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.

Administration

May be taken with or without food.

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 can increase the risk of birth defects and other severe problems.
Amlodipine and Valsartan can lower the patient's 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 the patient's risk of low blood pressure.
If the patient has liver disease, the patient's body may not metabolize Amlodipine and Valsartan as well as it should. Therefore, the patient may require extra monitoring by the patient's 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 the patient's 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 patient's healthcare provider prior to taking the drug.

Use In Pregnancy & Lactation

Amlodipine and valsartan is considered a pregnancy Category medication. This means that it is probably not safe for use during pregnancy. Amlodipine and Valsartan can increase the risk of birth defects and other severe problems.

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, cerviocobrachial 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 postmyocardial infarction patients, doubling of serum creatinine were reported in 4.2% of patients given Valsartan and in 3.4% of captopril-treated patients.
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, dyspnea, epistaxis, pneumonia, and dysphonia.

Storage

Store at temperatures not exceeding 30°C.

Action

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).

MedsGo Class

Angiotensin II Antagonists / Calcium Antagonists

VALIANZ Amlodipine Besilate / Valsartan 5mg / 80mg Film-Coated Tablet 1's