Rifampicin

J04A - Drugs for treatment of tuberculosis ATC J04AB02 Small molecule approved 1971 Oral Parenteral Natural product

JFDA label: Rifaram- 150mg capsules

Mechanism of Action

Inhibitor of Bacterial DNA-directed RNA polymerase — Bacterial DNA-directed RNA polymerase inhibitor

Target	Action	Gene / class
Bacterial DNA-directed RNA polymerase efficacy	INHIBITOR

Indications

Approved

Meningococcal prophylaxis
Tuberculosis

Off-label

Anaplasmosis
Brain abscess, empyema, and epidural abscess (MRSA)
Brucellosis
Cholestatic pruritus (adults)
Device-related osteoarticular infection (MRSA) (adults)
Endocarditis (prosthetic valve), treatment (adults)
Endocarditis (prosthetic valve), treatment (pediatric)
Group A streptococci (GAS) chronic carrier (treatment)
Haemophilus influenzae type B, chemoprophylaxis
Leprosy
Meningitis due to Streptococcus pneumoniae or staphylococci
Nasal decolonization of S. aureus
Nontuberculous mycobacterial disease, pulmonary
Osteomyelitis (MRSA)
Prosthetic joint infection
Septic thrombosis of cavernous or dural venous sinus (MRSA)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · openfda-label.

Bacteria

Organism	Activity	MIC
Corynebacterium spp.	Susceptible	0.06 mg/L
Haemophilus influenzae	Susceptible	1.0 mg/L
Helicobacter pylori	Susceptible	1.0 mg/L
Neisseria meningitidis	Susceptible	0.25 mg/L
Streptococcus A/B/C/G	Susceptible	0.25 mg/L
Streptococcus pneumoniae	Susceptible	0.125 mg/L

Mycobacteria

Organism	Activity	MIC
Mycobacterium leprae	Active	—
Mycobacterium tuberculosis	Active	—
Staphylococcus aureus	Active	—
Staphylococcus epidermidis	Active	—

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Jaundice associated with reduced bilirubin excretion Absolute
Hypersensitivity to rifampin, any rifamycins, or any component of the formulation Absolute
breastfeeding women Absolute
concurrent use of atazanavir, darunavir, fosamprenavir, ritonavir/saquinavir, saquinavir, or tipranavir Absolute
premature and newborn infants Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (4)

Not Known Decreased blood pressure · flushing · shock · vasculitis

Nervous system disorders (12)

Not Known Ataxia · behavioral changes · confusion · dizziness · drowsiness · fatigue · headache · lack of concentration · myasthenia · numbness · peripheral pain · sore mouth

Hepatobiliary disorders (4)

Not Known Abnormal hepatic function tests · hepatic insufficiency · hyperbilirubinemia · jaundice

Renal and urinary disorders (6)

Not Known Acute renal failure · hematuria · Hemoglobinuria · interstitial nephritis · renal insufficiency · renal tubular necrosis

Blood and lymphatic system disorders (7)

Not Known Decreased hemoglobin · disseminated intravascular coagulation · eosinophilia · hemolysis · hemolytic anemia · leukopenia · thrombocytopenia (especially with high-dose therapy)

Immune system disorders (1)

Not Known DRESS Syndrome

Metabolism and nutrition disorders (2)

Not Known Adrenocortical insufficiency · menstrual disease

Gastrointestinal disorders (10)

Not Known Abdominal cramps · anorexia · dental discoloration · diarrhea · epigastric distress · flatulence · glossalgia · heartburn · nausea · vomiting

Skin and subcutaneous tissue disorders (7)

Not Known Erythema multiforme · pemphigoid reaction · pruritus · skin rash · Stevens-Johnson syndrome · toxic epidermal necrolysis · urticaria

Musculoskeletal and connective tissue disorders (1)

Not Known Myopathy

Eye disorders (2)

Not Known Conjunctivitis · visual disturbance

General disorders and administration site conditions (1)

