Clindamycin is a white crystalline powder chemical with chemical formula CeighteenHthirty-threeClNtwoOfiveS，The molecular weight is 424.98.Clindamycin is an antibiotic. Clindamycin is mainly used for abdominal and gynecological infections caused by anaerobic bacteria, and is the first choice for treatment of Staphylococcus aureus osteomyelitis.
The main ingredient of this product is clindamycin phosphate.
pharmacology
The antibacterial spectrum of this product is the same as that of lincomycin, but its antibacterial activity is strong. Clindamycin is absorbed quickly and completely by oral administration (about 90%), and eating has little effect on absorption.The concentration of clindamycin in fetal blood is higher than that of lincomycin, and the concentration in milk can reach 3.8 μ g/ml. Pregnant women and lactating mothers should pay attention to its advantages and disadvantages when using this product.High protein binding rate (90%).The peak time of oral administration is 0.75~1 hour, T1/2 is 2.4~3 hours, children is 2~2.5 hours, and renal function decline is slightly prolonged, 3~5 hours;Within 24 hours, 10% was discharged from urine, and 3.6% was discharged with feces.
indication
1. This product is applicable to the following infectious diseases caused by gram-positive bacteria:
(1) Tonsillitis, suppurative otitis media, sinusitis, etc.
(2) Acute bronchitis, acute attack of chronic bronchitis, pneumonia, lung abscess and bronchiectasis with infection[2]。
(3) Skin and soft tissue infections: furuncles, carbuncles, abscesses, cellulitis, trauma, postoperative infections, etc.
(4) Urinary system infection: acute urethritis, acute pyelonephritis, prostatitis, etc.
(5) Others: osteomyelitis, sepsis, peritonitis, oral infection, etc.
2. This product is applicable to various infectious diseases caused by anaerobic bacteria:
(1) Pulmonary infection caused by empyema, lung abscess and anaerobic bacteria.
(2) Skin and soft tissue infection, septicemia.
(3) Intra abdominal infection: peritonitis, intra-abdominal abscess.
(4) Female pelvic and genital infections: endometritis, non gonococcal tubal and ovarian abscesses, pelvic cellulitis, and gynecological postoperative infections
Usage and dosage
Oral:Hydrochloride, adult severe infection, oral 150~300mg once, up to 450mg if necessary, once every 6 hoursFor children with severe infection, 8~16mg/kg a day, and 20mg/kg if necessary, divided into 3~4 times. Palmitate hydrochloride, for children, 8~12mg/kg a day for severe infection, and 20~25mg/kg a day for extremely severe infection, divided into 3~4 times
Injection:Phosphate injection, intravenous drip or intramuscular injection, adult Gram positive aerobic bacteria infection, 0.6~1.2g a day, anaerobic bacteria infection, 1.2~2.7g a day, extremely serious infection can be used up to 4.8g a day, divided into 2~4 times. Children over 1 month old, severe infection, 15~25mg/kg a day, extremely serious infection can be used as 25-40mg/kg, divided into 3~4 times. Intramuscular injection should not exceed 0.6g a time, more than this amount should be given intravenously
1. For adults, the dosage is as follows: moderate infection: 0.6~1.2g/day, which can be administered twice (once every 12 hours), three times (once every 8 hours) or four times (once every 6 hours);Serious infection: 1.2~2.4 g/day, which can be divided into 2 times (once every 12 hours), 3 times (once every 8 hours) or 4 times (once every 6 hours) or according to the doctor's advice.
2. For children, the dose is as follows: moderate infection: 15~25mg/kg/day, which can be administered 3 times (once every 8 hours) or 4 times (once every 6 hours);Serious infection: 25~40mg/kg/day, which can be divided into three times (once every 8 hours) or four times (once every 6 hours) or according to the doctor's advice.For intravenous drip, 0.6g of this product should be diluted with 100-200ml normal saline or 5% glucose solution to a concentration ≤ 6mg/ml, and the drip time per 100ml should not be less than 30 minutes.
