Rimactane

PO

Take on empty stomach

IV Compatibilities

Solution: D5W (at 1.2 g/L within 4 hours)

IV Incompatibilities

Solution: NS (may be used within 24 hours)

Additive: Minocycline

Y-Site: Diltiazem

IV Preparation

Add 10 mL of SWI to 600 mg of rifampin in vial

Before administration, solution may be added to 500 mL of D5W or 100 mL of D5W

IV Administration

Prepare and administer within 4 hours

In 500 mL of D5W: Infuse within 3 hours

In 100 mL of D5W: Infuse within 30 minutes

Rifampin is used together with other medicines to treat tuberculosis (TB) in many different parts of the body. It is also used by patients who have a meningitis bacteria in their nose or throat who do not show symptoms of the infection to prevent the spread of the bacteria to other patients. Rifampin belongs to the class of medicines called antibiotics and works to kill or prevent the growth of bacteria. However, it will not work for colds, flu, or other virus infections.

This medicine is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Agitation
• bleeding gums
• blood in the urine or stools
• bruising
• confusion
• cough or hoarseness
• coughing or vomiting blood
• dark urine
• darkening of the skin
• decreased frequency or amount of urine
• difficulty in breathing and swallowing
• dizziness
• fainting
• fast heartbeat
• fever with or without chills
• general feeling of tiredness or weakness
• headache
• hives
• hostility
• increased blood pressure
• increased thirst
• irritability
• lethargy
• light-colored stools
• loss of appetite
• lower back or side pain
• mental depression
• nausea and vomiting
• painful or difficult urination
• persistent bleeding or oozing from puncture sites, mouth, or nose
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• skin itching, rash, or redness
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain
• swelling of the face, ankles, fingers, hands, or lower legs
• tightness in the chest
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight gain
• yellow eyes or skin

• Blistering, peeling, or loosening of the skin
• bloating
• bloody, severe, or watery diarrhea
• bone pain
• chest pain
• chills
• cold, clammy skin
• difficulty with speaking
• double vision
• fast heartbeat
• fast, weak pulse
• inability to move the arms, legs, or facial muscles
• inability to speak
• joint or muscle pain
• lightheadedness
• pale skin
• pinpoint red spots on the skin
• red skin lesions, often with a purple center
• red, irritated eyes
• slow speech
• sores, welting, blisters
• sweating
• swollen glands
• unpleasant breath odor
• unusual weight loss

Get emergency help immediately if any of the following symptoms of overdose occur:

• Blurred vision
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast, pounding, or irregular heartbeat or pulse
• full feeling in the upper abdomen or stomach
• low blood pressure or slow pulse
• pain in the upper abdomen or stomach
• reddish-orange to reddish-brown color of the urine, stool, saliva, sputum, sweat, and tears
• seizures
• swelling around the eyes or face
• unconsciousness
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• feeling, seeing, or hearing things that are not there
• muscle pain, tenderness, wasting, or weakness
• severe mood or mental changes
• unusual behavior

• Belching
• bloated or full feeling
• drowsiness
• excess air or gas in the stomach or intestines
• indigestion
• not able to concentrate
• pain or discomfort in the chest, upper stomach, or throat

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Applies to rifampin: compounding powder, intravenous powder for injection, oral capsule

Gastrointestinal

Gastrointestinal side effects have included nausea and dyspepsia in 2% of patients. Heartburn, anorexia, vomiting, flatulence, cramps and diarrhea have also been observed. Rare cases of pill-induced esophagitis and pseudomembranous colitis have been associated with the use of rifampin (the active ingredient contained in Rimactane) [Ref]

Hepatic

Hyperbilirubinemia and hepatitis have been reported in up to 3% of patients. Approximately 50% of hepatotoxicity has been observed during the first month of therapy.

