rifampin

INDICATIONS AND USAGE 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 ® (Sanofi-aventis U.S. LLC)) 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 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. Rifampin 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.

DOSAGE AND ADMINISTRATION Rifampin can be administered by the oral route (see INDICATIONS AND USAGE ). 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, orally. Pediatric Patients 10 to 20 mg/kg, not to exceed 600 mg/day, orally. 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. 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: Rifampin 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 Rifampin 300 mg capsules or eight Rifampin 150 mg capsules onto a piece of weighing paper. 2. If necessary, gently crush the capsule contents with a spatula to product 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 to 8° C) for four weeks. This extemporaneously prepared suspension must be shaken well prior to administration.

CONTRAINDICATIONS Rifampin capsules are 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, tipranavir, cabotegravir, fostemsavir and lenacapavir (see prescribing information for SUNLENCA) due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in decreased antiviral efficacy and/or development of viral resistance. (See PRECAUTIONS, Drug Interactions ). 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 ).

ADVERSE REACTIONS The following adverse reactions associated with the use of rifampin were identical 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 casual 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, a 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 theombocytopenic 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 …

DRUG INTERACTIONS Pharmacodynamic Interactions Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated. (See CONTRAINDICATIONS.) When rifampin is given concomitantly with other hepatotoxic medications such as halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampin and halothane should be avoided. Patients receiving both rifampin and isoniazid should be monitored closely for hepatotoxicity. Effect of Rifampin on Other Drugs Induction of Drug Metabolizing Enzymes and Transporters Drug metabolizing enzymes and transporters affected by rifampin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways and these pathways may be induced by rifampin simultaneously. Therefore, rifampin may increase the metabolism and decrease the activity of certain coadministered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required), and has the potential to perpetuate clinically important drug-drug interactions against many drugs and across many drug classes (Table 1). Table 1 summarizes the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified. Table 1: Drug Interactions with Rifampin that Affect Concomitant Drug Concentrations* Drug or Drug Class and Prevention or Management Clinical Effect Antiretrovirals Prevention or Management: Concomitant use is contraindicated (see CONTRAINDICATIONS) Atazanavir Decrease AUC by 72% Darunavir† Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance. Tipranavir Fosamprenavir‡ Decrease AUC by 82% Saquinavir Decrease AUC by 70% Coadministration may result in severe hepatocellular toxicity. Cabotegravir Decrease AUC by 59% Fostemsavir Decrease AUC by 82% Lenacapavir (SUNLENCA) ¤ Decrease AUC by 84% Antiretrovirals Prevention or Management: Avoid concomitant use Zidovudine Decrease AUC by 47% Indinavir Decrease AUC by 92% Efavirenz Decrease AUC by 26% Antiretrovirals Prevention or Management : Dose adjustment is indicated Lenacapavir (YEZTUGO) Ə Refer to the YEZTUGO prescribing information for YEZTUGO dose adjustment. Decrease AUC by 84% 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 Phenytoin § 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 plas …

DESCRIPTION Rifampin Capsules, USP for oral administration contains 150 mg or 300 mg rifampin per capsule. The 150 mg and 300 mg capsules also contain, as inactive ingredients: magnesium stearate, docusate sodium, sodium benzoate, pregelatinized starch, talc, microcrystalline cellulose and colloidal silicon dioxide. The hard gelatin capsules contain gelatin, purified water, sodium lauryl sulfate, titanium dioxide, FD&C Red No. 40, D&C Red No. 28 and FD&C Blue No. 1. The imprinting ink contains shellac, black iron oxide, potassium hydroxide and propylene glycol. Rifampin is a semisynthetic antibiotic derivative of rifamycin SV. Rifampin is a red-brown crystalline powder very slightly soluble in water at neutral pH, freely soluble in chloroform, soluble in ethyl acetate and in methanol. Its molecular weight is 822.95 and its chemical formula is C 43 H 58 N 4 O 12 . The chemical name for rifampin is either: 3-[[(4-Methyl-1-piperazinyl)imino]methyl]rifamycin or 5,6,9,17,19,21-hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-[N-(4-methyl-1-piperazinyl)formimidoyl]-2,7-(epoxypentadeca[1,11,13]trienimino)naphtho[2,1- b ]furan-1,11(2H)-dione 21-acetate. Its structural formula is: FDA approved dissolution test specifications differ from USP. structure

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.

HOW SUPPLIED Rifampin capsules USP, 150 mg are orange capsules, imprinted E 801 in black ink on both cap and body. They are available as follows: NDC 42806-801-30, bottles of 30 capsules NDC 42806-801-01, bottles of 100 capsules Rifampin capsules USP, 300 mg are red capsules, imprinted E 799 in black ink on both cap and body. They are available as follows: NDC 42806-799-30, bottles of 30 capsules NDC 42806-799-60, bottles of 60 capsules NDC 42806-799-01, bottles of 100 capsules NDC 42806-799-05, bottles of 500 capsules Storage Store at 20o to 25o C (68o to 77o F) [See USP Controlled Room Temperature] Dispense contents in a tight light-resistant container as defined in the USP with a child resistant closure, as required. Store in a dry place. KEEP TIGHTLY CLOSED. Avoid excessive heat. KEEP OUT OF THE REACH OF CHILDREN. Rx only The brands listed are the registered trademarks of their respective owners and are not trademarks of Epic Pharma, LLC. Distributed by: Epic Pharma, LLC Laurelton, NY 11413 Rev. 07-2023-01 MF801REV07/23 OS0004