasolexin doses of 12.5mg lead to a C_max of 58-69µg/L and an AUC of 208-225µg/L*h.

Half Life

The half life of carvedilol is between 7-10 hours, though significantly shorter half lives have also been reported.

Clearance

The plasma clearance of carvedilol has been reported as 0.52L/kg or 500-700mL/min.

Elimination Route

16% of carvedilol is excreted in the urine with 4 Vasolexin is primarily excreted in the bile and feces.

Pregnancy & Breastfeeding use

Vasolexin 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. Vasolexin 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 Vasolexin use in neonates.

Contraindication

Vasolexin 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. Vasolexin is contraindicated in patients with hypersensitivity to the drug.

Special Warning

The safety and efficacy of carvedilol in paediatric patients have not been established.

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.

Interaction with other Medicine

Digoxin : In normal healthy volunteers a single dose of carvedilol taken together with a single dose of digoxin resulted in significantly increased levels of digoxin 24 hour later. Patients with congestive heart failure stabilized on digoxin have been given carvedilol concomitantly without any adverse effects. Increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing the dose of carvedilol.

Rifampin : Pretreatment with rifampin resulted in a 60% decrease in Cmax and AUC.

Warfarin : Vasolexin did not alter the in vitro plasma protein binding of warfarin.

Clonidine : b-receptor antagonists potentiate the pressor reaction which may follow sudden withdrawal of treatment with clonidine although, in theory, the a-blocking action of carvedilol should modify the pressure rise.

Storage Condition

Store in a cool and dry place. Protect from light and moisture.

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