Rifadin

Gastrointestinal

Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea have been noted in some patients. Although Clostridium difficile has been shown in vitro to be sensitive to rifampin, pseudomembranous colitis has been reported with the use of rifampin (and other broad spectrum antibiotics). Therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use.

Hepatic

Transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase,  serum transaminases) have been observed. Rarely, hepatitis or a shock-like syndrome with hepatic involvement and abnormal liver function tests has been reported.

Hematologic

Thrombocytopenia has occurred primarily with high dose intermittent therapy, but has also been noted after resumption of interrupted treatment. It rarely occurs during well supervised daily therapy. This effect is reversible if the drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura.

Rare reports of disseminated intravascular coagulation have been observed.

Leukopenia, hemolytic anemia, and decreased hemoglobin have been observed.

Agranulocytosis has been reported very rarely.

Central Nervous System

Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion,  behavioral changes, muscular weakness, pains in extremities, and generalized numbness have been observed.

Psychoses have been rarely reported.

Rare reports of myopathy have also been observed.

Ocular

Visual disturbances have been observed.

Endocrine

Menstrual disturbances have been observed.

Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.

Renal

Elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria,  hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted. These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted.

Dermatologic

Cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions.  Typically, they consist of flushing and itching with or without a rash. More serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon.

Hypersensitivity Reactions

Occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme including Stevens- Johnson Syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed.

Anaphylaxis has been reported rarely.

Miscellaneous

Edema of the face and extremities have been reported. Other reactions which have occurred with intermittent dosage regimens include “flu syndrome” (such as episodes of fever, chills, headache,  dizziness, and bone pain), shortness of breath, wheezing, decrease in blood pressure and shock. The “flu syndrome” may also appear if rifampin is taken irregularly by the patient or if daily administration is resumed after a drug free interval.

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 physicians promptly if they experience any of the following:  fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, 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.

Before taking rifampin, tell your doctor if you are allergic to any drugs, or if you have liver disease or porphyria ( (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system).

Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Rifampin will not treat a viral infection such as the common cold or flu.

Take the rifampin capsule on an empty stomach 1 hour before or 2 hours after a meal.

Rifampin can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking rifampin.

There are many other medicines that can interact with rifampin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor. Keep a list with you of all the medicines you use and show this list to any doctor or other healthcare provider who treats you.

Do not wear contact lenses while you are taking rifampin. This medicine may discolor your tears, which could permanently stain soft contact lenses.

Do not wear contact lenses while you are taking rifampin. This medicine may discolor your tears, which could permanently stain soft contact lenses.

• Pharma Pac (A Service Of H.J. Harkins Co., Inc.)

• Quality Care Pharmaceuticals

• Sanofi-Aventis U.S. LLC

Avoid drinking alcohol.

Do not wear contact lenses while you are taking rifampin. This medicine may discolor your tears, which could permanently stain soft contact lenses.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Rifadin.
• Talk with your doctor before you drink alcohol.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• This medicine may stain contact lenses.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• A very bad and sometimes deadly reaction has happened with Rifadin. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this medicine.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Rifadin while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Feeling very tired or weak.
• Feeling confused.
• Flu-like signs.
• Fever or chills.
• Sore throat.
• Swollen gland.
• Joint pain or swelling.
• Muscle pain or weakness.
• Shortness of breath.
• Swelling in the arms or legs.
• Any unexplained bruising or bleeding.
• Change in balance.
• Not able to focus.
• Change in how you act.
• Period (menstrual) pain.
• Change in eyesight.
• It is common to have diarrhea when taking Rifadin (rifampin capsules). Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.
• Very bad and sometimes deadly liver problems have happened with Rifadin. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

In the treatment of both tuberculosis and the meningococcal carrier state, the small number of resistant cells present within large populations of susceptible cells can rapidly become the predominant type. Bacteriologic cultures should be obtained before the start of therapy to confirm the susceptibility of the organism to rifampin and they should be repeated throughout therapy to monitor the response to treatment. Since resistance can emerge rapidly, susceptibility tests should be performed in the event of persistent positive cultures during the course of treatment. If test results show resistance to rifampin and the patient is not responding to therapy, the drug regimen should be modified.

Tuberculosis

Rifampin is indicated in the treatment of all forms of tuberculosis.

A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide (e.g., RIFATER®) 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 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 (e.g., RIFAMATE®) 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.

Rifadin IV is indicated for the initial treatment and retreatment of tuberculosis when the drug cannot be taken by mouth.

Meningococcal Carriers

Rifampin is indicated for the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx. Rifampin is not indicated for the treatment of meningococcal infection because of the possibility of the rapid emergence of resistant organisms. (See WARNINGS.)

