Rifampicin

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Rifampicin

  1. 1. Rifampicin by the pharmacist Ayia Nazum Kamal
  2. 2. Pharmacologic Class: Rrafimycin derivative Chemical Class: Antitubercular
  3. 3. <ul><li>Monocomponent products </li></ul><ul><li>1 -Capsules: 150 mg, 300 mg ,450mg,600mg. </li></ul><ul><li>2- Syrup : 100 mg/5 ml </li></ul><ul><li>3- Ophthalmic :1% ophthalmic ointment. </li></ul><ul><li>4- I.V. infusion: Powder for injection 600 mg </li></ul>
  4. 4. <ul><li>Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase, but does not inhibit the mammalian enzyme. </li></ul><ul><li>Rifampicin may be bacteriostatic or bactericidal depending on the concentration of drug </li></ul><ul><li>attained at site of infection . </li></ul>Pharmacology
  5. 5. <ul><li>1- The primary indications for rifampicin are for treatment of tuberculosis and inactive meningitis , along with isoniazid , ethambutol , pyrazinamide and streptomycin . It must be administered regularly daily for several months without break otherwise, the risk of drug-resistant tuberculosis is greatly increased . In fact, this is the primary reason that it is used in tandem with the three aforementioned drugs, particularly isoniazid . This is also the primary motivation behind directly observed therapy for tuberculosis.Rifampicin resistance develops quickly during treatment and rifampicin monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics . </li></ul>Indications
  6. 6. <ul><li>2- for leprosy. </li></ul><ul><li>3 for Gram positive(Staphylococcus aureus and epidermidis, Streptococcus pyogenes, viridans and pneumoniae) and gram negative bacteria (Haemophilus influenzae type B). </li></ul><ul><li>4 -It has some anti-chlamydial activity. </li></ul><ul><li>5- in vitro activity against some viruses (poxvirus and adenovirus) at high doses. </li></ul><ul><li>6- It has recently been used for brucellosis </li></ul>Indication
  7. 7. <ul><li>Tuberculosis </li></ul><ul><li>IV dosage form is for initial treatment or re treatment when drug cannot be taken by mouth. </li></ul><ul><li>Adult </li></ul><ul><li>PO/IV 10 mg/kg/day (max, 600 mg/day) or 10 mg/kg 2 or 3 times/wk (max, 600 mg). </li></ul><ul><li>Children </li></ul><ul><li>PO/IV 10 to 20 mg/kg/day (max, 600 mg/day) or 10 to 20 mg/kg 2 to 3 times/wk (max, 600 mg). </li></ul>Therapeutic dosage
  8. 8. <ul><li>Leproy: </li></ul><ul><li>600 mg once monthly,supervised (450 mg for those weighing less than 35 kg). </li></ul><ul><li>Haemophilus influenzae type B infection: </li></ul><ul><li>Adult </li></ul><ul><li>20 mg/kg bodyweight once a day for 4 days. (maximum daily dose 600 mg). </li></ul><ul><li>Children over 3-months old </li></ul><ul><li>20 mg/kg bodyweight once a day for 4 days. </li></ul>Therapeutic dosage
  9. 9. <ul><li>Meningococcal carriers </li></ul><ul><li>Adult : </li></ul><ul><li>Meningococcal carriers 600 mg twice daily for two days. </li></ul><ul><li>Children </li></ul><ul><li>1 to 12 years 10 mg/kg bodyweight </li></ul><ul><li>3 to 12 months 5 mg/kg bodyweight </li></ul><ul><li>Eye </li></ul><ul><li>Trachoma (i.e. hyperendemic trachoma or sexually transmitted trachoma-inclusion conjunctivitis)1% ophthalmic ointment applied three times daily for six weeks </li></ul>Therapeutic dosage
  10. 10. <ul><li>Cardiovascular </li></ul><ul><li>Hypotension; shock. </li></ul><ul><li>CNS </li></ul><ul><li>Headache; drowsiness; fatigue; dizziness; inability to concentrate; mental confusion; generalized numbness; behavioral changes; myopathy. </li></ul><ul><li>Dermatologic </li></ul><ul><li>Rash; pruritus; urticaria; pemphigoid reaction; flushing. </li></ul><ul><li>EENT </li></ul><ul><li>Visual disturbances; exudative conjunctivitis. </li></ul><ul><li>GI </li></ul><ul><li>Heartburn; epigastric distress; anorexia; nausea; vomiting; gas; cramps; diarrhea; sore mouth and tongue; pseudomembranous colitis; pancreatitis. </li></ul>Adverse Reactions
  11. 11. <ul><li>Genitourinary </li></ul><ul><li>Hemoglobinuria; hematuria; renal insufficiency; acute renal failure. </li></ul><ul><li>Hematologic </li></ul><ul><li>Eosinophilia; transient leukopenia; hemolytic anemia; decreased hemoglobin; hemolysis; thrombocytopenia. </li></ul><ul><li>Hepatic </li></ul><ul><li>Asymptomatic elevations of liver enzymes and hepatitis. </li></ul><ul><li>Respiratory </li></ul><ul><li>Shortness of breath; wheezing. </li></ul><ul><li>Miscellaneous </li></ul><ul><li>Ataxia; muscular weakness; pain in extremities; osteomalacia; myopathy; menstrual disturbances; fever;elevated serum uric acid; possible immunosuppression; abnormal growth of lung tumors; reduced 25-hydroxycholecalciferol levels; edema of face and extremities; discoloration of body fluids. </li></ul>Adverse Reactions
  12. 12. <ul><li>Pregnancy </li></ul><ul><li>Category C . </li></ul><ul><li>Lactation </li></ul><ul><li>Excreted in breast milk. Discontinue nursing or drug. </li></ul><ul><li>Hepatic Function </li></ul><ul><li>Dosage adjustment is necessary. For patients with liver dysfunction, use a dose no exceeding 8 mg/kg bodyweight </li></ul><ul><li>Body fluids </li></ul><ul><li>Medication may cause harmless red-orange discoloration of urine, feces, saliva, sputum, sweat, and tears. Soft contact lenses may be permanently stained </li></ul>Precautions
