nitial dose may be required [see Dosage and Administration (2.1)].
8.6 Hepatic Impairment
A lower initial dose may be required for patients with hepatic insufficiency [see Dosage and
Administration (2.1) and Clinical Pharmacology (12.3)].
10 OVERDOSAGE
Overdosage might be expected to cause excessive peripheral vasodilation with markedhypotension and possibly a reflex tachycardia. In humans, experience with intentionaloverdosage of amlodipine is limited.
Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mgamlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleatedoses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times themaximum recommended human dose on a mg/m2 basis) caused a marked peripheral vasodilationand hypotension.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequentblood pressure measurements are essential. Should hypotension occur, provide cardiovascularsupport including elevation of the extremities and the judicious administration of fluids. Ifhypotension remains unresponsive to these conservative measures, consider administration ofvasopressors (such as phenylephrine) with attention to circulating volume and urine output. Asamlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
11 DESCRIPTION
KATERZIA oral suspension contains 1.30 mg/mL amlodipine benzoate, equivalent to 1 mg/mLamlodipine, a long-acting calcium channel blocker.
Amlodipine benzoate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, benzenecarboxylate.
Its empirical formula is C20H25ClN2O5•C7H6O2, and its structural formula is:
C7H6O2
Amlodipine benzoate is a white crystalline powder with a molecular weight of 530.
KATERZIA is for oral administration. Inactive ingredients include citric acid, colloidal silicon
dioxide, hypromellose, maltodextrin, polysorbate 80, simethicone, sodium benzoate, sodium
besylate, sodium citrate, sodium hydroxide, sucralose, and water. It is a white to off-white oral
suspension.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channelblocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle andcardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine andnondihydropyridine binding sites. The contractile processes of cardiac muscle and vascularsmooth muscle are dependent upon the movement of extracellular calcium ions into these cellsthrough specific ion channels. Amlodipine inhibits calcium ion influx across cell membranesselectively, 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 intactanimals 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 kineticinteraction with the calcium channel receptor is characterized by a gradual rate of association anddissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that |
