What Are the Signs of a Clindamycin Allergy?

Clindamycin is a chemical with the appearance of white crystalline powder. Its chemical formula is C ₁₈ H ₃₃ ClN ₂ O ₅ S, its molecular weight is 424.98300, and its melting point is 141 ~ 143 ° C. Clindamycin is an antibiotic drug. It is mainly used for celiac and gynecological infections caused by anaerobic bacteria in clinic. It is the first choice for the treatment of staphylococcus osteomyelitis.

Chinese name: Clindamycin
Foreign name: clindamycin
CAS number: 18323-44-9

Molecular formula: C18H33ClN2O5S
Molecular weight: 424.98300
Melting point: 141-143

Introduction of clindamycin compounds

Clindamycin Basic Information

Chinese name: clindamycin

Chinese alias: clindamycin; clindamycin;

Chemical name: (2S-trans) -6- (1-methyl-4-propyl-2-pyrrolidinecarbonate) -1-thio-methyl-7-chloro-6,7,8- Trideoxy-L-threo--D-galactopyranoside-2-dihydrophosphate

English name: clindamycin English alias: clinimycin; Clindamycin; 7-cdl; sobelin; CLDM;

CAS number: 18323-44-9

Molecular formula: C ₁₈ H ₃₃ ClN ₂ O ₅ S

Molecular weight: 424.98300

Chemical structure:

Exact mass: 424.18000

PSA: 127.56000

LogP: 0.71830 ^[1]

Clindamycin physical and chemical properties

Appearance and properties: white crystalline powder

Density: 1.29 g / cm ³

Melting point: 141-143ºC

Boiling point: 628.11ºC at 760 mmHg

Vapor pressure: 2.07E-18mmHg at 25 ° C ^[1-2]

Clindamycin uses

Used as antibiotics ^[1] .

Clindamycin Drug Description

Clindamycin drug name

Chinese name: clindamycin

Alias: clindamycin phosphate; lindamycin phosphate; clindamycin; clindamycin, clindamycin

Foreign name: Clindamycin ^[2]

Clindamycin Ingredients

The main ingredient of this product is clindamycin phosphate ^[3] .

Clindamycin 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 mouth (about 90%), and eating has little effect on absorption ^[4] . The concentration of clindamycin in fetal blood is greater than that of lincomycin, and its concentration in milk can reach 3.8 g / ml. Pregnant women and nursing mothers should pay attention to its advantages and disadvantages when using this product. High protein binding rate (90%). Oral peak time is 0.75 to 1 hour, T1 / 2 is 2.4 to 3 hours, pediatrics are 2 to 2.5 hours, and renal function declines slightly, 3 to 5 hours; 10% is excreted by urine within 24 hours, 3.6 % Excreted with feces ^[4] .

Clindamycin indications

1. This product is suitable for the following various infectious diseases caused by Gram-positive bacteria:

(1) Tonsillitis, suppurative otitis media, sinusitis, etc.

(2) Acute bronchitis, acute exacerbation of chronic bronchitis, pneumonia, lung abscess, and bronchiectasis with infection ^[5] .

(3) Skin and soft tissue infections: pimple, palate, abscess, cellulitis, trauma, and post-operative infections.

(4) Urinary system infection: acute urethritis, acute pyelonephritis, prostatitis, etc.

(5) Others: osteomyelitis, sepsis, peritonitis, and oral infections.

2. This product is suitable for various infectious diseases caused by anaerobic bacteria:

(1) Lung infection caused by empyema, lung abscess, and anaerobic bacteria.

(2) Skin and soft tissue infections and sepsis.

(3) Intra-abdominal infection: peritonitis, intra-abdominal abscess.

