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Clindamycin Hydrochloride Capsules Instructions
Please read the instructions carefully and use under the direction of a physician
Warning
Almost all antibiotics, including clindamycin hydrochloride, cause Clostridium difficile (Clostridium difficile) associated diarrhea (CDAD), which can range in severity from mild diarrhea to fatal colitis. Antibacterial drug therapy can alter the normal intestinal flora, leading to overgrowth of C. difficile.
Clindamycin hydrochloride may cause severe colitis after administration. Severe colitis carries a risk of fatalities, so this product is indicated only for severe infections that cannot be treated with less toxic antimicrobials, as detailed in Indications and Usage. Clindamycin hydrochloride should not be used for non-bacterial infections, such as most upper respiratory tract infections.
Clostridium difficile can produce toxins A and toxins B, which in turn promote CDAD occurrence. Hypertoxin-producing strains of C. difficile can lead to increased morbidity and mortality, and because these infections can be ineffective to antimicrobial therapy, they may require colectomy for treatment. CDADshould be considered in all patients who develop diarrhea after antibiotics. Since there was a history of antimicrobial therapy given for more than 2months after the occurrence of CDAD has been reported, necessitating careful history taking.
If suspected or diagnosed with CDAD, then antimicrobial therapy not directed against C. difficile needs to be discontinued, appropriate fluid and electrolyte regulation, protein supplementation, and antimicrobial therapy directed against C. difficile needs to be administered according to clinical indications, and surgical evaluation needs to be performed if necessary.
[Drug Name]
Generic Name: Clindamycin Hydrochloride Capsules
English Name:Clindamycin Hydrochloride Capsules
Hanyu Pinyin:Yansuan Kelinmeisu Jiaonang
[Ingredients]
The main ingredient of this product is Clindamycin Hydrochloride.
Chemical name:7-chlorine-6,7,8-trideoxy-6-(1- “font-family:Arial”>Methyl-Inverse-4-propyl-L-2-pyrrolidinecarbonylamino)-l-thiothio span>-L-suf-α-D-Galactopyranoside methylglucoside hydrochloride.
Chemical structure formula:
Molecular Formula:C18H33ClN2O5S-HCl
Molecular weight:461.44
[Properties]
The content of this product is white powder or crystalline powder or granule.
[Indications]
Clindamycin is indicated for serious infections caused by sensitive anaerobic bacteria.
Clindamycin is indicated for serious infections caused by sensitive strains of streptococci, pneumococci, and staphylococci, but only in patients who are allergic to penicillin or in patients for whom penicillin is contraindicated by a physician’s judgment. Because of the risk of colitis (see [black box warning]), physicians should consider the severity of the infection and the availability of less toxic alternatives (e.g., erythromycin) before selecting clindamycin.
Anaerobes: severe respiratory infections such as septic chest, anaerobic pneumonia, and lung abscess; severe skin and soft tissue infections; sepsis; intra-abdominal infections such as peritonitis and intra-abdominal abscesses (typically caused by anaerobes retained in the gastrointestinal tract); female pelvic and Reproductive tract infections such as endometritis, non-gonococcal tubo-ovarian abscesses, pelvic cellulitis, and post-surgical vaginal vault infections.
Streptococcus: severe respiratory tract infections; severe skin and soft tissue infections.
Staphylococcus: severe respiratory infections; severe skin and soft tissue infections.
Pneumococcus: severe respiratory infections.
The pathogenic organism and its susceptibility to clindamycin should be determined by bacteriological studies.
To reduce the emergence of resistant bacteria and to ensure the effectiveness of clindamycin and other antimicrobial agents, clindamycin should only be used to treat or prevent infections that have been proven or are highly suspected to be caused by susceptible bacteria. Obtained culture and drug sensitivity information should be considered when selecting or adjusting antimicrobial therapy. If such information is not available, refer to local epidemiologic and pharmacologic characteristics and select therapy empirically.
