Rifater

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of isoniazid, pyrazinamide, and rifampin can be fatal, especially when this medicine is combined with alcohol.

The first signs of an overdose may include nausea, vomiting, stomach pain, lack of energy, headache, and itching. Later symptoms may include severe stomach pain, yellowing of your skin or eyes, brown or red-orange colored body fluids (tears, sweat, saliva, urine, stools), swelling in your face, fast heartbeats, seizures (convulsions) or loss of consciousness.

Avoid drinking alcohol. It may increase your risk of liver damage while you are taking this medicine.

Avoid taking an antacid within 1 hour before or after you take isoniazid, pyrazinamide, and rifampin. Some antacids can make it harder for your body to absorb isoniazid, pyrazinamide, and rifampin.

Do not wear soft contact lenses while taking isoniazid, pyrazinamide, and rifampin. This medicine may turn certain body fluids a red color (including tears, saliva, urine, and sweat). While this is a harmless side effect, it may permanently stain contact lenses.

Avoid foods that are high in tyramine or histamine, listed below. Tyramine or histamine can interact with this medication and cause unpleasant side effects. These foods include:

• beer (alcoholic and nonalcoholic), wine (especially red wine);

• cheese, especially aged or processed cheeses (American, blue, brie, cheddar, gruyere, mozzarella, parmesan, romano, Swiss, and others);

• sour cream and yogurt;

• tuna, skipjack, pickled or smoked fish, anchovies, dried fish, herring, caviar, shrimp paste, or other tropical fish;

• soy sauce, miso soup, bean curd, fava beans; or

• yeast extracts.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking isoniazid, pyrazinamide, and rifampin and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

In the U.S.

• Rifater

Available Dosage Forms:

