Rifampin interactions. Rifampin and Rifabutin Drug Interactions: A Comprehensive Guide for Healthcare Professionals
What are the major drug interactions with rifampin and rifabutin. How do these antibiotics affect other medications. What precautions should healthcare providers take when prescribing rifampin or rifabutin. How can potential drug interactions be managed effectively.
Overview of Rifampin and Rifabutin
Rifampin and rifabutin are antibiotics belonging to the rifamycin class of drugs. They are primarily used to treat tuberculosis and other mycobacterial infections. While highly effective, these medications are known for their significant potential to interact with numerous other drugs, which can have important clinical implications.
Rifampin, in particular, is a potent inducer of several hepatic enzymes, including cytochrome P450 (CYP) enzymes. This induction can lead to increased metabolism and decreased effectiveness of many medications metabolized by these enzymes. Rifabutin, while similar to rifampin, generally has fewer and less severe drug interactions.
Mechanism of Drug Interactions
The primary mechanism behind rifampin’s numerous drug interactions is its ability to induce hepatic enzymes. This induction leads to:
- Increased metabolism of many drugs
- Decreased plasma concentrations of affected medications
- Reduced therapeutic efficacy of these drugs
Rifabutin also induces hepatic enzymes, but to a lesser extent than rifampin. This difference in potency explains why rifabutin generally has fewer drug interactions compared to rifampin.
Major Drug Interactions with Rifampin
According to the data provided, rifampin has 556 known drug interactions, with 242 of these classified as major interactions. Some of the most significant interactions include:
Anticoagulants
Rifampin can significantly reduce the effectiveness of warfarin and other oral anticoagulants. This interaction can lead to inadequate anticoagulation and increased risk of thrombotic events.
Hormonal Contraceptives
The efficacy of oral contraceptives, as well as other hormonal contraceptive methods, can be severely compromised by rifampin. This interaction can result in unintended pregnancies if alternative contraceptive methods are not used.
Antiretroviral Medications
Rifampin can substantially decrease the plasma concentrations of many antiretroviral drugs used in HIV treatment. This interaction can lead to treatment failure and development of drug resistance in HIV patients.
Cardiovascular Medications
Many cardiovascular drugs, including certain beta-blockers, calcium channel blockers, and antiarrhythmic agents, can have reduced efficacy when co-administered with rifampin. This can result in inadequate control of blood pressure, heart rate, or cardiac arrhythmias.
Moderate and Minor Interactions
In addition to the major interactions, rifampin has 255 moderate and 59 minor interactions. While these may not be as clinically significant as the major interactions, they still warrant attention and potential management strategies.
Moderate Interactions
Some examples of moderate interactions include:
- Certain antidiabetic medications
- Some antiepileptic drugs
- Certain antidepressants
Minor Interactions
Minor interactions, while less likely to cause significant clinical issues, should still be monitored. Examples include interactions with some over-the-counter medications and certain nutritional supplements.
Rifabutin: A Potentially Safer Alternative
Rifabutin, while similar to rifampin in its antimicrobial activity, has a more favorable drug interaction profile. It induces hepatic enzymes to a lesser extent than rifampin, resulting in fewer and less severe drug interactions.
In situations where drug interactions with rifampin are a major concern, rifabutin may be considered as an alternative, particularly in patients with HIV who are on antiretroviral therapy.
Managing Drug Interactions
Healthcare providers must be vigilant when prescribing rifampin or rifabutin, especially in patients on multiple medications. Some strategies for managing these interactions include:
- Thorough medication review before initiating rifampin or rifabutin therapy
- Consideration of alternative antibiotics when possible
- Dose adjustments of interacting medications
- Close monitoring of drug levels and therapeutic effects
- Patient education about potential interactions and signs of reduced drug efficacy
Clinical Implications and Recommendations
The extensive drug interaction potential of rifampin and, to a lesser extent, rifabutin, has significant clinical implications. Healthcare providers should:
- Be aware of the major, moderate, and minor drug interactions associated with these antibiotics
- Carefully evaluate the risk-benefit ratio when prescribing rifampin or rifabutin in patients on multiple medications
- Consider rifabutin as a potentially safer alternative in situations where drug interactions are a major concern
- Implement appropriate monitoring and management strategies to mitigate the risk of clinically significant interactions
Have you considered the impact of rifampin-induced enzyme induction on drug metabolism. The induction of hepatic enzymes by rifampin can lead to accelerated metabolism of many drugs, potentially reducing their plasma concentrations and therapeutic efficacy. This effect can persist for up to two weeks after discontinuation of rifampin, necessitating continued monitoring even after the antibiotic course is completed.
