Clindamycin Injection - Product Information
|Manufacture:||Fresenius Kabi USA, LLC|
|Condition:||Bacteremia, Bacterial Infection, Bacterial Vaginitis, Pneumonia, Sinusitis, Skin or Soft Tissue Infection, Toxoplasmosis, Prophylaxis, Toxoplasmosis|
|Class:||Antibiotics/antineoplastics, Lincomycin derivatives|
|Form:||Liquid solution, Intravenous (IV)|
|Ingredients:||Clindamycin phosphate, edetate disodium, benzyl alcohol, sodium hydroxide, hydrochloric acid.|
Action and Clinical Pharmacology
Following parenteral administration, biologically inactive clindamycin phosphate is rapidly hydrolyzed in plasma to active clindamycin. Clindamycin exerts its antibacterial effect by binding to the 50 S ribosomal subunit of susceptible bacteria, causing a reduction in the rate of synthesis of nucleic acid, and cessation of protein synthesis.
Clindamycin is primarily bacteriostatic, but may be bactericidal at high concentrations. The mechanism of action of clindamycin in combination with primaquine on Pneumocystis jiroveci is not known.
Clindamycin is distributed into body fluids and tissues including bone, synovial fluid, bile and pleural fluid. Significant levels of clindamycin are not reached in cerebrospinal fluid even in the presence of inflamed meninges. Clindamycin readily crosses the placenta and is distributed into breast milk. The half-life of clindamycin phosphate is 3.5 to 4.5 hours. Approximately 10% of the microbiologically active form is excreted in the urine and about 4% in the feces. The remainder is excreted as biologically inactive metabolites.
|Clindamycin Phosphate Dosage
|Clindamycin mcg/mL||Clindamycin Phosphate
|Healthy Adult Male (Post Equilibrium)|
|300 mg i.v. in 10 min., q8h||7||15|
|600 mg i.v. in 20 min., q8h||10||23|
|900 mg i.v. in 30 min., q12h||11||29|
|1200 mg i.v. in 45 min., q12h||14||49|
|300 mg i.m. q8h||6||3|
|600 mg i.m. q12h*||9||3|
|Children (first dose)*|
|5 – 7 mg/kg i.v. in 1 hour||10|
|3 – 5 mg/kg i.m.||4|
|5 – 7 mg/kg i.m.||8|
*Data in this group from patients being treated for infection.
Indications and Clinical Use
Clindamycin Injection (clindamycin phosphate) is indicated for the treatment of serious infections due to susceptible anaerobic bacteria, such as Bacteroides species, Peptostreptococcus, anaerobic streptococci, Clostridium species and microaerophilic streptococci.
Clindamycin Injection is also indicated for the treatment of serious infections due to susceptible strains of gram-positive aerobic bacteria (staphylococci, including penicillinase-producing staphylococci, streptococci and pneumococci) as well as in the treatment of Chlamydia trachomatis, when the patient is intolerant of, or the organism is resistant to other appropriate antibiotics.
Because of the risk of Clostridium difficile-associated disease (CDAD) as described in the WARNINGS section, before selecting clindamycin the physician should consider the nature of the infection and the suitability of alternative therapy.
Clindamycin Injection is indicated for the treatment of the following serious infections when caused by susceptible strains of the designated organisms in the conditions listed below:
Lower respiratory infections including pneumonia, empyema, and lung abscess when caused by anaerobes, Streptococcus pneumoniae, other streptococci (except Enterococcus faecalis) and Staphylococcus aureus.
Skin and skin structure infections including cellulitis, abscesses, and wound infections when caused by Streptococcus pyogenes, Staphylococcus aureus and anaerobes.
Gynecological infections including endometritis, pelvic cellulitis, vaginal cuff infections, nongonococcal tubo-ovarian abscess, salpingitis, and pelvic inflammatory disease when caused by susceptible anaerobes or Chlamydia trachomatis. Clindamycin should be given in conjunction with an antibiotic of appropriate gram negative aerobic spectrum.
Intra-abdominal infections including peritonitis and abdominal abscess when caused by susceptible anaerobes. Clindamycin should be given in conjunction with an antibiotic of appropriate gram negative aerobic spectrum.
Septicemia caused by Staphylococcus aureus, streptococci (except Enterococcus faecalis) and susceptible anaerobes, where the bactericidal efficacy of clindamycin against the infecting organism has been determined in vitro at achievable serum levels.
Bone and joint infections including osteomyelitis and septic arthritis when caused by sensitive strains of Staphylococcus aureus and anaerobes.