• Tablet

Therapeutic Class: Antitubercular Combination

Chemical Class: Rifamycin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of rifampin, isoniazid, and pyrazinamide combination in children younger than 15 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of rifampin, isoniazid, and pyrazinamide combination in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Artemether
• Atazanavir
• Boceprevir
• Cobicistat
• Daclatasvir
• Darunavir
• Dasabuvir
• Delamanid
• Elbasvir
• Elvitegravir
• Fosamprenavir
• Grazoprevir
• Isavuconazonium
• Lopinavir
• Lurasidone
• Maraviroc
• Nelfinavir
• Ombitasvir
• Paritaprevir
• Praziquantel
• Ranolazine
• Rilpivirine
• Ritonavir
• Saquinavir
• Telaprevir
• Tipranavir
• Voriconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abiraterone
• Acetaminophen
• Afatinib
• Amiodarone
• Amprenavir
• Apixaban
• Apremilast
• Aprepitant
• Aripiprazole
• Atovaquone
• Axitinib
• Bedaquiline
• Bosutinib
• Brexpiprazole
• Brigatinib
• Brivaracetam
• Bupropion
• Cabozantinib
• Carbamazepine
• Cariprazine
• Ceritinib
• Cholera Vaccine, Live
• Clozapine
• Cobimetinib
• Crizotinib
• Cyclosporine
• Dabigatran Etexilate
• Dasatinib
• Deferasirox
• Deflazacort
• Delavirdine
• Desogestrel
• Dienogest
• Digoxin
• Dolutegravir
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Drospirenone
• Edoxaban
• Efavirenz
• Eliglustat
• Eluxadoline
• Enzalutamide
• Erlotinib
• Estradiol
• Ethinyl Estradiol
• Ethionamide
• Ethynodiol
• Etonogestrel
• Etravirine
• Everolimus
• Exemestane
• Fentanyl
• Fosaprepitant
• Fosphenytoin
• Gefitinib
• Gestodene
• Glimepiride
• Ibrutinib
• Idelalisib
• Ifosfamide
• Imatinib
• Indinavir
• Irinotecan
• Irinotecan Liposome
• Isoniazid
• Itraconazole
• Ivabradine
• Ivacaftor
• Ixabepilone
• Ixazomib
• Ketoconazole
• Lamotrigine
• Lapatinib
• Ledipasvir
• Levodopa
• Levonorgestrel
• Linagliptin
• Lorcainide
• Macitentan
• Manidipine
• Mestranol
• Methadone
• Midostaurin
• Mifepristone
• Mycophenolate Mofetil
• Mycophenolic Acid
• Naloxegol
• Netupitant
• Nevirapine
• Nifedipine
• Nilotinib
• Nimodipine
• Nintedanib
• Norethindrone
• Norgestimate
• Norgestrel
• Olaparib
• Osimertinib
• Palbociclib
• Panobinostat
• Pazopanib
• Perampanel
• Phenytoin
• Piperaquine
• Pitavastatin
• Pixantrone
• Ponatinib
• Posaconazole
• Pyrazinamide
• Quetiapine
• Quinine
• Regorafenib
• Ribociclib
• Rifampin
• Rivaroxaban
• Roflumilast
• Rolapitant
• Romidepsin
• Simeprevir
• Sirolimus
• Sofosbuvir
• Sonidegib
• Sorafenib
• Sunitinib
• Tacrolimus
• Tasimelteon
• Tegafur
• Telithromycin
• Temsirolimus
• Tenofovir Alafenamide
• Thiotepa
• Ticagrelor
• Tofacitinib
• Tolvaptan
• Trabectedin
• Ulipristal
• Valbenazine
• Vandetanib
• Velpatasvir
• Vemurafenib
• Venetoclax
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Vortioxetine
• Zidovudine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetyldigoxin
• Aliskiren
• Aminosalicylic Acid
• Anisindione
• Aripiprazole Lauroxil
• Atorvastatin
• Betamethasone
• Bexarotene
• Bosentan
• Buspirone
• Carbamazepine
• Carvedilol
• Caspofungin
• Chloramphenicol
• Chlorpropamide
• Citalopram
• Clarithromycin
• Clofibrate
• Cortisone
• Dexamethasone
• Diazepam
• Dicumarol
• Diltiazem
• Disopyramide
• Disulfiram
• Doxycycline
• Eltrombopag
• Enalaprilat
• Enalapril Maleate
• Enflurane
• Etoricoxib
• Fesoterodine
• Fluconazole
• Fludrocortisone
• Fosphenytoin
• Gliclazide
• Glyburide
• Haloperidol
• Isradipine
• Levomethadyl
• Levothyroxine
• Linezolid
• Losartan
• Mefloquine
• Meperidine
• Metformin
• Methylprednisolone
• Metoprolol
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nisoldipine
• Ospemifene
• Oxcarbazepine
• Oxycodone
• Phenprocoumon
• Phenytoin
• Pioglitazone
• Pirmenol
• Prednisolone
• Prednisone
• Propafenone
• Raltegravir
• Repaglinide
• Rofecoxib
• Rosiglitazone
• Sertraline
• Simvastatin
• Tadalafil
• Tamoxifen
• Theophylline
• Tocainide
• Triazolam
• Trimetrexate
• Valproic Acid
• Warfarin
• Zaleplon
• Zidovudine
• Zolpidem

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• food
• Tyramine Containing Food

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of—Use with caution. There may be an increased chance of getting hepatitis if you take this medicine and drink alcohol daily.

• Diabetes, history of or
• Porphyria (an enzyme problem)—Use with caution. May make these conditions worse.

• Gout, acute or
• Liver disease, acute or severe—Should not be used in patients with these conditions.

• It is used to treat TB (tuberculosis).

• If you have an allergy to rifampin, isoniazid, pyrazinamide, or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Gout or liver problems.
• If you have had very bad side effects while taking isoniazid in the past, like liver problems, drug fever, chills, or arthritis.
• If you had liver problems while taking some other drug in the past.
• If you are taking any of these drugs: Atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with Rifater.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• Take with a full glass of water.
• To gain the most benefit, do not miss doses.
• Keep taking Rifater (rifampin, isoniazid, and pyrazinamide) as you have been told by your doctor or other health care provider, even if you feel well.
• Do not take antacids within 1 hour of this medicine.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Rifater is a combination of the three drugs, rifampin, isoniazid, and pyrazinamide. Each of these individual drugs has been associated with liver dysfunction.

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

Rifampin

Rifampin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Because Rifater contains both rifampin and isoniazid, it should only be given with caution and under strict medical supervision to patients with impaired liver function. In these patients, careful monitoring of liver function, especially serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, Rifater should be withdrawn.

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

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

Isoniazid

(See the boxed WARNING.)

Since Rifater contains isoniazid, ophthalmologic examinations (including ophthalmoscopy) should be done before treatment is started and periodically thereafter, even without occurrence of visual symptoms.