(4) Pelvic and genital infections in women: endometritis, non-gonococcal fallopian tubes and ovarian abscesses, pelvic cellulitis, and infections after gynecological surgery. ^[3]

Clindamycin Usage and Dosage

Oral: Hydrochloride, severe infection in adults, 150 to 300 mg orally once, if necessary to 450 mg, once every 6 hours. Children with severe illness 8 to 16 mg / kg a day, to 20 mg / kg if necessary, 3 to 4 times Use. Palmitate hydrochloride, for children, 8 to 12 mg / kg a day for severe infections, which can be increased to 20 to 25 mg / kg a day for severe infections, and divided into 3 to 4 doses

Injection: Phosphate injection, intravenous or intramuscular injection, adult Gram-positive aerobic infection, 0.6 to 1.2g a day, anaerobic infection 1.2 to 2.7g a day, extremely severe infection can be used up to 4.8g a day, Use 2 to 4 times. Children over 1 month old, severe infection 15 to 25 mg / kg a day, 25-40 mg / kg for severe infections, 3 to 4 times. Intramuscular injection does not exceed 0.6g, more than This amount should be administered intravenously.

1. Adults, the dose is as follows: Moderate infection: 0.6 ~ 1.2g / day, divided into 2 times (1 time every 12 hours), 3 times (1 time every 8 hours) or 4 times (1 time every 6 hours). Severe infection: 1.2 ~ 2.4g / day, can be divided into 2 times (1 time every 12 hours), 3 times (1 time every 8 hours) or 4 times (1 time every 6 hours) or as prescribed by your doctor.

2. For children, the dose is as follows: Moderate infection: 15 ~ 25mg / kg / day, can be divided into 3 times (every 8 hours) or 4 times (every 6 hours); severe infection: 25 ~ 40mg / kg / day, can be divided into 3 times (once every 8 hours) or 4 times (once every 6 hours) or as prescribed by your doctor. Intravenous infusion requires diluting 0.6g of this product with 100 ~ 200ml physiological saline or 5% glucose solution to a concentration of 6mg / ml, and the infusion time per 100ml is not less than 30 minutes.

[ Preparation ] Clindamycin hydrochloride capsules: 75mg (active); 150mg (active) per capsule. Clindamycin phosphate injection: 150mg (2ml) each. Clindamycin phosphate injection: 2ml: 0.3g (calculated based on C ₁₈ H ₃₃ ClN ₂ O ₅ S) ^[3]

Clindamycin adverse reactions

Can cause gastrointestinal reactions ^[6] : nausea, vomiting, loss of appetite, bloating, diarrhea. Skin rash, leukopenia. Elevated transaminase. Can cause double infection, pseudomembranous colitis. May also have difficulty breathing, swelling of the lips Nasal swelling, tearing, and allergic reactions. It has been reported that the incidence of pseudomembranous enteritis caused by this product is the highest, which may exceed 2%. Rash occurs in about 10% of people treated with clindamycin, others such as exudative erythema polymorpha, reversible serum aspartate aminotransferase and elevated serum alanine aminotransferase, granulocytopenia, thrombocytopenia, and other allergies Reactions are occasionally visible ^[6] .

1. Local reaction: After intramuscular injection, pain, induration and sterile abscess may occasionally appear at the injection site. Long-term intravenous infusion should pay attention to the appearance of phlebitis.

2. Gastrointestinal reactions: occasional nausea, vomiting, abdominal pain and diarrhea. Pseudomembrane enteritis can occur in 1-2% of patients.

3. Allergic reactions: A small number of patients may develop drug-induced rashes and occasionally exfoliative dermatitis.

4. There is basically no toxic reaction to the hematopoietic system, which may cause neutropenia, eosinophilia, thrombocytopenia, etc. are generally transient.

5. Transient alkaline phosphatase, slight increase in serum aminotransferase, jaundice, and abnormal renal function can occur.

Clindamycin contraindications

Lincomycin and clindamycin have cross-resistance, and those with a history of allergies to clindamycin or lincomycin are contraindicated ^[3] .

Clindamycin precautions

1. No cross-allergic reaction with penicillin and cephalosporin antibiotics, can be used for those allergic to penicillin.

