Date of approval.
Date of revision.
Rifampicin Capsules Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Rifampicin Capsules
English name: Rifampicin Capsules
Hanyu Pinyin：Lifuping Jiaonang
Ingredients
The main ingredient of this product is rifampicin.
Chemical name: 3-[[(4-methyl-1-piperazinyl)imino]methyl]rifamycin
Chemical structure formula.
Molecular formula: C43H58N4O12
Molecular weight: 822.95
Properties
The content of this product is bright red powder or granule.
Indications】
To ensure the effectiveness of rifampicin and other antibacterial drugs and to reduce the occurrence of drug resistance, the antibacterial drug treatment regimen may be changed or adjusted according to the results of sputum culture and drug sensitivity. If such data are lacking, treatment will be given according to local epidemiological and drug sensitivity experience results.
1. This product is indicated for the treatment of all types of sensitive tuberculosis.
2. This product is indicated for the treatment of asymptomatic Neisseria meningitidis carriers.
It is used for the clearance of meningococci from the nasopharynx in Neisseria meningitidis carriers without symptoms of meningitis, and the treatment plan is based on the results of serotyping and drug sensitivity tests. Due to the problem of rapid drug resistance, it should be used only in patients at high risk of meningitis and should not be used to treat patients with meningococcal infections.
3. This product is indicated for the treatment of sensitive nontuberculous mycobacterial infections.
4. This product can be combined with other drugs for the treatment of leprosy.
5. According to the experience of domestic clinical use, this product can be used for the prophylactic treatment of people at high risk of tuberculosis, but there is no sufficient clinical research data to support it.
Specification
0.3g
Dosage and Administration
1. Tuberculosis
(1) Treatment of sensitive tuberculosis
Adults: 10mg/kg per day, not to exceed 600mg per day, taken in a single dose before meals. According to domestic clinical use experience, the maximum daily dose should not exceed 1.2g, but there is no sufficient clinical research data to support this.
Children: 10-20mg/kg, not more than 600mg per day, taken orally before meals.
(2) Prevention for people at high risk of tuberculosis
Adults: 10mg/kg per day, maximum daily dose not to exceed 600mg, taken orally before meals.
Children: 10-20mg/kg, maximum daily dose not exceeding 600mg, taken orally before meals.
2. Treatment of asymptomatic Neisseria meningitidis carriers
Adults: 300mg once every 12 hours for 2 days.
Children: 1 month of age and above, 10mg/kg once every 12 hours, maximum daily dose not exceeding 600mg for 2 days. under 1 month of age, 5mg/kg once every 12 hours for 2 days.
3. Treatment of non-tuberculous mycobacterial infection
450mg once daily, the maximum daily dose should not exceed 600mg.
4. Treatment of leprosy
600mg once daily, orally once or twice a month; or 450mg once daily, before meals. The dose should be adjusted according to age or symptom changes. Use in combination with other anti-leprosy drugs.
5. For patients with difficulty in swallowing capsules or for low dose applications, a suspension aqueous solution can be prepared as follows.
A 1% rifampicin suspension (10 mg/ml) can be prepared using syrup.
(1) Pour the contents of four 300 mg or eight 150 mg rifampicin capsules onto a piece of weighing paper.
(2) Lightly press the capsule contents into a fine powder.
(3) Transfer the rifampicin powder to a 118 ml amber glass or plastic (high-density polyethylene [HDPE], polypropylene, or polycarbonate) vial.
(4) Rinse the weighing paper and medicine spoon with 20 ml of syrup and add to the washed bottle and shake well.
(5) Add another 100 ml of syrup and shake thoroughly.
The 1% rifampicin suspension can be stored at room temperature (25±3°C) or in the refrigerator (2-8°C) for 4 weeks. The ready-made oral suspension must be fully shaken before use.
Adverse reactions
1. Gastrointestinal tract
Some patients may experience burning sensation in the stomach, epigastric pain, anorexia, nausea, vomiting, jaundice, gastrointestinal distention, cramps, and diarrhea. Although Clostridium perfringens is sensitive to rifampin in vitro, pseudomembranous colitis has been reported following the use of rifampin (in combination with other broad-spectrum antibiotics), so this diagnosis should be considered in the event of antibiotic-associated diarrhea.