[Specification] 0.15g (based onC18H33ClN2O5S =”font-family:Arial”>count)
[dosage]
Discontinue this product if significant diarrhea occurs during treatment (see [black box warning]).
Adults: severe infection: one dose 150 ~300 mg every 6 hours. More severe infections: once 300 ~ 450 mg every 6 hours.
Pediatric patients (children who can swallow capsules): severe infection: 8 ~ 16 mg/kg/day in3 ~ 4doses orally. More severe infections: 16 ~ 20 mg/kg/day in family:Times New Roman”>3~4times orally.
Take this product with sufficient amount of water to prevent drug irritation to the esophagus.
This product is not intended for use in children who cannot swallow the complete medication. Capsules do not provide an accurate mg/kg dose and in some cases clindamycin palmitate oral solution is required.
If B hemolytic streptococcal infection develops, treatment should continue for at least 10 days.
[Adverse Reactions]
1, Infection and Infestation: Clostridium difficile colitis
2, Gastrointestinal tract: abdominal pain, pseudomembranous colitis, esophagitis, nausea, vomiting and diarrhea (see [black box warning]). Symptoms of pseudomembranous colitis may occur during or after antimicrobial therapy (see [Caution]). Esophageal ulcers have been reported. An off-flavored or metallic taste has been reported following oral administration.
3, Hypersensitivity reactions: The most commonly reported adverse reaction is a mild to moderate measles-like (maculopapular) rash over the body. Blistering rash as well as urticaria have been observed during drug therapy. Severe skin reactions such as toxic epidermolysis bullosa, sometimes fatal, may occur (see [Precautions]). Acute generalized eruptive pustulosis (AGEP), erythema multiforme, partially manifested as =”font-family:Times New Roman”>Stevens-Johnson syndrome, anaphylaxis, allergic reactions, and hypersensitivity reactions have also been reported.
4, Skin and mucous membranes: Cases of pruritus, vaginitis, and angioedema have been reported, and rare cases of exfoliative dermatitis have been reported.
5, Liver: Jaundice and liver function abnormalities had been observed during clindamycin treatment.
6, Renal: Although a direct relationship between clindamycin and renal injury has not been established, azotemia, oliguria and/or proteinuria and other signs of renal dysfunction.
7, Hematopoietic system: There have been reports of transient neutropenia (leukopenia) and eosinophilia. Granulocyte deficiency and thrombocytopenia have also been reported. None of these reports could be definitively linked directly to clindamycin administration.
8, Immune system: Previous drug reactions with eosinophilia and systemic symptoms (DRESS) , Immune system: Previous drug reactions with eosinophilia and systemic symptoms (DRESS) case report.
9, musculoskeletal system:Cases of polyarthritis have been reported.
[Contraindicated]
Contraindicated in patients with a history of hypersensitivity to clindamycin and lincomycin.
[Precautions]
1, Clostridium difficile associated diarrhea
Almost all antibiotics, including clindamycin hydrochloride, cause Clostridium difficile ( Clostridium difficile) associated diarrhea (CDAD) span style=”font-family:Arial”>, which can range in severity from mild diarrhea to fatal colitis. Antibacterial drug therapy can alter the normal intestinal flora, leading to overgrowth of C. difficile.
Clindamycin hydrochloride may cause severe colitis after administration. Severe colitis carries a risk of fatalities, so this product should only be used for severe infections that cannot be treated with less toxic antimicrobials, as detailed in [Indications] and [Dosage and Administration]. Clindamycin hydrochloride should not be used for non-bacterial infections, such as most upper respiratory tract infections.
Clostridium difficile can produce toxins A and toxin B, which in turn promotes CDAD. Hypertoxin-producing strains of C. difficile can lead to increased morbidity and mortality, and because these infections can be ineffective to antimicrobial therapy, they may require colectomy for treatment. CDADshould be considered in all patients who develop diarrhea after antibiotics. Since there was a history of antimicrobial therapy given for more than 2months after the occurrence of CDAD has been reported, necessitating careful history taking.
