rifabutin

Action and Spectrum

Actions and Spectrum: 

rifabutin is a broad-spectrum antibiotic that belongs to the rifamycin class of drugs. It is primarily used to treat infections caused by Mycobacterium avium complex (MAC) and other mycobacterial infections in patients with HIV. 

rifabutin works by binding to the bacterial RNA polymerase enzyme, which is essential for the synthesis of bacterial RNA. This binding inhibits the transcription of bacterial RNA, leading to the inhibition of bacterial protein synthesis and eventually bacterial death. 

The spectrum of rifabutin is broad, and it is effective against a various types of bacteria including mycobacteria, Gram-positive cocci, and some Gram-negative bacteria. rifabutin is also effective against some atypical bacteria, such as Legionella pneumophila and Chlamydia trachomatis. 

In addition to its antibiotic properties, rifabutin also has immunomodulatory effects. It can stimulate the production of cytokines and enhance the activity of T cells, which may contribute to its efficacy in treating mycobacterial infections in patients with HIV. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Neutropenia (25%) 

Rash (11%) 

Leukopenia (17%) 

Discoloration of urine (30%) 

1-10% 

Abdominal pain (4%) 

Myalgia 

Anemia 

Thrombocytopenia (5%) 

Increased AST/ALT (7-9%) 

Eructation (3%) 

Diarrhea (3%) 

Anorexia (2%) 

Headache (3%) 

Flatulence (2%) 

Nausea/vomiting (3%) 

Black Box Warning

Black Box Warning: 

rifabutin has a black box warning regarding the potential for drug interactions. rifabutin is primarily metabolized by the liver enzyme CYP3A4, and it is a potent inducer of this enzyme. Therefore, rifabutin has the potential to diminish the efficacy of other drugs that are metabolized by CYP3A4. 

Some drugs that may interact with rifabutin include antiretroviral drugs, such as non-nucleoside reverse transcriptase inhibitors and protease inhibitors, which are commonly used to treat HIV. When rifabutin is co-administered with these drugs, it can lead to subtherapeutic levels of the antiretroviral drugs, which can lead to the development of drug-resistant HIV. 

Other drugs that may interact with rifabutin include some statins, immunosuppressive drugs, and oral contraceptives. Therefore, it is essential to monitor patients closely for potential drug interactions when prescribing rifabutin and adjust dosages accordingly. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

rifabutin is contraindicated in individuals with a known hypersensitivity to rifabutin or any of its components. It should not be used in patients with active tuberculosis, as rifabutin monotherapy is not recommended for the treatment of active tuberculosis. 

rifabutin is also contraindicated in patients with uveitis or other inflammatory eye disorders, as it has been associated with uveitis and other ocular adverse effects, such as red-green color blindness. 

rifabutin should be used with caution in patients with hepatic impairment, as it is primarily metabolized in the liver, and its clearance may be reduced in patients with hepatic dysfunction. Dosage adjustments may be necessary in such patients. 

Finally, rifabutin is not recommended for use during pregnancy, as there is limited information regarding its safety in pregnant women.  

Caution 

• Drug interactions: rifabutin is a potent inducer of the liver enzyme CYP3A4, which can increase the metabolism of other drugs that are metabolized by this enzyme. This can lead to reduced efficacy or increased toxicity of these drugs. Therefore, rifabutin should be used with caution in patients taking other medications metabolized by CYP3A4, and dose adjustments may be necessary. 
• Hepatic impairment: rifabutin is primarily metabolized in the liver, and its clearance may be reduced in patients with hepatic impairment. Caution in patients with hepatic dysfunction, and dose adjustments may be necessary. 
• Renal impairment: There is limited information regarding the use of rifabutin in patients with renal impairment.Caution in these patients, and dosage adjustments may be necessary. 
• Hematological effects: rifabutin has been associated with hematological adverse effects, such as leukopenia, neutropenia, and thrombocytopenia. Caution in patients with pre-existing hematological disorders, and regular monitoring of blood counts should be performed. 
• Ocular effects: rifabutin has been associated with uveitis and other ocular adverse effects, such as red-green color blindness. Caution in patients with a history of ocular disorders, and regular monitoring of visual acuity and color vision should be performed. 
• GI effects: rifabutin can cause gastrointestinal adverse effects, such as nausea, vomiting, and diarrhea. Caution in patients with a history of GI disorders, and patients should be advised to report any GI symptoms to their healthcare provider. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

rifabutin is a semisynthetic antibiotic that belongs to the rifamycin group of antibiotics. It works by inhibiting the bacterial DNA-dependent RNA polymerase, which is an essential enzyme for bacterial RNA transcription.