May cause gastrointestinal reaction[3]: nausea, vomiting, anorexia, abdominal distention, diarrhea, rash, leukopenia, elevated transaminase, which can cause double infection and pseudomembranous colitisThere may also be dyspnea, lip swelling, nasal cavity swelling, tears and allergic reactions. It is reported that the incidence of pseudomembranous enteritis caused by this product is the highest, which may exceed 2%.About 10% of the people treated with clindamycin developed skin rashes, and others, such as exudative erythema multiforme, reversible serum glutamic oxaloacetic aminotransferase and serum glutamic alanine aminotransferase, granulocytopenia, thrombocytopenia and other allergic reactions, were occasionally seen[3]。
oneLocal reaction: After intramuscular injection, pain, induration and aseptic abscess can occasionally be seen at the injection site.Long term intravenous drip should pay attention to the occurrence of phlebitis.
twoGastrointestinal reaction: nausea, vomiting, abdominal pain and diarrhea were occasionally seen.Pseudomembranous enteritis may occur in 1-2% of patients.
threeAllergic reaction: A few patients may have drug rash, and exfoliative dermatitis is occasionally seen.
fourIt has basically no toxic reaction to the hematopoietic system. It can occasionally cause neutropenia, eosinophilia, thrombocytopenia, etc. It is generally temporary.
fiveTransient alkaline phosphatase, slightly elevated serum transaminase, jaundice and abnormal renal function may occur.
taboo
Lincomycin has cross resistance to clindamycin, and it is forbidden for those who have allergies to clindamycin or lincomycin.
matters needing attention
oneIt has no cross allergic reaction with penicillin and cephalosporin antibiotics, and can be used for people allergic to penicillin.
twoIt has incompatibility with ampicillin, phenytoin sodium, barbital hydrochloride, aminophylline, calcium gluconate and magnesium sulfate. It has antagonistic effect with erythromycin and is not suitable for combination.
threePatients with liver and kidney function damage, and patients with gastrointestinal diseases such as ulcerative colitis, localized colitis, and antibiotic related colitis should use it with caution.
fourWhen using this product, attention should be paid to the possibility of pseudomembranous enteritis. If pseudomembranous enteritis occurs, water, electrolyte and protein should be supplemented first;Then take metronidazole orally, 250~500mg, three times a day. If it doesn't work, take vancomycin orally, 0.125~0.5g, four times a day.
Drugs for pregnant and lactating women
oneAt present, there is no detailed original research data, and no clear judgment can be made.Therefore, pregnant women should pay attention to the advantages and disadvantages of using this product.
twoIt has been reported that when taking 0.15g clindamycin orally and 0.6g clindamycin phosphate intravenously, the amount of the drug in the milk is 0.7-3.8mcg/ml. Because clindamycin may cause adverse reactions in newborns, lactating women must stop using this product.
Children's medication
1．This product contains benzyl alcohol, which is prohibited for intramuscular injection in children.
2．Not suitable for infants within one month.Children under 4 years old should use it with caution.When children (newborn to 16 years old) use this product, they should pay attention to the monitoring of liver and kidney functions.
Medication for the elderly
oneClindamycin pharmacokinetics research industry has proved that there is no significant difference in pharmacokinetics between young patients and elderly patients with normal liver and kidney functions after oral or intravenous administration of clindamycin.
twoClindamycin clinical studies have not yet included a sufficient number of patients aged 65 years and over, and it is difficult to determine whether the clinical response of elderly patients is significantly different from that of young patients.However, clinical experience suggests that antibiotic related colitis and diarrhea (caused by clostridium) are more common in the elderly (>60 years old) and more serious.Therefore, when elderly patients use this product, they should carefully observe or monitor the diarrhea of these patients.
Drug interaction
oneClindamycin has neuromuscular blocking effect, which may enhance the effect of other neuromuscular blockers.Therefore, patients who use these drugs should use clindamycin with caution.
twoIt has been proved that the antagonism between clindamycin and erythromycin, chloramphenicol has clinical significance, and the two drugs should not be used at the same time.
threeThis product has incompatibilities with neomycin, kanamycin, ampicillin, phenytoin sodium, barbital hydrochloride, aminophylline, calcium gluconate and magnesium sulfate.
fourThe combination of this product and opioid analgesics may aggravate the inhibition of respiratory center.
Overdose
oneSignificant lethality was found when the dosage of intravenous injection was 855mg/kg in mice and the dosage of oral or subcutaneous injection was about 2618mg/kg in rats. Seizures and depression were seen in mice.
twoBoth hemodialysis and peritoneal dialysis failed to effectively remove clindamycin from serum.
