Rifampicin

Registered South African indications:

Infections caused by:

• M. tuberculosis
• M. leprae
• M. lepromatosis
• Legionella
• N. meningitidis
• H. influenza

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients
• Porphyria
• Jaundice
• Coadministration with saquinavir/ritonavir

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (if dose >600mg/day)
• Hepatic impairment
• Elderly 
• Malnourished patients
• Children below 2 yrs
• Hyperbilirubinaemia
• Fructose intolerance (sus)
• Glucose-galactose malabsorption (sus)
• Sucrose-isomaltase insufficiency (sus)

Forms avail. in SA and covered in this monograph: cap, inj, sus, tab

Infections caused by M. tuberculosis; M. leprae; M. lepromatosis; Legionella; N. meningitidis; H. influenza

General dosing range

• Oral/IV (cap, sus, tab, inj): 7.5-12mg/kg, dly; Max: 600mg/24hrs

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Infective endocarditis- prosthetic valve
Brucellosis

• Oral/IV (sus, cap, tab, inj): 7.5mg/kg, 12hrly; Treatment duration: 6 weeks
  Refer to Infective endocarditis; EML, 2015
  Refer to Brucellosis; EML, 2015

Tuberculosis- drug sensitive: intensive phase (in combination with isoniazid, pyrazinamide and ethambutol)

• Oral (sus, cap, tab): 30-37kg: 300mg, dly; Treatment duration: 2 months
• Oral (sus, cap, tab): 38-54kg: 450mg, dly; Treatment duration: 2 months
• Oral (sus, cap, tab): 55-70kg: 600mg, dly; Treatment duration: 2 months
• Oral (sus, cap, tab): 71kg and over: 750mg, dly; Treatment duration: 2 months
  Refer to Tuberculosis; TB Guidelines, 2015

Tuberculosis- drug sensitive: continuation phase (in combination with isoniazid, pyrazinamide and ethambutol)

• Oral (sus, cap, tab): 30-37kg: 300mg, dly; Treatment duration: 4 months
• Oral (sus, cap, tab): 38-54kg: 450mg, dly; Treatment duration: 4 months
• Oral (sus, cap, tab): 55-70kg: 600mg, dly; Treatment duration: 4 months
• Oral (sus, cap, tab): 71kg and over: 600mg, dly; Treatment duration: 4 months
  Refer ro Tuberculosis; TB Guidelines, 2015

Tuberculosis- isoniazid monoresistance

• Oral (sus, cap, tab): 10mg/kg, dly; Treatment duration: 6 months

Meningitis

• Oral/IV (sus, cap, tab, inj): 600mg, 12hrly
  Refer to Meningitis; EML, 2015

Leprosy

• Oral (sus, cap, tab): 600mg, monthly; Treatment duration: 6-12 months

Meningococcal carriers

• Oral (sus, cap, tab): 600mg, 12hrly; Treatment duration: 2 days

Prophylaxis against meningitis due to Haemophilus influenza

• Oral (sus, cap, tab): 20mg/kg, dly; Treatment duration: 4 days; Max: 600mg

Forms avail. in SA and covered in this monograph: cap, inj, sus, tab

Infections caused by M. tuberculosis; M. leprae; M. lepromatosis; Legionella; N. meningitidis; H. influenza

General dosing range

• Oral/IV (cap, sus, tab, inj): 5-20mg/kg, dly; Max: 600mg/24hrs

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Tuberculosis- drug sensitive: intensive phase

Younger than 4 weeks

• Oral (sus, cap, tab): 10mg/kg, dly; Treatment duration: 2 months

Older than 4 weeks

• Oral (sus, cap, tab): 10-20mg/kg, dly; Treatment duration: 2 months
  Refer to Pulmonary tuberculosis; TB Guidelines, 2013
   

Tuberculosis- drug sensitive: continuation phase

Younger than 4 weeks

• Oral (sus, cap, tab): 10-15mg/kg, dly; Treatment duration: 4 months

Older than 4 weeks

• Oral (sus, cap, tab): 10-20mg/kg, dly; Treatment duration: 4 months
  Refer to Pulmonary tuberculosis; TB Guidelines, 2013