Special Populations and Considerations
Certain patient populations may be at higher risk for complications related to rifampin or rifabutin drug interactions. These include:
Patients with HIV
The interaction between rifampin and antiretroviral medications is of particular concern in HIV patients. Rifabutin is often preferred in this population due to its lesser effect on antiretroviral drug levels. However, dose adjustments of both the rifamycin and the antiretroviral drugs may be necessary.
Elderly Patients
Older adults are more likely to be on multiple medications, increasing the risk of drug interactions. Additionally, age-related changes in drug metabolism and elimination may further complicate the management of these interactions.
Patients with Hepatic Impairment
Given the hepatic metabolism of many drugs affected by rifampin and rifabutin, patients with liver disease may require special consideration and closer monitoring.
Is rifampin contraindicated in patients with liver disease. While rifampin is not absolutely contraindicated in liver disease, it should be used with caution. Patients with pre-existing liver conditions may be at increased risk of hepatotoxicity and may require more frequent liver function monitoring during treatment.
Future Directions and Research Needs
As our understanding of drug interactions continues to evolve, several areas warrant further research:
- Development of rifamycin antibiotics with even fewer drug interactions
- Improved strategies for predicting and managing drug interactions in clinical practice
- Investigation of genetic factors that may influence individual susceptibility to rifamycin-related drug interactions
- Long-term studies on the clinical outcomes of patients managed with various strategies for mitigating rifamycin drug interactions
Can pharmacogenomic testing help in managing rifampin drug interactions. While pharmacogenomic testing is not routinely used for managing rifampin interactions, it may have potential in identifying individuals who are more susceptible to certain interactions. For example, genetic variations in CYP enzymes could influence the extent of enzyme induction by rifampin. However, more research is needed to establish the clinical utility and cost-effectiveness of such testing in this context.
Conclusion
Rifampin and rifabutin are vital antibiotics in the treatment of tuberculosis and other mycobacterial infections. However, their significant potential for drug interactions presents a challenge in clinical practice. Healthcare providers must be well-informed about these interactions and implement appropriate strategies to manage them effectively.
Key points to remember include:
- Rifampin has a higher potential for drug interactions compared to rifabutin
- Major interactions can have significant clinical consequences and should be carefully managed
- Rifabutin may be a safer alternative in some situations, particularly in HIV patients
- Proper management of these interactions requires a comprehensive approach, including medication review, dose adjustments, and patient monitoring
By understanding and appropriately managing these drug interactions, healthcare providers can optimize the therapeutic benefits of rifamycin antibiotics while minimizing potential risks to patients.
Rifampin Interactions Checker – Drugs.com
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There are 556 drugs known to interact with
rifampin, along with
6 disease interactions.
Of the total drug interactions,
242 are major, 255 are moderate, and 59 are minor.
Does rifampin interact with my other drugs?
Enter other medications to view a detailed report.
- View all 556 medications that may interact with rifampin
- View rifampin disease interactions (6)
Most frequently checked interactions
View interaction reports for rifampin and the medicines listed below.
- Major
- Moderate
- Minor
- Unknown
- Advair Diskus (fluticasone / salmeterol)
- Aspirin Low Strength (aspirin)
- Augmentin (amoxicillin / clavulanate)
- Bactrim DS (sulfamethoxazole / trimethoprim)
- Benadryl (diphenhydramine)
- Celebrex (celecoxib)
- Cipro (ciprofloxacin)
- CoQ10 (ubiquinone)
- Cymbalta (duloxetine)
- Fish Oil (omega-3 polyunsaturated fatty acids)
- Lasix (furosemide)
- Lexapro (escitalopram)
- Lipitor (atorvastatin)
- Lyrica (pregabalin)
- Nexium (esomeprazole)
- Paracetamol (acetaminophen)
- Plavix (clopidogrel)
- Prilosec (omeprazole)
- Probiotic Formula (bifidobacterium infantis / lactobacillus acidophilus)
- Protonix (pantoprazole)
- Singulair (montelukast)
- Synthroid (levothyroxine)
- Tylenol (acetaminophen)
- Vitamin B12 (cyanocobalamin)
- Vitamin B6 (pyridoxine)
- Vitamin C (ascorbic acid)
- Vitamin D3 (cholecalciferol)
- Xanax (alprazolam)
- Zofran (ondansetron)
- Zyrtec (cetirizine)
Rifampin disease interactions
There are 6 disease interactions with rifampin which include:
- colitis
- hematopoietic disturbances
- hepatotoxicity
- liver disease
- porphyria
- enzyme induction
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Drug Interaction Classification
| Major | Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. |
|---|---|
| Moderate | Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. |
| Minor | Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. |
| Unknown | No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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Rifampin and rifabutin drug interactions: an update
Review
. 2002 May 13;162(9):985-92.
doi: 10.1001/archinte.162.9.985.
