Category : ANTIBIOTICS

Name : RIFAMPIN     Type & Dosage : Cap. ; 300 mg Package : 100

Pharmacologic Category Antibacterial (antimycobacterial ; antileprosy agent) Mechanism Of Action Rifampin , a semisynthetic broad – spectrum bactericidal antibiotic , inhibits bacterial RNA synthesis by binding strongly to the beta subunit of DNA – dependent RNA polymerase , preventing attachment of the enzyme to DNA , and thus blocking initiation of RNA transcription. Indications Tuberculosis ( treatment) ; Meningococcal infections (prophylaxis) ; Haemophilus influenzae type b infection (prophylaxis) ; Leprosy (treatment) ; Atypical mycobacterial infections (treatment) ; Concurrently with other antistaphylococcal agents in the treatment of serious infections caused by Staphylococcus species ( including methicillin – resistant and multidrug – resistant strains). Side Adverse Effects Flu – like syndrome (chills , difficult breathing , dizziness , fever , headache , muscle and bone pain , shivering ) ; Hypersensitivity (itching , redness , skin rash ) ; Blood dyscrasias (sore throat , unusual bleeding or bruising ) ; Hepatitis ; Hepatitis prodromal symptoms ( loss of appetite , nausea and vomiting , unusual tiredness or weakness) ; Interstitial nephritis ; Diarrhea ; Stomach cramps ; Sore mouth or tongue (due to fungal overgrowth ) ; Reddish – Orange to reddish – brown discoloration of urine, feces , saliva , sputum , sweat , and tears ; Flushing ; Edema ; Headache ; Drowsiness ; Dizziness ; Confusion ; Numbness ; Leukopenia ; Hemolysis ; Myalgia Contraindications Hypersensitivity to rifampin , any rifamycins , or any component of the formulation. Warnings Precautions Use with caution and modify dosage in patients with liver impairment , observe for hyperbilirubinemia , discontinue therapy if this in conjunction with clinical symptoms or any signs of significant hepatocellular damage develop . Use with caution in patients with porphyria . Do not use for meningococcal disease , only for short –term treatment of asymptomatic carrier states . Use with caution in patients receiving concurrent medications associated with hepatotoxicity (particularly with pyrazinamide) , or in patients with a history of alcoholism ( even if ethanol consumption is discontinued during therapy) . Remove soft contact lenses during therapy since permanent staining may occur. Pregnancy FDA pregnancy category C. Breast Feeding Rifampin is distributed into breast milk . Problems in humans have not been documented. Drug Interactions Concurrent daily consumption of alcohol may increase the risk of rifampin – induced hepatotoxicity and increased metabolism of rifampin . Rifampin may increase metabolism of theophylline, oxtriphylline , and aminophylline , resulting in increased theophylline clearance . Rifampin accelerates the metabolism of protease inhibitors , such as amprenavir , indinavir , nelfinavir , ritonavir , and saquinavir ; resulting in subtherapeutic levels of the protease inhibitors . In addition , protease inhibitors retard the metabolism of rifampin , resulting in increased levels of rifampin and the likelihood of increased toxicity. Chronic use of rifampin prior to anesthesia , except isoflurane may increase anesthetic metabolism , leading to increased risk of hepatotoxicity . Concurrent use with rifampin may enhance the metabolism of coumarin – or indandione –derivative anticoagulants , resulting in a considerable decrease in the activity and effectiveness of the anticoagulants . Concurrent use with rifampin may enhance the metabolism of tolbutamide , chlorpropamide , and glyburide , resulting in lower serum sulfonylurea concentrations . Concurrent use may increase the metabolism of the azole antifungals , lowering their plasma concentrations . Concurrent use with rifampin may enhance the metabolism of hexobarbital , resulting in lower serum concentrations . There are conflicting data on rifampin’s effect on phenobarbital . Concurrent use of metoprolol or propranolol with rifampin has resulted in reduced plasma concentrations of these two beta –adrenergic blocking agents . Concurrent use of bone marrow depressants with rifampin may increase the leukopenic and/or thrombocytopenic effects . Concurrent use with rifampin may enhance the metabolism of chloramphenicol , resulting in significantly lower serum chloramphenicol concentrations . Concurrent use of clofazimine