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Rifampin

Pronunciation

Pronunciation: rif-AM-pin
Class: Antituberculosis agent

Trade Names

Rifadin
- Capsules, oral 150 mg
- Capsules, oral 300 mg
- Injection, lyophilized powder for solution 600 mg

Rofact (Canada)

Pharmacology

Inhibits DNA-dependent RNA polymerase in susceptible Mycobacterium tuberculosis organisms. Also active against Neisseria meningitidis .

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Pharmacokinetics

Absorption

Almost completely absorbed (oral). T max is 1 to 4 h (oral). C max is 7 mcg/mL (oral average) and may vary from 4 to 32 mcg/mL (oral adults). C max is 9 to 17 mcg/mL (IV average). Oral absorption decreased 30% when taken with food.

Distribution

Vd is about 0.64 L/kg (600 mg IV); 0.66 L/kg (300 mg IV). Diffuses well into most body tissues and fluids, including CSF. Crosses placenta and distributes into breast milk. Protein binding is approximately 80%.

Metabolism

Metabolized in liver by deacetylation to active metabolite 25-desacetyl-rifampin. Undergoes enterohepatic circulation.

Elimination

Less than 30% of dose is excreted in the urine (active and metabolites).

Special Populations

Renal Function Impairment

Serum concentrations do not differ in patients with renal failure; no dosage adjustment required.

Children

After oral administration, the C max ranged from 3.5 to 15 mcg/mL, T max was 1 h, and half-life was approximately 2.9 h. After IV administration, the C max after the initial infusion was approximately 25.9 mcg/mL and half-life ranged from 1.04 to 3.81 h.

Indications and Usage

Adjunctive treatment of tuberculosis (TB); short-term management to eliminate meningococci from nasopharynx in asymptomatic N. meningitidis carriers.

Contraindications

Hypersensitivity to rifampin, product components, or to any rifamycin; concomitant therapy with unboosted or ritonavir-boosted saquinavir, atazanavir, darunavir, fosamprenavir, or tipranavir.

Dosage and Administration

Tuberculosis

IV dosage form is for initial treatment or re-treatment when rifampin cannot be taken by mouth.

Adults

PO/IV 10 mg/kg once daily or 2 or 3 times/wk (max, 600 mg/dose).

Children

PO/IV 10 to 20 mg/kg once daily or 2 times/wk (max, 600 mg/dose).

Meningococcal Carriers
Adults

PO/IV 600 mg twice daily for 2 days.

Children 1 mo or older

PO/IV 10 mg/kg (max, 600 mg/dose) every 12 h for 2 consecutive days.

Children younger than 1 mo

PO/IV 5 mg/kg every 12 h for 2 consecutive days.

General Advice

Oral
  • Administer 1 h before or 2 h after a meal with a full glass of water.
  • If patient is unable to swallow capsules or when lower dosages are needed, a liquid suspension may be compounded. Follow the manufacturer's instructions for preparation.
  • Shake extemporaneously prepared suspension well.
Injection
  • For IV infusion. Not for IM or subcutaneous injection.
  • Follow manufacturer's instructions for preparation. If reconstituted product is added to 500 mL diluent, administer over 3 h. If added to 100 mL diluent, administer over 30 min.
  • Incompatibilities: Physically incompatible with diltiazem.

Storage/Stability

Capsules

Store in a dry place; avoid excessive heat (temperatures above 104°F). Protect from light.

Extemporaneous oral suspension

Stable for 4 wk when stored at 77°F or in a refrigerator (36° to 46°F).

Injection

Avoid excessive heat (above 104°F). Protect from light. Reconstitutions with sterile water for injection are stable at room temperature for 24 h. Dilutions in dextrose 5% for injection are stable at room temperature for up to 4 h 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 24 h and should be prepared and used within this time.

Drug Interactions

ACE inhibitors (eg, enalapril)

The pharmacologic effects of enalapril may be decreased, resulting in a decrease in antihypertensive control. Monitor BP; consider an alternative antihypertensive if BP remains uncontrolled.

Aliskiren, aprepitant, axitinib, barbiturates (eg, phenobarbital), benzodiazepines (eg, diazepam, midazolam, triazolam), beta-blockers (eg, bisoprolol, metoprolol, propranolol), bupropion, buspirone, calcium channel blockers (eg, diltiazem, nifedipine), clofibrate, cyclosporine, digoxin, doxycycline, efavirenz, eszopiclone, exemestane, fluoroquinolones (eg, ciprofloxacin), gefitinib, haloperidol, HMG-CoA reductase inhibitors (eg, fluvastatin, simvastatin), hydantoins (eg, phenytoin), imatinib, losartan, nevirapine, quinine, ramelteon, risperidone, sulfones (eg, dapsone), tacrolimus, TCAs (eg, amitriptyline, nortriptyline), telithromycin, theophyllines, ulipristal, valproic acid, zidovudine, zolpidem

Plasma concentrations and pharmacologic effects of these agents may be decreased. Close laboratory and/or clinical monitoring is warranted. Larger doses of these agents may be needed.

Aminosalicylic acid

Aminosalicylic acid oral granules decrease the GI absorption of rifampin. Separate doses by 8 to 12 h.

Antacids

Rifampin absorption may be reduced. Rifampin should be given at least 1 h before antacid ingestion.

Antiarrhythmics (eg, amiodarone, disopyramide, mexiletine, propafenone, quinidine, tocainide)

Serum concentrations of antiarrhythmics may be decreased because of CYP3A4 induction by rifampin. Closely monitor serum concentrations when starting or stopping rifampin.

Anticoagulants (eg, warfarin)

The anticoagulation activity of warfarin may be decreased because of increased hepatic microsomal enzyme metabolism. Increased dosage of anticoagulants may be needed. Monitor coagulation parameters closely when rifampin is started or discontinued and adjust the warfarin dose as needed.

Atovaquone

Rifampin concentrations may be elevated, increasing the risk of adverse reactions, and atovaquone concentrations may be reduced, decreasing the therapeutic effect. Monitor the response to both agents and adjust the doses as needed.

Azole antifungal agents (eg, fluconazole, ketoconazole)

Rifampin may induce the metabolism of azole antifungal agents. Ketoconazole may interfere with rifampin absorption, decreasing serum rifampin levels. If concurrent use cannot be avoided, monitor and adjust the dosages as needed.

Boceprevir, telaprevir

Boceprevir and telaprevir plasma concentrations and pharmacologic effects may be decreased. Consider alternative therapy for rifampin.

Bortezomib, cabazitaxel, corticosteroids, crizotinib, dabigatran, delavirdine, dronedarone, etravirine, ivacaftor, ixabepilone, mTOR inhibitors (eg, everolimus, temsirolimus), quetiapine, rivaroxaban, roflumilast, ticagrelor, tolvaptan, tyrosine kinase receptor inhibitors (eg, dasatinib, nilotinib, pazopanib), vandetanib

Plasma concentrations and pharmacologic effects of these agents may be decreased. Avoid coadministration.

Bosentan

Bosentan plasma trough concentrations may be transiently increased then decreased. Closely monitor the clinical response when starting or stopping rifampin. Adjust the bosentan dose as needed.

Brentuximab

Brentuximab plasma concentrations and pharmacologic effects may be decreased. The therapeutic risk/benefit of continuing rifampin should be assessed because the therapeutic options for patients receiving brentuximab are limited.

Chloramphenicol

Chloramphenicol metabolism may be increased because of induction of hepatic microsomal enzymes by rifampin. If coadministration cannot be avoided, it may be necessary to adjust the chloramphenicol dose.

Clopidogrel

The antiplatelet effects of clopidogrel may be increased. Closely monitor platelet function when starting, stopping, or changing the dose of rifampin dose. Adjust the clopidogrel dose as needed.

Deferasirox

Deferasirox plasma concentrations and pharmacologic effects may be decreased. If coadministration cannot be avoided, an initial dose of deferasirox 30 mg/kg/d should be considered. Adjust deferasirox dosages according to serum ferritin concentrations and clinical response.

Food

Food interferes with the absorption of rifampin, possibly decreasing absorption by 30%. Administer on an empty stomach, either 1 h before or 2 h after a meal, with a full glass of water.

Erlotinib

Erlotinib plasma concentrations and pharmacologic effects may be decreased. If coadministration cannot be avoided, consider an erlotinib dose greater than 150 mg.

Estrogens

Rifampin may impair the effectiveness of estrogens by inducing drug metabolism, decreasing AUC and half-life. Consider a dose increase if an interaction is suspected.

Hormonal contraceptives

Reduced hormonal contraceptive efficacy and an increased incidence of menstrual abnormalities may occur. Advise patients to use an additional form of birth control while receiving rifampin therapy.

Isoniazid

May result in higher rate of hepatotoxicity. Closely monitor for hepatotoxicity. If alterations in LFTs occur, consider discontinuation of one or both agents.

Linagliptin

Linagliptin plasma concentrations and pharmacologic effects may be decreased. Close clinical and blood glucose monitoring is warranted. An alternative to linagliptin is strongly recommended.

Lurasidone, nifedipine, praziquantel, ranolazine, rilpivirine

Plasma concentrations and pharmacologic effects of these agents may be decreased. Coadministration is contraindicated.

Macrolide antibiotics (eg, clarithromycin)

The metabolism of rifampin may be inhibited, while the metabolism of the macrolide antibiotic may be increased. Monitor for increased adverse effects and a decrease in the response to the macrolide antibiotic.

Maraviroc

Maraviroc plasma concentrations and pharmacologic effects may be decreased. A dosage adjustment of maraviroc is recommended during coadministration with rifampin. Coadministration is contraindicated in patients with severe renal impairment (CrCl 30 mL/min).

Meglitinides (eg, nateglinide, repaglinide), sulfonylureas (eg, tolbutamide), thiazolidinediones (eg, pioglitazone, rosiglitazone)

Plasma concentrations and pharmacologic effects or these agents may be decreased. Closely monitor blood glucose concentrations. Adjust the dose of these agents when starting or stopping rifampin.

Mycophenolate

Mycophenolate plasma concentrations and pharmacologic effects may be decreased. If coadministration cannot be avoided, it may be necessary to increase the mycophenolate dose.

Narcotic analgesics (eg, methadone, morphine)

Patients may experience withdrawal symptoms. Rifampin primarily appears to stimulate the hepatic metabolism of methadone. A higher dose of narcotic analgesics may be required during coadministration of rifampin.

Ondansetron

Plasma concentrations of ondansetron may be reduced. Close clinical monitoring is warranted. Consider use of an alternative antiemetic.

Pitavastatin

Pitavastatin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Pitavastatin dose should not exceed 2 mg daily in patients receiving rifampin.

Probenecid

Elevates rifampin levels. Monitor the patient for rifampin adverse reaction.

Protease inhibitors (eg, atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir)

Rifampin may increase the metabolism of protease inhibitors and protease inhibitors may decrease rifampin metabolism. Rifampin is contraindicated in patients receiving ritonavir-boosted saquinavir. Patients administered rifampin and ritonavir-boosted saquinavir develop severe hepatocellular toxicity. Rifampin is contraindicated in patients receiving atazanavir, darunavir, fosamprenavir, unboosted saquinavir, or tipranavir.

Pyrazinamide

Liver necrosis and failure have been reported in patients receiving rifampin plus pyrazinamide for latent TB infection. When used as part of a standard 4-drug TB treatment regimen, close clinical monitoring is generally sufficient. If administered for latent TB infection, close clinical and laboratory monitoring for signs of liver toxicity is warranted and no more than a 2-week supply should be dispensed at one time to facilitate periodic clinical assessments.

Raltegravir

Raltegravir plasma concentrations and pharmacologic effects may be decreased. Coadminister with caution. Raltegravir 800 mg twice daily is recommended when coadministered with rifampin.

Thyroid hormones (eg, levothyroxine)

TSH levels may be increased, resulting in hypothyroidism. Monitor thyroid status in patients receiving both drugs. Adjust the thyroid hormone dose as needed.

Trimethoprim/Sulfamethoxazole

Rifampin plasma concentrations may be elevated, increasing the risk of adverse reactions.

Vemurafenib

Vemurafenib plasma concentrations and pharmacologic effects may be decreased. Coadminister with caution.

Verapamil

An increase in first-pass hepatic metabolism results in a lowered bioavailability of oral verapamil. Use IV verapamil or substitute another agent for either verapamil or rifampin.

Voriconazole

Plasma concentrations and pharmacologic effects of voriconazole may be decreased and plasma concentrations and pharmacologic effects of rifampin may be increased. Coadministration is contraindicated.

Laboratory Test Interactions

May inhibit standard assays for serum folate and vitamin B 12 . Use alternate assay methods. Transient abnormalities in LFTs (eg, elevation in serum bilirubin, abnormal bromsulfophthalein excretion, alkaline phosphatase, serum transaminases) and reduced biliary excretion of contrast media used for visualization of gallbladder may occur. Therefore, perform these tests before the morning dose of rifampin. Cross-reactivity and false-positive urine screening tests for opiates have been reported in patients taking rifampin and using the Kinetic Interaction of Microparticles in Solution method (eg, Abuscreen OnLine opiates assay; Roche Diagnostic Systems). Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish rifampin from opiates.

Adverse Reactions

Cardiovascular

Hypotension; shock.

CNS

Behavioral changes; dizziness; drowsiness; fatigue; generalized numbness; headache; inability to concentrate; mental confusion.

Dermatologic

Flushing; pruritus; rash.

EENT

Conjunctivitis; visual disturbances.

