Rofact
Rofact Medication Information:
Rofact medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Rofact 150 mg
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Rofact 300 mg
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Pharmacology
Pharmacokinetics
Absorption: Rifampin is well absorbed from the gastrointestinal tract.
Distribution: Rifampin diffuses well to most body tissues and fluids, including the cerebrospinal fluid, where concentrations are increased if the meninges are inflamed; concentrations in the liver, gallbladder, bile, and urine are higher than those found in the blood; therapeutic concentrations are achieved in the saliva, reaching 20% of serum concentrations; crosses the placenta, with fetal serum concentrations at birth found to be approximately 33% of the maternal serum concentration; penetrates into aqueous humor; and is distributed into breast milk. Being lipid-soluble, rifampin may reach and kill susceptible intracellular, as well as extracellular, bacteria and Mycobacteria species.
Volume of Distribution: 1.6 L/kg.
Protein binding: high to very high (89%).
Biotransformation: hepatic.
Metabolism: Rifampin is eliminated principally by the liver into bile but the maximum excretory capacity of the liver is surpassed at doses higher than 5 mg/kg body weight. The concentration of rifampin in the blood is dose-related. Metabolism of rifampin takes place by desacetylation at position 25 of the molecule resulting in desacetyl rifampin as the major metabolite in man. The antimycobacterial properties of rifampin are retained by desacetylated rifampin and they are detectable in the blood, bile and urine of man following an oral dose of rifampin. Six hours following administration of rifampin, the ratio of desacetylated rifampin to rifampin is up to 50% in serum, 30 to 60% in urine and 100% in bile.
Half-life: Absorption half-life approximately 0.6 hour. Elimination half-life initially 3 to 5 hours; with repeated administration half-life decreases to 2 to 3 hours.
Time to Peak Plasma Concentration: 1.5 to 4 hours after oral administration; peak concentration may be decreased and delayed following administration with food.
Peak Plasma Concentration: Adults: 7 to 9 µg/mL after 600 mg. Children (6 months to 5 years): approximately 11 µg/mL after a dose of 10 mg/kg of body weight (mg/kg) mixed in applesauce or simple syrup.
Elimination: biliary/fecal; enterohepatic recirculation of rifampin, but not of its deacetylated active metabolite; 60 to 65% of dose appear in feces; renal 6 to 15% excreted as unchanged drug, and 15% excreted as active metabolite in urine; 7% excreted as inactive 3-formyl derivative.
Rifampin does not accumulate in patients with impaired renal function; its rate of excretion is increased during the first 6 to 10 days of therapy, probably because of auto-induction of hepatic microsomal oxidative enzymes; after high doses, excretion may be slower because of saturation of its biliary excretory mechanism.
In dialysis: Rifampin is not removed from the blood by either hemodialysis or peritoneal dialysis.
Indications
Treatment of pulmonary tuberculosis. In order to avoid emergence of resistance, rifampin must be administered concomitantly with at least one other effective antituberculosis drug. Selection of the appropriate drug combinations should be determined on the basis of in vitro sensitivity tests, comparative safety as well as the patient's previous clinical history.
The following are the most frequently used treatment regimens for previously untreated patients: rifampin with isoniazid; with ethambutol; with isoniazid and ethambutol.
The possibility of a drug interaction as well as the individual properties and special precautions relating to drugs used in concomitant therapy should be taken into consideration, e.g., PAS is known to delay the absorption of rifampin. When such concomitant medication is employed, it is recommended that an interval of 8 to 12 hours between each drug be observed.
Precautions
Daily treatment with rifampin is often better tolerated than intermittent therapy, since rare hypersensitivity reactions may occur. Therefore, when resuming treatment with rifampin after short or prolonged interruptions, the drug should be given in small, gradually increasing doses. During the transitional period, renal function should be closely monitored.
If as may happen in exceptional cases, the patient develops thrombocytopenia, purpura, hemolytic anemia or renal failure, treatment with rifampin should be stopped immediately and not be reinstituted at a later date.