2. It is compatible with ampicillin, phenytoin sodium, barbiturate hydrochloride, aminophylline, calcium gluconate and magnesium sulfate, and it has an antagonistic effect with erythromycin, so it should not be combined.

3. Patients with impaired liver and kidney function, patients with gastrointestinal diseases such as ulcerative colitis, local enteritis, and antibiotic-related enteritis should be used with caution.

4. When using this product, it should be noted that pseudomembranous enteritis may occur. If pseudomembranous enteritis occurs, first supplement water, electrolytes, and protein; then give metronidazole orally, 250-500mg, 3 times a day, when it is ineffective Vancomycin was then taken orally 0.125 ~ 0.5g and treated 4 times a day.

Medication for pregnant and lactating women

1. There is no detailed original research data, and no clear judgment can be made yet. Therefore, pregnant women should pay attention to the pros and cons when using this product.

2. It has been reported that when 0.15 g of clindamycin is administered orally and 0.6 g of clindamycin phosphate is administered intravenously, the dose range in milk is 0.7-3.8 mcg / ml, because clindamycin may Cause adverse reactions in children, lactating women must stop using this product.

Medication for children

1. This product contains benzyl alcohol, which is prohibited for intramuscular injection in children.

2. Not suitable for infants within one month. Use with caution for children under 4 years of age. Children (newborn to 16 years old) should pay attention to liver and kidney function monitoring when using this product.

Geriatric medication

1. The pharmacokinetic study of clindamycin has proved that there is no significant difference in pharmacokinetics between young patients with normal liver and kidney function and elderly patients after oral or intravenous clindamycin.

2. The clinical study of clindamycin has not yet included a sufficient number of patients aged 65 and over, and it is currently difficult to determine whether the clinical response of the elderly is significantly different from that of young patients. However, clinical experience suggests that antibiotic-associated colitis and the diarrhea seen (caused by Clostridium spp.) Occur more frequently (> 60 years) in the elderly and are more severe. Therefore, when using this product in elderly patients, care should be taken to carefully observe or monitor the diarrhea in these patients ^[3] .

Clindamycin drug interactions

1. Clindamycin has a neuromuscular blockade and may increase the effects of other neuromuscular blockers. Therefore, clindamycin should be used with caution in patients using these drugs.

2. The antagonism between clindamycin and erythromycin and chloramphenicol has been clinically significant. The two drugs should not be used at the same time.

3. This product is compatible with neomycin, kanamycin, ampicillin, phenytoin, barbiturate hydrochloride, aminophylline, calcium gluconate and magnesium sulfate.

4. The combination of this product and opioid analgesics may exacerbate the central respiratory depression phenomenon ^[3] .

Clindamycin overdose

1. In mice, the intravenous dose was 855mg / kg and the oral or subcutaneous injection dose in rats was about 2618mg / kg. It was found to be significantly lethal, and convulsions and depression were seen in mice.

2. Both hemodialysis and peritoneal dialysis failed to effectively remove clindamycin from the serum ^[3] .

Clindamycin pharmacology and toxicology

Pharmacological action: Clindamycin phosphate is a chemically synthesized clindamycin derivative, which has no antibacterial activity in vitro. After entering the body, it is rapidly hydrolyzed to clindamycin to exert antibacterial activity ^[3] .

In vitro tests show that clindamycin is active against the following microorganisms; aerobic Gram-positive cocci: Staphylococcus aureus and Staphylococcus epidermidis (both include penicillinase-producing and non-penicillinase-producing strains), streptococci (feces Except enterococci), pneumococcus. Anaerobic Gram-negative genus: Bacteroides (including fragile Bacteroides and Bacteroides genus) and Fusobacterium. Anaerobic Gram-positive non-producing Bacillus: Propionibacterium, Eubacteria and Actinomycetes. Anaerobic and microaerobic Gram-positive bacteria: Peptococcus, Microaerobic Streptococcus, and Peptostreptococcus.