Not Known Fever

Respiratory, thoracic and mediastinal disorders (3)

Not Known Dyspnea · flu-like symptoms · wheezing

Dosing

Source: Lexicomp

Meningococcal prophylaxis: Oral, IV: 600 mg twice daily for 2 days Tuberculosis, active (drug-susceptible): Oral, IV: Note: Always administer in combination with other antitubercular drugs (Nahid 2016). Dosing: Manufacturer’s labeling: 10 mg/kg/day once daily (maximum: 600 mg/day) Alternate recommendations: ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016): Once-daily therapy: 10 mg/kg/day once daily (usual dose: 600 mg). Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative. Twice-weekly or three-times-weekly DOT: 10 mg/kg/dose (usual dose: 600 mg) administered 2 or 3 times weekly (Nahid 2016) Regimens: Treatment regimens for pulmonary tuberculosis and tuberculous meningitis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of rifampin and isoniazid for pulmonary tuberculosis and a continuation phase of an additional 7 to 10 months of rifampin and isoniazid for tuberculous meningitis (optimal duration is not defined although continuation phase must continue for a minimum of 7 additional months). Adjunctive corticosteroid therapy (eg, dexamethasone, prednisolone) tapered over 6 to 8 weeks is also recommended for tuberculous meningitis. Rifampin frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016). Tuberculosis, latent infection (LTBI): As an alternative to isoniazid: Oral, IV: 10 mg/kg/day (maximum: 600 mg/day) for 4 months. Note: Combination with pyrazinamide should not generally be offered (MMWR, Aug 8, 2003). Anaplasmosis, mild cases (patients with severe allergy to doxycycline) (off-label use): Oral: 300 mg twice daily for 7 to 10 days. Note: Rifampin is not an effective agent for Rocky Mountain spotted fever (RMSF); ensure that RMSF has been ruled out prior to use. Rifampin is also not effective for Lyme disease; if co-infection with B. burgdorferi is suspected, treat with an additional appropriate antimicrobial agent (CDC [Biggs 2016]; IDSA [Wormser 2006]). Brain abscess, empyema, and epidural abscess (MRSA) (off-label use): Oral, IV: 600 mg once daily or 300 to 450 mg twice daily with concomitant vancomycin for 4 to 6 weeks (IDSA [Liu 2011]) Brucellosis (off-label use): Oral: 600 to 900 mg once daily for 6 weeks; use in combination with doxycycline (WHO 2006). Additional data may be necessary to further define the role of rifampin in this condition. Cholestatic pruritus (off-label use) (Lindor 2009): Oral: Dose based on bilirubin value: Bilirubin Bilirubin ≥3 mg/dL: 150 mg twice daily Device-related osteoarticular infection (MRSA) (off-label use): Oral: 600 mg once daily or 300 to 450 mg twice daily in combination with another antistaphylococcal antibiotic (IDSA [Liu 2011]) Endocarditis, treatment (prosthetic