If a diagnosis of CDAD is suspected or confirmed, then antimicrobial therapy not directed against C. difficile needs to be discontinued, appropriate fluid and electrolyte regulation, protein supplementation, and antimicrobial therapy directed against C. difficile needs to be given according to clinical indications, and surgical evaluation needs to be performed if necessary.
2, allergic reactions and severe hypersensitivity reactions
Anaphylaxis and anaphylactic reactions have been reported (see [Adverse Reactions]).
Severe hypersensitivity reactions have been reported, including severe skin reactions such as toxic epidermal necrolysis relaxation (TEN), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome span style=”font-family:Times New Roman”> (SJS), which is sometimes fatal (see [Adverse Reactions]).
If anaphylactic reactions or severe hypersensitivity reactions occur, treatment should be permanently discontinued and appropriate therapy instituted.
Patients should be carefully questioned about their history of allergy to drugs and other allergens. It is possible that a patient who is allergic to lincomycin may also be allergic to clindamycin.
3, Clindamycin does not diffuse sufficiently into the cerebrospinal fluid and this product is not indicated for the treatment of meningitis.
4, The following conditions should be used with caution: ①Gastrointestinal disorders (especially colitis) or previous history. ②For patients with hereditary allergies.
5,
Experience has shown that a subset of elderly patients with concomitant severe disease tolerate diarrhea poorly. When using clindamycin in this group of patients, the change in stool frequency should be monitored.
6, no dose adjustment is required in patients with renal disease; in patients with moderate and severe hepatic disease, the clindamycin half-life is prolonged, but based on In patients with moderate and severe liver disease, the half-life of clindamycin is prolonged, but based on studies, it is inferred that drug accumulation is difficult to occur with every 8hour dosing and therefore no dose adjustment is required in patients with liver disease, but the dose should be monitored regularly during the dosing period Liver enzyme levels in patients with severe liver disease.
7. Overgrowth of non-susceptible bacteria (especially yeast) has occasionally been seen with this product, and in case of dual infection, appropriate measures should be taken according to the clinical situation. Take appropriate measures according to the clinical situation. .
8, when bacterial infection has not been diagnosed or is highly suspected, and when prophylactic indications are not met, administration of this product It does not provide benefit to patients and increases the risk of developing drug-resistant bacteria.
9, Liver and kidney function tests as well as blood counts should be performed regularly during the course of long-term treatment. .
[For pregnant and lactating women]
Pregnancy:
In clinical trials of women in pregnancy, the incidence of congenital anomalies was not found to be elevated with clindamycin in mid- to late-pregnancy. There are no adequate, well-controlled clinical studies in women in early gestation. Because animal reproduction studies are not necessarily predictive of human response, clindamycin should be used in pregnant women only if it is necessary.
Oral administration in mice and rats600 mg/kg/day (3.2times the maximum recommended dose for adults,and style=”font-family:Times New Roman”>1.6fold), transdermal administration 250 mg/kg/day (1.3of the highest recommended adult dose) -family:Arial”>fold,0.7fold), and no teratogenicity was observed.
Lactating women:
Clindamycin in breast milk at the time of dosing0.7 to 3.8 mcg/ml, Clindamycin may have adverse effects on the gastrointestinal flora of breastfed infants. If a breastfeeding woman requires oral or intravenous clindamycin, it is not necessary to discontinue breastfeeding and an alternative drug is preferred. Infants need to be monitored for possible adverse effects on gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash), or blood in the stool (rarer, suggesting possible antibiotic colitis). Consideration of the benefits of breastfeeding for the infant should be balanced with the clinical need for clindamycin in breastfeeding women and any potential adverse effects of clindamycin on the breastfed infant.
[Pediatric Use]
When pediatric patients (birth to16years) are taking this product, organ function should be monitored.