Prophylaxis against tuberculosis- isoniazid monoresistant contact

• Oral (sus, cap, tab): 15mg/kg, dly; Treatment duration: 4 months

Disseminated TB 

• Oral (sus, cap, tab): 20mg/kg, dly; Max: 600mg/24hrs; Treatment duration: 6 months
  Refer to Pulmonary tuberculosis; TB Guidelines, 2013

Tuberculous Meningitis

• Oral/IV (sus, cap, tab, inj): 20mg/kg, dly
  Refer to Tuberculous Meningitis; EML, 2013

Leprosy

Younger than 10 years

• Not established for use in children below 10 years

Between 10-14 year

• Oral (sus, cap, tab): 12-15mg/kg, monthly

Older than 14 years

• See adult dosage

Meningococcal carriers

Younger than 3 months

• Not established for use 

Between 3-12months

• Oral (sus, cap, tab): 5mg/kg, 12hrly; Treatment duration: 2 days

Between 1-12 years

• Oral (sus, cap, tab): 10mg/kg, 12hrly; Treatment duration: 2 days

Older than 12 years

• See adult dosage

Prophylaxis against meningitis due to Haemophilus influenza

Younger than 4 weeks

• Oral (sus, cap, tab): 10mg/kg, dly; Treatment duration: 4 days

Older than 4 weeks

• Oral (sus, cap, tab): 20mg/kg, dly; Treatment duration: 4 days; Max: 600mg

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy

• Caution
• At very high doses in animals, rifampicin has been shown to have teratogenic effects. There are no well-controlled studies with rifampicin in pregnant women. Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin, alone or in combination with other antituberculosis drugs, on the human foetus is not known. Therefore, rifampicin should be used in pregnant women or in women of childbearing potential only if the potential benefit justifies the potential risk to the foetus. When rifampicin is administered during the last few weeks of pregnancy it may cause postnatal haemorrhages in the mother and infant for which treatment with Vitamin K1 may be indicated

Breastfeeding

• Caution
• Rifampicin is excreted in breast milk. Use of rifampicin in breastfeeding mothers is not a contraindication, however, the amount of rifampicin present in breast milk is inadequate for tuberculosis treatment of the breastfed infant. Therefore, newborn infants of mothers with tuberculosis, with the newborn having any signs suggestive of tuberculosis infection should be given treatment (intensive stage of tuberculosis treatment)

Renal Impairment

• Caution; no dose adjustment recommended
  Caution should be taken if dose >600mg/day

Hepatic Impairment

• Caution; no dose adjustment recommended
  Closely monitor hepatic function (mainly ALT) and immediately discontinue therapy if signs of drug-induced liver injury (DILI) are observed (chemically and/or clinically)
  Stop all TB therapy (and other hepatotoxic-potentials drugs) once signs of DILI are observed
  * see additional prescribing points

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Porphyrinogenic (P)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Psychotic disorder
• Cerebral haemorrhage  

Cardiovascular Disorders

• Shock
• Flushing
• Vasculitis

Respiratory Disorders

• Dyspnoea
• Wheezing
• Sputum discoloured

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Gastrointestinal disorder
• Abdominal discomfort
• Anorexia
• Pseudomembranous colitis
• Sputum discolouration

Hepatobiliary Disorders

• Hepatitis  
• Hyperbilirubinaemia

Genitourinary Disorders

• Acute kidney injury  
• Renal tubular necrosis
• Tubulointerstitial nephritis
• Chromaturia
• Menstrual disorder
• Urine discolouration

Endocrine and Metabolic Disorders

• Adrenal insufficiency  
• Decreased appetite

Musculoskeletal Disorders

• Muscle weakness
• Myopathy
• Bone pain

Skin and Subcutaneous Tissue Disorders

• Erythema multiform
• Stevens-Johnson syndrome  
• Lyells syndrome
• Toxic epidermal necrolysis
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome  
• Skin reaction
• Pruritus
• Rash pruritic
• Urticaria
• Dermatitis allergic
• Pemphigoid
• Sweat discolouration
• Flushing
• Itching
• Exfoliate dermatitis
• Vasculitis 

