rifampin (rifampin 150 mg) Dailymed

General

Rifampin capsules should be used with caution in patients with a history of diabetes mellitus, as diabetes management may be more difficult.

Prescribing rifampin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

For the treatment of tuberculosis, rifampin is usually administered on a daily basis. Doses of rifampin greater than 600 mg given once or twice weekly have resulted in a higher incidence of adverse reactions, including the "flu syndrome" (fever, chills, and malaise), hematopoietic reactions (leukopenia, thrombocytopenia, or acute hemolytic anemia), cutaneous, gastrointestinal, and hepatic reactions, shortness of breath, shock, anaphylaxis, and renal failure. Recent studies indicate that regimens using twice-weekly doses of rifampin 600 mg plus isoniazid 15 mg/kg are much better tolerated.

Rifampin is not recommended for intermittent therapy; the patient should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases.

Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone.

Information for Patients

Patients should be counseled that antibacterial drugs including rifampin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When rifampin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by rifampin or other antibacterial drugs in the future.

The patient should be told that rifampin may produce a discoloration (yellow, orange, red, brown) of the teeth, urine, sweat, sputum, and tears, and the patient should be forewarned of this. Soft contact lenses may be permanently stained.

Rifampin is a well characterized and potent inducer of drug metabolizing enzymes and transporters and might therefore decrease or increase concomitant drug exposure and impact safety and efficacy (see DRUG INTERACTIONS ). Therefore, patients should be advised not to take any other medication without medical advice.

The patient 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 physician immediately if they experience any of the following: rash with fever or bulers, with or without peeling skin, itching, or swollen lymph nodes, loss of appetite, malaise, nausea, vomiting, abdominal pain, darkened urine, yellowish discoloration of the skin and eyes, light-colored bowel movements, fever, headache, fatigue, myalgias, cough, shortness of breath, chest pain, wheezing and pain or swelling of the joints.

Patients should be advised to seek medical advice immediately if their symptoms of mycobacterial disease, including, but not limited to, cough, fever, tiredness, shortness of breath, malaise, headache, pain, night sweats, swollen lymph nodes, loss of appetite, weight loss, weakness, skin ulcers or lesions, worsen (see ADVERSE REACTIONS ).

Advise patients to abstain from alcohol, hepatotoxic medications or herbal products while taking rifampin.

Compliance with the full course of therapy must be emphasized, and the importance of not missing any doses must be stressed.

Laboratory Tests

Adults treated for tuberculosis with rifampin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate). Baseline tests are unnecessary in pediatric patients unless a complicating condition is known or clinically suspected.

Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if necessary. Routine laboratory monitoring for toxicity in people with normal baseline measurements is generally not necessary.

Drug Interactions

Pharmacodynamic Interactions

Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated. (See CONTRAINDICATIONS.)

When rifampin is given concomitantly with other hepatotoxic medications such as 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 closely for hepatotoxicity.

Effect of rifampin on other drugs

Induction of Drug Metabolizing Enzymes and Transporters

Drug metabolizing enzymes and transporters affected by rifampin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways and these pathways may be induced by rifampin simultaneously. Therefore, rifampin may increase the metabolism and decrease the activity of certain coadministered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required) and has the potential to perpetuate clinically important drug-drug interactions against many drugs and across many drug classes (Table 1).

Table 1 summarizes the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified.

Table 1: Drug Interactions with Rifampin that Affect Concomitant Drug Concentrations^*

