5mg/50mg Film-Coated Tablet
Calcium Channel Blocker
Angiotensin II Receptor Blocker
Each film-coated tablet contains:
Amlodipine (as besilate) ………………………………………. 5 mg
Losartan (as Potassium) ……………………………………..50 mg
Amlodipine + Losartan contains the besilate salt of Amlodipine,a dihydropyridine calcium channel blocker (CCB). Amlodipine besilate is a white to pale yellow crystalline powder, slightly soluble in water and sparingly soluble in ethanol. Amlodipine besilate’s chemical name is 3,5- methyl(4RS)-2-[(2-aminoethoxy) methyl]-4-(2chlorophenyl)-6-methyl-1,4- dihydropyridine-3, 5-dicarboxylate benzenesulphonate. Its empirical formula is C20H25ClN2O5.C6H6O3S and its molecular weight is 567.1. Losartan potassium is an angiotensin II receptor (type ATI) antagonist. Losartan potassium, a non-peptide molecule, is a chemical described as 2-butyl-4-chloro-1- [p-(o-1H-tetrazol-5-ylphenyl) benzyl]imidazole-5- methanol monopotassium salt. Losartan potassium is a white to off- white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohol, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone. Oxidation of the 5-Hydroxymethyl group on the imidazole ring in the active metabolite of Losartan.
Used in the treatment of mild to moderate hypertension in case of inadequate control with monotherapy.
DOSAGE AND ADMINISTRATION:
Usual, initial dose is one (1) tablet daily. Increase if necessary to two (2) tablets daily or as prescribed by the physician.
Similar doses are given in the treatment of stable angina and Prinzmetal’s angina or as prescribed by the physician.
Combination of Amlodipine with Losartan is contraindicated in patients with hypersensitivity reaction to the said components, and to the other ingredient of this product.
Amlodipine should be used with caution in patients with hypotension, in patients whose cardiac reserve is poor, and in those with heart failure. It should not be used in cardiogenic shock, in patient who have recently suffered a myocardial infarction, or in acute unstable angina. It should not be used
to treat an angina attack in chronic stable angina. In patients with severe aortic stenosis it may increase the risk of developing heart failure. Sudden withdrawal might be associated with an exacerbation of angina. The dose may need to be reduced in patients with hepatic impairment.
It should be discontinued in patients who experience ischaemic pain following its administration. Losartan is contraindicated in pregnancy and should be used with care, if at all, during breast feeding. It should be used with caution in patients with renal artery stenosis.
Reduced doses may be required in patients with renal impairment and should be considered in patients with hepatic impairment. Patients with volume depletion (for example those who have received high- dose diuretic therapy) may experience hypotension, which may be minimized by initiating treatment with a low dose of Losartan. Since hyperkalemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and the concomitant use of potassium-sparing diuretics should generally be avoided.
Hypersensitivity to any component of this product.
Antihypertensive property of Amlodine plus may be enhanced by other antihypertensive drugs such as beta-blockers although combination is well-tolerated.
Adverse effects of Losartan have been reported to be usually mild and transient, and include dizziness and dose-related orthostatic hypotension. Hypotension may occur particularly in patients with volume depletion (for example those who have received high-dose diuretics).
Impaired renal function and, rarely, rash, angioedema, and raised liver enzyme values may occur. Hyperkalemia and myalgia have been reported. Losartan appears less likely than ACE inhibitors to cause cough. Other adverse effects that have been reported with angiotensin II receptor antagonists include respiratory-tract disorders, back pain, gastrointestinal disturbances, fatigue, and neutropenia. The most common adverse effects are associated with its vasodilator action and often diminish on continued therapy. They include dizziness, flushing, headache, hypotension, peripheral edema, tachycardia and palpitations. Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain, and mental depression have also occurred. A paradoxical increase in ischaemic chest pain may occur at the start of treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness. There have been reports of rashes (including erythema multiforme), fever, and abnormalities in liver function, including cholestasis, due to hyperplasia, myalgia, tremor and impotence have been reported. Overdose maybe associated with bradycardia and hypotension.
OVERDOSE AND TREATMENT:
Management of Calcium-channel blocker induced overdosage is mainly supportive. For bradycardia induced overdosage, Atropine is used. To reverse the effect. While intravenous fluids, sympathomimetics and inotropes are the mainstay of treatment.
Amlodipine is well absorbed following oral administration with peak blood concentrations occurring after 6 to 12 hours. The bioavailability is about 60 to 65%. Amlodipine is reported to be about 97.5% bound to plasma proteins.
It has a prolonged terminal elimination half-life of 35 to 50 hours and steady-state plasma concentrations are not achieved until 7 to 8 days of administration.
Amlodipine is extensively metabolized in the liver; metabolites are mostly excreted in urine together with less than 10% of dose as unchanged drug. Losartan is readily absorbed from the gastrointestinal tract following oral administration, with an oral bioavailability of about 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than Losartan, and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of Losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both Losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the faeces via bile, as unchanged drug and metabolites. Following oral dosing abut 35% of the dose if excreted in the urine and about 60% in the faeces. The terminal elimination half-lives of Losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
PREGNANCY AND LACTATION:
When pregnancy is detected, it is recommended to discontinue therapy of Amlodipine plus Losartan. It is also recommended to discontinue the combination while nursing.
Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.
Registration Number: DRP-5685
Date of First Authorization: October 28, 2014
ADR REPORTING STATEMENT:
“For suspected adverse drug reaction, report to the FDA: www.fda.gov.ph, ” Seek medical attention immediately at the first sign of any adverse drug reaction.
Clear PVDC Blister Pack x 10’s (Box of 30’s)
Store at temperatures not exceeding 30ºC
Lloyd Laboratories, Inc.
No. 10 Lloyd Ave., First Bulacan Industrial City, City of Malolos, Bulacan
Innogen Pharmaceuticals, Inc.
124-126 Dr. Lazcano St., Brgy. Sacred Heart, Quezon City
Rose Pharmacy, Incorporated
3rd Floor, FLC Center, 888 Hernan Cortes St, Subangdaku, Mandaue
City, 6014, Cebu, Philippines