2. Liver
This may manifest as transient abnormalities in liver function parameters (e.g., elevations in serum bilirubin, alkaline phospholipase, transaminases). Rarely hepatitis or shock-like syndrome with liver involvement and abnormal liver function.
3. Hematology
Thrombocytopenia usually occurs during the course of high-dose intermittent therapy or during recovery from interrupted therapy, and supervised regulated daily dosing regimens occur rarely. Purpura is reversible and disappears after discontinuation of the drug. Continued use of rifampicin after the development of purpura has been reported to lead to cerebral hemorrhage or even death.
Leukopenia, hemolytic anemia, and decreased hemoglobin may occur.
Rare granulocytic leukocyte deficiency. Rarely diffuse intravascular coagulation.
4. Central nervous system
May cause headache, fever, drowsiness, fatigue, ataxia, dizziness, inattention, mental sleepiness, behavioral changes, muscle weakness, pain in the extremities, and numbness.
Rarely, psychosis has been reported.
5. Ophthalmology
May cause visual impairment.
6. Endocrine
May lead to menstrual disorders.
Occasionally, renal insufficiency has been reported in patients with impaired adrenal cortical function.
7. Kidney
May cause elevated serum urea and uric acid. Occasionally, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been reported. It usually occurs during the resumption of treatment after intermittent dosing or interruption of the daily dosing regimen. The mechanism of occurrence is currently considered to be drug-induced allergic reaction, which can be relieved after discontinuation of rifampin and symptomatic treatment.
8. Skin
Skin reactions are mild and often self-limiting, usually manifesting as flushing and pruritus (with/without rash) and not as allergic reactions. Severe skin changes caused by hypersensitivity reactions are rare.
9. Allergic reactions
May present as pruritus, urticaria, rash, aspergillosis-like reactions, erythema multiforme including Stevens-Johnson syndrome, toxic epidermolysis bullosa, vasculitis, drug reactions with eosinophilia and systemic symptom syndrome, oral ulcers, tongue pain, conjunctivitis.
Allergic reactions have been reported relatively rarely.
10. Other
Tooth discoloration (possibly permanent). Rare reports of muscle lesions. Swelling of the face and extremities has been reported. Other reactions to intermittent therapy include “flu-like syndrome” (fever, chills, headache, vertigo, bone pain), shortness of breath, asthma, decreased blood pressure, and shock. Flu-like syndrome” may also occur in patients who are not taking the medication regularly.
Contraindications
Contraindicated in patients with hypersensitivity to rifampicin, rifamycin or other substances contained in capsules.
Rifampin is contraindicated in patients receiving ritonavir/saquinavir because of the increased risk of severe drug-related liver injury (see [Drug Interactions]).
Rifampin is contraindicated in patients receiving atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir because it significantly reduces plasma drug concentrations of these antiviral agents and may lead to decreased antiviral efficacy and/or viral resistance.
[Caution].
Warning.
1. Rifampin can cause drug-related hepatic impairment and lethal jaundice in patients with underlying liver disease or concomitant use of other hepatotoxic drugs. Use rifampicin with caution in patients with hepatic impairment, apply only when necessary, and monitor liver function (especially SGPT/ALT and SGOT/ AST) with tests before and every 2-4 weeks during treatment. Discontinue rifampicin immediately if signs of hepatocellular injury appear.
2. Some patients may develop hyperbilirubinemia early in treatment due to competition between rifampicin and bilirubin at the cellular level for the hepatic excretion pathway. Mild elevation of bilirubin and/or transaminases is not an indication for discontinuation of therapy and should be decided in the context of the patient’s clinical situation after repeated testing to observe the trend.
3. Rifampin has enzyme-inducing properties, including induction of delta-aminolevulinic acid synthase. Rifampicin-related exacerbations of porphyria have been reported individually.
