Rifaldazin

Rifaldazin - General Information

A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifaldazin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman&

Pharmacology of Rifaldazin

Rifaldazin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifaldazin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

Rifaldazin for patients

The patient should be told that rifampin may produce a reddish coloration of the urine, sweat, sputum, and tears, and the patient should be forewarned of this. Soft contact lenses may be permanently stained. The patients should be advised that the reliability of oral or other systemic hormonal contraceptives may be affected; consideration should be given to using alternative contraceptive measures. Patients should be instructed to take rifampin either 1 hour before or 2 hours after a meal with a full glass of water. Patients should be instructed to notify their physicians promptly if they experience any of the following: fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, and pain or swelling of the joints. Compliance with the full course of therapy must be emphasized, and the importance of not missing any doses must be stressed.

Rifaldazin Interactions

ENZYME INDUCTION: Rifampin is known to induce certain cytochrome P-450 enzymes. Administration of rifampin with drugs that undergo biotransformation through these metabolic pathways may accelerate elimination of coadministered drugs. To maintain optimum therapeutic blood levels, dosages of drugs metabolized by these enzymes may require adjustment when starting or stopping concomitantly administered rifampin.

Rifampin has been reported to accelerate the metabolism of the following drugs: anticonvulsants (eg, phenytoin), antiarrhythmics (eg, disopyramide, mexiletine, quinidine, tocainide), oral anticoagulants, antifungals (eg, fluconazole, itraconazole, ketoconazole), barbiturates, beta-blockers, calcium channel blockers (eg, diltiazem, nifedipine, verapamil), chloramphenicol, clarithromycin, corticosteroids, cyclosporine, cardiac glycoside preparations, clofibrate, oral or other systemic hormone contraceptives, dapsone, diazepam, doxycycline, fluoroquinolones (eg ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, nortriptyline, progestins, quinine, tacrolimus, theophylline tricyclic antidepressants (eg, amitriptyline, nortriptyline), and zidovudine. It may be necessary to adjust the dosages of these drugs if they are given concurrently with rifampin.

Patients using oral or other systemic hormonal contraceptives should be advised to change to nonhormonal methods of birth control during rifampin therapy.

Rifampin has been observed to increase the requirements for anticoagulant drugs of the coumarin type. In patients receiving anticoagulants and rifampin concurrently, it is recommended that the prothrombin time be performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant.

Diabetes may become more difficult to control.

OTHER INTERACTIONS: When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampin were observed.

Concurrent use of ketoconazole and rifampin has resulted in decreased serum concentrations of both drugs. Concurrent use of rifampin and enalapril has resulted in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments should be made if indicated by the patient's clinical condition.

Concomitant antacid administration may reduce the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids.

Probenecid and cotrimoxazole have been reported to increase the blood level of rifampin.

When rifampin is given concomitantly with either halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampin and halothane should be avoided. Patients receiving both rifampin and isoniazid should be monitored close for hepatotoxicity.

Plasma concentrations of sulfapyridine may be reduced following the concomitant administration of sulfasalazine and rifampin. This finding may be the result of alteration in the colonic bacteria responsible for the reduction of sulfasalazine to sulfapyridine and mesalamine.

Rifaldazin Contraindications

Rifampin is contraindicated in patients with a history of hypersensitivity to any of the rifamycins.

Additional information about Rifaldazin

Rifaldazin Indication: For the treatment of Tuberculosis and Tuberculosis-related mycobacterial infections.
Mechanism Of Action: Rifaldazin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
Drug Interactions: Not Available
Food Interactions: Avoid alcohol.
Take on empty stomach: 1 hour before or 2 hours after meals.
Take with a full glass of water.
Generic Name: Rifampin
Synonyms: RFP
Drug Category: Leprostatic Agents; Antibiotics; Antituberculosis Agents; Antibiotics, Antitubercular; Enzyme Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Rifampin: Archidyn; L-5103 Lepetit; R/AMP; RAMP; Rfamipicin; Rifa; Rifadin; Rifadin IV; Rifadine; Rifagen; Rifaldazin; Rifaldazine; Rifaldin; Rifampicin; Rifampicin SV; Rifamycin; Rifamycin Amp; Rifaprodin; Rifoldin; Rifoldine; Riforal; Rimactan; Rimactane; Rimactin; Rimazid; Rofact; Tubocin;
Absorption: Well absorbed from gastrointestinal tract.
Toxicity (Overdose): LD₅₀=1570 mg/kg (rat), chronic exposure may cause nausea and vomiting and unconsciousness
Protein Binding: 89%
Biotransformation: Primarily hepatic, rapidly deacetylated.
Half Life: 3.35 (+/- 0.66) hours
Dosage Forms of Rifaldazin: Capsule Oral
Chemical IUPAC Name: (7S,9E,11S,12S,13R,14S,15R,16S,17R,18S,26E)-2,15,17,29-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-{[(4-methylpiperazin-1-yl)amino]methylidene}-6,23,27-trioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1(28),2,4,9,19,21,25(29)-heptaen-13-yl acetate
Chemical Formula: C43H58N4O12
Rifampin on Wikipedia: https://en.wikipedia.org/wiki/Rifampin
Organisms Affected: Mycobacteria; Various gram-negative and gram-positive eubacteria