Rifabutin

MYCOBUTIN Capsules for oral administration contain 150 mg of the rifamycin antimycobacterial agent rifabutin, USP, per capsule, along with the inactive ingredients microcrystalline cellulose, magnesium stearate, red iron oxide, silica gel, sodium lauryl sulfate, titanium dioxide, and edible white ink.

The chemical name for rifabutin is 1',4-didehydro-1-deoxy-1,4-dihydro-5'-(2-methylpropyl)-1- oxorifamycin XIV (Chemical Abstracts Service, 9th Collective Index) or (9S,12E,14S,15R, 16S,17R,18R,19R,20S,21S,22E, 24Z)-6,16,18,20-tetrahydroxy-1'-isobutyl-14-methoxy- 7,9,15,17,19,21,25-heptamethyl-spiro [9,4-(epoxypentadeca[1,11,13]trienimino)-2Hfuro[ 2',3':7,8]naphth[1,2-d] imidazole-2,4'-piperidine]-5,10,26-(3H,9H)-trione-16-acetate. Rifabutin has a molecular formula of C46H62N4O11, a molecular weight of 847.02 and the following structure:

Rifabutin is a red-violet powder soluble in chloroform and methanol, sparingly soluble in ethanol, and very slightly soluble in water (0.19 mg/mL). Its log P value (the base 10 logarithm of the partition coefficient between n-octanol and water) is 3.2 (n-octanol/water).

MYCOBUTIN Capsules are indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.

Serious side effects have been reported with rifabutin. See the "Drug Precautions" section.

Common side effects of rifabutin include the following:

• nausea
• vomiting
• insomnia (trouble sleeping)
• Rash
• chest pain
• fever
• headache
• upset stomach
• brown-orange sweat, urine, saliva, tears, skin, and stool
• change in the way things taste
• muscle pain
• neutropenia (low number of white blood cells)
• anemia (blood does not carry enough oxygen to the rest of your body)

This is not a complete list of rifabutin side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Rifabutin is an antibiotic that fights bacteria.

Rifabutin is used to prevent mycobacterium avium complex (MAC) in people with HIV (human immunodeficiency virus) infection.

Rifabutin is also used with other medicines to treat tuberculosis in people with HIV.

Rifabutin may also be used for purposes not listed in this medication guide.

You should not use rifabutin if you have active tuberculosis, or if you are also taking delavirdine or voriconazole.

Metabolized by CYP3A.1

Induces CYP3A; induces hepatic enzymes to a lesser extent than rifampin.1 81

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A with possible alteration of the metabolism of rifabutin and/or other drug.1

Specific Drugs

Take rifabutin exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for side effects.

rifabutin should not be given to patients with active tuberculosis (TB). If you know you have TB or think you may have active TB, tell your doctor.

Rifabutin may be taken on an empty stomach (either 1 hour before or 2 hours after a meal). However, if rifabutin upsets your stomach, you may want to take it with food.

If you cannot swallow the capsule, you may open it and the contents of the capsules may be mixed with applesauce. Be sure to take all the food to get the full dose of medicine.

To help prevent MAC disease, it is very important that you keep using rifabutin for the full time of treatment. You may have to take it every day for many months. It is important that you do not miss any doses.

Dosing

The dose of rifabutin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of rifabutin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For the prevention of Mycobacterium avium complex (MAC):
    • Adults—300 milligrams (mg) once a day, or 150 mg two times a day with food.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of rifabutin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your progress at regular visits. Blood and urine tests may be needed to check for unwanted effects.

Rifabutin will cause your urine, stools, saliva, skin, sputum, sweat, and tears to turn reddish-orange to brown-orange. This is to be expected while you are taking rifabutin. This effect may cause soft contact lenses to become permanently discolored. Standard cleaning solutions may not take out all the discoloration. It is best not to wear soft contact lenses while taking rifabutin. Hard contact lenses are not discolored by rifabutin. If you have any questions about this, check with your doctor.

Check with your doctor immediately if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

rifabutin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop using rifabutin. Do not take any medicine to treat diarrhea without first checking with your doctor. If you have any questions or if mild diarrhea continues or gets worse, check with your doctor.

Rifabutin can lower the number of white blood cells in your blood temporarily, increasing the chance of getting infection. It can also lower the number of platelets, which are necessary for proper blood clotting. These problems may result in a greater chance of getting certain infections, slow healing, and bleeding of the gums. Be careful when using a regular toothbrush, dental floss, or toothpick. Dental work should be delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.

Birth control pills may not work properly if you take them while you are taking rifabutin. Unplanned pregnancies may occur. Use a different means of birth control while you are taking rifabutin. If you have any questions about this, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Allergic side effects may rarely happen.
• This medicine may stain contact lenses.
• This medicine may change the color of urine, stools, saliva, sweat, tears, and skin to a brown-orange color. This is normal and not harmful.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking rifabutin.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about rifabutin, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about rifabutin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using rifabutin.