Since rifampin has been observed to increase the requirements for anticoagulant drugs of the coumarin type, the same can be expected for Rofact. This effect was not observed until the fifth day following the initiation of treatment. The decrease in prothrombin time lasts 5 to 7 days on the average. The cause of this phenomenon is unknown. In patients receiving anticoagulants it is recommended that daily prothrombin times be performed until the required dose of the anticoagulant has been established.
Safe conditions for the use of ethambutol alone or in combination with rifampin have not been as yet established for children under the age of 13 years. Although renal insufficiency does not alter blood levels of rifampin, marked increases in ethambutol levels are observed under similar conditions; this should be taken into consideration in such patients receiving rifampin/ethambutol concomitantly. If in the opinion of the physician, ethambutol therapy is to be used in combination with rifampin, the possible visual deterioration associated with ethambutol should be carefully considered.
When instituting therapy with a combination of rifampin and isoniazid, caution is recommended in the elderly, the malnourished and in patients with impaired liver function.
Elevation of sulfobromophthalein (BSP) following administration of rifampin has been reported. Experimental studies indicate that rifampin and BSP compete with one another at the liver cell-bile boundary. Therefore, the BSP test should be performed prior to the daily dose of rifampin to avoid false-positive test results.
When rifampin is used concomitantly with other antituberculosis agents the possible adverse effects of each drug as well as the interaction between the different drugs should be taken into consideration.
In order to prevent undue anxiety, patients should be made aware of the possibility that urine, feces, saliva, sputum, sweat and tears may be colored red/orange by rifampin and its metabolites. Patients should be advised that soft contact lenses may be permanently stained.
Concurrent use of estrogen-containing contraceptives with rifampin may decrease the effectiveness of the contraceptive because of stimulation of estrogen metabolism or reduction in enterohepatic circulation of estrogens, resulting in menstrual irregularities, intermenstrual bleeding, and unplanned pregnancies. Patients should be advised to use an additional method of contraception throughout the whole cycle while taking rifampin and estrogen-containing oral contraceptives concurrently.
Both in the laboratory animal and man, the administration of rifampin has been associated with evidence of induction of drug metabolizing enzyme systems of the liver. As a consequence, the rate of metabolism of those compounds which are substrates of such enzymes can be altered and in some instances accelerated, a phenomenon which can result in a reduced pharmacological effect of the drug involved. Changes of possible clinical significance have been reported for the following: oral anticoagulants, hypoglycemic agents, dapsone, digitalis compounds and corticosteroids as well as oral contraceptives and ethambutol. Appropriate adjustment in the dosage and monitoring of effects of these drugs is therefore necessary when they are used concomitantly with rifampin. This is particularly important when rifampin administration is both initiated and withdrawn.
Microbiological techniques for assaying the serum concentrations of folic acid and vitamin B12 are not suitable for use during treatment with rifampin.
Upon completion of the treatment with rifampin, a renewed evaluation and readjustment of the dosage of any concomitantly administered drug should be made.
Supplied
300 mg
Each lok-type #1 capsule with brown opaque cap and scarlet opaque body branded “ICN R12” contains: rifampin USP 300 mg. Nonmedicinal ingredients: croscarmellose sodium, magnesium stearate, sodium lauryl sulfate and talc. Bottles of 100.
150 mg
Each coni-snap #4 elongated, maroon opaque colored capsule, branded radial “ICN R11” contains: rifampin USP 150 mg. Nonmedicinal ingredients: croscarmellose sodium, magnesium stearate and talc. Bottles of 100.
Contraindications
In patients with a history of previous sensitivity or hypersensitivity to any other ingredient in the formulation. Rifampin is contraindicated in hepatic function impairment since rifampin is metabolized in the liver and may also be hepatotoxic. Rifampin is contraindicated in premature and newborn infants in whom the liver is not yet capable of functioning with full efficiency. Rifampin passes into breast milk and therefore should not be given during lactation.
Warnings
Pregnancy
Pregnancy/Reproduction: Rifampin crosses the placenta. It is recommended that pregnant women with tuberculosis be treated for a minimum of 9 months with multidrug therapy, including rifampin. It has rarely caused postnatal hemorrhages in the mother and infant when administered during the last few weeks of pregnancy; vitamin K may be indicated. Neonates should be carefully observed for evidence of adverse effects.