  13. 13. <ul><li>1- Rifampicin is contraindicated in known cases of hypersensitivity to the drug. </li></ul><ul><li>2- It may be contraindicated in pregnancy (because of teratogenicity noted in animal studies and since the effects of drugs on fetus has not been established) except in the presence of a disease such as severe tuberculosis. </li></ul><ul><li>3- It is contraindicated in alcoholics with severely impaired liver function and with jaundice. </li></ul>Contraindication
  14. 14. <ul><li>Absorption </li></ul><ul><li>Rifampicin is readily absorbed fromGIT (90%). Peak plasma concentration occurs at1.5 to 4hrs after an oral dose,Absorption decreased 30% when taken with food . </li></ul><ul><li>Distribution: </li></ul><ul><li>Intravenous rifampicin has the same distribution as in oral route , Diffuses well into most body tissues and fluids, including CSF.Crosses placenta and distributes into breast milk. Protein binding is 89%. </li></ul>Kinetics
  15. 15. <ul><li>T1/2 = three hours range (2 to 5 hours). </li></ul><ul><li>This half-life increases with single high doses or with liver disease. </li></ul><ul><li>but shortens on repeated dosing because rifampicin is avery effective enzyme inducer and increase its own metabolism(as well as that of several other drugs). </li></ul>Biological half-life
  16. 16. <ul><li>Approximately 85% of rifampicin is metabolised by the liver microsomal enzymes to its main and active metabolite -deacetylrifampicin. </li></ul><ul><li>Rifampicin undergoes enterohepatic recirculation but not the deacetylated form.Rifampicin increases its own rate of metabolism. </li></ul><ul><li>Rifampicin may also be inactivated in other parts of the body.Formylrifampicin is a urinary metabolite that spontaneously forms in the urine . </li></ul>Metabolism
  17. 17. <ul><li>Primarily through bile/fecal (60% to 65% in feces);renal (6% to 15% excreted as unchanged, 15% excreted as active metabolites, 7% as inactive metabolites). </li></ul>Elimination
  18. 18. <ul><li>Drug Interactions </li></ul><ul><li>1- Azole antifungal agents, benzodiazepines, beta-blockers, chloramphenicol, clarithromycin, clozapine, oral contraceptives, corticosteroids, cyclosporine, delavirdine, digitoxin, doxycycline, erythromycin, estrogens, haloperidol, hydantoins,losartan, methadone, mexiletine, morphine, ondansetron, oral anticoagulants,sulfonylureas, tacrolimus, theophyllines,TCA,verapamil </li></ul><ul><li>Therapeutic efficacy may be decreased because of liver enzyme-inducing properties of rifampin </li></ul>Interaction
  19. 19. <ul><li>Digoxin </li></ul><ul><li>May decrease digoxin serum concentrations. </li></ul><ul><li>Enalapril </li></ul><ul><li>May significantly increase BP. </li></ul><ul><li>Halothane </li></ul><ul><li>Hepatotoxicity and hepatic encephalopathy have been reported with coadministration. </li></ul><ul><li>Isoniazid </li></ul><ul><li>May result in higher rate of hepatotoxicity. </li></ul><ul><li>Ketoconazol e </li></ul><ul><li>May cause treatment failure of either ketoconazole or rifampin. </li></ul><ul><li>Probenecid </li></ul><ul><li>Elevates rifampin levels. </li></ul>Drug Interactions
  20. 20. <ul><li>May inhibit standard microbiological assays for serum folate and vitamin B 12 . Thus, 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 </li></ul>Laboratory Test Interactions
  21. 21. <ul><li>Symptoms </li></ul><ul><li>Nausea, vomiting, increasing lethargy, unconsciousness, liver enlargement, jaundice, increased direct and total bilirubin levels, altered hepatic enzyme levels . </li></ul>Overdosage
  22. 22. <ul><li>1- Instruct patient to take drug on empty stomach, 1 h before or 2 h after meals. </li></ul><ul><li>2- Inform patient that body fluids may turn red-orange in color and that soft contact lenses may become permanently stained. Advise patient to wear glasses during course of therapy. </li></ul><ul><li>3- Instruct patient to notify 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. </li></ul><ul><li>4- Tell patient to notify health care provider of drowsiness, fatigue, dizziness, inability to concentrate, confusion, or visual or behavioral changes. </li></ul>Patient Information
  23. 23. <ul><li>5- Advise patient who uses oral contraceptives to use nonhormonal form of contraception during therapy. </li></ul><ul><li>6- Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness. </li></ul><ul><li>7- Advise patient of importance of medication compliance in treatment of tuberculosis. Medication noncompliance reduces efficacy and promotes resistance. </li></ul><ul><li>8- Caution patient to avoid alcohol </li></ul><ul><li>9- In patients receiving anticoagulants and rifampicin concurrently, it is recommended that the prothrombin timebe performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant. </li></ul>

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