Toxicological studies: Genetic toxicity: Ames Salmonella reverse mutation test and rat micronucleus test results were negative. Reproductive toxicity: The dose of this product is 0.3g / kg given orally to rats. No effect on mating and fertility in animals has been seen. Rats and mice were orally given clindamycin at a dose of up to 0.6 g / kg or subcutaneously at a dose of 0.25 mg / kg, with no teratogenic effects. However, adequate and rigorous clinical studies have not been performed on pregnant women, and animal reproduction studies have not fully predicted human response. Carcinogenicity: Long-term carcinogenic potential has not been studied in animals ^[3] ^[5] ^[4] .

Clindamycin pharmacokinetics

1. Clindamycin phosphate is quickly hydrolyzed to clindamycin under the action of alkaline phosphatase in the blood after entering the body ^[3] . The pharmacokinetics of normal people showed that: a single intravenous infusion of 0.6 g of clindamycin phosphate, the peak of clindamycin in the blood immediately reached a concentration of 11.09 ± 2.02 mg / L, and the blood drug concentration for 8 hours was 1.69 ± 0.35mg / L; a single intramuscular injection of 0.6g, the clindamycin in the blood reached a peak in 1 to 2 hours, the concentration was 5.92 ± 1.45mg / L, the blood concentration in 8 hours was 2.51 ± 0.91mg / L, and the effective blood drug The concentration can be maintained for more than 8 hours. After administration of clindamycin phosphate, it is mainly metabolized in the liver and excreted through bile and feces. Intravenous infusion and intramuscular injection of 0.6g every 6 hours, the concentration in bile can reach 48-55mg / L, some are excreted through urine, intravenous infusion of 0.6g, and the 8-hour excretion rates are 11.72 ± 1.33% and 10.51 ± 2.68% ^{[ 3]} .

2. According to Physicians & acute; Desk Reference (54th Edition):

1) At the end of the short-term intravenous drip of this product, the clindamycin of serum activity reaches the peak level. The biologically inactivated clindamycin phosphate disappears rapidly from the serum with an average clearance half-life of 6 minutes; however, the active clindamycin has a serum-eliminated half-life of 3 hours in adults and 2.5 hours in pediatric patients. Adult clindamycin reaches a peak in serum within 3 hours after intramuscular injection of clindamycin phosphate in adults, and within one hour in pediatric patients. The serum drug concentration level curve can be obtained from the peak serum concentration value of intravenous drip or intramuscular injection. For the elimination half-life described above, the serum drug concentration level is shown in Table 1. Table 1. Serum average peak and trough concentration of active clindamycin after administration of clindamycin phosphate Peak concentration mcg / mL Valley concentration mcg / mL Healthy adult male (after equilibrium) 0.6 g intravenous drip, drip The injection time is half an hour, 10.92.00.6g intravenous drip every 6 hours, the drip time is half an hour, 10.81.10.9g intravenous drip every 8 hours, the drip time is half an hour, 14.11 every 8 hours. 70.6g intramuscularly, once every 12 hours for pediatric patients (first dose) * 9 5-7mg / kg intravenous infusion, the infusion time is 1 hour. 10 5-7 mg / kg intramuscular injection 8 3-5 mg / kg intramuscular injection 4 * This group of data comes from the infected patients being treated ^[3] .

2) For most adults, every 8 to 12 hours, and for pediatric patients to use clindamycin every 6 to 8 hours, or continuous intravenous drip of clindamycin, the serum drug concentration can be maintained at the lowest level in in vitro tests. Above the bacteriostatic concentration. Three times in a row, the blood concentration can reach steady state.