Adverse Effects
Gastrointestinal disturbances including dyspepsia, epigastric distress, anorexia, nausea, vomiting, gas, cramps and diarrhea have been reported. Headache, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, visual disturbances, muscular weakness, fever, pain in extremities and generalized numbness have also been noted. Pruritus, urticaria, skin rashes, eosinophilia, sore mouth and/or tongue, dyspnea and acute renal failure have occasionally been encountered. Thrombocytopenia, purpura, leukopenia, hemolytic anemia and decreased hemoglobin have been observed. Thrombocytopenia has been reported to occur in patients given ethambutol and rifampin concomitantly on an intermittent dose schedule twice weekly and in high doses. Elevations in blood urea nitrogen (BUN) and serum uric acid have been reported.
Transient abnormalities in liver function tests such as elevations of serum bilirubin and BSP, elevation of alkaline phosphatase and serum transaminases have been reported particularly during the first few weeks of treatment. The following menstrual disturbances, breakthrough bleeding, spotting, amenorrhea and prolongation of both the menstrual interval and menses have been reported to occur in women taking rifampin.
A few cases of jaundice with evidence of hepato-cellular damage have been reported in patients receiving rifampin. In some of them it was possible, under careful laboratory control, to resume treatment after an interval without recurrence of abnormalities.
Clinical trials have not shown any harmful effects on the cochleovestibular system caused by rifampin.
Overdose
Symptoms
Overdosage of rifampin produces symptoms that are principally extensions of common adverse reactions. These include nausea, vomiting, lethargy, and brownish-red or orange discoloration of skin, urine, sweat, saliva, tears, and feces in proportion to the amount of drug ingested. Following massive overdosage of rifampin, hepatic involvement can develop within a few hours and is manifested by liver enlargement, possibly with tenderness, jaundice, rapid increases in total and direct serum bilirubin and liver enzymes, and loss of consciousness.
Treatment
In acute rifampin overdosage, the stomach should be emptied by gastric lavage. Activated charcoal slurry then may be instilled into the stomach to adsorb any drug remaining in the gastrointestinal tract. An antiemetic may be required to control severe nausea and vomiting. Active diuresis, with measured intake and output, may promote excretion of the drug. If serious hepatic impairment occurs which lasts more than 24 to 48 hours, bile drainage or hemodialysis may be indicated. Reversal of liver enlargement and improvement of impaired hepatic function usually occur within 72 hours in patients with previously adequate hepatic function.
Dosage
It is recommended that rifampin be administered once daily on an empty stomach (1 hour before a meal) to ensure optimum absorption.
In the treatment of pulmonary tuberculosis, rifampin must be given in conjunction with at least one other antituberculosis agent. In general, therapy should be continued until bacterial conversion has been established and maximum clinical improvement has occurred.
If a rifampin-PAS combination therapy is employed, it is recommended that the two drugs be administered at intervals of 8 to 12 hours.
Usual Adult and Adolescent Dose: Tuberculosis: in combination with other antituberculosis medications: oral, 600 mg once a day for the entire treatment period; or 10 mg/kg of body weight, up to 600 mg, 2 or 3 times a week, depending on the treatment regimen. Meningococcal infection (prophylaxis): oral, 600 mg 2 times a day for 2 days.
In patients with impaired liver function, a daily dose of 8 mg/kg should not be exceeded. A daily dosage of 10 mg/kg of body weight is recommended for frail and elderly persons.
Usual Pediatric Dose: Infants up to 1 month of age: Tuberculosis: in combination with other antituberculosis medications: oral, 10 to 20 mg/kg of body weight once a day; or 10 to 20 mg/kg of body weight, 2 or 3 times a week, depending on the treatment regimen. Meningococcal infection (prophylaxis): oral, 5 mg/kg of body weight every 12 hours for 2 days.
Children 1 month of age and over: Tuberculosis: in combination with other antituberculosis medications: oral, 10 to 20 mg/kg of body weight, up to 600 mg, once a day; or 10 to 20 mg/kg of body weight, up to 600 mg, 2 or 3 times a week, depending on the treatment regimen. Meningococcal infection (prophylaxis): oral, 10 mg/kg of body weight every 12 hours for 2 days. The maximum daily dose should not exceed 600 mg.
