Rifadin IV (rifampin 300 mg) Dailymed

Contraindications

RIFADIN 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.

Rifampin is contraindicated in patients receiving praziquantel since therapeutically effective blood levels of praziquantel may not be achieved. In patients receiving rifampin who need immediate treatment with praziquantel alternative agents should be considered. However, if treatment with praziquantel is necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment.

Rifampin is contraindicated in patients receiving lurasidone. Concomitant use of lurasidone with strong CYP3A4 inducers (e.g., rifampin) decreased the exposure of lurasidone compared to the use of lurasidone alone. (See PRECAUTIONS, Drug Interactions).

Warnings

Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns has been reported in patients treated with rifampin. Severity ranged from asymptomatic elevations in liver enzymes, isolated jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant liver failure and death. Severe hepatic dysfunction including fatalities were reported in patients with liver disease and in patients taking rifampin with other hepatotoxic agents.

Monitor for symptoms and clinical/laboratory signs of liver injury, especially if treatment is prolonged or given with other hepatotoxic drugs. Patients with impaired liver function should be given rifampin only in cases of necessity and then under strict medical supervision. In these patients, careful monitoring of liver function should be done prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatic damage occur or worsen, discontinue rifampin.

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 were reported with RIFADIN administration. 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). 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.

Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported with rifampin. If symptoms or signs of severe cutaneous adverse reactions develop, discontinue RIFADIN immediately and institute appropriate therapy.

Rifampin may cause vitamin K–dependent coagulation disorders and bleeding (see ADVERSE REACTIONS). Monitor coagulation tests during rifampin treatment (prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency (such as those with chronic liver disease, poor nutritional status, on prolonged antibacterial drugs or anticoagulants). Consider discontinuation of RIFADIN if abnormal coagulation tests and/or bleeding occur. Supplemental vitamin K administration should be considered when appropriate.

Pulmonary toxicity manifested as interstitial lung disease (including, but not limited to, pneumonitis, hypersensitivity pneumonitis, eosinophilic pneumonia, pulmonary infiltrates, and organizing pneumonia) has been reported with rifampin treatment. Pulmonary toxicity could be fatal. If symptoms or signs of severe pulmonary toxicity (including respiratory failure, pulmonary fibrosis, and acute respiratory distress syndrome) develop, discontinue RIFADIN immediately and initiate appropriate treatment.

Postmarketing reports suggest that concomitant administration of high doses of cefazolin and rifampin may prolong the prothrombin time, leading to severe vitamin K–dependent coagulation disorders that may be life-threatening or fatal. Avoid concomitant use of cefazolin and rifampin in patients at increased risk for bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated.

Postmarketing cases of paradoxical drug reaction (recurrence or appearance of new symptoms, physical and radiological signs in a patient who had previously shown improvement with appropriate antimycobacterial treatment, in the absence of disease relapse, poor treatment compliance, drug resistance, side effects of treatment, or secondary infection/diagnosis) have been reported with RIFADIN (see ADVERSE REACTIONS). Paradoxical drug reactions are often transient and should not be misinterpreted as failure to respond to treatment. If worsening of symptoms or signs occurs during antimycobacterial treatment, consider paradoxical drug reaction in the differential diagnosis, monitor, or treat accordingly.

Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremia syndrome, some fatal, have been reported with rifampin. Discontinue RIFADIN if clinical symptoms and laboratory findings consistent with TMA occur. The findings of unexplained thrombocytopenia and anemia should prompt further evaluation and consideration of the diagnosis of TMA.

Precautions

General

RIFADIN 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.

