Rifampin Injection

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Loose stools (diarrhea).
• Dizziness.
• Feeling sleepy.
• Gas.
• Headache.
• Upset stomach or throwing up.
• Not hungry.
• Heartburn.
• Stomach cramps.
• Feeling tired or weak.
• Change in color of body fluids to orange or red.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about rifampin injection, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about rifampin injection. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using rifampin injection.

Review Date: October 4, 2017

Rifampin is contraindicated in patients with a history of hypersensitivity to rifampin or any of the components, or to any of the rifamycins. (See WARNINGS .)

Rifampin is contraindicated in patients who are also receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity. (See PRECAUTIONS, Drug Interactions.)

Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance.

General

Rifampin 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.

Rifampin for Injection

For intravenous infusion only. Must not be administered by intramuscular or subcutaneous route. Avoid extravasation during injection: local irritation and inflammation due to extravascular infiltration of the infusion have been observed. If these occur, the infusion should be discontinued and restarted at another site.

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 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 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, fever, or swollen lymph nodes, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, cough, shortness of breath, wheezing 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.

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

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.)

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 substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. (See CONTRAINDICATIONS.)

Rifampin has been reported to accelerate the metabolism of the following drugs: anticonvulsants (e.g., phenytoin), digitoxin, antiarrhythmics (e.g., disopyramide, mexiletine, quinidine, tocainide), oral anticoagulants, antifungals (e.g., fluconazole, itraconazole, ketoconazole), barbiturates, beta-blockers, calcium channel blockers (e.g., diltiazem, nifedipine, verapamil), chloramphenicol, clarithromycin, corticosteroids, cyclosporine, cardiac glycoside preparations, clofibrate, oral or other systemic hormonal contraceptives, dapsone, diazepam, doxycycline, fluoroquinolones (e.g., ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, progestins, quinine, tacrolimus, theophylline, tricyclic antidepressants (e.g., 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.

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.

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 rifampicin 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. 

Pregnancy–Teratogenic Effects

Category C. 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.

Pregnancy–Non-Teratogenic Effects

When administered during the last few weeks of pregnancy, rifampin can cause post-natal 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). 

Rifampin for Injection can be administered by IV infusion only (see INDICATIONS AND USAGE). IV doses are the same as those for oral. 

See CLINICAL PHARMACOLOGY for dosing information in patients with renal failure.

Tuberculosis

Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV

Pediatric Patients: 10-20 mg/kg, not to exceed 600 mg/day, oral or IV

It is recommended that oral rifampin be administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water.

Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months. The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered.

Following the initial phase, treatment should be continued with rifampin and isoniazid (for at least 4 months. Treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.

Preparation of Solution for IV Infusion: Reconstitute the lyophilized powder by transferring 10 mL of sterile water for injection to a vial containing 600 mg of rifampin for injection. Swirl vial gently to completely dissolve the antibiotic. The reconstituted solution contains 60 mg rifampin per mL and is stable at room temperature for 24 hours. Prior to administration, withdraw from the reconstituted solution a volume equivalent to the amount of rifampin calculated to be administered and add to 500 mL of infusion medium. Mix well and infuse at a rate allowing for complete infusion within 3 hours. Alternatively, the amount of rifampin calculated to be administered may be added to 100 mL of infusion medium and infused in 30 minutes. 

Dilutions in dextrose 5% for injection (D5W) are stable at room temperature for up to 4 hours and should be prepared and used within this time. Precipitation of rifampin from the infusion solution may occur beyond this time. Dilutions in normal saline are stable at room temperature for up to 24 hours and should be prepared and used within this time. Other infusion solutions are not recommended.

Incompatibilities: Physical incompatibility (precipitate) was observed with undiluted (5 mg/mL) and diluted (1 mg/mL in normal saline) diltiazem hydrochloride and rifampin (6 mg/mL in normal saline) during simulated Y-site administration.

Meningococcal Carriers

Adults: For adults, it is recommended that 600 mg rifampin be administered twice daily for two days.

Pediatric Patients: Pediatric patients 1 month of age or older: 10 mg/kg (not to exceed 600 mg per dose) every 12 hours for two days.

Pediatric patients under 1 month of age: 5 mg/kg every 12 hours for two days.

NDC 0143-9230-01
RIFAMPIN
FOR INJECTION, USP
600 mg/vial
Sterile
FOR INTRAVENOUS
INFUSION ONLY
Rx ONLY
Each Rifampin for Injection vial contains
600 mg rifampin, 10 mg sodium formaldehyde
sulfoxylate and sodium hydroxide to adjust pH.
Reconstitute with 10 mL sterile diluent (see
accompanying literature). When dissolved,
withdraw 10 mL which is equivalent to 600 mg
rifampin (60 mg/mL). Use within 24 hours.
DOSAGE AND ADMINISTRATION: see
package insert for dosage information.
Store at 20º to 25ºC (68º to 77ºF) [See USP].
Avoid excessive heat (temperatures above
40ºC or 104ºF). Protect from light.

NDC 0143-9230-01
1 x 600 mg vial
RIFAMPIN
FOR INJECTION, USP
600 mg/vial
Sterile
FOR INTRAVENOUS
INFUSION ONLY
Rx ONLY

Each Rifampin for Injection vial
contains 600 mg rifampin, 10 mg
sodium formaldehyde sulfoxylate
and sodium hydroxide to adjust pH.
Reconstitute with 10 mL sterile
diluent (see accompanying
literature). When dissolved,
withdraw 10 mL which is
equivalent to 600 mg rifampin
(60 mg/mL).
Use within 24 hours.
DOSAGE AND ADMINISTRATION:
see package insert for dosage
information.
Store at 20º to 25ºC (68º to 77ºF)
[See USP Controlled Room
Temperature].
Avoid excessive heat
(temperatures above 40ºC or
104ºF).
Protect from light.