This inhibition leads to the prevention of bacterial RNA synthesis, which results in the inhibition of bacterial protein synthesis and ultimately, the death of the bacteria. 

rifabutin has broad-spectrum activity against both gram-positive and gram-negative bacteria, including Mycobacterium tuberculosis and Mycobacterium avium complex. It is also active against some strains of Helicobacter pylori. 

Pharmacodynamics: 

Mechanism of action: The pharmacodynamics of rifabutin involve its mechanism of action as an antibiotic and its effects on bacterial growth and survival. rifabutin works by inhibiting the bacterial DNA-dependent RNA polymerase, which is an essential enzyme for bacterial RNA transcription. This inhibition leads to the prevention of bacterial RNA synthesis, which results in the inhibition of bacterial protein synthesis and ultimately, the death of the bacteria. 

Pharmacokinetics: 

Absorption 

Approximately 53% of the substance is readily absorbed. In HIV infected individuals, the absolute bioavailability is around 20%. The peak plasma time is between 2 to 4 hours. 

Distribution 

The substance is distributed throughout various body tissues, including the lungs, liver, spleen, eyes, and kidneys. Its volume of distribution (Vd) is 9.32 L/kg, and it is highly protein-bound, with approximately 85% bound to proteins. 

Metabolism 

The substance undergoes hepatic metabolism primarily by the enzyme CYP3A4, which results in the formation of both active and inactive metabolites. 

Elimination and Excretion 

The substance has a half-life of approximately 45 hours (range: 16-69 hours). It is eliminated primarily through the urine and feces. Around 10% of the substance is excreted unchanged in the urine and feces, while approximately 53% of the substance is excreted as metabolites in the urine and 30% as metabolites in the feces. 

Adminstartion

Administration: 

Oral administration 

rifabutin is available as an oral capsule and is typically taken once daily with food. The dosage, duration of treatment depend on the indication for which it is being used and the patient’s age, weight, and renal and hepatic function. It is key to follow the dosage instructions provided by the healthcare provider. 

When taking rifabutin, it is essential to swallow the capsule whole and not crush or chew it, as this can affect the absorption of the drug. If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose. 

rifabutin should be used with caution in patients with renal or hepatic impairment, and dosage adjustments may be necessary. It should also be used with caution in patients taking other medications, as rifabutin can interact with other drugs and affect their efficacy or toxicity. Patients should be advised to complete the full course of rifabutin treatment, even if they feel better before the treatment is completed. Skipping doses or stopping treatment early can lead to the development of antibiotic-resistant bacteria and can result in treatment failure. 

Patient Information Leaflet

Patient information leaflet 

Generic Name:  rifabutin 

Pronounced: [ RIF-a-BUE-tin ] 

Why do we use rifabutin? 

rifabutin is an antibiotic that is used to treat a variety of bacterial infections. Some of the main uses of rifabutin include: 

• Treatment of tuberculosis: rifabutin is used in combination with other antibiotics to treat active tuberculosis. It is also used as a prophylactic treatment to prevent the development of tuberculosis in patients with HIV. 
• Treatment of Mycobacterium avium complex (MAC) infections: rifabutin is generally used in combination with other antibiotics to treat MAC infections in patients with HIV. MAC is a type of bacterial infection that can leads to severe illness in people with weakened immune systems. 
• Prevention of MAC infections: rifabutin is also used as a prophylactic treatment to prevent the development of MAC infections in patients with HIV. 
• Treatment of Helicobacter pylori infections: rifabutin is sometimes used as a combination therapy to treat Helicobacter pylori infections, which can cause peptic ulcers and other gastrointestinal disorders. 
• Treatment of other bacterial infections: rifabutin is also sometimes used to treat other bacterial infections, such as leprosy, and as a prophylactic treatment to prevent the development of bacterial infections in patients with weakened immune systems.