RIFADIN IV

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 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

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 ConcentrationsAdministered with rifampin 600 mg daily, unless otherwise specified

Drug or Drug Class and Prevention or Management	Clinical Effect
AUC = area under the time-concentration curve
Antiretrovirals Prevention or Management: Concomitant use is contraindicated (see CONTRAINDICATIONS)
Atazanavir	Decrease AUC by 72%
DarunavirRifampin dosage used concomitantly with the drug(s) is not specified in the proposed package insert.	Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance.
Tipranavir
FosamprenavirAdministered with rifampin 300 mg daily	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 concomitant 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
PhenytoinAdministered with rifampin 450 mg daily	Decrease exposure
Antiarrhythmics
Disopyramide	Decrease exposure
Mexiletine	Decrease exposure
Quinidine	Decrease exposure
Propafenone	Decrease AUC by 50%–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
Beta-blockers
Metoprolol	Decrease exposure
Propranolol	Decrease exposure
Benzodiazepines
Diazepam , Administered with rifampin 1200 mg daily	Decrease exposure
Benzodiazepine-related drugs
Zopiclone	Decrease AUC by 82%
Zolpidem	Decrease AUC by 73%
Calcium Channel Blockers
Diltiazem	Decrease exposure
NifedipineRifampin 1200 mg administered as a single oral dose 8 hours before administering a single oral dose of nifedipine 10 mg	Decrease exposure
Verapamil	Decrease exposure
Corticosteroids 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.
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%–40% as necessary.	Decrease exposure
Digitoxin	Decrease exposure
Fluoroquinolones
PefloxacinAdministered with rifampin 900 mg daily	Decrease exposure
Moxifloxacin ,	Decrease exposure
Oral Hypoglycemic Agents (e.g., sulfonylureas)
Glyburide	Decrease exposureRifampin 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 posttreatment 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
NortriptylineA 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.	Decrease exposure
Other Drugs
Enalapril	Decrease active metabolite exposure
ChloramphenicolConcomitant use with rifampin in 2 children	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.
DoxycyclineAdministered with rifampin (10 mg/kg daily)	Decrease exposure
IrinotecanAdministered with an antibiotic regimen including rifampin (450 mg/day), isoniazid (300 mg/day), and streptomycin (0.5 g/day) IM Prevention or Management: Avoid the use of rifampin, a 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%–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 RIFADIN toxicities. Monitor for adverse reactions associated with RIFADIN 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 RIFADIN 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.

PREGNANCY SECTION

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 RIFADIN in pregnant women. Rifampin has been reported to cross the placental barrier and appear in cord blood. RIFADIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 RIFADIN 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.)

Adverse Reactions

The following adverse reactions associated with the use of RIFADIN were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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. Tooth discoloration (which may be permanent) may occur.

Hepatic

Hepatotoxicity including transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum transaminases, gamma-glutamyl transferase), hepatitis, shock-like syndrome with hepatic involvement and abnormal liver function tests, and cholestasis have been reported (see WARNINGS).

Hematologic

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, have been reported (see WARNINGS).

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, decreased hemoglobin, bleeding, and vitamin K–dependent coagulation disorders (abnormal prolongation of prothrombin time or low vitamin K–dependent coagulation factors) 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, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms syndrome (see WARNINGS), vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed.

Anaphylaxis has been reported rarely.

Respiratory, Thoracic and Mediastinal Disorders

Pulmonary toxicity (including, but not limited to, interstitial lung disease, pneumonitis, hypersensitivity pneumonitis, eosinophilic pneumonia, pulmonary infiltrates, organizing pneumonia, respiratory failure, pulmonary fibrosis, and acute respiratory distress syndrome) has been observed (see WARNINGS).

Miscellaneous

Paradoxical drug reaction has been reported with RIFADIN (see WARNINGS). Edema of the face and extremities has 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.

Overdosage

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.

Dosage And Administration

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 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 up to 30 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 8 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 6 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.

Preparation of Extemporaneous Oral Suspension

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).

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

How Supplied

RIFADIN IV (rifampin for injection USP) is available in sterile glass vials containing 600 mg rifampin (NDC 0068-0597-01).

STORAGE AND HANDLING SECTION

Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Avoid excessive heat (temperatures above 40°C or 104°F). Protect from light.

Rx only

Rifadin IV (rifampin for injection USP) is manufactured by:sanofi-aventis U.S. LLCBridgewater, NJ 08807A SANOFI COMPANY

Revised: December 2023

©2023 sanofi-aventis U.S. LLC

Principal Display Panel - 600 Mg Vial Carton

NDC 0068-0597-01 Rx ONLY

Rifadin^® IV rifampin for injection USP

600mg/vial

For IV Infusion Only

1 Sterile Vial

SANOFI