* Administered with rifampin 600 mg daily, unless otherwise specified
† Rifampin dosage used concomitantly with the drug(s) is not specified in the proposed package insert.
‡ Administered with rifampin 300 mg daily
§ Administered with rifampin 450 mg daily
¶ Administered with rifampin 1200 mg daily
# Rifampin 1200 mg administered as a single oral dose 8 hours before administering a single oral dose of nifedipine 10 mg
Þ Numerous cases in the literature describe a decrease in glucocorticoid effect when used concomitantly with rifampin. The literature contains reports of acute adrenal crisis or adrenal insufficiency induced by the combination of rifampin-isoniazid-ethambutol or rifampin-isoniazid in patients with Addison's disease
ß Administered with rifampin 900 mg daily
À A tuberculosis treatment regimen including rifampin (600 mg/day) isoniazid (300 mg/day), pyrazinamide (500 mg 3× per day), and pyridoxine (25 mg) was associated with higher than expected doses of nortriptyline were required to obtain a therapeutic drug level. Following the discontinuation of rifampin, the patient became drowsy and the serum nortriptyline levels rose precipitously (3-fold) into the toxic range.
È Concomitant use with rifampin in 2 children
Ð Administered with rifampin (10 mg/kg daily)
Ø Administered with an antibiotic regimen including rifampin (450 mg/day), isoniazid (300 mg/day), and streptomycin (0.5 g/day) IM
AUC = area under the time-concentration curve
Drug or Drug Class and Prevention or Management	Clinical Effect
Antiretrovirals Prevention or Management: Concomitant use is contraindicated (see CONTRAINDICATIONS)
Atazanavir	Decrease AUC by 72%
Darunavir†	Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance.
Tipranavir
Fosamprenavir‡	Decrease AUC by 82%
Saquinavir	Decrease AUC by 70% Coadministration may result in severe hepatocellular toxicity
Antiretrovirals Prevention or Management: Avoid concomitant use
Zidovudine	Decrease AUC by 47%
Indinavir	Decrease AUC by 92%
Efavirenz	Decrease AUC by 26 %
Cortisol Receptor Blocker
Mifepristone Prevention or Management: Avoid concominant use	Decrease exposure
Hepatitis C Antiviral Prevention or Management: Avoid concomitant use
Daclatasvir	Decrease AUC by 79%
Simeprevir	Decrease AUC by 48%
Sofosbuvir†	Decrease AUC by 72% Coadministration of sofosbuvir with rifampin, may decrease sofosbuvir plasma concentrations, leading to reduced therapeutic effect of sofosbuvir.
Telaprevir	Decrease AUC by 92%
Systemic Hormonal Contraceptives Prevention or Management: Advise patients to change to non-hormonal methods of birth control during rifampin therapy
Estrogens	Decrease exposure
Progestins
Anticonvulsants
Phenytoin§	Decrease exposure§
Antiarrhythmics
Disopyramide	Decrease exposure
Mexiletine	Decrease exposure
Quinidine	Decrease exposure
Propafenone	Decrease AUC by 50% to 67%
Tocainide	Decrease exposure
Antiestrogens
Tamoxifen	Decrease AUC by 86%
Toremifene	Decrease steady state concentrations of toremifene in serum
Antithrombotic Agents
Clopidogrel Prevention or Management: Concomitant use of clopidogrel and rifampin should be discouraged	Increase active metabolite exposure and risk of bleeding
Ticagrelor  Prevention or Management: Avoid use	Decrease exposure
Antipsychotics
Haloperidol	Decrease plasma concentrations by 70%
Lurasidone Prevention or Management : Concomitant use is contraindicated (See CONTRAINDICATIONS )	Decrease exposure
Oral Anticoagulants Prevention or Management: Perform prothrombin time daily or as frequently as necessary to establish and maintain the required dose of anticoagulant
Warfarin	Decrease exposure
Antifungals
Fluconazole	Decrease AUC by 23%
Itraconazole Prevention or Management: Not recommended 2 weeks before and during itraconazole treatment	Decrease exposure
Ketoconazole	Decrease exposure
Caspofungin Prevention or Management: Refer to the caspofungin prescribing information for caspofungin dose adjustment.	Decrease exposure
Beta-blockers
Metoprolol	Decrease exposure
Propranolol	Decrease exposure
Benzodiazepines
Diazepam*, ¶	Decrease exposure
Benzodiazepine-related drugs
Zopiclone	Decrease AUC by 82%
Zolpidem	Decrease AUC by 73%
Calcium Channel Blockers ¶
Diltiazem	Decrease exposure
Nifedipine#	Decrease exposure
Verapamil	Decrease exposure
Corticosteroids Þ
Prednisolone	Decrease exposure
Cardiac Glycosides
Digoxin Prevention or Management: Measure serum digoxin concentrations before initiating rifampin. Continue monitoring and increase digoxin dose by approximately 20% to 40% as necessary.	Decrease exposure
Digitoxin	Decrease exposure
Fluoroquinolones
Pefloxacinß	Decrease exposure
Moxifloxacin*, §	Decrease exposure
Oral Hypoglycemic Agents (e.g. sulfonylureas)
Glyburide	Decrease exposure Rifampin may worsen glucose control of glyburide
Glipizide	Decrease exposure
Immunosuppressive Agents
Cyclosporine	Decrease exposure
Tacrolimus Prevention or Management: Monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when rifampin and tacrolimus are used concomitantly.	Decrease AUC by 56%
Narcotic Analgesics
Oxycodone	Decrease AUC by 86%
Morphine	Decrease exposure
Progestin Antagonist
Mifepristone Prevention or Management: Refer to the post-treatment assessment in the mifepristone prescribing information to verify that treatment has been successful.	Decrease exposure
Selective 5-HT3 Receptor Antagonists
Ondansetron	Decrease exposure
Statins Metabolized by CYP3A4
Simvastatin	Decrease exposure
Thiazolidinediones
Rosiglitazone	Decrease AUC by 66%
Tricyclic Antidepressants
NortriptylineÀ	Decrease exposure
Other Drugs
Enalapril	Decrease active metabolite exposure
ChloramphenicolÈ	Decrease exposure
Clarithromycin	Decrease exposure
Dapsone	Rifampin has been shown to increase the clearance of dapsone and, accordingly, decrease dapsone exposure. Rifampin has also been shown to increase the production of the hydroxylamine metabolite of dapsone which could increase the risk of methemoglobinemia
DoxycyclineÐ	Decrease exposure
IrinotecanØ Prevention or Management : Avoid the use of rifampin, strong CYP3A4 inducer, if possible. Substitute non-enzyme inducing therapies at least 2 weeks prior to initiation of irinotecan therapy	Decrease irinotecan and active metabolite exposure
Levothyroxine	Decrease exposure
Losartan	Parent	Decrease AUC by 30%
	Active metabolite (E3174)	Decrease AUC by 40%.
Methadone	In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms.
Praziquantel Prevention or Management: Concomitant use is contraindicated (See CONTRAINDICATIONS)	Decrease plasma praziquantel concentrations to undetectable levels.
Quinine Prevention or Management: Avoid concomitant use	Decrease AUC by 75% to 85%
Telithromycin	Decrease AUC by 86%
Theophylline	Decrease exposure by 20% to 40%