If rifampin (the active ingredient contained in Rimactane) is essential in the treatment of patients with liver disease, extreme caution and strict medical supervision should be exercised. Baseline liver function tests should be obtained and monitored every two weeks during therapy.[Ref]

Hepatic side effects have included cases of hepatitis and severe hepatotoxicity with fatal outcome. Fatal cases of hepatotoxicity have been observed in patients with existing liver dysfunction and in patients with normal liver function who are also taking other hepatotoxic drugs. Jaundice, hepatitis, transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, BSP, alkaline phosphatase, serum transaminases), and hyperbilirubinemia have been reported. Baseline and periodic liver function testing are recommended for all patients on long-term rifampin therapy.[Ref]

Immunologic

The 'flu-like syndrome' generally occurs with intermittent dosing of rifampin (the active ingredient contained in Rimactane) in patients with poor adherence to daily rifampin therapy, and when daily rifampin is resumed after a drug free period.[Ref]

Immunologic side effects have included flu-like syndrome presenting as fever, malaise, nausea, vomiting, petechiae and myalgias. This syndrome is probably an immune-mediated reaction. Rarely, dyspnea and shock have been associated with once-daily rifampin therapy.[Ref]

Renal

Renal side effects have included elevations in BUN and serum uric acid. Hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been reported. These events are generally associated with an immune-mediated reaction which occurs after interruption in rifampin (the active ingredient contained in Rimactane) therapy. Standard doses may produce orange-colored urine.[Ref]

There have been rare case reports of reversible acute renal failure due to glomerulonephritis and renal epithelial cell injury in patients receiving rifampin. Often in these patients other immune-mediated reactions occur, such as hemolysis and thrombocytopenia. Antibodies to rifampin have been identified in some affected patients. Generally these reactions occur after reintroduction of the drug following a lapse in therapy, although they have also been associated with continuous therapy.[Ref]

Hematologic

Petechiae associated with thrombocytopenia may occur in 1% of patients who are receiving rifampin (the active ingredient contained in Rimactane) Rifampin antibodies have been demonstrated in some of these patients. Thrombocytopenia is seen most frequently in patients receiving weekly therapy or after a lapse in therapy, but has also been reported during daily therapy. Decreased hemoglobin and transient leukopenia have been reported in patients who had chronic diseases and in whom other medications were given, which made it difficult to definitively determine if these adverse effects were due to rifampin.

A 76-year-old male with a diagnosis of Mycobacterium kansasii pulmonary disease experienced leukocytoclastic vasculitis, thrombocytopenia, and acute renal failure coincident with rifampin therapy. He was admitted to the hospital with a one-week history of fever, dry cough, dyspnea, oliguria, and bilateral edema in lower extremities. He was treated for the Mycobacterium kansasii pulmonary disease with a combined preparation of isoniazid 50 mg, rifampin 250 mg, rifampin 600 mg, and pyrazinamide 1500 mg (Rifater). On the patients admission, laboratory data showed acute renal failure (serum creatinine 9.6 mg/dL, urea 168 mg/dL) and thrombocytopenia (platelets 85 x 10 (3)/ microliter). Other results were WBC count 13,300/ microliter, hemoglobin 13.9 g/dL, and proteinuria, with urine protein 1.5 g/L. Pyrazinamide was discontinued and broad spectrum antimicrobials were introduced. Two weeks after pyrazinamide was discontinued, clinical and analytical parameters normalized. With the goal of treating Mycobacterium kansasii, a controlled trial of rifampin at increasing doses (80 mg the first day, 150 mg the second day, 200 mg the third day) was attempted a week later. The day following reintroduction, a palpable purpura appeared, serum creatinine increased (1.9 mg/dL), and the platelet count dropped. Rifampin was withdrawn on the fourth day; 4 days later, the serum creatinine level returned to within normal limits and skin purpura disappeared. Skin purpura biopsy demonstrated leukocytoclastic vasculitis. Two weeks later, the patient was discharged with normal renal function and platelet count.[Ref]