Rifampin should not be used indiscriminately, and therefore, diagnostic laboratory procedures, including serotyping and susceptibility testing, should be performed for establishment of the carrier state and the correct treatment. So that the usefulness of rifampin in the treatment of asymptomatic meningococcal carriers is preserved, the drug should be used only when the risk of meningococcal disease is high.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of rifampin and other antibacterial drugs, rifampin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Rifampin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Patients with impaired liver function should be given rifampin only in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially SGPT/ALT and SGOT/AST should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, rifampin should be withdrawn.

In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels, and considering them in conjunction with the patient's clinical condition.

Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin administration.

The possibility of rapid emergence of resistant meningococci restricts the use of Rifadin to short-term treatment of the asymptomatic carrier state. Rifadin is not to be used for the treatment of meningococcal disease.

Systemic hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome may occur in patients receiving Rifadin (See ADVERSE REACTIONS). Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). These reactions may be severe and DRESS may be fatal. Manifestations of hypersensitivity, such as fever, lymphadenopathy or laboratory abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. Monitor patients receiving Rifadin for signs and/or symptoms of hypersensitivity reactions. If these signs or symptoms occur, discontinue Rifadin and administer supportive measures.

Signs and Symptoms

Nausea, vomiting, abdominal pain, pruritus, headache, and increasing lethargy will probably occur within a short time after ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and its intensity is proportional to the amount ingested.

Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage; bilirubin levels may increase and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal. A direct effect upon the hematopoietic system, electrolyte levels, or acid-base balance is unlikely.

Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

Acute Toxicity

The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm rifampin. Fatal acute overdoses in adults have been reported with doses ranging from 14 to 60 gm. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports. Nonfatal overdoses in pediatric patients ages 1 to 4 years old of 100 mg/kg for one to two doses has been reported.

Treatment

Intensive support measures should be instituted and individual symptoms treated as they arise. The airway should be secured and adequate respiratory exchange established. Since nausea and vomiting are likely to be present, gastric lavage within the first 2 to 3 hours after ingestion is probably preferable to induction of emesis. Following evacuation of the gastric contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting.

Active diuresis (with measured intake and output) will help promote excretion of the drug.

For severe cases, extracorporeal hemodialysis may be required. If this is not available, peritoneal dialysis can be used along with forced diuresis.

Rifampin can be administered by the oral route or by IV infusion (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 (e.g., RIFATER®) 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 (e.g., RIFAMATE®) 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.

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.

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.

For pediatric and adult patients in whom capsule swallowing is difficult or where lower doses are needed, a liquid suspension may be prepared as follows:

Rifadin 1% w/v suspension (10 mg/mL) can be compounded using one of four syrups–Simple Syrup (Syrup NF), Simple Syrup (Humco Laboratories), SyrPalta® Syrup (Emerson Laboratories), or Raspberry Syrup (Humco Laboratories).

1. Empty the contents of four Rifadin 300 mg capsules or eight Rifadin 150 mg capsules onto a piece of weighing paper.
2. If necessary, gently crush the capsule contents with a spatula to produce a fine powder.
3. Transfer the rifampin powder blend to a 4-ounce amber glass or plastic (high density polyethylene [HDPE], polypropylene, or polycarbonate) prescription bottle.
4. Rinse the paper and spatula with 20 mL of one of the above-mentioned syrups, and add the rinse to the bottle. Shake vigorously.
5. Add 100 mL of syrup to the bottle and shake vigorously.

This compounding procedure results in a 1% w/v suspension containing 10 mg rifampin/mL. Stability studies indicate that the suspension is stable when stored at room temperature (25 ± 3°C) or in a refrigerator (2–8°C) for four weeks. This extemporaneously prepared suspension must be shaken well prior to administration.

FDA pregnancy category: C Potential benefit should outweigh the potential risk.

Animal studies have revealed evidence of embryotoxicity and teratogenicity. Congenital malformations (mainly spina bifida) were increased in the offspring of rats given rifampin during organogenesis at oral doses about 1 to 2 times the maximum recommended human dose (based on body surface area comparisons). Cleft palate was increased in fetuses of mice given oral doses about 0.2 to 0.8 times the maximum recommended human dose (based on body surface area comparisons). Imperfect osteogenesis and embryotoxicity were reported in rabbits given oral doses up to about 3 times the maximum recommended human dose (based on body surface area comparisons). There are no controlled data in human pregnancy. Rifampin crosses the human placenta and appears in cord blood. Data reveal a fetal:maternal serum concentration ratio of 0.23. Reports of the use of rifampin during pregnancy generally involve multiple drug therapy. In a review of 204 pregnancies during which exposure to rifampin occurred, 7 malformations were thought to be due to drug therapy, including anencephaly (1 case), hydrocephalus (2 cases), limb malformations (3 cases), and renal tract abnormalities (1 case). Postnatal hemorrhages in the mother and infant have been associated with the use of rifampin during the last few weeks of pregnancy; administration of vitamin K may be indicated. The initial therapy of active tuberculosis in pregnant patients recommended by the Centers for Disease Control includes rifampin. Rifampin is also recommended by the American Thoracic Society. FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

LactMed Record Number

473

Last Revision Date

20170601

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