rifabutin

Absorption: Well absorbed following oral administration (50–85%). Absorption ↓ in patients with HIV (20%).

Distribution: Widely distributed to body tissues and fluids.

Metabolism/Excretion: Mostly metabolized by the liver; <5% excreted unchanged by the kidneys.

Half-Life: 45 hr.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE		ONSET		PEAK		DURATION
PO		rapid		2–4 hr		24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity. Cross-sensitivity with other rifamycins (rifampin) may occur;
Active tuberculosis (TB);
Concurrent use of cabotegravir/rilpivirine or voriconazole;
Lactation: Lactation.

Use Cautiously in:

OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, chest pressure

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, skin discoloration, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: ocular disturbances

GI: altered taste, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), drug-induced hepatitis

Hemat: hemolysis, neutropenia, thrombocytopenia

MS: arthralgia, myositis

Resp: dyspnea

Misc: brown-orange discoloration of body fluids (urine, tears, saliva), flu-like syndrome

Interactions ⬆ ⬇

Drug-drug:

May significantly ↓ levels and effectiveness of rilpivirine; concurrent use with cabotegravir/rilpivirine contraindicated.
Voriconazole may significantly ↑ levels and risk of toxicity of both rifabutin and voriconazole; concurrent use contraindicated.
May ↓ levels and effectiveness of estrogen-containing contraceptives.
May ↓ levels and effectiveness of bictegravir and tenofovir alafenamide; concurrent use with bictegravir/emtricitabine/tenofovir alafenamide is not recommended.
May ↓ levels and effectiveness of doravirine; ↑ doravirine dose.
May ↓ levels and effectiveness of rilpivirine and tenofovir alafenamide; concurrent use with rilpivirine/tenofovir alafenamide/emtricitabine not recommended.
Atazanavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir may ↑ levels and risk of toxicity; ↓ rifabutin dose to 150 mg every other day or 150 mg 3 times weekly.
May ↑ levels and risk of toxicity of darunavir/ritonavir; ↓ rifabutin dose to 150 mg every other day or 150 mg 3 times weekly.
May ↓ levels and effectiveness of elvitegravir; concurrent use with elvitegravir/cobicistat not recommended.
May ↓ levels and effectiveness of etravirine; concurrent use with etravirine with ritonavir or another protease inhibitor not recommended.
Nelfinavir may ↑ levels and risk of toxicity; ↓ rifabutin dose to 150 mg once daily and ↓ nelfinavir dose.
May ↓ levels and effectiveness of sofosbuvir; concurrent use not recommended.
May ↑ levels and risk of toxicity of metabolite of bedaquiline; concurrent use not recommended.
Fluconazole may ↑ levels and risk of toxicity.
Concurrent use with itraconazole or posaconazole may ↑ levels and risk of toxicity of rifabutin and ↓ levels and effectiveness of itraconazole or posaconazole; avoid concurrent use.
May ↓ levels and effectiveness of dapsone and sulfamethoxazole/trimethoprim.
Concurrent use with clarithromycin may ↑ levels and risk of toxicity of rifabutin and ↓ levels and effectiveness of clarithromycin.

Route/Dosage ⬆ ⬇

PO (Adults ): 300 mg once daily. If GI upset occurs, may give as 150 mg twice daily with food.

Availability ⬆ ⬇

(Generic available)

Capsules: 150 mg
In combination with:
amoxicillin and omeprazole (Talicia). See Combination Drugs.

Assessment ⬆ ⬇

Monitor for signs of active TB (purified protein derivative [PPD], chest x-ray, sputum culture, blood culture, urine culture, biopsy of suspicious lymph nodes) prior to and during therapy. Rifabutin must not be administered to patients with active TB.
Mycobacterial studies and susceptibility tests should be performed before and periodically during therapy to detect possible resistance. Perform chest x-ray after 2–3 mo and at end of treatment in patients with negative initial cultures.
Assess lung sounds and character and amount of sputum periodically during therapy.
Monitor for signs/symptoms of CDAD including watery diarrhea with mucus, fever, abdominal pain or cramping, anorexia, nausea, and, in severe cases, dehydration and blood or pus in the stool. May begin ≥2 mo after therapy. Report promptly to health care provider.
Monitor patients for development of severe cutaneous adverse reactions, including DRESS, SJS, and TEN, including signs and symptoms of prodrome of fever, malaise, mucosal lesions, progressive skin rash, blisters, lymphadenopathy, conjunctivitis, myalgias, hepatitis, or eosinophilia. If a severe cutaneous adverse reaction is suspected, interrupt therapy until etiology of reaction is determined. Consultation with a dermatologist is recommended. If a severe cutaneous adverse reaction is confirmed or for other Grade 4 skin reactions, permanently discontinue rifabutin.
Monitor for signs/symptoms of hypersensitivity reactions (hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia) or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, fever, chills, aches, rash, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). If hypersensitivity reaction occurs, discontinue rifabutin.

Lab Test Considerations:

Monitor CBC periodically during therapy. May cause neutropenia and thrombocytopenia.
Obtain acid-fast bacilli smear and culture from sputum monthly until two consecutive specimens are negative.

Implementation ⬆ ⬇

Do not confuse rifabutin with rifapentine.
PO: Administer without regard to meals unless GI upset occurs on empty stomach. High-fat meals slow rate but do not ↓ absorption. May be mixed with foods such as applesauce.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of rifabutin. Advise patient to take as directed. Do not skip doses or double up on missed doses. Emphasize the importance of continuing full course of therapy even if asymptomatic. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Emphasize the importance of regular follow-up exams to monitor progress and to check for side effects.
Advise patient to notify health care provider promptly if signs and symptoms of neutropenia (sore throat, fever, signs of infection), thrombocytopenia (unusual bleeding or bruising), or hepatitis (yellow eyes and skin, nausea, vomiting, anorexia, unusual tiredness, weakness) occur.
Advise patients and family to call 911 and seek urgent treatment for signs and symptoms of hypersensitivity reactions (difficulty breathing; chest tightness; hives; rash; feeling light-headed; itching; swelling of the face, lips, tongue, or throat).
Caution patient to avoid the use of alcohol during this therapy, because this may ↑ the risk of hepatotoxicity.
Instruct patient to notify health care provider immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care providers.
Instruct patient to report symptoms of myositis (myalgia, arthralgia) or uveitis (intraocular inflammation) to health care provider promptly.
Inform patient that skin, saliva, sputum, sweat, tears, urine, and feces may become brown-orange and that soft contact lenses may become permanently discolored.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