4. The rapid emergence of meningococcal resistance limits the short-term treatment of rifampicin in asymptomatic Neisseria meningitidis carriers. Rifampin should not be used to treat patients with meningococcal infections.
5. Rifampin can cause Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (see [ADVERSE REACTIONS]). Signs and symptoms of an allergic reaction include: fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases, or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, pain, itching, sweating, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). These reactions can be serious and even fatal. Allergy may be present even if the rash is not obvious, as evidenced by fever, lymphadenitis, or laboratory abnormalities (including eosinophilia and abnormal liver function).
Monitor the patient for signs and/or symptoms of an allergic reaction. If present discontinue rifampicin immediately and treat symptomatically.
General Precautions.
1. Rifampicin should be used with caution in patients with more difficult management of diabetes mellitus.
2. Use of this product in the absence of a confirmed or not highly suspected bacterial infection, or in the absence of indications for prophylaxis, may not be beneficial to the patient and may increase the risk of development of drug-resistant bacteria.
3. For the treatment of tuberculosis, rifampin is usually given daily. When rifampicin is administered at doses greater than 600 mg once or twice a week, it can lead to a higher incidence of adverse reactions, including “flu symptoms” (fever, chills, malaise), hematopoietic reactions (leukopenia, thrombocytopenia, acute hemolytic anemia), skin, gastrointestinal, and hepatic reactions, shortness of breath, shock, allergic reactions, and renal hypofunction.
4. Intermittent application of rifampicin is not recommended to avoid intentional or accidental interruption of medication. Renal hypersensitivity reactions occur in very few cases when treatment is resumed in such cases. Advise patients to continue drug therapy even after symptoms improve with early treatment. Irregularity in drug doses and regimens can reduce efficacy, promote the development of bacterial resistance, and further lead to drug resistance.
5 Rifampin has enzyme-inducing properties that enhance the metabolism of endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter the metabolism of vitamin D. In some cases, a decrease in circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D is accompanied by a decrease in plasma calcium ions and phosphate, and an increase in parathyroid hormone.
6. Patients should be informed before taking this product that rifampicin may discolor teeth, urine, sweat, sputum, and tears (yellow, orange, red, brown). Soft contact lenses may be permanently stained.
7. The reliability of oral or other systemic hormonal contraceptives may be affected, and patients should be advised to use other contraceptive measures.
8. Patients should be advised to seek immediate medical attention if any of the following occur: rash, fever or swollen lymph nodes, loss of appetite, malaise, nausea and vomiting, darkening of the urine, yellowing of the skin and eyes, cough, shortness of breath, wheezing, joint pain or swelling.
9. Baseline testing should be performed before rifampicin is administered to adults. The testing should include liver enzymes, bilirubin, serum creatinine, complete blood count and platelet count. Baseline testing is not necessary for pediatric patients unless the clinical situation is complex or a suspected case.
10. Effects on laboratory tests.
Cross-reactivity with opioids and false-positive urine screening test results have been reported in patients using rifampicin when tested by the KIMS (kinetic interaction analysis of particles in solution) method. Confirmatory tests, such as gas chromatography/mass spectrometry methods, can distinguish rifampicin from opioids.
Therapeutic doses of rifampicin have been shown to inhibit standard microbiological assays for serum folate and vitamin B12. Therefore, alternative assays should be considered. Transient abnormalities in liver function tests (e.g., elevated serum bilirubin, alkaline phosphatase, serum transaminases) and decreased biliary excretion of contrast agents used for biliary tract imaging have also been observed. Therefore, these tests should be performed in the morning before taking rifampicin.
[For Pregnant and Lactating Women].
Pregnant women.
There are no clinical studies on the use of rifampicin in women with tightly controlled pregnancies. Because rifampicin is able to cross the placental barrier and appear in the cord blood, it should be used only when the potential benefit outweighs the risk to the fetus.
When administered in the late weeks of pregnancy, rifampicin can cause postpartum hemorrhage in mother and baby and may be given as vitamin K therapy.
Lactating women.
Because rifampicin has shown potential carcinogenicity in animal studies, the decision to discontinue breastfeeding or to discontinue the drug needs to be considered in light of the importance of the drug to the mother.
