CLINDO (Amp)

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CLINDO (Amp)

Chemical Name:

Clindamycin (Phosphate)
Therapeutic Category:

Antimicrobial
Pharmacologic Category:

Antibiotic, Lincosamide
Pharmaceutical Form:

Ampoule
Composition:

Clindamycin (Phosphate) 300mg/2ml

CLINDO-PLUS Ampoule

Clindamycin

1- PROPERTIES:

The active ingredient of the product is the semi-synthetic antibiotic clindamycin. Depending on the sensitivity of the micro-organism and the concentration of clindamycin, clindamycin may be either bactericidal or bacteriostatic.

Clindamycin has been shown to have in vitro activity against the following organisms:

1.Aerobic grampositive cocci, including:

Staphylococcus aureus

Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains). When tested in vitro, some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin.

Streptococci (except S. faecalis)

Pneumococci

2.Anaerobic gramnegative bacilli, including:

Bacteroides species (including B. fragilis group and B.melaninogenicus group).

Fusobacterium species

3.Anaerobic grampositive, nonsporeforming bacilli, including:

Propionibacterium

Eubacterium

Actinomyces species

4.Anaerobic and micro-aerophilic grampositive cocci, including:

Peptococcus species

Peptostreptococcus species

Microaerophilic streptococci

Clostridia: Clostridia are more resistant than most anaerobes to clindamycin but Clostridium perfringens are susceptible.

5.Miscellaneous organisms including Chlamydia trachomatis, Toxoplasma gondii, Plasmodium falciparum, and Pneumocystis carinii (in combination with primaquine), Gardnerella vaginalis, Mobiluncus mulieris, Mobiluncus curtisii and Mycoplasma hominis.

The following organisms are generally resistant to clindamycin:

-Aerobic gramnegative bacilli

-Streptococcus faecalis

-Nocardia species

-Neisseria meningitidis

-Strains of methicillin-resistant Staphylococcus aureus and strains of Haemophilus lnfluenzae.

Cross resistance has been demonstrated between lincomycin and clindamycin.

Antagonism has been demonstrated between clindamycin and erythromycin.

2-PHARMACOKINETICS

-Absorption

After intravenous infusion of 300 mg in 10 min., resp. 600 mg in 20 min. peak serum levels of 7 µg/ml and 10 µg/ml respectively are reached at the end of the infusion.

-Distribution

Protein binding is between 40 and 90% of the administered dose. Clindamycin easily penetrates in most body fluids and tissues. However clindamycin dose not penetrate in the liquor cerebrospinalis, even not in case of meningitis.

-Biotransformation

Half-life of clindamycin is somewhat increased in patients with markedly reduced renal or hepatic function. Dosage schedule need not to be modified in the presence of mild or moderate renal or hepatic disease. Clindamycin is relatively strong metabolized.

-Excretion

Excretion in active form in the urine varies from 10-20%, and is about 4% in the feces. The remainder is being excreted as biological non-active metabolites. The excretion takes place mainly through the bile and the feces.

3- INDICATIONS:

CLINDO-PLUS is indicated in the treatment of the following infections

1.Upper respiratory infections including tonsillitis, pharyngitis, sinusitis, otitis media and scarlet fever.

2.Lower respiratory infections including bronchitis, pneumonia, empyema and lung abscess.

3.Skin and soft tissue infections including acne, furuncles, cellulitis, impetigo, abscesses and wound infections, specific skin and soft tissue infections caused by susceptible organisms like erysipelas and paranychia.

4.Bone and joint infections including osteomyelitis and septic arthritis.

5.Gynecological infections including endometritis, cellulitis, vaginal cuff infection, tubo-ovarian abscess, salpingitis, and pelvic inflammatory disease when given in conjunction with an antibiotic of appropriate gramnegative spectrum. In cases of cervicitis due to Chlamydia trachomatis, single drug therapy with clindamycin has been shown to be effective in eradicating the organism.

6.Intra-abdominal infections including peritonitis and abdominal abscess when given in conjunction with an antibiotic of appropriate gramnegative aerobic spectrum.