(For additional information see "Rifampin (rifampicin): Pediatric drug information") Tuberculosis, active (drug-susceptible) (excludes meningitis): Oral, IV: Use as part of a multidrug regimen: Manufacturer’s labeling: Infants, Children, and Adolescents: 10 to 20 mg/kg/day once daily (maximum: 600 mg/day) Alternate dosing: ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016): Dosing: Once-daily therapy: Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative. Infants, Children, and Adolescents Children and Adolescents 40 kg and Adolescents ≥15 years: 10 mg/kg/dose once daily (usual dose: 600 mg) Three-times-weekly directly observed therapy (DOT): Note: Although suggested dosing based on experience with twice-weekly regimen; experts suggest three-times-weekly regimens are more effective than twice-weekly DOT regimens; three-times-weekly DOT may be used as part of an intensive phase and/or continuation phase dosing regimen; consult guidelines for specific information. Infants, Children, and Adolescents Children and Adolescents 40 kg and Adolescents ≥15 years: 10 mg/kg/dose (usual dose: 600 mg) administered 3 times weekly Regimens: Treatment regimens for pulmonary tuberculosis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of rifampin and isoniazid. Rifampin frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016). Tuberculosis, latent infection (LTBI): As an alternative to isoniazid: Children: 10 to 20 mg/kg/day (maximum: 600 mg/day) for 6 months Group A streptococci (GAS) chronic carrier, treatment (off-label use): Children and Adolescents: Refer to adult dosing. Anaplasmosis, mild cases (patients with severe allergy to doxycycline) (off-label use): Children and Adolescents: Oral: 20 mg/kg/day in 2 divided doses, not to exceed 300 mg/dose. Note: Rifampin is not an effective agent for Rocky Mountain spotted fever (RMSF); ensure that RMSF has been ruled out prior to use. Rifampin is also not effective for Lyme disease; if co-infection with B. burgdorferi is suspected, treat with an additional appropriate antimicrobial agent (CDC [Biggs 2016]; IDSA [Wormser 2006]). Endocarditis, treatment (prosthetic valve/material) (off-label use): Note: Use in combination with other antibiotics: Empiric therapy: Children and Adolescents: Oral, IV: Early infection (≤1 year postop)/nosocomial infection associated with cannulation: 20 mg/kg/day divided every 8 hours; maximum daily dose: 900 mg/day (AHA [Baltimore 2015]) Late infection (>1 year postop): 15 to 20 mg/kg/day divided every 12 hours; maximum daily dose: 600 mg/day (AHA [Baltimore 2015]) MRS A infection: Infants, Children, and Adolescents: Oral, IV: 15 mg/kg/day divided every 8 hours;

Refer to adult dosing.

Treatment of drug-susceptible TB: Adults: CrCl Intermittent hemodialysis: 600 mg once daily or 600 mg administered 3 times weekly; administer after hemodialysis on the day of dialysis (Nahid 2016).

There are no dosage adjustments provided in manufacturer’s labeling; use with caution.

Warnings & Precautions

Source: Lexicomp

Flu-like syndrome

Regimens of >600 mg once or twice weekly in adults have been associated with a high incidence of adverse reactions including a flu-like syndrome.

Hematologic effects

May cause thrombocytopenia, leukopenia, or anemia with regimens >600 mg once or twice weekly in adults.

Hepatotoxicity

May cause hepatic dysfunction; fatal cases have occurred in patients with hepatic disease taking rifampin with other hepatotoxic agents. Closely monitor hepatic function and discontinue use if hepatocellular damage occurs.

Hyperbilirubinemia

Hyperbilirubinemia may occur early in therapy as a result of competition between rifampin and bilirubin for excretory pathways in the liver. Discontinue therapy if hyperbilirubinemia occurs in conjunction with clinical symptoms or any signs of significant hepatocellular damage develop.

Hypersensitivity

Hypersensitivity reactions, including severe and potentially fatal reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, have occurred with anti-tuberculosis therapy. 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. Monitor patients for signs/symptoms of hypersensitivity; discontinue therapy if signs/symptoms suggestive of hypersensitivity (eg, fever, lymphadenopathy, eosinophilia, liver abnormalities) occur, even if rash is not evident.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Alcoholism

Use with caution in patients with a history of alcoholism (even if ethanol consumption is discontinued during therapy).

Diabetes mellitus

Use with caution in patients with diabetes mellitus; management of diabetes may be more difficult in patients taking rifampin.

Hepatic impairment

Use with caution and close monitoring in patients with hepatic impairment.

Meningococcal disease

Do not use for treatment of meningococcal disease, only for short-term treatment of asymptomatic carrier states.

Porphyria

Use with caution in patients with porphyria; exacerbations have been reported due to enzyme-inducing properties. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Appropriate administration

Do not administer IV form via IM or SubQ routes; restart infusion at another site if extravasation occurs.

Compliance

Monitor for compliance in patients on intermittent therapy.