Hematologic side effects have included thrombocytopenia, leukopenia, hemolytic anemia, and decreased hemoglobin, in less than 1% of patients. Thrombocytopenia has occurred primarily with high dose intermittent therapy, and after resumption of interrupted therapy. Red cell aplasia, agranulocytosis, methemoglobinemia, and disseminated intravascular coagulation have been reported very rarely. Hemolysis has been described as part of an immune-mediated reaction which generally occurs after interruptions in therapy. At least one case of rifampin-related leukocytoclastic vasculitis, thrombocytopenia, and acute renal failure has been reported.[Ref]

Dermatologic

Dermatologic side effects have included cutaneous reactions that are mild and self-limiting and usually not associated with a hypersensitivity to rifampin (the active ingredient contained in Rimactane) These reactions generally manifest as itching and flushing with or without rash. Serious dermatologic reactions that resulted from hypersensitivity have been reported rarely.[Ref]

Nervous system

Nervous system side effects have included headache, paresthesias, and weakness. Other central nervous system side effects reported have included drowsiness, fatigue, ataxia, dizziness, decreased concentration, mental confusion, behavioral changes, muscular weakness, pain, and numbness.[Ref]

Metabolic

Drug level monitoring may be necessary in patients who remain acid-fast bacilli smear positive after 3 months of directly observed therapy. Dosage may be titrated upwards to keep the rifampin (the active ingredient contained in Rimactane) level in the therapeutic range.[Ref]

Metabolic side effects have included increases in hepatic metabolism of thyroxine (T4) and triiodothyronine (T3). A fall in plasma concentration time curve of rifampin and an increase in renal clearance due to a decrease in protein-bound drug has been reported in pulmonary tuberculosis patients who are often malnourished.[Ref]

Cardiovascular

Cardiovascular side effects have been reported rarely. These have included decreased blood pressure when rifampin (the active ingredient contained in Rimactane) dosages were administered intermittently.[Ref]

Hypersensitivity

Hypersensitivity side effects have included urticaria, rash, pruritus, pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis. Rarely, anaphylaxis has been reported. At least one case of multiple hypersensitivity reactions including anaphylactic shock, liver injury, hemolytic anemia, acute renal failure, and disseminated intravascular coagulation have also been reported.[Ref]

A 35-year-old male who was diagnosed with pulmonary tuberculosis experienced multiple hypersensitivity reactions coincident with rifampin therapy. After being admitted to the hospital with multiple symptoms of tuberculosis, the patient was prescribed rifampin, isoniazid, pyrazinamide, and ethambutol. Two hours after taking the first pill of rifampin (600 mg), the patient developed anaphylactic shock, liver injury, hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. Direct and indirect antiglobulin (Coombs) tests were positive. RFP-dependent IgG and IgM antibodies with complement fixing capability were observed in the serum. The patient was transferred to the intensive care unit and underwent hemodialysis. Clinical recovery and return of laboratory data to normal levels occurred over a 5-week period. The patient was subsequently given isoniazid, pyrazinamide, ethambutol, ciprofloxacin, and recovered from tuberculosis.[Ref]

Endocrine

Endocrine side effects have included menstrual disturbances and rare reports of adrenal insufficiency in patients with impaired adrenal function.[Ref]

Musculoskeletal

Musculoskeletal side effects have included myopathy and muscular weakness.[Ref]

Ocular

Ocular side effects have included visual disturbances. Ocular side effects are generally limited to patients who wear contact lenses. Rifampin (the active ingredient contained in Rimactane) can cause a red-brown or orange discoloration of tears which can stain contact lenses.[Ref]

Psychiatric

Psychiatric side effects have rarely included psychoses.[Ref]

Respiratory

Respiratory side effects have included shortness of breath and wheezing with the use of intermittent dosage regimens. A 'flu syndrome' may appear if rifampin (the active ingredient contained in Rimactane) is taken irregularly or if daily administration is resumed after a drug free interval.[Ref]

Other

Other side effects have rarely included edema of the face and extremities.[Ref]

Fatal acute overdoses have been reported with doses ranging from 14 to 60 grams of rifampin. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal cases. The minimum acute lethal or toxic dose is not well established.[Ref]

Some side effects of Rimactane may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.