with rifampin has resulted in reduced absorption of rifampin , delaying its time to peak concentration , and increasing its half – life . Concurrent use with rifampin may enhance the metabolism of clofibrate , resulting in significantly lower serum clofibrate concentrations . Concurrent use with rifampin may decrease the effectiveness of estrogen – containing oral contraceptives ; patients should be advised to use an additional method of contraception throughout the whole cycle while taking rifampin and estrogen –containing oral contraceptives concurrently . Concurrent use with rifampin may enhance the metabolism of corticosteroids , resulting in a considerable decrease in corticosteroid plasma concentrations. Rifampin may enhance metabolism of cyclosporin . Concurrent use with rifampin may decrease the effect of dapsone because of increased metabolism ; dapsone dosage adjustments are not required during concurrent therapy with rifampin for leprosy . Rifampin accelerates the metabolism of nonnucleoside reverse transcriptase inhibitors (NNRTIs) , such as delavirdine , efavirenz , and nevirapine , resulting in subtherapeutic levels of NNRTIs . In addition NNRTIs retard the metabolism of rifampin , resulting in increased serum levels of rifampin and the likelihood of increased toxicity . Concurrent use with rifampin may enhance the elimination of diazepam , resulting in decreased plasma concentrations . Concurrent use with rifampin may enhance the metabolism of digoxin or digitoxin , resulting in significantly lower serum digoxin or digitoxin concentrations. Concurrent use with rifampin may enhance the metabolism of disopyramide , mexiletine , propafenone , quinidine and tocainide , resulting in significantly lower serum concentrations of these antiarrhythmic drugs. Concurrent use of estramustine or estrogen with rifampin may result in significantly reduced estrogenic effect of them. Concurrent use of rifampin and other hepatotoxic medications may increase the potential for hepatotoxicity . Concurrent use of isoniazid with rifampin may increase the risk of hepatotoxicity , especially in patients with pre – existing hepatic function impairment and/or in fast acetylators of isoniazid . Concurrent use with rifampin may decrease the effects of methadone , resulting in symptoms of methadone withdrawal if the patient is dependent on methadone . Concurrent use with rifampin may stimulate the hepatic metabolism of phenytoin , increasing its elimination and thus counteracting its anticonvulsant effects . Probenecid may compete with rifampin for hepatic uptake when used concurrently , resulting in increased and more prolonged rifampin serum concentrations and/or toxicity . Concurrent use with rifampin may significantly increase the elimination and shorten the elimination half – life of trimethoprim . Rifampin has been found to accelerate the metabolism of oral verapamil , resulting in a significant decrease in serum verapamil concentration and reversing its cardiovascular effects . Monitoring Parameters Periodic ( baseline and every 2-4 weeks during therapy ) monitoring of AST , ALT , alkaline phosphatase and bilirubin. Dietary Considerations Rifampin is best taken on an empty stomach. Administration And Dosage RIFAMPIN-HAKIM :: Antibacterial (Antimycobacterial, antileprosy) :: Cap. 150, 300 mg Oral Drop 150 mg/ml Pharmacologic category Antibacterial (antimycobacterial ; antileprosy agent) Mechanism of action Rifampin , a semisynthetic broad – spectrum bactericidal antibiotic , inhibits bacterial RNA synthesis by binding strongly to the beta subunit of DNA – dependent RNA polymerase , preventing attachment of the enzyme to DNA , and thus blocking initiation of RNA transcription. Indications Tuberculosis ( treatment) ; Meningococcal infections (prophylaxis) ; Haemophilus influenzae type b infection (prophylaxis) ; Leprosy (treatment) ; Atypical mycobacterial infections (treatment) ; Concurrently with other antistaphylococcal agents in the treatment of serious infections caused by Staphylococcus species ( including methicillin – resistant and multidrug – resistant strains). Side/Adverse effects Flu – like syndrome (chills , difficult breathing , dizziness , fever , headache , muscle and bone pain , shivering ) ; Hypersensitivity (itching , redness , skin rash ) ; Blood dyscrasias (sore throat , unusual bleeding or bruising ) ; Hepatitis ; Hepatitis prodromal symptoms ( loss of appetite , nausea and vomiting , unusual tiredness or weakness) ; Interstitial nephritis ; Diarrhea ; Stomach cramps ; Sore mouth or tongue (due to fungal overgrowth ) ; Reddish – Orange to reddish – brown discoloration of urine, feces , saliva , sputum , sweat , and tears ; Flushing ; Edema ; Headache ; Drowsiness ; Dizziness ; Confusion ; Numbness ; Leukopenia ; Hemolysis ; Myalgia Contraindications Hypersensitivity to rifampin , any rifamycins , or any component of the formulation. Warnings / Precautions Use with caution and modify dosage in patients with liver impairment , observe for hyperbilirubinemia , discontinue therapy if this in conjunction with clinical symptoms or any signs of significant hepatocellular damage develop . Use with caution in patients with porphyria . Do not use for meningococcal disease , only for short –term treatment of asymptomatic carrier states . Use with caution in patients receiving concurrent medications associated with hepatotoxicity (particularly with pyrazinamide) , or in patients with a history of alcoholism ( even if ethanol consumption is discontinued during therapy) . Remove soft contact lenses during therapy since permanent staining may occur. Pregnancy FDA pregnancy category C. Breast–Feeding Rifampin is distributed into breast milk . Problems in humans have not been documented. Drug Interactions Concurrent daily consumption of alcohol may increase the risk of rifampin – induced hepatotoxicity and increased metabolism of rifampin . Rifampin may increase metabolism of theophylline, oxtriphylline , and aminophylline , resulting in increased theophylline clearance . Rifampin accelerates the metabolism of protease inhibitors , such as amprenavir , indinavir , nelfinavir , ritonavir , and saquinavir ; resulting in subtherapeutic levels of the protease inhibitors . In addition , protease inhibitors retard the metabolism of rifampin , resulting in increased levels of rifampin and the likelihood of increased toxicity. Chronic use of rifampin prior to anesthesia , except isoflurane may increase anesthetic metabolism , leading to increased risk of hepatotoxicity . Concurrent use with rifampin may enhance the metabolism of coumarin – or indandione –derivative anticoagulants , resulting in a considerable decrease in the activity and effectiveness of the anticoagulants . Concurrent use with rifampin may enhance the metabolism of tolbutamide , chlorpropamide , and glyburide , resulting in lower serum sulfonylurea concentrations . Concurrent use may increase the metabolism of the azole antifungals , lowering their plasma concentrations . Concurrent use with rifampin may enhance the metabolism of hexobarbital , resulting in lower serum concentrations . There are conflicting data on rifampin’s effect on phenobarbital . Concurrent use of metoprolol or propranolol with rifampin has resulted in reduced plasma concentrations of these two beta –adrenergic blocking agents . Concurrent use of bone marrow depressants with rifampin may increase the leukopenic and/or thrombocytopenic effects . Concurrent use with rifampin may enhance the metabolism of chloramphenicol , resulting in significantly lower serum chloramphenicol concentrations . Concurrent use of clofazimine with rifampin has resulted in reduced absorption of rifampin , delaying its time to peak concentration , and increasing its half – life . Concurrent use with rifampin may enhance the metabolism of clofibrate , resulting in significantly lower serum clofibrate concentrations . Concurrent use with rifampin may decrease the effectiveness of estrogen – containing oral contraceptives ; patients should be advised to use an additional method of contraception throughout the whole cycle while taking rifampin and estrogen –containing oral contraceptives concurrently . Concurrent use with rifampin may enhance the metabolism of corticosteroids , resulting in a considerable decrease in corticosteroid plasma concentrations. Rifampin may enhance metabolism of cyclosporin . Concurrent use with rifampin may decrease the effect of dapsone because of increased metabolism ; dapsone dosage adjustments are not required during concurrent therapy with rifampin for leprosy . Rifampin accelerates the metabolism of nonnucleoside reverse transcriptase inhibitors (NNRTIs) , such as delavirdine , efavirenz , and nevirapine , resulting in