[Geriatric Use]
Clindamycin clinical studies did not include enough65years and older, and it is uncertain whether adverse reactions in this group differ from those in younger patients. Additional clinical experience has been reported suggesting that most antibiotic-associated antibiotic colitis and diarrhea (due to Clostridium difficile) in older adults (>60years) have a higher incidence and may be more severe. In these patients, their diarrhea should be monitored closely.
No clinically significant differences in pharmacokinetics were demonstrated for young subjects with normal hepatic function and normal (age-adjusted) renal function and older subjects given clindamycin orally or intravenously.
[Drug Interactions]
(1) Clindamycin has been shown to have neuromuscular blocking properties that potentiate the effects of other neuromuscular blocking agents. Clindamycin should be used with caution in patients receiving such medications.
(2) Clindamycin is mainly metabolized by CYP3A4 , with a small amount being metabolized by CYP3A5 metabolism, CYP3A4 and CYP3A5 inhibitors of CYP3A4 increase clindamycin blood levels of clindamycin, while its inducers can decrease clindamycin blood levels. If this product is combined with a strong inhibitor of CYP3A4 , monitor for adverse effects; if combined with “font-family:Times New Roman”> strong inducers of CYP3A4 , such as rifampin, the effectiveness of this product needs to be monitored. In vitro studies have shown that clindamycin does not inhibit CYP1A2, , CYP2C9, CYP2C19,CYP2E1,CYP2D6, only moderately inhibited CYP3A4.
(3) Use with anti-peristaltic antidiarrheal drugs and antidiarrheal drugs containing white clay: Clindamycin has the potential to cause pseudomembranous enteritis with severe watery diarrhea during the course of treatment, and even weeks afterwards. Because of the delayed discharge of toxins from the colon, which leads to prolonged and increased diarrhea, anti-peristaltic antidiarrheal drugs should not be used together. The absorption of clindamycin and antidiarrheal drugs containing white clay will be significantly reduced when the latter is taken orally at the same time, so they should not be taken at the same time and must be separated by a certain time (at least 2hour).
(4) can enhance the neuromuscular blocking phenomenon of inhaled anesthetics, leading to skeletal muscle weakness and respiratory depression or paralysis (apnea), and care should be taken when co-administered during or after surgery. Treatment with anticholinesterase drugs or calcium salts can be expected to be effective.
(5) In combination with opioid analgesics, the respiratory depressant effect of this product and the central respiratory depressant effect of opioids may cause prolonged respiratory depression or respiratory paralysis (apnea) due to the cumulative phenomenon, so the patient must be closely observed or monitored.
(6) This product has a neuromuscular blocking effect, and when combined with antimuscarinic drugs will result in a diminished effect of the latter on skeletal muscle. In order to control the symptoms of myasthenia gravis, the dose of antimuscarinic drugs should be adjusted during the combined regimen.
(7)Either chloramphenicol or erythromycin can displace this product at the target site or inhibit the binding of the latter to the bacterial ribosomal50Ssubunit, and in vitro tests have shown that It is antagonistic to erythromycin and should not be used in combination with chloramphenicol or erythromycin.
[Drug overdose]
Mice administered intravenously855 mg/kgand in rats when administered orally or subcutaneously2618 mg/kg, a statistically significant mortality. Mice showed convulsions and depressive symptoms.
Clindamycin was not effectively cleared from serum by hemodialysis and peritoneal dialysis.
[Pharmacology and Toxicology]
The antibacterial spectrum of this product is the same as that of lincomycin, with stronger antibacterial activity than lincomycin4~8fold. It has high antibacterial activity against aerobic gram-positive cocci, such as Staphylococcus spp (including penicillin-resistant and methicillin-sensitive strains), Streptococcus haemolyticus, Streptococcus gramineus, Streptococcus pneumoniae, etc. It also has good antibacterial activity against anaerobic bacteria. It also has good antibacterial effect on anaerobic bacteria, most of which are sensitive to this product, such as Bacillus spp, Clostridium spp, Actinomyces spp, Streptococcus pepticus and Streptococcus pepticus.
