clindamycin 300 MG in 2 ML Injection
WARNINGS
See WARNING box.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile .
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.
This product contains benzyl alcohol as a preservative.
Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants.
(See PRECAUTIONS − Pediatric Use ).
Usage in Meningitis: Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.
SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE.
OXYGEN AND INTRAVENOUS CORTICOSTEROIDS SHOULD ALSO BE ADMINISTERED AS INDICATED.
OVERDOSAGE
Significant mortality was observed in mice at an intravenous dose of 855 mg/kg and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg.
In the mice, convulsions and depression were observed.
Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
DESCRIPTION
Clindamycin Injection, USP, a water soluble ester of clindamycin and phosphoric acid, is a sterile solution for intramuscular or intravenous use.
May contain sodium hydroxide and/or hydrochloric acid for pH adjustment.
pH is 6.5 range 5.5 to 7.0.
Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7 (R)-hydroxyl group of the parent compound lincomycin.
The chemical name of clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans -4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo -α-D- galacto -octopyranoside 2-(dihydrogen phosphate).
The molecular formula is C 18 H 34 ClN 2 O 8 PS and the molecular weight is 504.97.
The structural formula is represented below: Each mL contains clindamycin phosphate equivalent to 150 mg clindamycin, 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as a preservative.
image of chemical structure
HOW SUPPLIED
Clindamycin Injection, USP (150 mg/mL) is supplied as follows: List No.
Volume Type Container Clindamycin base Total Content 54868-3695-0 2 mL Single-dose fliptop vial/ 25 vials per tray 300 mg Store at 20 to 25°C (68 to 77°F).
[See USP Controlled Room Temperature.] Do not refrigerate.
INDICATIONS AND USAGE
Clindamycin Injection, USP is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.
Clindamycin Injection, USP is also indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci.
Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate.
Because of the risk of antibiotic-associated pseudomembranous colitis, as described in the WARNING box, before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).
Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.
Indicated surgical procedures should be performed in conjunction with antibiotic therapy.
Clindamycin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, Streptococcus pneumoniae , other streptococci (except E.
faecalis ), and Staphylococcus aureus .
Skin and skin structure infections caused by Streptococcus pyogenes , Staphylococcus aureus , and anaerobes.
Gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes.
Intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms.
Septicemia caused by Staphylococcus aureus , streptococci (except Enterococcus faecalis ), and susceptible anaerobes.
Bone and joint infections including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin and other antibacterial drugs, clindamycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
BOXED WARNING
WARNING Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile .
Because clindamycin therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS AND USAGE section.
It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections.
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
DOSAGE AND ADMINISTRATION
If diarrhea occurs during therapy, this antibiotic should be discontinued.
(See WARNING box).
Adults: Parenteral (I.M.
or I.V.
Administration): Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis , Peptococcus species and Clostridium species other than Clostridium perfringens ): 600 to 1200 mg/day in 2, 3 or 4 equal doses.
More severe infections, particularly those due to proven or suspected Bacteroides fragilis , Peptococcus species, or Clostridium species other than Clostridium perfringens : 1200 to 2700 mg/day in 2, 3 or 4 equal doses.
For more serious infections, these doses may have to be increased.
In life-threatening situations due to either aerobes or anaerobes, these doses may be increased.
Doses of as much as 4800 mg daily have been given intravenously to adults.
See Dilution and Infusion Rates section below.
Single I.M.
injections of greater than 600 mg are not recommended.
Alternatively, 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 clindamycin levels Above 4 mcg/mL Above 5 mcg/mL Above 6 mcg/mL Rapid infusion rate 10 mg/min for 30 min 15 mg/min for 30 min 20 mg/min for 30 min Maintenance infusion rate 0.75 mg/min 1 mg/min 1.25 mg/min Neonates (less than 1 month): 15 to 20 mg/kg/day in three to four equal doses.
The lower dosage may be adequate for small prematures.
Pediatric patients (1 month of age to 16 years): Parenteral (I.M.
or I.V.) administration: 20 to 40 mg/kg/day in 3 or 4 equal doses.
The higher doses would be used for more severe infections.
As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m 2 /day for serious infections and 450 mg/m 2 /day for more severe infections.
Parenteral therapy may be changed to clindamycin palmitate hydrochloride for oral solution or clindamycin hydrochloride capsules when the condition warrants and at the discretion of the physician.
In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days.
Dilution and Infusion Rates: Clindamycin phosphate must be diluted prior to I.V.
administration.
The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL.
Infusion rates should not exceed 30 mg per minute.
The usual infusion dilutions and rates are as follows: Dose Diluent Time 300 mg 600 mg 900 mg 1200 mg 50 mL 50 mL 50-100 mL 100 mL 10 min 20 min 30 min 40 min Administration of more than 1200 mg in a single 1-hour infusion is not recommended.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Dilution and Compatibility: Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of clindamycin phosphate in I.V.
solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin B complex in concentrations usually used clinically.
No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin.
The following drugs are physically incompatible with clindamycin phosphate: ampicillin sodium, phenytoin sodium, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate.
The compatibility and duration of stability of drug admixtures will vary depending on concentration and other conditions.
Physico-Chemical Stability of Diluted Solutions of Clindamycin: Room temperature: 6, 9, and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 16 days at 25°C.
Also, 18 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, in minibags, demonstrated physical and chemical stability for at least 16 days at 25°C.
Refrigeration: 6, 9 and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 32 days at 4°C.
IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time.
Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.
Frozen: 6, 9 and 12 mg/mL (equivalent to clindamycin base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in minibags demonstrated physical and chemical stability for at least eight weeks at -10°C.
Frozen solutions should be thawed at room temperature and not refrozen.
Caution: Do not use plastic containers in series connections.
Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.