Effect of other drugs on rifampin

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.

Concomitant use with probenecid and cotrimoxazole increases the concentration of rifampin which may increase the risk of rifampin toxicities. Monitor for adverse reactions associated with rifampin during coadministration.

Other Interactions

Atovaquone: Concomitant use of rifampin with atovaquone decrease concentrations of atovaquone and increase concentrations of rifampin which may increase the risk of rifampin toxicities. Coadministration of rifampin with atovaquone is not recommended.

Drug/Laboratory Interactions

Cross-reactivity and false-positive urine screening tests for opiates have been reported in patients receiving rifampin when using the KIMS (Kinetic Interaction of Microparticles in Solution) method (e.g., Abuscreen OnLine opiates assay; Roche Diagnostic Systems). Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish rifampin from opiates.

Therapeutic levels of rifampin have been shown to inhibit standard microbiological assays for serum folate and vitamin B₁₂. Thus, alternate assay methods should be considered. Transient abnormalities in liver function tests (e.g., elevation in serum bilirubin, alkaline phosphatase, and serum transaminases) and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed. Therefore, these tests should be performed before the morning dose of rifampin.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A few cases of accelerated growth of lung carcinoma have been reported in man, but a causal relationship with the drug has not been established. Hepatomas were increased in female (C3Hf/DP) mice dosed for 60 weeks with rifampin followed by an observation period of 46 weeks, at 20 to 120 mg/kg (equivalent to 0.1 to 0.5 times the maximum dosage used clinically, based on body surface area comparisons). There was no evidence of tumorigenicity in male C3Hf/DP mice or in similar studies in BALB/c mice, or in two year studies in Wistar rats.

There was no evidence of mutagenicity in both prokaryotic (Salmonella typhi, Escherichia coli) and eukaryotic (Saccharomyces cerevisiae) bacteria, Drosophila melanogaster, or ICR/Ha Swiss mice. An increase in chromatid breaks was noted when whole blood cell cultures were treated with rifampin. Increased frequency of chromosomal aberrations was observed in vitro in lymphocytes obtained from patients treated with combinations of rifampin, isoniazid, and pyrazinamide and combinations of streptomycin, rifampin, isoniazid, and pyrazinamide.

PregnancyTeratogenic Effects

Rifampin has been shown to be teratogenic in rodents. Congenital malformations, primarily spina bifida, were increased in the offspring of pregnant rats given rifampin during organogenesis at oral doses of 150 to 250 mg/kg/day (about 1 to 2 times the maximum recommended human dose based on body surface area comparisons). Cleft palate was increased in a dose-dependent fashion in fetuses of pregnant mice treated at oral doses of 50 to 200 mg/kg (about 0.2 to 0.8 times the maximum recommended human dose based on body surface area comparisons). Imperfect osteogenesis and embryotoxicity were also reported in pregnant rabbits given rifampin at oral doses up to 200 mg/kg/day (about 3 times the maximum recommended human dose based on body surface area comparisons). There are no adequate and well-controlled studies of rifampin in pregnant women. Rifampin has been reported to cross the placental barrier and appear in cord blood. Rifampin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

PregnancyNon-Teratogenic Effects

When administered during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant for which treatment with vitamin K may be indicated.

Nursing Mothers

Because of the potential for tumorigenicity shown for rifampin in animal studies, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

See CLINICAL PHARMACOLOGY–Pediatrics ; see also DOSAGE AND ADMINISTRATION .

Geriatric Use

Clinical studies of rifampin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Caution should therefore be observed in using rifampin in elderly patients. (See WARNINGS ).