Generic Name: RIFAMPIN
Brand Name: Rifadin IV
- Substance Name(s):
- RIFAMPIN
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.
DRUG INTERACTIONS
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 Administered 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% Darunavir Rifampin 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 Fosamprenavir Administered 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% 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 Administered 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% 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 Nifedipine Rifampin 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 Pefloxacin Administered with rifampin 900 mg daily Decrease exposure Moxifloxacin , Decrease exposure Oral Hypoglycemic Agents (e.g., sulfonylureas) Glyburide Decrease exposure Rifampin 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 Selective 5-HT3 Receptor Antagonists Ondansetron Decrease exposure Statins Metabolized by CYP3A4 Simvastatin Decrease exposure Thiazolidinediones Rosiglitazone Decrease AUC by 66% Tricyclic Antidepressants Nortriptyline A 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 Chloramphenicol Concomitant 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.
Doxycycline Administered with rifampin (10 mg/kg daily) Decrease exposure Irinotecan Administered 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.
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.
DESCRIPTION
RIFADIN (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: corn starch, D&C Red No.
28, FD&C Blue No.
1, FD&C Red No.
40, gelatin, magnesium stearate, and titanium dioxide.
RIFADIN IV (rifampin for injection USP) contains rifampin 600 mg, sodium formaldehyde sulfoxylate 10 mg, and sodium hydroxide to adjust pH.
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: Chemical Structure
HOW SUPPLIED
RIFADIN IV (rifampin for injection USP) is available in sterile glass vials containing 600 mg rifampin (NDC 0068-0597-01).
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
GERIATRIC USE
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 .)
MECHANISM OF ACTION
Mechanism of Action Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible Mycobacterium tuberculosis organisms.
Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
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 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.
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.
PEDIATRIC USE
Pediatric Use See CLINICAL PHARMACOLOGY–Pediatrics; see also DOSAGE AND ADMINISTRATION .
PREGNANCY
Pregnancy–Teratogenic Effects 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.
Pregnancy–Non-Teratogenic Effects 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.
NUSRING MOTHERS
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.
INFORMATION FOR PATIENTS
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 blisters, 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.
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.