Pharmacology and toxicology
Pharmacological action: Clindamycin phosphate is a chemically synthesized clindamycin derivative, which has no antibacterial activity in vitro, and is quickly hydrolyzed into clindamycin after entering the body to exert antibacterial activity.
In vitro tests showed that clindamycin was active to the following microorganisms;Aerobic gram-positive cocci: Staphylococcus aureus and Staphylococcus epidermidis (both including penicillinase producing and non penicillinase producing strains), streptococci (except fecal enterococci), pneumococci.Anaerobic Gram negative bacilli: Bacteroides (including fragile Bacteroides and Bacteroides niger) and Fusobacterium.Anaerobic Gram positive non Bacillus: Propionibacterium, Eubacteria and Actinomyces.Anaerobic and microaerobic gram-positive bacilli: digestive coccus, microaerobic streptococcus and digestive streptococcus.
Toxicological study: genetic toxicity: the results of Ames Salmonella reverse mutation test and rat micronucleus test were negative.Reproductive toxicity: the dosage of this product given orally to rats is 0.3g/kg, which has no effect on the mating and fertility of animals.Clindamycin was administered orally to rats and mice at a dose of up to 0.6g/kg or subcutaneously at a dose of 0.25mg/kg, respectively, with no teratogenic effect.However, pregnant women have not been fully and strictly studied clinically, and animal reproductive research cannot fully predict human responses.Carcinogenicity: no long-term carcinogenic potential research has been conducted on animals[2]。
Pharmacokinetics
oneClindamycin phosphate is quickly hydrolyzed into clindamycin by alkaline phosphatase in the blood after entering the body.The pharmacokinetics of normal people showed that after a single intravenous drip of 0.6g clindamycin phosphate, the concentration of clindamycin in the blood reached the peak immediately, which was 11.09 ± 2.02mg/L, and the 8-hour blood concentration was 1.69 ± 0.35mg/L;After a single intramuscular injection of 0.6g, clindamycin in the blood reached the peak in 1~2 hours, with the concentration of 5.92 ± 1.45mg/L, and the blood drug concentration in 8 hours was 2.51 ± 0.91mg/L. The effective blood drug concentration can be maintained for more than 8 hours.Clindamycin phosphate is mainly metabolized in the liver and excreted through bile and feces after administration.0.6g intravenous drip and intramuscular injection every 6 hours, the concentration of bile can reach 48-55mg/L, part of which is excreted through urine, 0.6g intravenous drip, and the 8-hour excretion rate is 11.72 ± 1.33% and 10.51 ± 2.68% respectively.
twoAccording to Physicians´Desk Reference (Version 54) Introduction:
1) At the end of short-term intravenous drip, the serum activity of clindamycin reached the peak level.Clindamycin phosphate, which was biologically inactivated, disappeared rapidly from the serum with an average half-life of 6 minutes;However, the half-life of serum elimination of active clindamycin is 3 hours in adults and 2.5 hours in children.The active clindamycin reached the serum peak within 3 hours after intramuscular injection of clindamycin phosphate in adults, and within one hour in children.The serum drug concentration level curve can be obtained from the serum peak concentration values of intravenous drip or intramuscular injection. For the above elimination half-life, the serum drug concentration level is shown in Table 1.Table 1. After administration of clindamycin phosphate, the average peak concentration and valley concentration of active clindamycin in serum, dosage, peak concentration mcg/mL, valley concentration mcg/mL, healthy adult male (after balance) 0.6g, intravenous drip for half an hour, 10.92.00.6g once every 6 hours, intravenous drip for half an hour, 10.81.10.9g once every 8 hours, intravenous drip for half an hour,14.11.70.6g intramuscular injection once every 8 hours, and intravenous drip once every 12 hours for children (the first dose) * 9 5-7mg/kg for 1 hour.10 5-7mg/kg intramuscular injection 8 3-5 mg/kg intramuscular injection 4 * Data in this group are from infected patients under treatment.
2) Clindamycin is used once every 8~12 hours for most adults, once every 6~8 hours for children, or by continuous intravenous drip of clindamycin, the serum drug concentration can be maintained above the minimum inhibitory concentration in vitro tests.After three times of continuous use, the blood concentration can reach steady state.
