QuickView for Rifabutin (compound)

Summary
General Info

PubChem

PubChem Compound 5361912

Name:	Rifabutin
PubChem Compound ID:	5361912
Description:	A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.
Molecular formula:	C₄₆H₆₂N₄O₁₁
Molecular weight:	847.005 g/mol
Synonyms:	SPBio_003089; Prestwick0_001109; Prestwick1_001109

DrugBank

Identification

Name:	Rifabutin
Name (isomeric):	DB00615
Drug Type:	small molecule
Description:	A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.
Synonyms:	Rifabutina [Spanish]; Antibiotic LM 427; RBT; Rifabutinum [Latin]; Rifabutine [French]; Ansatipin; Ansatipine
Brand:	Mycobutin, Ansamycin, Alfacid
Category:	Anti-Bacterial Agents, Antibiotics, Antitubercular
CAS number:	72559-06-9

Pharmacology

Indication:	For the prevention of disseminated <i>Mycobacterium avium</i> complex (MAC) disease in patients with advanced HIV infection.
Pharmacology:	Rifabutin 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 aerugin... show more » Rifabutin 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. Rifabutin 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. show less «
Mechanism of Action:	Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.
Absorption:	Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%.
Protein binding:	85%
Biotransformation:	Hepatic. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity.
Route of elimination:	A mass-balance study in three healthy adult volunteers with 14C-labeled rifabutin showed that 53% of the oral dose was excreted in the urine, primarily as metabolites. About 30% of the dose is excreted in the feces.
Half Life:	45 (± 17) hours
Clearance:	0.69 +/- 0.32 L/hr/kg
Toxicity:	LD₅₀ = 4.8 g/kg (mouse, male)
Affected organisms:	Enteric bacteria and other eubacteria

Interactions

Food interaction:

Take with food to reduce irritation.

High-fat meals slow the rate of absorption.

Drug interaction:

Voriconazole	Rifabutin may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifabutin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.
Haloperidol	The rifamycin decreases the effect of haloperidol
Mestranol	This product may cause a slight decrease of the contraceptive effect
Indinavir	Rifabutin decreases the effect of indinavir
Atazanavir	Atazanavir may increase levels/toxicity of rifabutin.

Voriconazole	Rifabutin may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifabutin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.
Haloperidol	The rifamycin decreases the effect of haloperidol
Mestranol	This product may cause a slight decrease of the contraceptive effect
Indinavir	Rifabutin decreases the effect of indinavir
Atazanavir	Atazanavir may increase levels/toxicity of rifabutin.
Tipranavir	Tipranavir increases the concentration of Rifabutin. Adjust Rifabutin dose and monitor for adverse/toxic effects.
Norethindrone	Rifabutin may decrease the contraceptive effect of norethindrone. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.
Amprenavir	Amprenavir may increase the effect and toxicity of rifabutin.
Tamoxifen	The rifamycin decreases the effect of anti-estrogen
Simvastatin	Rifabutin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic effect of simvastatin if rifabutin is initiated, discontinued or dose changed.
Tacrolimus	Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
Bupropion	Rifampin reduces bupropion levels
Methadone	The rifamycin decreases the effect of methadone
Trimipramine	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifabutin is initiated, discontinued or dose changed.
Dapsone	Decreased levels of dapsone
Fosamprenavir	Amprenavir increases the effect and toxicity of rifabutin
Sirolimus	The rifamycin decreases the effect of sirolimus
Buspirone	Rifabutin decreases the effect of buspirone
Josamycin	The rifamycin, rifabutin, may decrease the effect of the macrolide, josamycin.
Lovastatin	Rifabutin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifabutin is initiated, discontinued or dose changed.
Doxepin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifabutin is initiated, discontinued or dose changed.
Trazodone	The CYP3A4 inducer, Rifabutin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifabutin is initiated, discontinued or dose changed.
Amoxapine	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifabutin is initiated, discontinued or dose changed.
Delavirdine	Rifabutin decreases the effect of delavirdine
Warfarin	Rifabutin may decrease the anticoagulant effect of warfarin by increasing its metabolism.
Fluvastatin	Rifabutin may decrease the effect of fluvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluvastatin if rifabutin is initiated, discontinued or dose changed.
Propafenone	Rifampin decreases the effect of propafenone
Ethinyl Estradiol	Rifabutin may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied on alone during concomitant therapy with rifabutin.
Cyclosporine	The rifamycin decreases the effect of cyclosporine
Cerivastatin	Rifabutin may decrease the effect of cerivastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cerivastatin if rifabutin is initiated, discontinued or dose changed.
Imipramine	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifabutin is initiated, discontinued or dose changed.
Itraconazole	Rifabutin decreases the effect of itraconazole
Dicumarol	Rifabutin may decrease the anticoagulant effect of dicumarol.
Protriptyline	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, protriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of protriptyline if rifabutin is initiated, discontinued or dose changed.
Verapamil	Rifabutin, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifabutin is initiated, discontinued or dose changed.
Doxycycline	The rifamycin decreases the effect of doxycycline
Atovaquone	Rifabutin decreases the effect of atovaquone
Zidovudine	The rifamycin decreases levels of zidovudine
Erlotinib	Decreased levels/effect of erlotinib
Atorvastatin	Rifabutin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifabutin is initiated, discontinued or dose changed.
Clomipramine	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed.
Desipramine	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if rifabutin is initiated, discontinued or dose changed.
Ritonavir	Rifabutin decreases the effect of ritonavir
Clarithromycin	The rifamycin, rifabutin, may decrease the effect of the macrolide, clarithromycin.
Fluconazole	Fluconazole may increase levels/toxicity of rifabutin.
Posaconazole	Modification of drug levels for both agents
Tramadol	Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Erythromycin	The rifamycin, rifabutin, may decrease the effect of the macrolide, erythromycin.
Toremifene	The rifamycin decreases the effect of anti-estrogen
Clozapine	Rifabutin decreases the effect of clozapine
Telithromycin	Rifabutin may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Saquinavir	Rifabutin decreases the effect of saquinavir
Sunitinib	Possible decrease in sunitinib levels
Anisindione	Rifabutin, may decrease the anticoagulant effect of anisindione.
Temsirolimus	Rifabutin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Terbinafine	Rifabutin may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.
Acenocoumarol	Rifabutin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
Bromazepam	Rifabutin may decrease the serum concentration of bromazepam by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if rifabutin is initiated, discontinued or dose changed.
Amitriptyline	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
Nortriptyline	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed.

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Targets

DNA-directed RNA polymerase alpha chain

DNA-directed RNA polymerase beta chain

DNA-directed RNA polymerase subunit beta'

Heat shock protein HSP 90-alpha

Endoplasmin

Enzymes

Cytochrome P450 3A4

Cytochrome P450 1A2