Pediatric Use
See [Dosage and Administration].
Geriatric use
Geriatric patients with reduced hepatic function should reduce the dose as appropriate. Drug Interactions
Rifampicin 600mg once a day in healthy subjects along with saquinavir 1000mg / ritonavir 100mg twice a day (ritonavir-boosted saquinavir) can cause severe hepatocellular toxicity. Therefore, concomitant use of these drugs is contraindicated (see [Contraindications]).
Rifampin is capable of inducing certain cytochrome P-450 enzymes. The combination of rifampicin with drugs biotransformed via these metabolic pathways may accelerate clearance of the coadministered drug. To maintain optimal blood levels, it may be necessary to adjust the dose of drugs that are metabolized by these enzymes or to discontinue rifampicin.
Rifampin significantly reduces the blood levels of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs should not be used in combination with rifampicin (see [Contraindications]).
Rifampin accelerates the metabolism of the following drugs: anticonvulsants (e.g., phenytoin sodium), digitalis toxins, antiarrhythmic drugs (e.g., propyzamide, mexiletine, quinidine, tocainide), oral anticoagulants, antifungals (e.g., fluconazole, itraconazole, ketoconazole), barbiturates, beta-blockers, calcium channel blockers (e.g., diltiazem, nifedipine, verapamil) chloramphenicol, clarithromycin, glucocorticoids, cyclosporine, cardiac glycoside preparations, antomin, oral or other systemic hormonal contraceptives, amphetamine, diazepam, doxycycline, fluoroquinolones (e.g., ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, progesterone, quinine, tacrolimus, theophylline, tricyclic antidepressants (e.g., amitriptyline, nortriptyline) and zidovudine. In combination with rifampicin, the doses of these drugs need to be adjusted appropriately.
Patients using oral or other systemic hormonal contraceptives are advised to switch to a non-hormonal method of contraception while taking rifampicin.
Rifampin can increase the need for coumarin-based anticoagulants. Patients on combined rifampin and anticoagulants are advised to monitor clotting time daily and maintain an effective dose of anticoagulant.
In the combination of atovaquone and rifampicin, the blood concentration of atovaquone decreases and the blood concentration of rifampicin increases.
The combination of ketoconazole and rifampicin results in a decrease in the blood concentration of both. Combined application of rifampicin and enalapril results in decreased concentrations of enalapril and its active metabolites. The dose should be adjusted appropriately according to the clinical condition of the patient at the time of use.
The combination of antacids and rifampicin decreases the absorption of rifampicin. It is recommended that rifampicin be taken at least 1 hour prior to antacids.
Probenecid and compounded sulfamethoxazole will increase the blood concentration of rifampicin.
Combination of rifampicin with halothane or isoniazid will increase the risk of hepatotoxicity and should be avoided; close monitoring of liver function is required when rifampicin and isoniazid are combined.
The blood concentration of sulfasalazine is reduced when the combination of salazopyridine and rifampicin is used. This may be due to reduced conversion of colonic bacteria from sulfadiazine to sulfadiazine and aminosalicylate.
The absorption of rifampicin can be affected by p-aminosalicylates, resulting in lower blood levels; if the combination is necessary, the two should be administered at least 6 hours apart.
The combination of rifampicin and ethionamide may increase its adverse effects.
Chlorpheniramine may reduce the absorption of rifampicin, delaying the time to peak and prolonging the half-life.
Drug Overdose
The minimum acute lethal dose or minimum toxic dose has not been determined. However, non-lethal acute overdoses of rifampicin in adults have been reported in the range of 9-12 g and lethal acute overdoses in the range of 14-60 g. Alcohol consumption or a history of alcohol abuse has been involved in lethal and non-lethal cases. Non-fatal drug overdose reactions have been reported in pediatric patients 1 to 4 years of age with a single or two doses of 100 mg/kg.
