eaningfuleffect on rifamycin systemic exposure necessitating a dose adjustment.
8.7 Hepatic Impairment
The pharmacokinetics of AEMCOLO in patients with impaired hepatic function has not been studied.
Given the minimal systemic exposure of rifamycin (taken as AEMCOLO) hepatic impairment is notexpected to have a clinically meaningful effect on rifamycin systemic exposure necessitating a doseadjustment.
10 OVERDOSAGE
No specific information is available on the treatment of overdose with AEMCOLO. In the case ofoverdose, discontinue AEMCOLO, treat symptomatically, and institute supportive measures asrequired.
11 DESCRIPTION
AEMCOLO, delayed-release tablet, for oral administration, contains 194 mg of rifamycin equivalent to200 mg of rifamycin sodium.
Rifamycin sodium is a rifamycin antibacterial. It is designated chemically as: Sodium(2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-21-(acetyloxy)-6,9,17,19-tetrahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,11,13]trienimino)naphtho[2,1-b]furan-5-olate. Its empirical formula isC37H46NNaO12. The molecular weight is 720 g/mol.
Its structural formula is:
Rifamycin sodium is a fine or slightly granular powder, soluble in water, and freely soluble inanhydrous ethanol.
AEMCOLO, delayed-release tablets are enteric coated with a pH-resistant polymer film which breaksdown above pH 7. The tablet core contains rifamycin. The tablets are yellow brown and ellipsoidal.
Each tablet contains the following inactive ingredients: ammonio methacrylate copolymer (Type B),ascorbic acid, glyceryl distearate, lecithin, magnesium stearate, mannitol, methacrylic acid and methylmethacrylate copolymer (1:2), polyethylene glycol 6000, colloidal silicon dioxide, talc, titaniumdioxide, triethylcitrate, yellow ferric oxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Rifamycin is an antibacterial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
AEMCOLO exposure-response relationships and time course of pharmacodynamic response are
unknown.
12.3 Pharmacokinetics
Plasma Concentrations
In healthy adults receiving the recommended dose of 388 mg rifamycin (taken as AEMCOLO) twicedaily for 3 days, the maximum observed rifamycin concentration in plasma was 8.72 ng/mL (6 hoursafter the last dose). A majority (67%) of rifamycin concentrations in plasma were below the limit ofquantification (< 2 ng/mL) at this time point.
Absorption
Rifamycin (taken as AEMCOLO) has limited systemic exposure after oral administration of therecommended dosage. Based on total urinary excretion data, bioavailability was < 0.1% under fastingconditions.
Food EffectA food-effect study involving administration of AEMCOLO to healthy volunteers under a fasted stateand with a meal (approximately 1,000 kcal including 500 kcal from fat) indicated that food decreasedsystemic exposure of rifamycin. The decrease in systemic exposure of rifamycin is not expected to beclinically relevant [see Dosage and Administration (2.2)].
Distribution
Plasma protein binding was approximately 80% in vitro. Binding was primarily to albumin and wasinversely proportional to concentration.
Elimination
The apparent half-life of orally administered rifamycin (taken as AEMCOLO) in plasma is unknown.
Metabolism
Cytochrome P450 (CYP) based metabolism of rifamycin was not observed in vit |
