Antihypertensive drugs
Amlodipine Besylate 6,9 mg Equivalent Amlodipine 5 mg-Valsartan 160 mg
30Coated Tablets
T105
113/2015
20/5/2015
Excipients | Microcrystalline cellulose ‚ Crospovidone ‚Colloidal silicon oxide ‚Magnesium stearate ‚ Sodium starch glycolate ‚PEG 4000 ‚Talc ‚Tio2 ‚HPMC ‚Yellow iron oxide ‚Red iron oxide . |
Mechanism Of Action | Amlodipine: Amlodipine is a dihydropyridine calcium channel blocker that inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.Serum calcium concentration is not affected by Amlodipine. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Valsartan: Valsartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of valsartan on blood pressure. |
INDICATIONS | Amlodipine/ valsartan is indicated for the treatment of hypertension. This drug may be used: • In patients whose blood pressure is not adequately controlled on either monotherapy. • As initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The choice of Amlodipine/ valsartan as 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 of Amlodipine/ valsartan. Patients with stage 2 hypertension (moderate or severe) are at a relatively higher risk for cardiovascular events, kidney failure and vision problems, so prompt treatment is clinically relevant. The decision to use this 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. |
CONTRAINDICATIONS | It is contraindicated in patients with known hypersensitivity to any component. |
Side EFFECTS | dizziness) were seen in less than 1% of patients. Other adverse reactions that occurred in (0.2%) are listed below. It cannot be determined whether these events were causally related to (Amlodipine and Valsartan). Blood and Lymphatic System Disorders: Lymphadenopathy Cardiac Disorders: Palpitations, tachycardia Ear and Labyrinth Disorders: Ear pain Gastrointestinal Disorders: Diarrhea, nausea, constipation, dyspepsia, abdominal pain, abdominal pain upper, gastritis, vomiting, abdominal discomfort, abdominal distention, dry mouth and colitis General Disorders: Fatigue, chest pain, asthenia, pitting edema, pyrexia, edema Immune System Disorders: Seasonal allergies Infections and Infestations: Nasopharyngitis, sinusitis, bronchitis acute, pharyngitis, gastroenteritis, pharyngotonsillitis. Injury and Poisoning: Epicondylitis, joint sprain, limb injury Metabolism and Nutrition Disorders: Gout, non-insulin-dependent diabetes mellitus, hypercholesterolemia Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, muscle spasms, pain in extremity, myalgia, osteoarthritis, joint swelling, musculoskeletal chest pain Nervous System Disorders: Headache, sciatica, paresthesia, cervicobrachial syndrome, carpal tunnel syndrome, hypoesthesia, sinus headache, somnolence Psychiatric Disorders: Insomnia, anxiety, depression Renal and Urinary Disorders: Hematuria, nephrolithiasis, pollakiuria Reproductive System and Breast Disorders: Erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders: Cough, pharyngolaryngeal pain, sinus congestion, dyspnea, epistaxis, productive cough, nasal congestion Skin and Subcutaneous Tissue Disorders: Pruritus, rash, hyperhidrosis, eczema, erythema Vascular Disorders: Flushing, exanthema, syncope, visual disturbance, hypersensitivity, tinnitus, hypotension |
WARNINGS | Hypotension: In patients with an activated renin-angiotensin system, such as volume-and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur in patients receiving angiotensin receptor blockers. Volume depletion should be corrected prior to administration of (Amlodipine and Valsartan). Treatment with (Amlodipine and Valsartan) should start under close medical supervision.If excessive hypotension occurs with (Amlodipine and Valsartan), the patient should be placed in a supine position and, if necessary, given an intravenous infusion of normal saline.A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized. Risk of Myocardial Infarction or Increased Angina: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. Impaired Renal Function: Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Monitor renal function periodically in these patients. Hyperkalemia; Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Monitor serum electrolytes periodically. Specific Populations: Pediatric Use: Safety and effectiveness of drug in pediatric patients have not been established. Elderly: no overall difference in the efficacy or safety of drug was observed in this patient population, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment: Safety and effectiveness of drug in patients with severe renal impairment (CrCl< 30 mL/min) have not been established. No dose adjustment is required in patients with mild (60-90 mL/min) or moderate (CrCl 30-60ml/min) renal impairment. Hepatic Impairment Amlodipine Exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of( Amlodipine and Valsartan) Valsartan No dose adjustment is necessary for patients with mild-to-moderate disease. No dosing recommendations can be provided for patients with severe liver disease |
DRUG INTERACTIONS | No drug interaction studies have been conducted with combination of Amlodipine and Valsartan and other drugs, although studies have been conducted with theindividual amlodipine and valsartan components. Amlodipine: Simvastatin:Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose ofsimvastatin in patients on amlodipine to 20 mg daily. CYP3A4 Inhibitors:Coadministration with CYP3A4 inhibitors (moderate and strong) result in increased systemic exposure toamlodipine warranting dose reduction. Monitor for symptoms of hypotension and edema in this coadministration withCYP3A4 inhibitors to determine the need for dose adjustment. CYP3A4 Inducers:No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers. Valsartan: No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin. NSAIDs including COX-2 Inhibitor:In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs,including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in these patients. The antihypertensive effect of angiotensin II receptor antagonists, including valsartan may be attenuated by NSAIDs including selective COX-2 inhibitors. Potassium:Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium sparing diuretics (e.g.,spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-medication is considered necessary, monitoring of serum potassium is advisable. CYP 450 Interactions:CYP 450 mediated drug interactions between valsartan and coadministered drugs are unlikely because of low extent of metabolism. Rifampin,Cyclosporine, Ritonavir:Coadministration of Rifampin,Cyclosporine or Ritonavir may increase the systemic exposure to valsartan. |
Pregnancy And lactations | Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. The drug should not be used during pregnancy, When pregnancy is detected, discontinue drug as soon as possible. Nursing Mothers: It is not known whether amlodipine or valsartan is excreted in human milk. Because many drugs are excreted into human milk and because of the potential for adverse reactions in nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
Dosage And Administration | General considerations: Dose once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one (Amlodipine and Valsartan) 10 mg / 320 mg tablet once daily as needed to control blood pressure. The majority of the antihypertensive effect is attained within 2 weeks after initiation of therapy or a change in dose. It may be administered with or without food, and may be administered with other antihypertensive agents. Add-on Therapy: A patient whose blood pressure is not adequately controlled with amlodipine (or another dihydropyridine calcium-channel blocker) alone or with valsartan (or another angiotensin II receptor blocker) alone may be switched to combination therapy with (Amlodipine and Valsartan). The clinical response to (Amlodipine and Valsartan) should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of (Amlodipine and Valsartan) 10 mg / 320 mg. Initial Therapy A patient may be initiated on (Amlodipine and Valsartan) if it is unlikely that control of blood pressure would be achieved with a single agent. The usual starting dose is Welvas 5/160 mg once daily in patients who are not volume-depleted. |
OVERDOSE | Amlodipine: If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit. Valsartan: The most likely effect of overdose with valsartan would be peripheral vasodilation, hypotension, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse, and shock have been reported. If symptomatic hypotension should occur, supportive treatment should be instituted. Valsartan is not removed from the plasma by hemodialysis. |
Storage Conditions | Store at room temperature, between 15° – 30 °C‚ away from moisture . Out of reach of children . Prescription only medicine |