Pneumocystis jiroveci pneumonia in patients with AIDS. Clindamycin in combination with primaquine may be used in patients who are intolerant to, or fail to respond to conventional therapy.
Note: Clindamycin Injection is not indicated in the treatment of meningitis since it penetrates poorly into cerebrospinal fluid, even in the presence of inflamed meninges.
Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.
Indicated surgical procedures and drainage should be performed in conjunction with antibiotic therapy.
Clindamycin Injection (clindamycin phosphate) is contraindicated in patients with a known hypersensitivity to preparations containing clindamycin or lincomycin or to any component of the formulation.
Clostridium difficile-associated disease (CDAD) has been reported with use of many antibacterial agents, including clindamycin phosphate. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of Clostridium difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy.
If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against Clostridium difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against Clostridium difficile. Surgical evaluation should be instituted as clinically indicated, as surgical intervention may be required in certain severe cases (see ADVERSE REACTIONS).
In patients with G-6-PD deficiency, the combination of clindamycin with primaquine may cause hemolytic reactions; reference should also be made to the primaquine product monograph for other possible risk groups for other hematologic reactions.
Clindamycin Injection contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.
Clindamycin Injection should be prescribed with caution in atopic individuals and individuals with a history of gastrointestinal disease, particularly colitis.
Clindamycin Injection does not diffuse adequately into cerebrospinal fluid and thus should not be used in the treatment of meningitis.
Clindamycin Injection must be diluted for intravenous administration. It should not be injected undiluted as an intravenous bolus (see DOSAGE AND ADMINISTRATION).
The use of antibiotics occasionally results in overgrowth of nonsusceptible organisms, particularly yeasts. Should superinfections occur, appropriate measures should be taken as dictated by the clinical situation.
Periodic liver and kidney functions tests and blood counts should be performed during prolonged therapy. Routine blood examinations should be done during therapy with primaquine to monitor potential hematologic toxicities.
Clindamycin Injection dose modification may not be necessary in patients with renal disease. The serum half-life of clindamycin is increased slightly in patients with markedly reduced renal function.
In patients with moderate to severe liver disease, prolongation of the half-life of clindamycin has been found. However, it was postulated from studies that when given every eight hours, accumulation of clindamycin should rarely occur. Therefore, dosage reduction in liver disease is not generally considered necessary. Periodic liver enzyme determinations should be made when treating patients with severe liver disease (see PHARMACOLOGY).
Use in the elderly
Experience has demonstrated that antibiotic-associated colitis may occur more frequently and with increased severity among elderly (> 60 years) and debilitated patients.
Use in pregnancy
Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin ranging from 20 to 600 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to clindamycin. In one mouse strain, cleft palates were observed in treated fetuses; this response was not produced in other mouse strains or in other species, and therefore may be a strain specific effect.
Safety for use in pregnancy has not been established.
Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations. Clindamycin was widely distributed in fetal tissues with the highest concentration found in liver. Clindamycin should not be used in pregnancy unless clearly needed.
Clindamycin has been reported to appear in human breast milk in the range of 0.7 to 3.8 mcg/mL at doses of 150 mg orally to 600 mg intravenously. Because of the potential for adverse reactions in neonates, a decision should be made whether to discontinue nursing or to not administer clindamycin after taking into account the importance of the drug to the mother.
Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of a possible clinical significance, the two drugs should not be administered concurrently.
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.
Gastrointestinal - Abdominal pain, nausea, vomiting, diarrhea, colitis. Clostridium difficile-associated disease (CDAD) has been observed and may manifest as a range of symptoms varying from watery diarrhea to fatal colitis, the onset of which may occur during or after antibacterial treatment (see WARNINGS).
Hypersensitivity Reactions - Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported reactions. A few cases of anaphylactoid reactions have been reported.
Liver - Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.
Skin and Mucous Membranes - Pruritus, vaginitis and rare instances of exfoliative and vesiculobullous dermatitis have been reported.
Hematopoietic - Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of these instances. However, in clindamycin/primaquine combination studies, serious hematologic toxicities (grade III, grade IV neutropenia or anemia, platelet counts < 50 x 109/L, or methemoglobin levels of 15% or greater) have been observed.
Cardiovascular - Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration (see DOSAGE AND ADMINISTRATION).
Renal - Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria and/or proteinuria has been observed in rare instances.
Musculoskeletal - Rare instances of polyarthritis have been reported.
Local Reactions - Local irritation, pain, abscess formation have been seen with i.m. injection. Thrombophlebitis has been reported with i.v. injection. These reactions can be minimized by deep i.m. injection and avoidance of indwelling intravenous catheters.