3) The half-life of clindamycin clearance slightly increased in patients with significantly decreased liver and kidney functions.Hemodialysis and peritoneal dialysis have no effect on clearing clindamycin in serum.There is no need to change the dose for patients with mild to moderate renal disease.4) Even in patients with meningeal inflammation, clindamycin did not reach a significant level in cerebrospinal fluid.In elderly (61-79 years old) and young adult (18-39 years old) volunteers, after intravenous infusion of clindamycin phosphate, the pharmacokinetics study showed that age factors would not change the pharmacokinetics of clindamycin alone (clearance rate, elimination half-life, volume distribution and area under the blood concentration time curve).The elimination half-life of clindamycin hydrochloride was extended to about 4 hours (3.4-5.1 hours) in the elderly and 3.2 hours (2.1-4.2 hours) in the young after oral administration of clindamycin hydrochloride.However, there is no difference in the degree of absorption between ages, and no adjustment is needed for the dose of the elderly with normal liver and kidney functions.
Storage
Shading, sealed storage.
Adverse reaction report
Announce
edit
In the case report database of the National Adverse Drug Reaction Monitoring Center, the adverse reactions/events of clindamycin injection are relatively serious, mainly including systemic damage, respiratory system damage and urinary system damage, among which acute renal function damage and hematuria are relatively prominent
Clinical manifestations of a serious case
The manifestations of adverse reactions/events of each system are as follows: systemic damage is mainly manifested as anaphylactic shock, anaphylactoid reaction, high fever, chills, etc., of which anaphylactic shock accounts for 15% of severe cases;The main manifestations of respiratory system damage are laryngeal edema, dyspnea, etc;The main manifestations of urinary system damage were hematuria and acute renal function damage, accounting for 15.9% of severe cases;The main manifestations of skin and its accessories damage are rash, exfoliative dermatitis, etc;Other damages include convulsion, abnormal liver function, nausea, vomiting, syncope, leukopenia, hemolysis, abdominal pain, hypotension, anaphylactoid purpura, tinnitus, hearing loss, etc[2].
II. Acute renal function damage, hematuria
In the case reports of clindamycin injection, the problems of acute renal function damage and hematuria are relatively prominent. The specific analysis of database cases shows that there are differences in the number of reports of hematuria and renal function damage in clindamycin hydrochloride and clindamycin phosphate and their proportion in the total number of reports. In the serious case reports of clindamycin injection,344 cases clearly marked as clindamycin hydrochloride were reported, including 48 cases of acute renal impairment, 48 cases of hematuria, and 19 cases of acute renal impairment with hematuria;There were 339 cases clearly marked as clindamycin phosphate, 15 cases of acute renal impairment, 9 cases of hematuria, and 3 cases of acute renal impairment with hematuria
Unreasonable drug use in three serious cases
The analysis of serious adverse reaction/event reports of clindamycin injection in the national center database shows that the product has been used unreasonably in clinical practice, and some irrational drug use has been the main cause of serious adverse events. The main manifestations of irrational drug use are as follows:
1. Use beyond indications
The instruction manual of clindamycin injection clearly points out that it is applicable to infectious diseases caused by gram-positive bacteria and anaerobic bacteria, but there are over indications for the use of clindamycin injection due to virus infection in the database of the National Center
Typical case: patient, female, 34 years old, was given 250ml clindamycin phosphate and sodium chloride intravenously for oral herpes. When half of the infusion was given, the patient developed palpitations, chills, chills, blood pressure of 60/30mmHg, and was given dopamine and Alamin pressure boosting treatment
2. The dosage is too high and the usage is improper
The instruction manual of clindamycin injection clearly indicates that this product can be administered by intravenous drip or intramuscular injection. For adults, the dose is as follows: moderate infection: 0.6~1.2g/day, which can be divided into 2~4 doses;Serious infection: 1.2~2.4 g/day, which can be divided into 2~4 times of administration, or according to the doctor's advice. The database of the National Center shows that the use of overdose is serious, with 157 cases (15.0%) receiving only 1.2~6.0 g of single dose. At the same time, the number of times of administration is unreasonable, with 868 cases (83.7%) receiving once a day. The number of times of administration is unreasonably reduced and the dosage is increased,It is more likely to cause adverse reactions and cannot maintain effective blood concentration