3) In patients with significantly reduced liver and kidney function, the clearance half-life of clindamycin is slightly increased. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from serum. There is no need to change the dose for patients with mild to moderate renal disease. 4) Even in patients with inflammation of the meninges, clindamycin did not reach significant levels in the cerebrospinal fluid. In elderly (61-79 years) and young adults (18-39 years) volunteers, after intravenous infusion of clindamycin phosphate, pharmacokinetic studies show that age factors do not change the pharmacokinetics of clindamycin alone Science (clearance rate, elimination half-life, volume distribution, and area under blood concentration time curve). After oral administration of clindamycin hydrochloride in the elderly, the elimination half-life was extended to about 4 hours (3.4 to 5.1 hours), while in the young, it was 3.2 hours (2.1 to 4.2 hours). However, there is no difference in the degree of absorption between ages, and no adjustment is necessary for elderly with normal liver and kidney function ^[3] .

Clindamycin storage

Shaded and sealed.

Clindamycin Adverse Reaction Report

In the case report database of the National Center for Adverse Drug Reaction Monitoring, the adverse reactions / events of clindamycin injection are more serious, mainly systemic damage, respiratory damage, and urinary system damage. Among them, acute renal damage, hematuria, etc. The problem is relatively prominent.

Clinical manifestations of a severe case

The adverse reactions / events of each system are as follows: systemic damage is mainly manifested by anaphylactic shock, allergic-like reactions, high fever, chills, etc., of which anaphylactic shock accounts for 15% of severe cases; respiratory damage is mainly manifested by laryngeal edema and dyspnea Etc .; urinary system damage mainly manifested as hematuria, acute renal damage, etc., accounting for 15.9% of severe cases; skin and its accessory damage mainly manifested as rash, exfoliative dermatitis, etc .; other damage included convulsions, abnormal liver function, nausea, vomiting , Syncope, leukopenia, hemolysis, abdominal pain, hypotension, allergic purpura, tinnitus, hearing loss, etc. ^[5] .

Two acute renal impairment, hematuria

In the case report of clindamycin injection, the problems of acute renal impairment and hematuria are relatively prominent. Specific analysis of database cases shows that the number and proportion of reports of hematuria and renal impairment in clindamycin hydrochloride and clindamycin phosphate There are differences in the proportion of the total number of reports. In the severe case report of clindamycin injection, 344 cases were clearly marked as clindamycin hydrochloride, including 48 cases of acute renal impairment, 48 cases of hematuria, and acute kidney function. There were 19 cases of damage accompanied by hematuria; 339 cases were clearly marked as clindamycin phosphate, 15 cases of acute renal impairment, 9 cases of hematuria, and 3 cases of acute renal impairment with hematuria.

Irrational medication in three severe cases

The analysis of severe adverse reactions / incidents of clindamycin injection in the national central database shows that the product has clinically unreasonable use, and some of the unreasonable medication problems have been the main causes of serious adverse events. The main manifestations of unreasonable medication are as follows :

1. Super indication use

The instructions for clindamycin injection clearly indicate that it is suitable for infectious diseases caused by gram-positive bacteria and anaerobic bacteria, but there are super indications in the national center database for the use of clindamycin injection due to viral infection.

Typical case: patient, female, 34 years old. Clindamycin phosphate sodium chloride 250ml was given intravenously for herpes labialis. Nearly half of the infusion, the patient developed palpitations, chills, chills, blood pressure 60 / 30mmHg, dopamine and Allah Ming boost therapy.

2. Overdose, improper usage

The instructions of clindamycin injection clearly indicate that this product can be administered intravenously or intramuscularly. For adults, the dosage is as follows: Moderate infection: 0.6 1.2g / day, which can be divided into 2 4 times. Dosage; severe infection: 1.2 2.4g / day, which can be divided into 2 4 doses, or as prescribed by the doctor. The National Center database shows that overdose use is severe, and only a single dose of 1.2 6.0g is 157 Cases, accounting for 15.0%. At the same time, the unreasonable frequency of administration is serious. 868 cases were administered once a day, accounting for 83.7%. Improperly reducing the number of administrations and increasing the dosage per use are more likely to cause adverse reactions. And can not maintain effective blood concentration.