Review Date: October 4, 2017

• Mycobutin

• Antitubercular Agent
• Rifamycin

May be administered with meals to minimize nausea or vomiting.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), angina, flu-like symptoms, chills, pharyngitis, bruising, bleeding, severe loss of strength and energy, muscle pain, joint pain, shortness of breath, vision changes, eye pain, severe eye irritation, sensitivity to light, dizziness, passing out, severe nausea, severe vomiting, cough, arrhythmia, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Applies to rifabutin: oral capsule

General

Rifabutin was generally well tolerated in clinical trials. Discontinuation due to a side effect was reported in 16% of patients taking rifabutin compared to 8% of patients taking placebo. Discontinuation of rifabutin was mainly due to rash (4%), gastrointestinal intolerance (3%), and neutropenia (2%).[Ref]

Hematologic

Hematologic side effects have included neutropenia (less than 750/mm3; 25%), leukopenia (less than 1500/mm3; 17%), anemia (less than 8 g/dL; 6%), thrombocytopenia (less than 50,000/mm3; 5%), eosinophilia (1%), and hemolysis (less than 1%). At least one case of thrombotic thrombocytopenic purpura has been reported.[Ref]

Neutropenia and thrombocytopenia have been associated with rifabutin use. However, the latter may be related to underlying disease since it has been observed at a similar rate in control groups in placebo-controlled trials.[Ref]

Dermatologic

Dermatologic side effects have included rash (11%) and skin discoloration (less than 1%). Perspiration and skin may be discolored brown-orange with rifabutin and some of its metabolites. At least one case of acute generalized exanthematous pustulosis has been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea (6%), nausea and vomiting (3%), dyspepsia (3%), diarrhea (3%), eructation (3%), anorexia (2%), flatulence (2%), vomiting (1%), and Clostridium difficile associated diarrhea. Feces and saliva may be discolored brown-orange with rifabutin and some of its metabolites. Aphthous stomatitis has rarely been reported.[Ref]

Ocular

Ocular side effects have included uveitis, resulting in itching, decreased vision, photophobia, pain, and temporary blindness in some patients. Uveitis was reported at doses from 1050 mg/day to 2400 mg/day. Tears may be discolored brown-orange with rifabutin and some of its metabolites. Soft contact lenses may be permanently stained.[Ref]

Uveitis was rare when rifabutin was used as a single agent at 300 mg/day, even in combination with fluconazole and/or macrolides. However, the incidence of uveitis was greater if higher doses of rifabutin were used with these agents. Patients who developed uveitis had mild to severe symptoms that resolved following therapy with corticosteroids and/or mydriatic eye drops; however, in some severe cases, resolution of symptoms occurred after several weeks.[Ref]

Hepatic

Hepatic side effects have included increased SGPT (greater than 150 units/L; 9%), increased SGOT (greater than 150 units/L; 7%), and hepatitis (less than 1%).[Ref]

Other

Other side effects have included abdominal pain (4%), taste perversion (3%), fever (2%), asthenia (1%), chest pain (1%), pain (1%), and influenza-like syndrome. Sputum may be discolored brown-orange with rifabutin and some of its metabolites. Drug-induced lupus syndrome has been reported.[Ref]

Three cases of drug-induced lupus syndrome (DILS) have been reported. All cases were receiving standard doses of rifabutin and all had positive antinuclear antibodies during their lupus-like reactions. Symptoms of DILS included malaise, myalgias, arthralgias, and fever. None of the cases experienced lupus-type nephritis or skin and CNS involvement.[Ref]

Nervous system

Nervous system side effects have included headache (3%), insomnia (1%), seizure, paresthesia, aphasia, and confusion.[Ref]

Musculoskeletal

In one study of 10 patients receiving greater than 1 gram of rifabutin per day, nine developed significant distal, small joint arthralgias. No evidence of concomitant rheumatic disease was evident and no effusions were observed.[Ref]

Musculoskeletal side effects have included myalgia (2%), arthralgia (less than 1%), myositis (less than 1%), and polyarthralgia-arthritis syndrome (rare). Generalized arthralgia was reported at doses from 1050 mg/day to 2400 mg/day.[Ref]

Cardiovascular

Cardiovascular side effects have included nonspecific T wave changes on electrocardiogram.[Ref]

Metabolic

Metabolic side effects have included increased alkaline phosphatase (greater than 450 units/L; less than 1%).

Respiratory

Respiratory side effects have included chest pressure or pain with dyspnea in less than 1% of patients.

Genitourinary

Genitourinary side effects have included urine discoloration (30%).[Ref]

Urine may be discolored brown-orange with rifabutin and some of its metabolites.[Ref]

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

300 mg orally once a day. If nausea of vomiting becomes a problem, rifabutin 150 mg orally every 12 hours is an alternative regimen.

Rifabutin is recommended by the USPHS/IDSA (U.S. Public Health Service/Infectious Diseases Society of America) Prevention of Opportunistic Infections Working Group as an alternative to rifampin for chemoprophylaxis when exposure to isoniazid-resistant tuberculosis is suspected.

For HIV-infected patients, chemoprophylaxis is recommended for those with a positive tuberculin skin test (greater than or equal to 5 mm), prior positive skin test result without treatment, or contact with cases of active tuberculosis. In addition, tuberculin skin test negative, HIV-infected patients from high risk groups or geographic areas with a high prevalence of Mycobacterium tuberculosis may be candidates for chemoprophylaxis. Active tuberculosis should be ruled out prior to initiating preventive therapy.

There isn't general agreement on how to use rifabutin for preventive therapy. The decision to use non-isoniazid-containing regimens for chemoprophylaxis should require consultation with public health authorities.

Rifabutin is typically administered for 6 months to prevent the development of active tuberculosis in patients with no complicating factors. Patients with complicating factors such as HIV infection, diabetes, hematologic malignancy, or scars on chest X-ray should receive prophylaxis for 12 months.

5 mg/kg/day orally has been used in a limited number of cases. Used in combination with at least 2 other antimicrobials. Doses of rifabutin may be administered mixed with foods such as applesauce.