subtherapeutic levels of NNRTIs . In addition NNRTIs retard the metabolism of rifampin , resulting in increased serum levels of rifampin and the likelihood of increased toxicity . Concurrent use with rifampin may enhance the elimination of diazepam , resulting in decreased plasma concentrations . Concurrent use with rifampin may enhance the metabolism of digoxin or digitoxin , resulting in significantly lower serum digoxin or digitoxin concentrations. Concurrent use with rifampin may enhance the metabolism of disopyramide , mexiletine , propafenone , quinidine and tocainide , resulting in significantly lower serum concentrations of these antiarrhythmic drugs. Concurrent use of estramustine or estrogen with rifampin may result in significantly reduced estrogenic effect of them. Concurrent use of rifampin and other hepatotoxic medications may increase the potential for hepatotoxicity . Concurrent use of isoniazid with rifampin may increase the risk of hepatotoxicity , especially in patients with pre – existing hepatic function impairment and/or in fast acetylators of isoniazid . Concurrent use with rifampin may decrease the effects of methadone , resulting in symptoms of methadone withdrawal if the patient is dependent on methadone . Concurrent use with rifampin may stimulate the hepatic metabolism of phenytoin , increasing its elimination and thus counteracting its anticonvulsant effects . Probenecid may compete with rifampin for hepatic uptake when used concurrently , resulting in increased and more prolonged rifampin serum concentrations and/or toxicity . Concurrent use with rifampin may significantly increase the elimination and shorten the elimination half – life of trimethoprim . Rifampin has been found to accelerate the metabolism of oral verapamil , resulting in a significant decrease in serum verapamil concentration and reversing its cardiovascular effects . Monitoring Parameters Periodic ( baseline and every 2-4 weeks during therapy ) monitoring of AST , ALT , alkaline phosphatase and bilirubin. Dietary Considerations Rifampin is best taken on an empty stomach. Administration and dosage Tuberculosis – In combination with other antituberculosis medications: Oral , 600 mg once a day for the entire treatment period ; or 10 mg per kg of body weight , up to 600 mg , two or three times a week , depending on the treatment regimen . Meningococcal infection(prophylaxis) – Oral , 600 mg once a day for four days. H. influenzae infection(prophylaxis) – Oral , 600 mg once a day for four days. Leprosy – In combination with other antileprosy agents: For multibacillary leprosy – Oral , 600 mg once a month for a minimum of two years or until smear is negative , whichever is longer. For paucibacillary leprosy – Oral , 600 mg once a month for a minimum of six months . Note: Debilitated patients – Oral , 10 mg per kg of body weight once a day. Usual adult prescribing limits: 600 mg daily. Usual pediatric dose: Infants up to 1 month of age- Tuberculosis: In combination with other antituberculosis medications –Oral , 10 to 20 mg per kg of body weight once a day ; or 10 to 20 mg per kg of body weight , two or three times a week . Meningococcal infection (prophylaxis )– Oral , 5 mg per kg of body weight every twelve hours for two days . H. influenzae infection( prophylaxis) – Oral , 10 mg per kg of body weight once a day for four days. Children 1 month of age and over – Tuberculosis : In combination with other antituberculosis medications – Oral , 10 to 20 mg per kg of body weight , up to 600 mg , once a day ; or 10 to 20 mg per kg of body weight , up to 600 mg , two or three times a week , depending on the treatment regimen . Meningococcal infection (prophylaxis) – Oral , 10 mg per kg of body weight every twelve hours for two days. H. influenzae prophylaxis – Oral , 20 mg per kg of body weight once a day for four days. Note: The maximum daily dose should not exceed 600 mg . Usual geriatric dose: Tuberculosis – Oral , 10 mg per kg of body weight once a day. How Supplied Capsule, 150 and 300 mg Oral drops, 152 mg /1 ml, bottles of 13.2 ml, with dropper. Oral drops contains sodium saccharin as sweetener. Storage Capsule: store below 30° C. Protect from direct light and moisture Oral drops: Store in a cool place. Protect from light and freezing References USP DI, 2004 Up To Date, Vol. 13.1 (2005) Martindale, The Complete Drug Reference, 33 rd edition 2002