7.Septicemia and endocarditis. The effectiveness of clindamycin in the treatment of selected cases of endocarditis has been documented when clindamycin is determined to be bactericidal to the infecting organism by in vitro testing

8.Dental infections such as periodontal abscess and periodontitis.

9.Toxoplasmic encephalitis in patients with AIDS. In patients who are intolerant to conventional treatment, clindamycin in combination with pyrimethamine has been shown to be efficacious.

10.Pneumocystis carinii pneumonia in patients with AIDS. In patients who are intolerant to, or do not respond adequately to conventional treatment, clindamycin may be used in combination with primaquine.

Clindamycin phosphate, when used concurrently with an aminoglycoside antibiotic such as gentamicin or tobramycin, has been shown to be effective in preventing peritonitis or intra-abdominal abscess after bowel perforation and bacterial contamination secondary to trauma.

Limited data from uncontrolled studies using a variety of doses suggest that clindamycin, either orally or parenterally at a dose of 20 mg/kg/day for a minimum of 5 days, is useful alternative therapy when used alone or in combination with quinine or amodiaquine, for the treatment of multi-drug resistant Plasmodium falciparum infection.

4- CONTRA-INDICATIONS:

Clindamycin is contra-indicated in patients previously found to be sensitive to clindamycin or lincomycin.

- PRECAUTIONS:

The injectable dosage form of this product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "gasping syndrome" in premature infants. As is the case for almost all antibiotic therapy the clindamycin therapy has been associated with severe colitis, which may end fatally.

The clinical spectrum varies from mild, watery diarrhea to severe, persistent diarrhea, leukocytosis, fever, severe abdominal cramps which may be associated with the passage of blood and mucus which, if allowed to progress, may produce peritonitis, shock and toxic megacolon.

The diagnosis of antibiotic-associated colitis is usually made by the recognition of the clinical symptoms. It can be substantiated by endoscopic demonstration of pseudomembranous colitis and may be further confirmed by culture of the stool for Clostridium difficile on selective media and assay of the stool specimen for the toxin(s) of the C.difficile.

Onset of antibiotic-associated colitis has occurred during the administration or even two or three weeks following administration of the antibiotic. The disease is likely to take a more severe course in older patients or in patients who are debilitated. In case of occurrence of mild antibiotic-associated colitis, discontinuance of clindamycin is recommended. Treatment with cholestyramine and colestipol resins is recommended as these products have been shown to bind the toxin in vitro. The suggested dose of colestipol is 5 g three times daily, and the suggested dose of cholestyramine is 4 g three times daily. When severe antibiotic-associated colitis occurs, this has to be treated with appropriate fluid, electrolyte and protein supplementation. Studies have also indicated that a toxin(s) produced by Clostridia (especially C. difficile) is (are) the principal direct cause of antibiotic-associated colitis. These studies also indicate that this toxigenic Clostridium is usually sensitive in vitro to vancomycin. When 125 to 500 mg vancomycin 4 times daily is administered, there is a rapid observed disappearance of the toxin from faecal samples and a coincident clinical recovery from the diarrhea.

In rare cases colitis may reoccur after cessation of vancomycin treatment. Cholestyramine- or colestipol resins bind vancomycin in vitro. If both a resin and vancomycin are to be administered concurrently, it may be advisable to separate the time of administration of each drug.

As an alternative therapy oral bacitracin 25,000 units q.i.d. for 7-10 days could be considered.

Drugs which cause bowel stasis should be avoided.

Caution should be exercised in prescribing clindamycin doses in patients with a history of GI disease, particularly colitis. Since clindamycin does not diffuse adequately into cerebrospinal fluid, the drug should not be used in the treatment of meningitis. Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently. If therapy is prolonged, liver and kidney function tests should be performed.

The use of clindamycin phosphate may result in overgrowth of organisms, particularly yeasts.

Clindamycin phosphate should not be injected intravenously undiluted as a bolus, but should be infused over at least 10-60 minutes as directed in the DOSAGE AND ADMINISTRATION section.

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.

Clindamycin phosphate should be administered with caution in atopic individuals.

Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, .pro of the half-life of clindamycin has been found, but a pharmacokinetic study has shown that, when given every eight hours, accumulation of clindamycin should rarely occur. Therefore, dosage reduction in liver disease is not considered necessary.

5- ADVERSE REACTIONS:

1.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. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported.

2.Liver

Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.

3.Skin and mucous membranes

Pruritus, vaginitis and rare instances of exfoliative and vesiculobullous dermatitis have been reported.

4.Hematopoietic

Rare neutropenia eosinophilia agranulocytosis and thrombocytopenia have been reported.

5.Cardiovascular

Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration

6.Local reactions

Local irritation, pain, abscess formation have been seen with IM injection. Thrombophlebitis has been reported with IV injection. These reactions can be minimized by deep IM Injection and avoidance of indwelling catheters.

6- PREGNANCY AND LACTATION:

Safety for use in pregnancy has not been established.

Clindamycin has been reported to appear in breast milk in ranges from 0.7 to 3.8 µg/ml.

7- INTERACTIONS:

The following drugs are physically incompatible with clindamycin phosphate: ampicillin, phenytoin, barbiturates, aminophylline, calcium gluconate and magnesium sulphate.

Clindamycin phosphate is physically and chemically compatible for 24 hours with solutions containing dextrose 5% water and sodium chloride, and antibiotics: amikacin sulfate, aztreonam, cefamandole nafate, cefazolin sodium, cefotaxime sodium, cefoxitin sodium, ceftazidime sodium, ceftizoxime sodium, netilmicin sulfate, gentamicin sulfate piperacillin and tobramycin.

8- DOSAGE AND ADMINISTRATION:

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 micro-organisms.

CLINDO-PLUS Ampoule

Adults (IM or IV administration)

The usual daily adult dosage of clindamycin phosphate 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 due to more susceptible micro-organisms 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 successfully. Single IM doses of greater than 600 mg are not recommended.

Children over one month of age (IM or IV administration)

20-40 mg/kg/day in 3 or 4 equal doses.

Neonates (Under 1 month of age) (IM or IV administration)

15-20 mg/kg/day in 3 or 4 equal doses. The lower dosage may be adequate for small prematures.

For treatment of pelvic inflammatory disease and chlamydia trachomatis infection of the cervix

1.Pelvic inflammatory disease - Inpatient treatment

Clindamycin phosphate 900 mg (IV) q8h daily plus an antibiotic with an appropriate gramnegative aerobic spectrum administered IV; e.g. gentamicin 2.0 mg/kg followed by 1.5 mg/kg q8h daily in patients with normal renal function. Continue (IV) drugs for at least 4 days and at least 48 hours after the patient improves. Then continue oral clindamycin hydrochloride 450 mg q6h daily to complete 10-14 days total therapy.

2.For cervicitis due to Chlamydia trachomatis

Clindamycin hydrochloride by mouth 450 mg 4 times daily for 10-14 days.

Toxoplasmic encephalitis in patients with AIDS

Clindamycin phosphate IV or clindamycin hydrochloride by mouth 600-1200 mg every 6 hours for two weeks followed by 300-600 mg by mouth every 6 hours. The usual total duration of therapy is 8 to 10 weeks. The dose of pyrimethamine is 25 to 75 mg by mouth daily for 8 to 10 weeks. Folinic acid 10 to 20 mg/day should be given with higher doses of pyrimethamine.

Pneumocystis carinii pneumonia in patients with AIDS

Clindamycin phosphate IV 600 to 900 mg every 6 hours or 900 mg IV every 8 hours or clindamycin hydrochloride 300 to 450 mg by mouth every 6 hours for 21 days and primaquine 15 to 30 mg dose by mouth once daily for 21 days.

Treatment of acute streptococcal tonsillitis/pharyngitis

Dosage of oral clindamycin hydrochloride capsules 300 mg twice daily for 10 days.

Dilution and infusion rates

The concentration of clindamycin in diluent for infusion should not exceed 18 mg per ml and INFUSION RATES SHOULD NOT EXCEED 30 mg PER MINUTE. The usual infusion rates are as follows: