rifampin

Rifampin is a semisynthetic antibiotic used to treat latent or active tuberculosis, a disease caused by mycobacterial infection, and the asymptomatic carrier state of meningococcal disease.

Rifampin is also used off-label to treat other mycobacterial infections such as leprosy, and in select invasive staphylococcal infections, as part of combination therapy.

Rifampin belongs to a group of antibiotics known as rifamycins which kill bacteria (bactericidal) by preventing bacterial RNA synthesis. Rifampin binds to the bacterial DNA-dependent RNA polymerase, an enzyme that is essential for the transcription of DNA into RNA, and prevents the elongation or RNA chain. Without RNA transcription the bacterial cells cannot produce the proteins they require for survival, and the bacteria die.

Mycobacteria are obligate intracellular bacteria that only live inside the host cell. Rifampin is a potent antibiotic for mycobacteria because it can penetrate into the human cells, unlike some of the other antibiotics, as well as into the bacterial cell walls and membranes. Rifampin, however, has a high rate for development of bacterial resistance and should not be used indiscriminately. Organisms that are resistant to rifampin are likely to be resistant to other rifamycins as well.

Before the initiation of rifampin, bacteriologic culture tests should be performed to identify the infecting organism and its susceptibility to rifampin. To 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.

Rifampin is FDA-approved for the following:

• Treatment of all forms of tuberculosis, caused by Mycobacterium tuberculosis, typically with another antibacterial agent
• Prevention of infection in asymptomatic carriers after exposure to Neisseria meningitidis, bacteria that cause meningococcal diseases. Rifampin is not used in the treatment of meningococcal infection because of the possibility of rapid emergence of resistant organisms.

Off-label uses of rifampin include the following bacterial infections:

• Prophylaxis of contacts of patients with Haemophilus influenzae type B infection
• Leprosy, caused by Mycobacterium leprae
• Anaplasmosis, a tickborne disease caused by Anaplasma phagocytophilum
• Bartonella species infections
• Brucellosis, caused by Brucella species of bacteria
• Staphylococcus species infections
• Nontuberculous mycobacterial diseases caused by Mycobacterium avium complex
• Streptococcus (group A) chronic carriage

• Do not use in patients with a history of hypersensitivity to rifampin or any of its components, or any of the other rifamycins.
• Do not use rifampin concurrently with atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir, because rifampin may decrease the plasma concentration of these antiviral drugs, reducing their efficacy and increasing the risk for viral resistance.
• Do not use rifampin concurrently with ritonavir-boosted saquinavir, it can increase the risk for liver toxicity.
• In meningococcal disease, rifampin should be used only for a short term to prevent infection in individuals exposed to meningococci, it should not be used to treat meningococcal disease.
• Use with caution in patients with diabetes mellitus, rifampin may make diabetes management more difficult.
• Rifampin can damage liver and the risk is higher for patients with impaired liver function
  • Discontinue rifampin if signs of liver damage develop
  • Use with caution in patients with a history of alcoholism, even if alcohol consumption is discontinued during therapy
  • Use with caution in patients on other drugs that are hepatotoxic
  • Use with caution in patients with porphyria, a group of liver disorders
• Rifampin regimen should not be interrupted, there have been reports of rare renal hypersensitivity reactions with resumption of therapy after interruption.
• Prolonged use may result in fungal or bacterial superinfection, including Clostridium difficile-associated diarrhea (CDAD) and pseudomembranous colitis.
• Discontinue rifampin if hypersensitivity reactions develop.
• Discontinue therapy if signs of pulmonary toxicity develop.
• Cases of severe cutaneous adverse reactions (SCAR), including 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, monitor for signs and discontinue therapy if symptoms occur.
• May cause vitamin K-dependent coagulation disorders and bleeding, monitor closely.
• Regimens of more than 600 mg once or twice weekly may cause blood disorders such as leukopenia, anemia, or thrombocytopenia, or adverse reactions such as flu-like syndrome.
• Rifampin may decrease the effectiveness of oral contraceptive pills.

Common side effects of rifampin include:

• Gastrointestinal effects including:
  • Heartburn
  • Abdominal distress
  • Nausea
  • Vomiting
  • Gas (flatulence)
  • Abdominal cramps
  • Diarrhea
  • Loss of appetite (anorexia)
• Elevated liver enzymes
• Mild itching and flushing with or without rash

Less common side effects of rifampin include:

• Headache
• Fever
• Drowsiness
• Fatigue
• Dizziness
• Inability to concentrate
• Mental confusion
• Behavioral changes
• Muscular weakness
• Pain in extremities
• Generalized numbness
• Impaired coordination, balance and speech (ataxia)
• Visual disturbances
• Blood disorders including:
  • Low platelet count (thrombocytopenia), with high-dose intermittent therapy
  • Low count of leukocyte immune cells (leukopenia)
  • Low red blood cell count due to rapid destruction (hemolytic anemia)
  • Decrease in hemoglobin level
• Elevation in blood urea nitrogen (BUN) and serum uric acid
• Menstrual disturbances
• Swelling of extremities (peripheral edema)
• Facial edema
• Flu syndrome
• Hypersensitivity skin reactions including:
  • Rash
  • Hives (urticaria)
  • Itching (pruritus)
  • Pemphigoid reaction
  • Erythema multiforme
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Acute generalized exanthematous pustulosis (AGEP)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Blood vessel inflammation (vasculitis)
• High count of eosinophils (eosinophilia)
• Sore mouth
• Sore tongue
• Inflammation of conjunctiva, the membrane over the eye whites and inner eyelids (conjunctivitis)

Rare side effects of rifampin include:

• Pseudomembranous colitis, a type of colon inflammation due to overgrowth of Clostridium difficile bacteria, typically due to antibiotic use
• Clostridium difficile-associated diarrhea (CDAD)
• Liver inflammation (hepatitis)
• Shock-like syndrome due to liver toxicity
• Low blood count of granulocyte immune cells (agranulocytosis)
• Disseminated intravascular coagulation
• Blood in urine (hematuria)
• Hemoglobin in urine (hemoglobinuria)
• Kidney inflammation (nephritis)
• Renal insufficiency
• Acute renal failure
• Adrenal insufficiency in patients with compromised adrenal function
• Psychosis
• Muscle disease (myopathy)
• Severe hypersensitivity reaction (anaphylaxis)
• Pulmonary toxicity
• Shortness of breath (dyspnea)
• Low blood pressure (hypotension)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Capsule

• 150mg
• 300mg

Injectable Powder

• 600mg

Adult:

Tuberculosis

• 10 mg/kg/day orally or 10 mg/kg orally twice weekly (directly observed therapy [DOT]); not to exceed 600 mg/day  

Dosing considerations

• May be given in conjunction with isoniazid or with isoniazid and pyrazinamide
• Rifampin dosage not to exceed 600 mg/day

Meningococcal Carrier

• Indicated for treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx
• 600 mg once every 12 hours for 2 days

Haemophilus Influenzae Type B Infection (Off-label)

• Prophylaxis of contacts of patients with Haemophilus influenzae type B infection
• 600 mg/day oral/intravenous (IV) for 4 days

Pediatric:

Tuberculosis

• 10-20 mg/kg/day IV/oral or 10-20 mg/kg oral twice weekly (DOT); not to exceed 600 mg/day

Meningococcal Carrier

• Indicated for treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx
• Children 1 month or younger: 10 mg/kg/day orally divided every 12 hours for 2 days  
• Children older than 1 month: 20 mg/kg/day orally divided every 12 hours for 2 days; not to exceed 600 mg/day

Haemophilus Influenzae Type B Infection (Off-label)

• Prophylaxis of contacts of patients with Haemophilus influenzae type B infection
• Children 1 month or younger: 10 mg/kg/day orally for 4 days  
• Children older than 1 month: 20 mg/kg/day orally for 4 days; not to exceed 600 mg/day

Overdose of rifampin can cause nausea, vomiting, headache, itching and lethargy, with unconsciousness in people with severe liver disease, within a short time after ingestion. There may be elevation of liver enzymes and/or bilirubin which can cause reddish-brown or orange discoloration of skin and body fluids.

Severe overdose can be fatal, with liver enlargement, liver function impairment, hypotension, irregular heart rhythms, seizures, cardiac arrest and death.

Overdose treatment includes:

• Intensive care including respiratory support
• Gastric lavage if ingestion is within 2 or 3 hours, followed by treatment with activated charcoal to eliminate unabsorbed drug
• Increasing urination (diuresis) to promote drug excretion in the urine
• Peritoneal or extracorporeal hemodialysis, if required

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Rifampin has severe interactions with at least 41 different drugs.
• Rifampin has serious interactions with at least 221 different drugs.
• Rifampin has moderate interactions with at least 289 different drugs.
• Rifampin has mild interactions with at least 63 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on rifampin use in pregnant women. Animal studies of rifampin during pregnancy reveal evidence of fetal harm.
• Rifampin crosses the human placenta and is present in cord blood.
• There have been reports of postnatal hemorrhage in the mother and the infant, with maternal use of rifampin in late pregnancy.
• Use rifampin during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Rifampin is present in breast milk. Breastfeeding women should discontinue nursing or discontinue the drug because of the potential for severe adverse reactions in the infant.

• Take rifampin exactly as instructed, do not skip doses, and complete the full prescribed course even if you feel better, because interrupting the course can reduce the treatment efficacy and lead to development antibiotic-resistant bacteria.
• Rifampin is used only for bacterial infections, do not use it to treat viral infections such as common cold.
• While on rifampin therapy, avoid alcohol, herbal products and other medications that are toxic to the liver.
• Rifampin may affect the reliability of oral or systemic hormonal contraceptives, consider alternate methods of contraception while on treatment.
• Rifampin may cause yellow, orange, red, or brown discoloration of teeth, urine, feces, saliva, tears and sweat. Avoid using contact lenses while on therapy, may become permanently stained.
• Contact your physician immediately if you experience fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, and pain or swelling of the joints.
• Store rifampin carefully out of reach of children.