Valazyd AM

Valazyd AM

amlodipine + valsartan

Manufacturer:

Zydus Healthcare Phils

Distributor:

Lloyd
Full Prescribing Info
Contents
Amlodipine besilate, valsartan.
Description
Each film coated tablet contains: Amlodipine (as besilate) 10 mg, valsartan 160 mg.
Amlodipine (as besilate) 5 mg, valsartan 160 mg.
Action
Experimental data suggest that Amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly or vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
The precise mechanism by which amlodipine relieves angina have not been fully delineated, but are thought to include the following: Exertional Angina: In patients with exertional angina, amlodipine reduces the total peripheral resistance (after-load) against which the heart works and reduces the rate pressure product and thus myocardial oxygen demand, at any given level of exercise.
Vasospastic Angina: Amlodipine has been demonstrated to block constriction and restore brood flow in corona), arteries and arterioles in response to calcium, potassium epinephrine, serotonin and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro, This inhibition of coronary spasm is responsible for the effectiveness of amlodipine in vasospastic (Prinzmetal's or variant) angina.
Valsartan inhibits the pressor effect of angiotensin II infusions. An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decrease in plasma aldosterone were observed after administration of Valsartan; very little effect on serum potassium was observed. In multiple dose studies in hypertensive patients with stable renal insufficiency and patients with renovascular hypertension, Valsartan had no clinically significant effects on glomerular filtration rate, filtration fraction, creatinine clearance, or renal plasma flow.
Administration of Valsartan to patients with essential hypertension results in a significant reduction of sitting, supine and standing systolic blood pressure, usually with little or no orthostatic change.
Pharmacology: Pharmacokinetics: Absorption: After oral administration of therapeutic doses of Amlodipine alone, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of Amlodipine when administered alone is not altered by the presence of food.
Following oral administration of Valsartan alone peak plasma concentrations of Valsartan are reached in 2-4 hours. Absolute bioavailability is about 25% (range 10%-35%). Food decreases the exposure (as measured by AUC) to Valsartan by about 40% and peak plasma concentration (Cmax) by about 50%.
Distribution: Ex vivo studies have shown that approximately 93% of the circulating Amlodipine drug is bound to plasma proteins in hypertensive patients. Steady-state plasma levels of Amlodipine are reached after 7 to 8 days of consecutive daily dosing.
Metabolism: Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism.
Valsartan shows bi-exponential decay kinetics following intravenous administration with an average elimination half-life of about 6 hours. The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites. The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan. The enzyme(s) responsible for Valsartan metabolism have not been identified but do not seem to be CYP 450 isoenzymes.
Excretion: Elimination from the plasma is biphasic with a terminal elimination half-life of about 30-50 hours. Ten percent of the parent Amlodipine compound and 60% of the metabolites of Amlodipine are excreted in the urine.
Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). Following intravenous administration, plasma clearance of valsartan is about 2 L/h and its renal clearance is 0.62 L/h (about 30% of total clearance).
Indications/Uses
Hypertension: Combination of Amlodipine besilate and Valsartan is indicated for the treatment of hypertension. It may be used in patients whose blood pressure is not adequately controlled on either monotherapy. It may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The initial therapy for hypertension should be based on an assessment of potential benefits and risks including whether the patient is likely to tolerate the lowest dose.
Patients with stage 2 hypertension (moderate or severe) are at a relatively higher risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient's risk.
Dosage/Direction for Use
Amlodipine is an effective treatment of hypertension in once daily doses of 2.5 mg to 10 mg while Valsartan is effective in doses of 80 mg to 320 mg. In clinical trials with once daily of Amlodipine and Valsartan using Amlodipine doses of 5 mg to 10 mg and Valsartan doses of 80 mg to 320 mg, the antihypertensive effects increased with increasing doses.
The majority of the antihypertensive effect is attained within 2 weeks after initiation of therapy or a change in dose. It may be taken with or without food.
Children: The effective antihypertensive oral dose of Amlodipine in pediatric patients' ages 6-17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients.
Special Precautions
Amlodipine and valsartan is considered a pregnancy category medication. This means that it is probably not safe for use during pregnancy. Amlodipine and Valsartan car increase the risk of birth defects and other severe problems.