This product acts on the ribosome of sensitive bacteria50S. family:Arial”>subunit, preventing the extension of the peptide chain and thus inhibiting protein synthesis in bacterial cells, is generally a bacteriostatic agent, but at high concentrations, it is also bactericidal for some bacteria.
[Pharmacokinetics]
Absorption
24 normal adult volunteers administered orally in a single dose 150 mg clindamycin hydrochloride, showed that clindamycin hydrochloride was rapidly absorbed after oral administration;45 minutes later, the serum concentration peaked at a mean of 2.50 mcg /mL; 3 hours later The mean serum concentration was 1.51 mcg/mL, and family:Times New Roman”> 6 hours later was 0.70 mcg/mL. The oral absorption rate was 90% and there was no effect of diet on serum concentration. Serum concentrations were consistent and regular across individuals and across doses. No changes in drug accumulation or drug metabolism were observed after repeated dosing for up to 14 days. Healthy volunteers received 2 g of clindamycin daily for family:Times New Roman”> 14 days, which was well tolerated, but the incidence of gastrointestinal side effects increased with the dose.
Distribution
Serum concentrations of clindamycin increased linearly with increasing dose. Serum concentrations can be maintained above the minimum effective inhibitory concentration for at least six hours after administration using the generally recommended dose. Clindamycin is widely distributed in body fluids and tissues (including bone), but is rarely distributed in the cerebrospinal fluid and does not reach effective concentrations even when the meninges are inflamed.
Metabolism
In vitro studies in human liver and intestinal microsomes have shown that clindamycin is predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) and to a lesser extent via CYP3A5. “font-family:Arial”> metabolized by clindamycin sulfoxide and a small amount of N-demethylclindamycin Clindamycin.
Excretion
Average half-life of2.4hours. Approximately10% of the active substance is excreted through urine,3.6% of the active material is excreted in the feces, and the remainder is excreted as inactive metabolites.
Special Populations
Patients with kidney injury
The serum half-life of clindamycin is slightly prolonged in patients with significantly decreased renal function. Serum clindamycin is not effectively cleared by hemodialysis and peritoneal dialysis.
Elderly patients
Senior Volunteers (61to79 years old) and younger volunteers (18to39After intravenous administration of clindamycin phosphate, age has a significant impact on the pharmacokinetics of clindamycin (clearance, elimination half-life, volume of distribution, and serum concentration-area under the time curve) were not affected. The mean elimination half-life after oral administration of clindamycin hydrochloride was longer in elderly patients, approximately 4.0 hours (range:3.4~5.1hours), whereas the mean elimination half-life in young adult patients was 3.2hours (range:2.1to4.2hours). However, the degree of absorption did not differ between the age groups. Therefore, no dose changes are necessary for the administration of the drug to elderly patients with normal hepatic and renal function (according to age-adjusted criteria).
[Storage]
Seal and store.
[Packaging]
Aluminium-plastic blister packaging (polyvinyl chloride solid pharmaceutical rigid tablets, aluminium foil for pharmaceutical packaging) with a polyester jacket/aluminum/polyethylene laminated film and bags for pharmaceutical packaging;6grain plate×1plate/box,6grain/plate×2boardbox, 6grain/plate ×3board/box,6capsules plate×4plate/box;10grain/plate×1board/box, 10grain /board×2boards/boxes.
[Expiration date] 12 12 months
[Executive Standard]
[Approval number]
State PharmacopoeiaH13020795
[Manufacturer]
Company Name: Shiyao Group Ouyi Pharmaceutical Co.
Production Address: Yangzi Road, Shijiazhuang Economic and Technological Development Zone88No.
Postal Code:052165
Tel:0311-67163660 0311-87886158
Fax Number:0311-87171665
Website:http://www.ouyipharma.com/
In case of questions, please contact the manufacturer directly.