Christopher K Finch
1
, Cary R Chrisman, Anne M Baciewicz, Timothy H Self
Affiliations
Affiliation
- 1 Department of Clinical Pharmacy, University of Tennessee, 26 S Dunlap, Suite 210, Memphis, TN 38163, USA.
PMID:
11996607
DOI:
10.1001/archinte.162.9.985
Review
Christopher K Finch et al.
Arch Intern Med.
.
. 2002 May 13;162(9):985-92.
doi: 10.1001/archinte.162.9.985.
Authors
Christopher K Finch
1
, Cary R Chrisman, Anne M Baciewicz, Timothy H Self
Affiliation
- 1 Department of Clinical Pharmacy, University of Tennessee, 26 S Dunlap, Suite 210, Memphis, TN 38163, USA.
PMID:
11996607
DOI:
10.
1001/archinte.162.9.985
1001/archinte.162.9.985Abstract
Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few examples of well-documented clinically significant interactions include interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or digoxin, verapamil hydrochloride, human immunodeficiency virus-related protease inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent reports have demonstrated clinically relevant interactions with numerous other drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin, propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions.
Enhanced knowledge of known interactions will continue to develop, including research on the induction of specific cytochrome P-450 isoenzymes and on the importance of the P-glycoprotein transport system. New rifampin and rifabutin interactions will be discovered with further investigations.
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Author: Lanz B. Author: Lanz B. Author: Lanz B. Author: Lanz B. Author: Lantz B. Author: Team of authors Author: Lantz B. Rifampicin (lat. Rifampicinum , active ingredient: 3-[[(4-methyl-1-piperazinyl)imino]methyl]rifamycin) is an anti-tuberculosis drug. Trade names: Makoks, R-tsin, Rimpin, Eremfat. Semi-synthetic broad-spectrum antibiotic, from the rifamycin group. It has a bacteriostatic, and in high concentrations – a bactericidal effect. Highly active against Mycobacterium tuberculosis, is a first-line anti-tuberculosis drug. Rifampicin is well absorbed from the gastrointestinal tract. The maximum concentration in the blood is reached 2-2.5 hours after ingestion. With intravenous drip administration, the maximum concentration of rifampicin is observed by the end of the infusion. At the therapeutic level, the concentration of the drug when taken orally and intravenously is maintained for 8-12 hours, for highly sensitive pathogens – for 24 hours. Rifampicin penetrates well into tissues and body fluids and is found at therapeutic concentrations in pleural exudate, sputum, and cavity contents. Possible: nausea, vomiting, diarrhea, loss of appetite, increased levels of hepatic transaminases, bilirubin in the blood serum; headache, impaired coordination of movements, visual impairment; violation of the menstrual cycle; leukopenia; urticaria, eosinophilia, angioedema, bronchospasm, flu-like symptoms, herpes. is taken orally on an empty stomach (0.5 – 1 hour before meals) or administered intravenously by drip (adults only). To prepare the solution, dilute 0.15 g of rifampicin in 2.5 ml of sterile water for injection, vigorously shake the ampoule with the powder until completely dissolved, dilute the resulting solution in 125 ml of 5% glucose solution. Enter at a rate of 60 – 80 drops per minute. In the treatment of tuberculosis, the average daily dose for adults orally is 0.45 g 1 time per day. In patients (especially during an exacerbation) with a body weight above 50 kg, the daily dose may be increased to 0.6 g. The average daily dose for children over 3 years old is 10 mg / kg (but not more than 0.45 g per day) 1 time in a day. PAS preparations containing bentonite (hydrous aluminum silicate) should be administered no earlier than 4 hours after taking Rifampicin. Rifampicin helps to reduce the activity of oral anticoagulants, oral antidiabetic drugs, hormonal contraceptives, digitalis preparations, quinidine, GCS. In neonates and premature infants, Rifampicin should only be used when absolutely necessary. When using the drug during lactation, it is necessary to resolve the issue of stopping breastfeeding. With extreme caution prescribed for liver diseases, exhaustion. In the treatment of non-tuberculous infections, the rapid development of resistance of microorganisms is possible. This process can be prevented by combining rifampicin with other chemotherapeutic agents.
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Publication date: 06/01/2013 Ri fampin | is… What is Rifampin?