Amlodipine and Valsartan can lower blood pressure too much. Signs of low blood pressure include lightheadedness, dizziness, or fainting. Congestive heart failure, a recent heart attack, or surgery can increase risk of low blood pressure.
If the patient has liver disease, the body may not metabolize Amlodipine and Valsartan as well as it should. Therefore, the patient may require extra monitoring by the healthcare provider and the patient may need to take a lower amlodipine and valsartan dosage.
Amlodipine and Valsartan may decrease kidney function, which is not a problem for most people. However, if the patient has kidney disease or heart failure, this may cause problems.
If the patient has severe coronary artery disease, there is a low possibility that taking amlodipine and valsartan may increase chances of worsening chest pain or heart attack.
Amlodipine and Valsartan can interact with a number of other medications. It is not known if amlodipine and valsartan passes through breast milk. Therefore, if the patient is breastfeeding or plan to start, discuss this with the healthcare provider prior to taking the drug.
Adverse Reactions
Cardiovascular: Cardiovascular side effects for Amlodipine-Valsartan in relation to placebo therapy have included peripheral edema (5.4% vs 3.0%). Additional cardiovascular side effects reported include orthostatic events (orthostatic hypotension and postural dizziness) in less than 1% of patients, palpitations, bradycardia, vasculitis, syncope, arrhythmia, heart murmur, and tachycardia. The incidence of peripheral edema is lower with the combination of Amlodipine-Valsartan than with Amlodipine alone.
Dermatologic: Dermatologic side effects including flushing, pruritus, rash, hyperhidrosis, exanthema, eczema, alopecia, and erythema multiforme have been reported.
Endocrine: Endocrine side effects have included diabetes mellitus.
Gastrointestinal: Gastrointestinal side effects have included diarrhea, nausea, constipation, dyspepsia, abdominal pain, anorexia, dysphagia, pancreatitis, gastritis, vomiting, abdominal discomfort and distention, gastroenteritis, dry mouth, flatulence, tonsillitis, and colitis.
Genitourinary: Genitourinary side effects have included hematuria, pollakiuria, micturation frequency, nocturia, impotence, erectile dysfunction, and cystitis.
Hematologic: Hematologic side effects have included leucopenia, neutropenia, purpura, and thrombocytopenia.
Hepatic: Hepatic side effects including elevated liver enzymes have been reported in patients treated with amlodipine-valsartan.
Metabolic: Metabolic side effects have included hyperkalemia, gout, hyperglycemia, weight gain, weight loss, and hypercholesterolemia.
Musculoskeletal: Musculoskeletal side effects including arthralgia, back pain, muscle spasms, pain in extremities, myalgia, osteoarthritis, joint swelling, muscle cramps, and musculoskeletal chest pain have been reported.
Nervous system: Nervous system side effects for Amlodipine-Valsartan in relation to placebo therapy have included dizziness (2.1% vs 0.9%). Other nervous system side effects including headache (4.3%), insomnia, peripheral neuropathy, tremor, sciatica, paresthesia, cervicobrachial syndrome, carpal tunnel syndrome, hypoesthesia, and somnolence have been reported.
Ocular: Ocular side effects including abnormal vision, conjunctivitis, diplopia, and eye pain have been reported.
Other: Other side effects have included ear pain, tinnitus, fatigue, asthenia, malaise, lymphadenopathy, fever, edema, and chest pain.
Psychiatric: Psychiatric side effects including anxiety, nervousness, abnormal dreams, depersonalization, and depression have been reported.
Renal: Renal side effects including nephrolithiasis, and increases in serum creatinine and blood urea nitrogen (BUN) have been reported, In hypertensive patients, greater than 50% increases in serum creatinine were reported in 0.4% of patients given Amlodipine-Valsartan compared with 0.6% in those given placebo. In heart failure patients, greater than 50% increases in creatinine were reported in 3.9% of Valsartan-treated patients compared with 0.9% of placebo-treated patients. In post-myocardial infarction patients, doubling of serum creatinine were reported in 4.2% of patients given Valsartan and in 3.4% of captopril-treated patents.
In hypertensive patients, greater than 50% increases in BUN were reported in 5.5% of Amlodipine-Valsartan treated patients compared with 4.7% of placebo-treated patients. In heart failure patients, greater than 50% increases in BUN were reported in 16.6% of patients given Valsartan compared with 6.3% of patients given placebo.
Respiratory: Respiratory side effects for Amlodipine-Valsartan in relation to placebo therapy have included nasopharyngitis (4.3% vs 1.8%) and upper respiratory tract infection (2.9% vs 2.1%). Other respiratory side effects have included cough, dyspnea, nasopharyngitis, sinusitis, bronchitis, pharyngitis, pharyngolaryngeal pain, sinus/nasal congestion, epistaxis, pneumonia, and dysphonia.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
C09DB01 - valsartan and amlodipine ; Belongs to the class of angiotensin II receptor blockers (ARBs) and calcium channel blockers. Used in the treatment of cardiovascular disease.
Presentation/Packing
5/160 mg FC tab 21's. 10/160 mg FC tab 21's.
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