Contact lenses

Remove soft contact lenses during therapy since permanent staining may occur.

Discoloration

Teeth (may be permanent), urine, feces, saliva, sweat, and tears may be discolored (yellow, orange, red, or brown).

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies. Rifampin crosses the human placenta. Postnatal hemorrhages have been reported in the infant and mother with administration during the last few weeks of pregnancy. Maternal treatment of tuberculosis is recommended when the probability of maternal disease is moderate to high due to the risk of infection to the fetus (ATC/CDC 2003). Rifampin may be considered for use as an alternative agent in pregnant women for the treatment of mild illness due to human anaplasmosis (also known as human granulocytic anaplasmosis [HGA]); case reports have shown favorable maternal and pregnancy outcomes in small numbers of rifampin-treated pregnant women (CDC [Biggs 2016]).

Lactation

Rifampin is present in breast milk (Vorherr 1974). Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. In the treatment of drug-susceptible tuberculosis, use of rifampin is not a contraindication to breastfeeding in women deemed non-infectious who are treated with first-line agents (ie, rifampin)

Monitoring

Clinical pearl	Periodic (baseline and every 2 to 4 weeks during therapy) monitoring of liver function (AST, ALT, bilirubin), CBC, mental status, sputum culture, chest x-ray 2 to 3 months into treatment

Chemistry & Properties

Formula	C43H58N4O12
Molecular weight	822.95 g/mol
IUPAC name	[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(E)-(4-methylpiperazin-1-yl)iminomethyl]-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate
CAS	13292-46-1
PubChem CID	135398735
InChIKey	`JQXXHWHPUNPDRT-WLSIYKJHSA-N`
logP	4.34 (XLogP 4.9)
Polar surface area	220.15 Å²
H-bond acceptors / donors	15 / 6
Drug-likeness (QED)	0.11
Lipinski violations	3

SMILES

CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C)c(O)c4c(O)c(c(/C=N/N5CCN(C)CC5)c(O)c4c3C2=O)NC(=O)/C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	2.033 h
Volume of distribution	2.764 L/kg
Protein binding	84.1%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MCT1 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OAT (Inhibitor)OAT1 (Inhibitor)OAT2 (Inhibitor)OAT3 (Inhibitor)OATP (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT(unspecified) (Inhibitor)OCT1 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)Transporter(unspecified) (Inhibitor)MDR1 (Substrate)MRP1 (Substrate)MRP2 (Substrate)OATP1B1 (Substrate)OATP1B3 (Substrate)OATP2B1 (Substrate)P-gp (Substrate)Transporter(unspecified) (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abemaciclib	major
Abiraterone	major
Acalabrutinib	major
Alpelisib	major
Apixaban	major
Apremilast	major
Artemether	major
Avatrombopag	major
Axitinib	major
Bortezomib	major
Bosutinib	major
Brigatinib	major
Cabozantinib	major
Ceritinib	major
Cobicistat	major
Cobimetinib	major
Copanlisib	major
Crizotinib	major
Cyclosporine	major
Darolutamide	major
Dasatinib	major
Deflazacort	major
Dicoumarol	major
Edoxaban	major
Elagolix	major
Eliglustat	major
Eluxadoline	major
Encorafenib	major
Entrectinib	major
Ethinylestradiol	major
Everolimus	major
Fedratinib	major
Fluconazole	major
Fostamatinib	major
Gilteritinib	major
Glasdegib	major
Hemin	major
Hydrocodone	major
Ibrutinib	major
Idelalisib	major

Showing 40 of 100+.

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Rifaram-	Capsule 150 mg	8 cap pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	1.130
RIFASYNT CAP	Capsule 300 mg	8 cap	Al Hilal Drug Store	1.690
Rifaram-	Capsule 300 mg	8 cap pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	1.800
Rifaram-	Capsule 150 mg	1000 cap pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	127.130
Rifaram-	Capsule 300 mg	1000 cap pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	202.500