Typical case: patient, female, 35 years old. Due to hysteromyoma with chronic cervicitis, abdominal hysterectomy was planned. Routine examination of urine before operation was normal, liver function was normal, and renal function was normal: creatinine 51.4umol/L, urea 3.98mmol/L. One day before operation, the patient was given 2.4 g of clindamycin hydrochloride for injection and intravenous drip once a day. The patient had decreased urine volume on the first day after operation. On the second day after operation,B-ultrasonic examination: echo changes in both renal parenchyma, bilateral ureters do not dilate;Renal function test: creatinine 363.1 μ mol/L
3. Children's medication problems
In the database of the National Center, there are 100 cases of children under the age of 14, accounting for 10.0% of serious cases, of which children under the age of 6 account for 59% of all children. Although the dosage per kilogram of weight of children is indicated in the "Usage and Dosage" section of the instruction manual, children still have the phenomenon of overdose in varying degrees
Typical case: a child, male, 2 years old, 8 months old, 15 kg. Because of tonsillitis, she was given cefminox (cefminox skin test was negative) 1.0 g plus 100 ml of normal saline intravenously. After two days of medication, she was given 0.4 g of clindamycin plus 100 ml of 5% glucose injection intravenously. After about one minute of medication, the child developed laryngeal edema, pale face, cyanosis of lips, nausea, vomiting,The whole body was wet and cold, and the drug was stopped immediately. After giving dexamethasone 5mg intravenously, adrenaline hydrochloride 0.25mg subcutaneously, and oxygen inhalation with mask, the vital signs of the child were basically stable[3].
IV. Relevant suggestions
1. It is recommended that clinicians should strictly grasp the indications when using clindamycin injection, and ask about the drug allergy history in detail before use, and those with allergic constitution should be cautious when using clindamycin injection;Use strictly according to the usage and dosage (including the number of times of administration and the route of administration) in the instructions. In addition to intravenous infusion, try to use oral or intramuscular injection;For intravenous administration, attention should be paid to avoid excessive dosage, too fast infusion speed, and too high concentration. The elderly, children, renal insufficiency and other high-risk groups should be used with caution or under strict supervision. Traditional Chinese medicine and nursing staff should carefully observe the symptoms and signs of patients during the use process. Once abnormalities are found, the drug should be stopped immediately, and a clear diagnosis should be made as soon as possible, and timely symptomatic treatment should be given
2. It is suggested that relevant manufacturers comprehensively analyze the causes of adverse reactions and study the mechanism leading to acute renal function damage and hematuria
3. It is suggested that drug manufacturers, distributors and medical institutions should strengthen education and publicity on the rational use of clindamycin injection in clinical practice, fully inform doctors and patients of the potential risks that may exist, and avoid the recurrence of such serious adverse reactions and drug-induced diseases[4]。
Impair renal function
Announce
edit
It was learned from the State Food and Drug Administration that it had issued a notice to revise the "adverse reactions" column of the instructions for clindamycin injection. The newly revised content said that the use of the product "may cause renal function damage and hematuria".In the revised content, gastrointestinal reactions, such as nausea, vomiting, abdominal pain, diarrhea, etc., are changed from "occasional" to "common". Severe cases include abdominal colic, abdominal tenderness, severe diarrhea, accompanied by fever, abnormal thirst and fatigue.New in the column of adverse reactions: adverse reactions of domestic clindamycin phosphate and clindamycin hydrochloride injection reported that the use of this product may cause renal function damage and hematuria, and adverse reactions of very few serious cases include dyspnea, anaphylactic shock, acute renal failure, anaphylactoid purpura, convulsions, and liver dysfunction[4], chest tightness, palpitations, chills, high fever, dizziness, hypotension, tinnitus, hearing loss, etc.
It is understood that clindamycin injection is suitable for infections of respiratory tract, joints and soft tissue, bone tissue, biliary tract, septicemia, endocarditis, etc. caused by gram-positive bacteria;It is also suitable for abdominal cavity and pelvic cavity infections caused by anaerobic bacteria, as well as anaerobic septicemia, etc[4]。