Severe cutaneous reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), some with a fatal outcome, have been reported with the use of isoniazid (see ADVERSE REACTIONS). Monitor for skin reactions and advise patients to report skin rashes or mucosal lesions immediately. Discontinue Rifater if these reactions occur.

Pyrazinamide

Since Rifater contains pyrazinamide, patients started on Rifater should have baseline serum uric acid and liver function determinations. Patients with preexisting liver disease or those patients at increased risk for drug related hepatitis (e.g., alcohol abusers) should be followed closely.

Because it contains pyrazinamide, Rifater should be discontinued and not be resumed if signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear. If hyperuricemia accompanied by an acute gouty arthritis occurs without liver dysfunction, the patient should be transferred to a regimen not containing pyrazinamide.

Rifater tablets are light beige, smooth, round, and shiny sugar-coated tablets imprinted with "Rifater" in black ink and contain 120 mg rifampin, 50 mg isoniazid, and 300 mg pyrazinamide, and are supplied as:

Bottles of 60 tablets (NDC 0088-0576-41).

Storage

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from excessive humidity.

Reference

1. Clinical Laboratory Standards Institute. 2003. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Document M24-A.

sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY

Revised April 2017

©2017 sanofi-aventis U.S. LLC

Applies to isoniazid / pyrazinamide / rifampin: oral tablet

Along with its needed effects, isoniazid / pyrazinamide / rifampin 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 while taking isoniazid / pyrazinamide / rifampin:

More common

• Clumsiness or unsteadiness
• coughing or spitting up blood
• dark urine
• fast, irregular, pounding, or racing heartbeat or pulse
• loss of appetite
• nausea and vomiting
• numbness, tingling, burning, or pain in the hands and feet
• pain in large and small joints
• tightness in the chest
• unusual tiredness or weakness
• yellow eyes or skin

Less common

• Chills
• difficulty in breathing
• dizziness
• fever
• headache
• hearing loss
• muscle and bone pain
• ringing or buzzing or other unexplained noise in ears
• shivering
• skin rash, itching, or redness

Rare

• Black, tarry stools
• bleeding gums
• blistering, peeling, loosening of skin
• bloody or cloudy urine
• blurred vision or loss of vision, with or without eye pain
• greatly decreased frequency of urination or amount of urine
• mental depression
• mood or mental changes
• pinpoint red spots on skin
• seizures
• sore throat
• unusual bleeding or bruising

Some side effects of isoniazid / pyrazinamide / rifampin 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:

More common

• Diarrhea
• stomach pain

Less common

• Sore mouth or tongue

Antibacterial and antimycobacterial agent; semisynthetic derivative of rifamycin SV.161

Administration

Administer orally.161 May be given by IV infusion if oral therapy is not feasible.161 b Should not be given IM or sub-Q.161 b

Used in conjunction with other anti-infectives for treatment of active (clinical) TB, anthrax, brucellosis, legionella infections, leprosy, MAC or other mycobacterial infections, rhodococcus infections, and staphylococcal and streptococcal infections.127 146 176 161 166 176 191 198 200 203 204 206 207 226 227 229 230 232 258

Fixed-combination preparations (Rifamate containing rifampin and isoniazid; Rifater containing rifampin, isoniazid, and pyrazinamide) can be used for treatment of active TB infection to reduce the pill burden and ensure compliance, especially when directly observed (supervised) therapy (DOT) cannot be used.258 A fixed-combination preparation should be used only when all drugs in the preparation are indicated.258

Oral Administration

Administer single-entity rifampin or fixed-combination preparations (Rifamate , Rifater) orally with a full glass of water 1 hour before or 2 hours after a meal.161 172 259

For individuals who are unable to swallow rifampin capsules and when lower doses are needed for children, a 1% suspension can be prepared using Syrup NF (simple syrup), Syrpalta syrup (Emerson Laboratories), or Raspberry syrup (HumCo Laboratories).161 To prepare a suspension containing rifampin 10 mg/mL, empty the contents of four 300-mg or eight 150-mg capsules and mix the contents vigorously with 20 mL of a recommended syrup; then further dilute with 100 mL of the syrup.161 Shake well prior to administration.161

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.161 b

Avoid extravasation.161 b Discontinue infusion and restart at another site if local irritation and inflammation occur at the site of infusion.161 b

Reconstitution and Dilution

Reconstitute vial containing 600 mg of rifampin powder by adding 10 mL sterile water for injection and gently swirling the vial.161 b Reconstituted solution contains 60 mg/mL.161 b