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia with or without purpura
• Leukopenia
• Disseminated intravascular coagulation
• Eosinophilia
• Agranulocytosis
• Hemolytic anemia
• Anaphylactic reaction
• Influenza consisting of episodes of pyrexia, chills, headache, dizziness

Sensory Disorders

• Tear discolouration

Others

• Post-partum haemorrhage
• Fetal-maternal haemorrhage
• Porphyria
• Oedema

• Saquinavir/ritonavir
• CYP450 substrates
• Antiarrhythmics 
• Antiepileptics
• Hormone antagonist 
• Antipsychotics
• Anticoagulants 
• Antifungals 
• Antivirals 
• Barbiturates
• Beta blockers 
• Central nervous system depressants
• Calcium channel blockers
• Antibacterials 
• Corticosteroids
• Cardiac glycosides
• Clofibrate
• Systemic hormonal contraceptives
• Oestrogen
• Antidiabetic 
• Immunosuppressive agents 
• Irinotecan
• Thyroid hormone 
• Losartan
• Analgestics 
• Praziquantel
• Progestogens
• Quinine
• Riluzole
• Selective 5-HT3 receptor antagonists
• Statins metabolised by CYP 3A4 
• Theophylline
• Tricyclic antidepressants 
• Cytotoxics 
• Diuretics
• Oral contraceptives
• Enalapril
• Antacids
• Halothane
• Isoniazid
• Microbiological assays for serum folate and Vitamin B12
• Contrast media used for visualization of the gallbladder

• Hepatic function
• Full blood count
• Sputum culture
• Chest X-ray

Capsule 150mg - EML (Primary)

Injection 300mg - EML (Tertiary)

All other formulations - Non-EML

Hepatic impairment

• Stop all TB therapy (and other hepatotoxic-potentials drugs) once signs of DILI are observed
• Consider rechallenge protocol once the ALT has settled to <100 and jaundice has resolved (American Thoracic Society guidelines)
• In patients on both TB and ARV therapy, the priority is to establish the TB therapy first, followed by the ART

Rifampicin is an active bactericidial antituberculosis drug which is particularly active against the rapidly growing extracellular organisms and also has bactericidial activity intracellularly. Rifampicin has activity against slow and intermittently-growing M. Tuberculosis.

Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown with other rifamycins.

Capsule 150mg

• Rimactane (Sandoz)

Tablet  450mg

• Rimactane (Sandoz)

Capsule 600mg

• R-Cin 600 (Pharma Dynamics)

Tablet  600mg

• Rimactane (Sandoz)

Suspension (per 5ml) 100mg

• R-Cin (Litha)

Injection (per vial) 300mg

• Rimactane (Sandoz)

COMBINATION PREPARATIONS

Rifampicin/ Isoniazid

Tablet 60mg/30mg

• Rimactazid Paed 60/30 (Sandoz)

Tablet 60mg/60mg

• Rimactazid Paed 60/60 (Sandoz)

Tablet 150mg/75mg

• Rimactazid 150/75 (Sandoz)

Tablet 150mg/100mg

• Rifinah-150 (Sanofi)

Tablet 300mg/150mg

• Ebsar-2 DS (Dezzo)
• Rimactazid 300/150 (Sandoz)
• Rifinah-300 (Sanofi)

Isoniazid/ Rifampicin/ Pyrazinamide

Tablet 30mg/60mg/150mg

• Rimcure Paed 3-Fdc (Sandoz)

Isoniazid/ Rifampicin/ Pyrazinamide/ Ethambutol Hcl

Tablet 75mg/150mg/400mg/275mg

• Antib-4 (Medicine Dev)
• Rifafour E-275 (Sanofi)
• Rimstar 4-Fdc (Sandoz)