Post-marketing Adverse Drug Reactions:
Adverse events not listed above which have been reported in temporal association with clindamycin phosphate since market introduction include: cases of toxic epidermal necrolysis and Stevens-Johnson syndrome, cases of erythema multiforme (SJS) and/or anaphylactoid reactions, dysgeusia have been reported during post-marketing surveillance. Because they are reported voluntarily from a population of unknown size, estimates of frequency or causal relationship with clindamycin phosphate cannot be established.
Symptoms and Treatment of Overdosage
Reported cases of overdosage with clindamycin phosphate have occurred very infrequently. The majority of these reports have involved infants and young children ranging in age from one day to three years. In this age group, doses as high as 2.4 grams have been used intravenously in 36 hours without observation of adverse reactions. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. No specific antidote is known.
|For management of a suspected drug overdose, contact your regional Poison Control Centre.|
Dosage and Administration
NOTE: If diarrhea occurs during treatment, this antibiotic should be discontinued (see WARNINGS).
Dosage and route of administration should be determined by the severity of the infection, the condition of the patient and the susceptibility of the causative microorganisms.
In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days.
Adults (IM or IV Administration)
The usual daily adult dosage of Clindamycin Injection for infections of the intra-abdominal area, female pelvis, and other complicated or serious infections is 2400 - 2700 mg given in 2, 3 or 4 equal doses. Less complicated infections may respond to lower doses such as 1200 - 1800 mg/day administered in 3 or 4 equal doses.
Doses of up to 4800 mg daily have been used without adverse effects. Single intramuscular doses of greater than 600 mg are not recommended.
Pelvic Inflammatory Disease
Clindamycin Injection 900 mg (i.v.) every 8 hours plus an antibiotic with appropriate gram negative aerobic spectrum administered i.v. Treatment with intravenous drugs should continue for at least 48 hours after the patient demonstrates significant clinical improvement. Then continue with appropriate oral therapy to complete 10 - 14 days total therapy.
Pneumocystis Jiroveci Pneumonia in Patients With AIDS
Clindamycin Injection 600 - 900 mg (i.v.) every 6 hours or 900 mg (i.v.) every 8 hours in combination with oral daily dose of 15 - 30 mg of primaquine. Alternatively, clindamycin hydrochloride 300 - 450 mg may be given orally every 6 hours in combination with 15 - 30 mg of primaquine for 21 days. If patients should develop serious hematologic adverse effects, reducing the dosage regimen of primaquine and/or Clindamycin Injection should be considered.
Children Over One Month of Age (IM or IV Administration)
20 - 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections.
Neonates Under one Month of Age (IM or IV Administration)
10 - 20 mg/kg/day in 3 or 4 equal doses. The lower dosage may be adequate for small prematures.
|<2 kg||0 – 7 days||5 mg/kg q12h||i.v.|
|<2 kg||8 – 30 days||5 mg/kg q8h||i.v.|
|≥2 kg||0 – 7 days||5 mg/kg q8h||i.v.|
|≥2 kg||8 – 30 days||5 mg/kg q6h||i.v.|
NOTE: Clindamycin Injection should be administered with caution to newborn infants less than 30 days of age. This product contains benzyl alcohol which has been associated with a fatal gasping syndrome in infants.
Dilution and Infusion Rates
Clindamycin Injection must be diluted prior to intravenous administration (see Preparation for Intravenous Use for a listing of infusion solutions). The concentration in diluent for infusion should not exceed 18 mg/mL. Infusion rates should NOT EXCEED 30 MG PER MINUTE as indicated below:
|Dose (mg)||Diluent (mL)||Time (min.)|
Administration of more than 1200 mg in a single 1-hour infusion is not recommended.
Alternately, the drug may be administered in the form of a single rapid infusion of the first dose followed by continuous i.v. infusion as follows:
|To Maintain Serum
|Rapid Infusion Rate||Maintenance Infusion
|Above 4 μg/mL||10 mg/min. for 30 min.||0.75 mg/min.|
|Above 5 μg/mL||15 mg/min. for 30 min.||1.00 mg/min.|
|Above 6 μg/mL||20 mg/min. for 30 min.||1.25 mg/min.|
Use in the Elderly
Pharmacokinetic studies with clindamycin have shown no clinically important differences between young and elderly subjects with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration. Therefore, dosage adjustments are not necessary in the elderly with normal hepatic function and normal (age-adjusted) renal function.