1. Signs and symptoms.
Nausea, vomiting, abdominal pain, pruritus, headache, drowsiness, and coma in patients with severe liver disease may occur within a short period of dosing. Liver enzymes and bilirubin may be transiently elevated. Skin, urine, sweat, saliva, tears, and stool may change to a brownish-red or orange color, with the coloration proportional to the amount taken.
Liver enlargement may occur within hours of a severe overdose and may be accompanied by pressure pain. Bilirubin levels may be elevated and may rapidly progress to jaundice. Liver-related symptoms may be more pronounced in patients who have had prior hepatic impairment. Other physical signs are essentially normal. There is unlikely to be an effect on the hematopoietic system, electrolytes, or acid-base balance.
Facial or periorbital edema has been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures, and cardiac arrest have been reported in some cases of death.
2. Treatment
Strong supportive therapy should be given, immediately at the onset of symptoms. Keep breathing open and give respiratory support. Nausea and vomiting may occur and gastric lavage within 2 to 3 hours after administration is preferable to inducing vomiting. Injection of an activated charcoal suspension into the stomach after the stomach contents have emptied may help absorb the remaining drug in the gastrointestinal tract. Antiemetic medications can help relieve severe nausea and vomiting.
Aggressive diuresis (by measuring intake and excretion) will help facilitate drug excretion.
Severe cases may require extracorporeal hemodialysis. If hemodialysis is not possible, a combination of peritoneal dialysis and a potent diuretic may be used.
Pharmacology and Toxicology
Pharmacological action
Mechanism of action.
Rifampicin inhibits the DNA-dependent RNA polymerase activity of Mycobacterium tuberculosis-susceptible bacteria. Specifically, rifampicin interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
Drug resistance.
Microorganisms resistant to rifampicin may be resistant to other rifamycins.
In the treatment of tuberculosis and meningococcal carriers (see [Indications]), a few resistant organisms among a large number of sensitive organisms can rapidly become dominant. In addition, it has been established that rifampicin resistance occurs as a single-step mutation in DNA-dependent RNA polymerase. Given that resistance can emerge rapidly, appropriate drug sensitivity testing should be performed once bacterial cultures are consistently positive.
In vitro and in vivo activity.
Rifampicin has in vitro antibacterial activity against chronic and intermittently growing Mycobacterium tuberculosis.
In in vitro tests and in the clinical infections described in [Indication], rifampicin showed antibacterial activity against most strains of the following bacteria
Aerobic Gram-negative bacteria.
Neisseria meningitidis
“Other” bacteria.
Mycobacterium tuberculosis
The following in vitro test data have been obtained, but their clinical significance is unknown.
Rifampicin is active in vitro against most strains of the following bacteria; however, the safety and efficacy of rifampicin in the treatment of clinical infections caused by these bacteria has not been established in adequate, well-controlled clinical trials.
Aerobic Gram-positive bacteria.
Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus/MRSA)
Staphylococcus epidermidis
Aerobic Gram-negative bacteria.
Haemophilus influenzae
“Other” bacteria.
Mycobacterium leprae
β-lactamase production should have no effect on rifampicin activity.
Drug sensitivity testing.
Prior to initiating treatment, appropriate specimens should be collected to identify the infecting organism and in vitro drug sensitivity testing should be performed.
In vitro testing of Mycobacterium tuberculosis isolates.
Two standardized in vitro drug-sensitivity testing methods are available to test the susceptibility of rifampicin to Mycobacterium tuberculosis. Agar ratio method (CDC or CLSI M24-A): Using Middlebrook 7H10 medium, rifampicin at a final concentration of 1.0 μg/mL is added to determine drug resistance. After three weeks of incubation, MIC was calculated by comparing the amount of bacterial growth in the drug-containing medium to that of the control medium.99 Mycobacterium growth in the presence of drug ≥1% compared to the control indicated drug resistance.
Radioactive broth method: The BACTEC 460 instrument was used to compare the growth index (GI) of drug-free medium with that of medium containing 2 μg/ml of rifampicin. This test requires strict adherence to the manufacturer’s sample handling methods and data resolution.
