RIFAMPIN

Chemistry - A semi-synthetic zwitterion derivative of rifamycin B, rifampin occurs as a red-brown, crystalline powder with a pKa of 7.9. It is very slightly soluble in water and slightly soluble in alcohol.

Storage, Stability, Compatibility

Rifampin capsules should be stored in tight, light-resistantcontainers, preferably at room temperature (15-30°C).

Pharmacology - RIFAMPIN

Rifampin may act as either a bactericidal or bacteriostatic antimicrobial dependentupon the susceptibility of the organism and the concentration of the drug. Rifampin acts byinhibiting DNA-dependent RNA polymerase in susceptible organisms, thereby suppressing theinitiation of chain formation for RNA synthesis. It does not inhibit the mammalian enzyme.
Rifampin is active against a variety of mycobacterium species and Staphylococcus aureus,
Neisseria, Haemophilus, and Rhodococcus equi (C. equi). At very high levels, rifampin also hasactivity against poxviruses, adenoviruses, and Chlamydia trachomatis. Rifampin also has antifungalactivity when combined with other antifungal agents.
Uses, Indications - At the present time, the principle use of rifampin in veterinary medicine is in thetreatment of Rhodococcus equi (Corynebacterium equi) infections (usually with erythromycinestolate) in young horses.
In small animals, the drug is sometimes used in combination with other antifungal agents(amphotericin B and 5-FC) in the treatment of histoplasmosis or aspergillosis with CNS involvement.

Pharmacokinetics - RIFAMPIN

After oral administration, rifampin is relatively well absorbed from the GItract. Oral bioavailability is reportedly about 40-70% in horses and 37% in adult sheep. If food isgiven concurrently, peak plasma levels may be delayed and slightly reduced.
Rifampin is very lipophilic and penetrates most body tissues (including bone and prostate), cellsand fluids (including CSF) well. It also penetrates abscesses and caseous material. Rifampin is 70-90% bound to serum proteins and is distributed into milk and crosses the placenta. Mean volume ofdistribution is approximately 0.9 L/kg in horses, and 1.3 L/kg in sheep.
Rifampin is metabolized in the liver to a deacetylated form which also has antibacterial activity.
Both this metabolite and unchanged drug are excreted primarily in the bile, but up to 30% may beexcreted in the urine. The parent drug is substantially reabsorbed in the gut, but the metabolite isnot. Reported elimination half-lives for various species are: 6-8 hours (horses), 8 hours (dogs), 3-5hours (sheep). Because rifampin can induce hepatic microsomal enzymes, elimination rates mayincrease with time.

Contraindications, Precautions, Reproductive Safety

Rifampin is contraindicated in patientshypersensitive to it or other rifamycins. It should be used with caution in patients with preexistinghepatic dysfunction.
Rodents given high doses of rifampin 150 - 250 mg/kg/day resulted in some congenital malformations in offspring, but the drug has been used in pregnant women with no reported increasesin teratogenicity.

Adverse Effects, Warnings

Rifampin can cause red-orange colored urine, tears, sweat and saliva.
There are no harmful consequences from this effect. In some species (e.g., humans), rashes, GIdistress, and increases in liver enzymes may occur, particularly with long-term use.
Adverse effects in horses are apparently rare when rifampin is given orally. Although not commercially available, intravenous rifampin has caused CNS depression, sweating, hemolysis and anorexia in horses.

Overdosage, Acute Toxicity

Symptoms associated with overdosage of oral rifampin generallyare extensions of the adverse effects outlined above (GI, orange-red coloring of fluids, and skin), but massive overdoses may cause hepatotoxicity. Should a massive oral overdosage occur, the gutshould be emptied following standard protocols. Liver enzymes should be monitored andsupportive treatment initiated if necessary.

Drug Interactions

Because rifampin has been documented to induce hepatic microsomal enzymes, drugs that are metabolized by these enzymes may have their elimination half-lives shortenedand serum levels decreased Drugs that may be affected by this process include propranolol, quinidine, dapsone, chloramphenicol, corticosteroids, oral anticoagulants (e.g., warfarin), benzodiazepines (e.g., diazepam), and barbiturates (e.g., phenobarbital).
Rifampin may cause decreased serum concentrations of ketoconazole if administered concurrently.
Drug/Laboratory Interactions - Microbiologic methods of assaying serum folate and vitamin
B12 are interfered with by rifampin.
Rifampin can cause false-positive BSP (bromosulfophthalein, sulfobromophthalein) test results, by inhibiting the hepatic uptake of the drug.