Typical case: patient, female, 35 years old. Factor uterine fibroids with chronic cervicitis, planned abdominal hysterectomy, routine urine examination before surgery, normal liver function, renal function examination: creatinine 51.4umol / L, urea 3.98mmol / L. One day before the operation, the patient was given 2.4 g of clindamycin hydrochloride for injection, once a day at a static point. The patient's urine output decreased on the first postoperative day. On the second postoperative day, B-ultrasound examination: double Renal parenchymal echo changes, bilateral ureters do not dilate; renal function tests: creatinine 363.1 mol / L.

3. Child medication problems

In the National Center database, there were 100 children under 14 years old, accounting for 10.0% of severe cases, of which children under 6 years old accounted for 59% of all children. Although the instructions in the "Usage and Dosage" section indicate the amount of children per kilogram body weight However, there are still varying degrees of overdose in children.

Typical case: Child, male, 2 years and 8 months, 15 kg. Cefminox (negative cefminox skin test) 1.0g was given intravenously as a result of tonsillitis. Intravenous infusion of 100ml of normal saline was added. Two days later, g Linomycin 0.4g was added to 100ml of 5% glucose injection intravenously. After about 1 minute of administration, the patient developed edema of the throat, pale face, lip cyanosis, nausea, vomiting, cold and cold throughout the body, and the drug was stopped immediately. Dexamethasone 5mg intravenously After injection, subcutaneous injection of epinephrine hydrochloride 0.25mg, oxygen inhalation with mask, etc., the vital signs of the children were basically stable ^[4] ^[6] .

Four related suggestions

1. Clinicians are advised to strictly grasp the indications when using clindamycin injections, and to inquire about the history of drug allergies before use, and those with allergies should be used with caution; strictly follow the usage and dosage (including the number of medications and the route of administration) in the instructions. In addition to the need for intravenous infusion, try to choose oral or intramuscular injection; try to avoid excessive doses, too fast infusion rate, too high concentration. The elderly, children, renal dysfunction and other high risk, special populations should Use with caution or under strict supervision. During use, medical staff should carefully observe the patient's symptoms and signs. Once abnormalities are found, the drug should be discontinued immediately, and the diagnosis should be confirmed as soon as possible and symptomatic treatment should be given in time.

2. It is recommended that relevant manufacturers comprehensively analyze the causes of adverse reactions and study the mechanisms leading to acute renal impairment and hematuria.

3. It is recommended that all parties in pharmaceutical production, business enterprises and medical institutions strengthen education and publicity on the rational use of clindamycin injections, fully inform doctors and patients of potential risks, and avoid such serious adverse reactions and drug-borne diseases. Repeatedly ^[7] .

Clindamycin damages kidney function

It is learned from the State Food and Drug Administration that the bureau has issued a notice to amend the "adverse reaction" column in the instructions for clindamycin injections. The newly revised content states that the use of this product "may cause kidney damage and hematuria. In the revised content, gastrointestinal reactions such as nausea, vomiting, abdominal pain, and diarrhea were changed from "infrequent" to "common". In severe cases, abdominal cramps, abdominal tenderness, severe diarrhea, fever, and abnormal thirst And tired. New column for adverse reactions: adverse reactions of domestic clindamycin phosphate and clindamycin hydrochloride injections have been reported. The use of this product may cause renal damage and hematuria. In addition, adverse reactions in very few serious cases include breathing. Difficulty, anaphylactic shock, acute renal failure, allergic purpura, convulsions, abnormal liver function ^[7] , chest tightness, palpitations, chills, high fever, dizziness, hypotension, tinnitus, hearing loss, etc.

It is understood that clindamycin injection is suitable for infection of respiratory tract, joints and soft tissues, bone tissue, biliary tract, etc., as well as sepsis and endocarditis caused by gram-positive bacteria; it is also suitable for abdominal and pelvic infections caused by anaerobic bacteria , And anaerobic septicemia ^[7] .