The drug sensitivity results obtained by the above two different methods are comparable only when the above concentrations of rifampicin are used. Both methods require the use of Mycobacterium tuberculosis H37Rv ATCC 27294 as a quality control organism.
The clinical relevance of in vitro susceptibility test results obtained using radiometric or proportional methods for mycobacteria other than Mycobacterium tuberculosis is unclear.
In vitro tests for Neisseria meningitidis isolates.
Dilution methods: Quantitative methods for determining the minimum inhibitory concentration provide a reproducible assessment of bacterial susceptibility to antimicrobial drugs. One such standard method uses a standard dilution method (broth method, agar method, or microdilution method) or an equivalent amount of rifampicin powder. The MIC values obtained should be interpreted according to the following criteria for Neisseria meningitidis.
MIC (μg/mL) Interpretation ≤1 (S) Sensitive 2 (I) Intermediary ≥4 (R) Resistance reported as “sensitive” (S) indicates that the antimicrobial drug may inhibit the growth of the pathogen at concentrations normally achievable in the blood. A report of “intermediate” (I) indicates that the results are ambiguous and that testing should be repeated if the microorganism is not fully susceptible to clinically available alternative drugs. This category implies the possible clinical applicability at the body site where the drug is physiologically aggregated or at the maximum acceptable dose. This category provides a buffer to prevent small, uncontrollable technical factors from leading to significant differences in interpretation. A report of “resistant” (R) indicates that the normally achievable concentration of the antimicrobial drug in the blood may not inhibit the growth of the pathogen and that an alternative treatment should be selected.
The determination of MIC or minimum bacterial concentration (MBC) and achievable antimicrobial drug concentrations can guide the treatment of some infections.
Standard methods of drug sensitivity testing require the use of laboratory quality control strains. The use of these strains does not imply clinical efficacy (see [Indications]), but is used to control the technical aspects of the test procedure. Rifampicin standards should give the following MIC values.
Strain MIC (μg/mL) Staphylococcus aureus ATCC 292130.008~0.06 Enterococcus faecalis ATCC 292121~4 Escherichia coli ATCC 259228~32 Pseudomonas aeruginosa ATCC 2785332~64 Haemophilus influenzae ATCC 492470.25~1 Diffusion method: A quantitative method for measuring the diameter of the inhibition circle can provide a reproducible assessment of bacterial susceptibility to antimicrobial drugs. A recommended standard method is the flat dish method, in which the susceptibility of the strain is tested in a flat dish containing 5 μg of rifampicin. The correlation between the diameter of the inhibition circle obtained from the flat dish test and the MIC value of rifampicin is determined.
The results of the standard single-dish susceptibility test for 5 μg rifampicin in a flat dish should be interpreted according to the following criteria for Neisseria meningitidis.
Inhibition circle diameter (mm) Interpretation ≥ 20 (S) Sensitive 17-19 (I) Intermediary ≤ 16 (R) Resistance should be interpreted using the interpretation of the results of the dilution method as described previously.
As with the standard dilution method, the diffusion method requires the use of laboratory quality control strains. The use of these strains does not imply clinical efficacy (see [Indications]), but is used to control technical aspects of the test procedure. For the following QC strains, 5 μg rifampicin flat dishes should give the following inhibition circle diameters.
Strain Bacterial circle diameter (mm) Staphylococcus aureus ATCC 2592326~34 Escherichia coli ATCC 259228~10 Haemophilus influenzae ATCC 4924722~30
Toxicological studies
Genotoxicity: Rifampicin has not been shown to be mutagenic in prokaryotic bacteria (Salmonella typhi, Escherichia coli), eukaryotic bacteria (Saccharomyces cerevisiae), Drosophila, or ICR/Ha Swiss mice tests. Increased chromosome breakage was seen when rifampicin was given in whole blood cell cultures. Increased chromosomal aberrations were observed in lymphocyte in vitro assays obtained in patients treated with combination rifampicin, isoniazid, pyrazinamide and combination streptomycin, rifampicin, isoniazid, pyrazinamide.