It is active against Mycobacterium tuberculosis and leprosy, acts on gram-positive (especially staphylococci) and gram-negative (meningococci, gonococci) cocci, less active against gram-negative bacteria. The mechanism of action is associated with the suppression of DNA and RNA polymerase of microorganisms. Microorganisms become resistant to the drug rather quickly. Contents
Pharmacological action
Active against gram-positive microorganisms (Staphylococcus spp., including multi-resistant; Streptococcus spp., Bacillus anthracis), as well as against some gram-negative microorganisms. Acts on pathogens Brucella spp., Legionella pneumophila, Salmonella typhi, Mycobacterium leprae, Chlamydia trachomatis. Resistance to rifamycin develops rapidly. Cross-resistance with other anti-tuberculosis drugs (with the exception of other rifampicins) has not been noted. Pharmacokinetics
, bone tissue. The highest concentration of the drug is created in the tissues of the liver and kidneys. It is excreted from the body with bile and urine. Rifampicin resistance develops rapidly. Cross-resistance with other antibiotics is not observed (with the exception of rifamycin). The main indication for use is tuberculosis of the lungs and other organs. In addition, the drug is used for various forms of leprosy and inflammatory diseases of the lungs and respiratory tract (bronchitis, pneumonia) caused by multiresistant staphylococci, osteomyelitis, infections of the urinary and biliary tract, acute gonorrhea and other diseases caused by pathogens sensitive to rifampicin. Due to the rapid development of microbial resistance, rifampicin is prescribed for non-tuberculous diseases only when other antibiotics are ineffective. Rifampicin has a virucidal effect on the rabies virus, inhibits the development of rabies encephalitis; in this regard, it is used for the complex treatment of rabies in the incubation period.
The drug has a bright brown-red color. It stains (especially at the beginning of treatment) urine, sputum, lacrimal fluid in an orange-reddish color. Indications
Contraindications
Side effect
Rarely – acute liver failure; hemolytic anemia, thrombocytopenic purpura (with intermittent or irregular therapy or when treatment is resumed after a break). Very rarely – renal tubular necrosis, interstitial nephritis, acute renal failure. Dosing regimen
With poor tolerance to rifampicin, the daily dose can be divided into 2 doses. Intravenous administration of rifampicin is recommended for acutely progressive and widespread forms of destructive pulmonary tuberculosis, severe purulent-septic processes, when it is necessary to quickly create a high concentration of the drug in the blood, and if the drug is difficult or poorly tolerated by the patient. With intravenous administration, the daily dose for adults is 0.45 g, for severe rapidly progressive forms – 0.6 g and is administered in 1 dose. The drug is administered intravenously for 1 month. and more with the subsequent transition to oral administration and depends on the tolerability of the drug. The total duration of the use of rifampicin in tuberculosis is determined by the effectiveness of treatment and can reach 1 year. In the treatment of tuberculosis with rifampicin (intravenously), in patients with diabetes mellitus, it is recommended to administer 2 units of insulin for every 4-5 g of glucose (solvent).
Monotherapy of tuberculosis with rifampicin is often accompanied by an increase in the resistance of the pathogen to the antibiotic, so it should be combined with other anti-tuberculosis drugs (streptomycin, isoniazid, ethambutol, etc.), to which the sensitivity of Mycobacterium tuberculosis is preserved. For leprosy, rifampicin is used according to the following schemes: a) a daily dose of 0.3-0.45 g, administered in 1 dose; with poor tolerance – in 2 doses. The duration of treatment is 3-6 months, the courses are repeated with an interval of 1 month; b) against the background of combination therapy, a daily dose of 0.45 g is prescribed in 2-3 doses for 2-3 weeks with an interval of 2-3 months. within 1 year – 2 years or at the same dose 2 – 3 times in 1 week for 6 months. Treatment is carried out in combination with immunostimulating agents. For infections of a non-tuberculous nature, adults take rifampicin orally at 0.45 – 0.9g per day, and children – 8 – 10 mg / kg in 2 – 3 doses. Intravenously administered to adults in a daily dose of 0.
3 – 0.9 g (2 – 3 injections). Enter within 7 – 10 days. As soon as the opportunity arises, they switch to taking the drug inside. In acute gonorrhea, it is prescribed orally at a dose of 0.9 g per day once or for 1 to 2 days. For the prevention of rabies, adults are given orally 0.45 – 0.6 g per day, with severe injuries (bite to the face, head, hands) – 0.9 g per day; children under 12 years old – 8 – 10 mg / kg. The daily dose is divided into 2 – 3 doses. Duration of application 5 – 7 days. Treatment is carried out simultaneously with active immunization. Treatment with rifampicin should be carried out under close medical supervision. Allergic reactions (of varying severity) are possible, although they are relatively rare; in addition – dyspeptic symptoms, dysfunction of the liver and pancreas. With prolonged use of the drug, it is necessary to periodically examine the function of the liver and conduct blood tests (due to the possibility of developing leukopenia). With rapid intravenous administration, blood pressure may decrease, and with prolonged administration, phlebitis may develop.
The drug reduces the activity of indirect anticoagulants, oral hypoglycemic agents, digitalis preparations. With the simultaneous use of anticoagulants and rifampicin, when the latter is canceled, the dose of anticoagulants should be reduced. Drug interactions
Special instructions
