600 mg dose of Rifadin infusion infused over 30 minutes to healthy male volunteers (n = 12), mean peak plasma concentrations were 9.0 and 17.5 µg/ml, respectively. The average plasma concentrations in these volunteers remained detectable for 8 and 12 hours, respectively.
The pharmacokinetics (oral and intravenous) in children are similar to adults.
In normal subjects the biological half-life of rifampicin in serum averages about 3 hours after a 600 mg dose and increases to 5.1 hours after a 900 mg dose. With repeated administration, the half-life decreases and reaches average values of approximately 2-3 hours. At a dose of up to 600 mg/day, it does not differ in patients with renal failure and consequently, no dosage adjustment is required.
Rifampicin is rapidly eliminated in the bile and an enterohepatic circulation ensues. During this process, rifampicin undergoes progressive deacetylation, so that nearly all the drug in the bile is in this form in about 6 hours. This metabolite retains essentially complete antibacterial activity. Intestinal reabsorption is reduced by deacetylation and elimination is facilitated. Up to 30 % of a dose is excreted in the urine, with about half of this being unchanged drug.
Rifampicin is widely distributed throughout the body. It is present in effective concentrations in many organs and body fluids, including cerebrospinal fluid. Rifampicin is about 80 % protein bound. Most of the unbound fraction is not ionized and therefore is diffused freely in tissues.
5.3 Preclinical safety data
Not applicable
6. Pharmaceutical particulars
6.1 List of excipients
Sodium sulfoxylate formaldehyde
Sodium hydroxide
Solvent
Water for Injections.
6.2 Incompatibilities
Compatibilities: Rifadin for Infusion is compatible with the following infusion solutions for up to 6 hours: Glucose 5% and Saline Solution.
Incompatibilities: Rifadin for Infusion is incompatible with the following: Perfudex, Sodium Bicarbonate 5%, Sodium Lactate 0.167M, Ringer Acetate with Glucose.
6.3 Shelf life
Unopened vial of lyophilisate: 48 months
Unopened ampoule of solvent:60 months
Reconstituted Solution: 6 hours
6.4 Special precautions for storage
Store below 25°C.
6.5 Nature and contents of container
20ml clear neutral glass vial sealed with butyl rubber stopper and aluminium/plastic “flip-off” cap (colour coded blue) containing 600mg Rifampicin and 10ml clear glass ampoule containing solvent.
Pack size: combination of 1 vial of lyophilisate and 1 ampoule of solvent.
6.6 Special precautions for disposal and other handling
Not applicable.
7. Marketing authorisation holder
Aventis Pharma Limited
Trading as Marion Merrell or Aventis Pharma
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
Or trading as
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
8. Marketing authorisation number(s)
PL 04425/0051
9. Date of first authorisation/renewal of the authorisation
7th December 1982 / 9th April 2005
10. Date of revision of the text
13 January 2017