GI

Anorexia; cramps; diarrhea; epigastric distress; gas; heartburn; nausea; pseudomembranous colitis; sore mouth and tongue; vomiting.

Hematologic

Decreased Hgb; eosinophilia; hemolytic anemia; leukopenia; thrombocytopenia.

Hepatic

Jaundice; transient elevations of LFTs (eg, serum bilirubin, bromsulphalein, alkaline phosphatase, serum transaminases).

Hypersensitivity

Anaphylaxis; erythema multiforme including Stevens-Johnson syndrome; pemphigoid reaction; pruritus; TEN; urticaria; vasculitis.

Musculoskeletal

Ataxia; muscular weakness; pain in extremities.

Respiratory

Shortness of breath; wheezing.

Miscellaneous

Discoloration of body fluids (eg, urine, sweat, sputum, tears); edema of face and extremities; elevated serum uric acid; elevations in BUN; fever; flu syndrome (eg, fever, chills, headache, malaise, dizziness, bone pain); menstrual disturbances.

Precautions

Monitor

Perform baseline measurements of hepatic enzymes, bilirubin, serum creatinine, CBC, and platelet count in adults treated for TB. Baseline tests are not necessary for pediatric patients unless a complicating condition is known or suspected. In patients with liver impairment, carefully monitor liver function (AST, ALT) prior to therapy and then every 2 to 4 wk during therapy. Question patients at least monthly concerning symptoms of adverse reactions.


Pregnancy

Category C . Considered safe in pregnancy according to the CDC.

Lactation

Excreted in breast milk but does not produce toxic effects in breast-feeding infants (according to the CDC). The American Academy of Pediatrics classifies rifampin as compatible with breast-feeding.

Hepatic Function

Give only in cases of necessity and then with caution under strict medical supervision.

Diabetes mellitus

Use with caution in these patients. Diabetes management may be more difficult.

Discoloration of body fluids

Medication may cause harmless red-orange discoloration of urine, feces, saliva, sputum, sweat, and tears. Soft contact lenses may be permanently stained.

Enzyme induction

May enhance the metabolism of endogenous substrates (eg, adrenal hormones, thyroid hormones, vitamin D).

Extravasation

Avoid extravasation during injection; local irritation and inflammation have been observed.

Hepatotoxicity

May produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Monitor carefully. Discontinue if signs of hepatocellular damage occur.

Hyperbilirubinemia

May occur. Monitor closely.

Intermittent therapy

According to the manufacturer, intermittent therapy is not recommended and rifampin should be administered daily. Rare renal hypersensitivity reactions have been reported when therapy was resumed in cases of intermittent usage. However, the CDC guidelines include 2 to 3 times/wk dosing.

Meningococci resistance

Rapid emergence of resistant meningococci restricts use to short-term treatment of asymptomatic carriers. Not to be used for treatment of meningococcal disease.

Porphyria

Isolated reports have associated porphyria exacerbation with rifampin.

Thrombocytopenia

May occur. Effect is reversible if drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have occurred when rifampin administration has continued or resumed after appearance of purpura.

Overdosage

Symptoms

Abdominal pain; brownish-red or orange discoloration of skin, urine, sweat, saliva, tears, and feces; facial or periorbital edema (seen in pediatric patients); headache; hypotension, sinus tachycardia, ventricular arrhythmias, seizures, and cardiac arrest were reported in some fatal cases; increasing lethargy; liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage, and jaundice may develop rapidly; nausea, pruritus; transient increases in liver enzymes or bilirubin; unconsciousness may occur with severe hepatic disease; vomiting.

Patient Information

  • Instruct patients to take drug on empty stomach 1 h before or 2 h after meals.
  • Inform patients that body fluids may turn red-orange in color and that soft contact lenses may become permanently stained. Advise patients to wear glasses during course of therapy.
  • Instruct patients to notify their health care provider of persistent anorexia, nausea, vomiting, diarrhea, jaundice, fever, change in color or consistency of stools, malaise or right upper quadrant abdominal pain, unusual bleeding or bruising, petechiae, hematuria, bleeding gums, or pallor.
  • Tell patients to notify their health care provider of drowsiness, fatigue, dizziness, inability to concentrate, confusion, or visual or behavioral changes.
  • Advise patients using oral contraceptives to use a nonhormonal form of contraception during therapy.
  • Advise patients that rifampin may cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness.
  • Advise patients of the importance of medication compliance in treatment of tuberculosis. Medication noncompliance reduces efficacy and promotes resistance.
  • Caution patients to avoid alcohol.

Copyright © 2009 Wolters Kluwer Health.

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