Reproductive toxicity: Rifampicin was seen to be teratogenic in rodents. An increase in congenital malformations, spina bifida, was seen in the offspring of pregnant rats given rifampicin 150-250 mg/kg/day (approximately 1-2 times the maximum recommended human dose in terms of body surface area) orally during the organogenesis period. A dose-dependent increase in cleft palate was seen in fetuses of pregnant mice administered orally at 50-200 mg/kg (approximately 0.2-0.8 times the maximum recommended human dose in terms of body surface area). Osteogenesis and embryotoxicity were seen in pregnant rabbits given rifampicin orally at doses up to 200 mg/kg/day (approximately 3 times the maximum recommended human dose in terms of body surface area).
Carcinogenicity: In humans, several cases of accelerated growth of lung cancer have been reported, but a causal relationship with the drug has not been established. In female CH3f/DP mice given rifampicin 20-120 mg/kg (equivalent to 0.1-0.5 times the maximum human dose in terms of body surface area) for 60 consecutive weeks, followed by 46 weeks of observation, the incidence of hepatocellular carcinoma was increased. No carcinogenicity was seen in similar tests in male C3Hf/DP mice or BALB/c mice, or in a two-year test in Wistar rats.
[Pharmacokinetics].
Rifampicin is well absorbed orally. Peak serum drug concentrations in healthy adults and pediatric populations vary widely between individuals. The mean peak serum drug concentration was 7 μg/ml after a single oral dose of 600 mg of rifampicin in healthy adults, with a distribution range of 4 to 32 μg/ml. rifampicin absorption was reduced by 30% when the drug was ingested with food.
Rifampicin is widely distributed in the body and can reach effective concentrations in a variety of organs and body fluids, including cerebrospinal fluid. Plasma protein binding is approximately 80%, and most of the unbound drug is nonionized and therefore freely diffuses into tissues.
In healthy adults, the mean biological half-life of rifampicin in serum was 3.35 ± 0.66 hours for a 600 mg oral dose and 5.08 ± 2.45 hours after increasing to a 900 mg dose. After repeated dosing, the half-life decreased with a mean value of approximately 2 to 3 hours. In patients with renal failure, there was no effect on the half-life when the daily dose did not exceed 600 mg and therefore no dose adjustment was required; when the daily dose reached 720 mg, the effect on the half-life has not been determined; when patients suffering from different degrees of renal insufficiency received a single oral dose of 900 mg, for patients with glomerular filtration rates of 30 to 50 ml/min, less than 30 ml/ min, and anuric patients, the mean half-life increased from 3.6 hours in healthy adults to 5.0 hours, 7.3 hours, and 11.0 hours, respectively.
After absorption, the drug is rapidly excreted via the bile and enters the hepatic-intestinal circulation. During this process, rifampicin is continuously deacetylated and within 6 hours of dosing almost all of the drug in the bile is present in the deacetylated form, a metabolite with antimicrobial activity. Deacetylation reduces intestinal reabsorption and promotes excretion. Up to 30% of the drug is excreted in the urine, with the prototype accounting for about half of the drug.
In one study, rifampicin mixed monosaccharide or dried powdered applesauce mixture of the drug was given at a dose of 10 mg/kg before meals in pediatric patients aged 6 to 58 months, and the blood concentrations 1 hour after administration were 10.7 ± 3.7 μg/ml and 11.5 ± 5.1 μg/ml, respectively, with a half-life of 2.9 hours for both dosing regimens. Notably, the mean peak serum drug concentrations in other studies in the pediatric population after administration at a dose of 10 mg/kg ranged from 3.5 to 15 μg/ml.
Storage】 Seal and store in a dark and dry place.
Package】 Oral solid medicine in high-density polyethylene bottle, 60 capsules/bottle.
Expiration date】 12 months
Execution Standard
Approval number
State Drug Certificate H21022450
Manufacturer
Enterprise name: Shenyang Hongqi Pharmaceutical Co.
Production Address: No. 6, Xinluo Street, Hunnan New District, Shenyang
Postal Code: 110179
Telephone number: (024) 23786260 23786261
Fax number: (024) 23786263
Web address: www.hongqipharma.com