Prior to administration, add the appropriate dose of reconstituted solution to 100 or 500 mL of 5% dextrose injection or 0.9% sodium chloride injection.161 b

Rate of Administration

If infusion volume is 100 mL, give IV at a rate that allows complete infusion within 30 minutes.161 b

If infusion volume is 500 mL, give IV at a rate that allows complete infusion within 3 hours.161 b

Dosage

Oral and IV dosages are the same.161

Dosage of Rifamate expressed as number of capsules;259 dosage of Rifater expressed as number of tablets.172

Pediatric Patients

General Dosage for Infants and Children Oral or IV

Children ≥1 month of age: AAP recommends 10–20 mg/kg (up to 600 mg) daily given in 1 or 2 divided doses for mild to moderate infections or 20 mg/kg (up to 600 mg) daily in 2 divided doses for severe infections.176

Tuberculosis Treatment of Active (Clinical) Tuberculosis Oral

Children <15 years of age or weighing ≤40 kg: 10–20 mg/kg (up to 600 mg) daily recommended by manufacturer, ATS, CDC, IDSA, AAP, and others.161 176 258 s v If an intermittent regimen is used, 10–20 mg/kg (up to 600 mg) 2 or 3 times weekly.176 258 s v

Adolescents ≥15 years of age: 10 mg/kg (up to 600 mg) daily.258 v If an intermittent regimen is used, 10 mg/kg (up to 600 mg) 2 or 3 times weekly.258 v

Rifater in adolescents ≥15 years of age: 4 tablets once daily in those weighing ≤44 kg, 5 tablets once daily in those weighing 45–54 kg, or 6 tablets once daily in those weighing ≥55 kg.172 Used only in the initial phase of treatment.172

When used for the treatment of active TB in HIV-infected individuals with CD4+ T-cell counts <100/mm3, rifampin should be given at least 3 times weekly.101 r CDC and others recommend these patients receive a once-daily regimen during the initial intensive treatment phase and either a once-daily or 3-times weekly regimen during the continuation phase.100 r

IV

10–20 mg/kg (up to 600 mg) daily.161 b v

Latent Tuberculosis Infection (LTBI) Oral

10–20 mg/kg (up to 600 mg) once daily for 4–6 months.176 177 194 215 269 v If daily regimen cannot be used, AAP states 10–20 mg/kg (up to 600 mg) twice weekly for 6 months can be administered using directly observed (supervised) therapy (DOT) .176

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.194 215 When rifampin monotherapy is used, at least 120 doses should be administered within 6 months.215 Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.215 If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.194 215

Brucellosis† Treatment or Prevention† Oral

15–20 mg/kg (up to 600–900 mg) daily; given in conjunction with other anti-infectives.176

For postexposure prophylaxis, continue for 3–6 weeks;139 for treatment, continue for 4–6 weeks (more prolonged therapy may be needed in serious infections or when there are complications).139 176

Ehrlichiosis and Anaplasmosis† Mild Anaplasmosis† Oral

10 mg/kg (up to 300 mg) twice daily for 7–10 days.k

Leprosy† Multibacillary Leprosy† Oral

Children <10 years of age: 300 mg once monthly in conjunction with dapsone (25 mg once daily) and clofazimine (50 mg twice weekly and 100 mg once monthly).204

Children 10–14 years of age: 450 mg once monthly in conjunction with dapsone (50 mg once daily) and clofazimine (50 mg every other day and 150 mg once monthly).204 jj

Usual duration of treatment is 12 months.198 200 206 207 jj An additional 12 months of treatment may be necessary in some patients (e.g., those with a high baseline bacterial index who have no evidence of improvement or have evidence of deterioration after the initial 12 months of treatment).jj

Paucibacillary Leprosy† Oral

Children <10 years of age: 300 mg once monthly in conjunction with dapsone (25 mg once daily).204

Children 10–14 years of age: 450 mg once monthly in conjunction with dapsone (50 mg once daily).204 jj

Usual duration of treatment is 6 months.204 jj

Single-lesion Paucibacillary Leprosy† Oral

Children 5–14 years of age: A single 300-mg dose of rifampin in conjunction with a single dose of ofloxacin (200 mg) and a single dose of minocycline (50 mg).204

Children <5 years of age: Use an appropriately adjusted dose of each drug in the above single-dose regimen.204

