ic contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting. Active diuresis (with measured intake and output) will help promote excretion of the drug. Haemodialysis may be of value in some patients.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Rifampicin is an active bactericidial antituberculosis drug which is particularly active against the rapidly growing extracellular organisms and also has bactericidial activity intracellularly. Rifampicin has activity against slow and intermittently-growing M. Tuberculosis.
Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown with other rifamycins.
5.2 Pharmacokinetic properties
Rifampicin is readily absorbed from the gastrointestinal tract. Peak serum concentrations of the order of 10 µg/ml occur about 2 to 4 hours after a dose of 10 mg/kg body weight on an empty stomach.
Absorption of rifampicin is reduced when the drug is ingested with food.
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 enterophepatic 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
Agar
Sucrose
Methyl-p-hydroxybenzoate (E218)
Propyl-p-hydroxybenzoate (E216)
Potassium sorbate
Sodium metabisulphite (E223)
Tween 80
Raspberry essence (Contains small amount of ethanol)
Saccharin
Diethanolamine
Purified water
6.2 Incompatibilities
None stated
6.3 Shelf life
3 years from date of manufacture
6.4 Special precautions for storage
Do not store above 25°C.
Do not dilute.
Dispense in clear or amber glass bottles.
6.5 Nature and contents of container
120ml in amber glass bottles
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