Neisseria meningitidis Infections Prophylaxis in Household or Other Close Contacts† Oral

Neonates <1 month of age: 5 mg/kg every 12 hours for 2 days.176 179 187

Children ≥1 month of age: 10 mg/kg (up to 600 mg) every 12 hours for 2 days.176 179 187

Initiate as soon as possible after contact, preferably within 24 hours after identification of the index case.176 179 187

Elimination of Pharyngeal Carrier State Oral

Neonates <1 month of age: 5 mg/kg every 12 hours for 2 days.161

Children ≥1 month of age: 10 mg/kg (up to 600 mg) every 12 hours for 2 days.161

Staphylococcal and Streptococcal Infections† Meningitis Caused by S. pneumoniae† IV

Children ≥1 month of age: 20 mg/kg daily given in divided doses every 12 hours; used as an adjunct to other anti-infectives (e.g., vancomycin).176

Prevention of Haemophilus influenzae Type b Infection† Oral

Neonates <1 month of age: Some clinicians recommend 10 mg/kg once daily for 4 consecutive days.134 176

Children ≥1 month of age: 20 mg/kg (up to 600 mg) once daily for 4 consecutive days.134 138 176

Adults

Tuberculosis Treatment of Active (Clinical) Tuberculosis Oral

10 mg/kg (up to 600 mg) once daily recommended by the manufacturers, ATS, CDC, IDSA, and others.161 258 r v If an intermittent regimen is used, 10 mg/kg (up to 600 mg daily) 2 or 3 times weekly.258 v

Rifamate: 2 capsules once daily.259

Rifater: 4 tablets once daily in adults weighing ≤44 kg, 5 tablets once daily in adults weighing 45–54 kg, or 6 tablets once daily in adults weighing ≥55 kg.172 Used only in the initial phase of treatment.172

When used for the treatment of active TB in HIV-infected individuals with CD4+ T-cell counts <100/mm3, rifampin should be given at least 3 times weekly.r CDC and others recommend these patients receive a once-daily regimen during the initial intensive phase and either a once-daily or 3-times weekly regimen during the continuation phase.100 r

IV

10 mg/kg (up to 600 mg) once daily.161

Latent Tuberculosis Infection (LTBI) Oral

10 mg/kg (up to 600 mg) once daily for 4 months.177 194 215 v

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.194 215 When rifampin monotherapy is used, at least 120 doses should be administered within 6 months.215 Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.215 If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.194 215

Anthrax† Inhalational Anthrax† IV

300 mg every 12 hours has been used in conjunction with other anti-infectives.127

Anthrax Meningitis† IV

20 mg/kg daily in conjunction with other anti-infectives.139

Brucellosis† Oral

15–20 mg/kg (up to 600–900 mg) daily in conjunction with other anti-infectives.139 176 227 229 230 Some clinicians suggest 0.6–1.2 g daily in conjunction with other anti-infectives.270

For postexposure prophylaxis, continue for 3–6 weeks; 139 for treatment, continue for 4–6 weeks (more prolonged therapy may be needed in serious infections or when there are complications).139 176 Some clinicians state that 6–8 weeks of treatment may be necessary in patients with skeletal disease and ≥3 months (and possibly >6 months) of treatment may be necessary in those with meningoencephalitis or endocarditis.139

Ehrlichiosis and Anaplasmosis† Mild Anaplasmosis† Oral

300 mg twice daily for 7–10 days.k

Leprosy† Multibacillary Leprosy† Oral

600 mg once monthly in conjunction with dapsone (100 mg once daily) and clofazimine (50 mg once daily and 300 mg once monthly).198 200 204 206 207 jj

Usual duration of treatment is 12 months.198 200 206 207 jj An additional 12 months of treatment may be necessary in some patients (e.g., those with a high baseline bacterial index who have no evidence of improvement or have evidence of deterioration after the initial 12 months of treatment).jj

Paucibacillary Leprosy† Oral

600 mg once monthly in conjunction with dapsone (100 mg once daily).198 200 204 206 207 jj

Usual duration of treatment is 6 months.198 200 204 206 207 jj

Single-lesion Paucibacillary Leprosy† Oral

A single 600-mg dose of rifampin in conjunction with a single dose of ofloxacin (400 mg) and a single dose of minocycline (100 mg).204 jj

Mycobacterium avium Complex (MAC) Infections† Initial Treatment of Pulmonary MAC Infections (Nodular/bronchiectatic Disease) Caused by Macrolide-susceptible Strains† Oral

600 mg 3 times weekly in conjunction with ethambutol (25 mg/kg 3 times weekly) and either clarithromycin (1 g 3 times weekly) or azithromycin (500 mg 3 times weekly) recommended by ATS and IDSA.191 Continue until patient has been culture negative on treatment for 1 year.191

Intermittent (3-times weekly) regimen is not recommended for those with cavitary or moderate or severe disease or those who have been previously treated.191

Initial Treatment of Pulmonary MAC Infections (Fibrocavitary or Severe Nodular/bronchiectatic Disease) Caused by Macrolide-susceptible Strains† Oral

10 mg/kg (up to 600 mg) once daily in conjunction with ethambutol (15 mg/kg once daily) and either clarithromycin (0.5–1 g daily) or azithromycin (250 mg once daily) recommended by ATS and IDSA.191 Continue until patient has been culture negative on treatment for 1 year.191 Consideration can be given to including amikacin or streptomycin 3 times weekly during the first 2–3 months of treatment for extensive, especially fibrocavitary, disease or when previous therapy has failed.191

Mycobacterium kansasii and Other Mycobacterial Infections† Treatment of Pulmonary or Disseminated Infections Caused by Rifampin-susceptible M. kansasii† Oral

10 mg/kg (up to 600 mg) daily in conjunction with ethambutol (15 mg/kg once daily), isoniazid (5 mg/kg [up to 300 mg] daily), and pyridoxine (50 mg daily) recommended by ATS and IDSA.191

Continue until patient has been culture negative on treatment for 1 year.191 A longer duration may be needed in HIV-infected individuals with disseminated infections.191

Treatment of M. marinum Infections† Oral

600 mg dailybb ff in conjunction with ethambutol (15–25 mg/kg daily).bb ff

Optimal duration of treatment not known; continue for 3–6 months or until at least 1–2 months after resolution of symptoms.191 bb cc ff

Neisseria meningitidis Infections Prophylaxis in Household or Other Close Contacts† Oral

600 mg every 12 hours for 2 days.187

Initiate as soon as possible after contact, preferably within 24 hours after identification of the index case.176 179 187

Elimination of Pharyngeal Carrier State Oral or IV

600 mg twice daily for 2 days.161 b

Prevention of Haemophilus influenzae Type b Infection† Oral

20 mg/kg (up to 600 mg) once daily for 4 consecutive days.134 138 176

Prescribing Limits

Pediatric Patients

Tuberculosis Active (Clinical) Tuberculosis Oral or IV

Maximum 600 mg per dose in once-daily or 2- or 3-times weekly regimens.161 176 258 269 s v

Latent Tuberculosis Infection (LTBI) Oral or IV

Maximum 600 mg per dose in once-daily or twice-weekly regimens.161 176 258 269 s v

Brucellosis Oral

Maximum 600–900 mg daily.176

Ehrlichiosis and Anaplasmosis† Mild Anaplasmosis† Oral

Maximum 300 mg twice daily.176

Neisseria meningitidis Infections Prophylaxis or Elimination of Pharyngeal Carrier State Oral

Children ≥1 month of age: Maximum 600 mg every 12 hours.161

Prevention of Haemophilus influenzae Type b Infection Oral

Maximum 600 mg once daily.134 138 176

Adults

Tuberculosis Active (Clinical) Tuberculosis Oral or IV

Maximum 600 mg per dose in once-daily or 2- or 3-times weekly regimens.161 215 258 v

Latent Tuberculosis Infection (LTBI) Oral or IV

Maximum 600 mg once daily.161 215 258 v

Brucellosis Oral

Maximum 600–900 mg daily.139 227 229 230

Mycobacterium avium Complex (MAC) Infections† Initial Treatment of Pulmonary MAC Infections (Fibrocavitary or Severe Nodular/bronchiectatic Disease) Caused by Macrolide-susceptible Strains† Oral

Maximum 600 mg once daily.139 227 229 230

Mycobacterium kansasii and Other Mycobacterial Infections† Treatment of Pulmonary or Disseminated Infections Caused by Rifampin-susceptible M. kansasii† Oral

Maximum 600 mg daily.139 227 229 230

Special Populations

Renal Impairment

Dosage adjustment not required in renal impairment or end-stage renal disease if dosage is ≤600 mg daily.161 258