Peldacyn

Peldacyn

clindamycin

Manufacturer:

Natrapharm

Distributor:

Natrapharm
Full Prescribing Info
Contents
Clindamycin (cap: hydochloride; soln for inj: phosphate).
Description
Capsule: Each capsule contains approximately 338.47 mg of Clindamycin Hydrochloride. 1 H2O equivalent to 300 mg clindamycin.
Solution for Injection: Each 2 mL and 4 mL ampoule contains: Clindamycin (as phosphate) 300 mg and 600 mg, respectively.
Action
Capsule: Pharmacotherapeutic group: Antibacterials for systemic use; macrolides, lincosamides and streptogramins, lincosamides. ATC code: J01FF01.
Pharmacology: Pharmacodynamics: Clindamycin is a semi-synthetic pyranoside. Pyranosides do not show a relationship with other known antibiotics.
Mechanism of action: The mechanism of action of clindamycin is based on the inhibition of protein biosynthesis due to binding to the 50s subunit of bacterial ribosome, resulting in a bacteriostatic effect for the most part.
Relationship between pharmacokinetics and pharmacodynamics: The efficacy mainly depends on the duration of time during which agent level is above the minimum inhibitory concentration (MIC) of the pathogen.
Mechanism of resistance: A resistance to clindamycin may be based on the following mechanisms: The resistance in staphylococci and streptococci is mostly based on an increased corporation of methyl groups into 23S rRNA (so-called constitutive MLSB resistance) with the binding affinity of clindamycin to the ribosome considerably reduced thereby.
The majority of methicillin-resistant S. aureus (MRSA) shows the constitutive MLSB phenotype and is therefore clindamycin resistant. Infections due to macrolide-resistant staphylococci should not be treated with clindamycin even in case of proven in vitro sensitivity, as there is the risk that mutants with constitutive MLSB resistance are selected during therapy.
In strains with constitutive MLSB resistance, there is complete cross resistance of clindamycin with lincomycin, macrolides (e.g. azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin) as well as streptogramin B.
Breakpoints: Clindamycin was tested while using the usual dilution series. The following minimal inhibitory concentrations were determined for susceptible and resistant germs: See Table 1.

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The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary; expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Particularly in severe infections or if therapy has failed, microbiology diagnosis is to be attempted with the proof of the pathogen and its sensitivity to clindamycin. (See Table 2.)

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Pharmacokinetics: Absorption: Clindamycin hydrochloride is absorbed quickly when administered orally.
The peak concentration in serum is achieved in. 45 to 60 minutes if taken on empty stomach and after two hours if taken at mealtimes, because absorption is delayed slightly by simultaneous intake of food.
The concentration remains above minimum inhibiting concentration (MIC) for most gram-positive organism for at least six hours when normal recommended doses are used.
The biological half-life of the produce is 2.4 hours.
The serum half-life is extended in patients with impaired renal function and moderate to severe hepatic insufficiency.
Distribution: After absorption clindamycin is distributed quickly in body fluids, tissues including bone, but it does not reach the CSF in significant concentrations, even if the meninges are inflamed. It diffuses across the placenta into the foetal circulation and has been reported to appear in breast milk. High concentrations occur in bile. It accumulates in leucocytes and macrophages.
The binding of clindamycin to plasma proteins is concentration-dependent and lies in the therapeutic range between 60% and 94%.
The average volume of distribution is 1.1 L/kg.
Biotransformation: Most of a clindamycin dose undergoes metabolism, and less than 10% of the dose is excreted unchanged in the urine. The known metabolites of clindamycin are N-demethyl clindamycin, clindamycin sulphoxide and N-demethyl clindamycin sulphoxide, which are excreted mainly in the faeces. Some metabolites have an anti-microbial activity. Agents which act as enzyme inducers in the liver reduce the mean dwell time of clindamycin in the body.
Elimination: Clindamycin is eliminated for 2/3 in the faeces and 1/3 in the urine.
Toxicology: Preclinical safety data: Symptoms of intoxication are decreased activity of the animals and convulsions.
After repeated doses (i.m.) of clindamycin to dogs an increase of the SGOT and SGPT was reported. And also a slight increase of the liver-weight without morphologic changes was documented. Long term administration of clindamycin to dogs induced damages to gastric mucosa and to the gallbladder.
Mutagenecity and cancerogenecity: In vitro and in vivo studies did not reveal and mutagenic potential of clindamycin. Long-term studies in animals with regard to tumorigenic potential of clindamycin have not been carried out.
Reproduction toxicity: Studies with clindamycin in rats and mice did neither give a hint on fertility disorders nor embryofoetotoxic properties.
Solution for Injection: Clindamycin is active against most gram-positive and gram-negative bacteria eg, Bacteroides, Fusobacterium spp. Especially, it is highly active against Staphylococcus aureus.
Clindamycin is better absorbed into gastrointestinal tract and has stronger antibacterial action. It has less side effect than lincomycin and shows better therapeutical profile.
Clindamycin injection is active against penicillin-resistant microorganism, hence it has been effectively used as replacement of penicillin preparations if applicable.
Indications/Uses
Capsule: Clindamycin is indicated in infections caused by bacteria susceptible to clindamycin (see Pharmacology: Pharmacodynamics under Actions), such as: Infections of upper respiratory tract, such as chronic or recurrent tonsillitis, pharyngitis, sinusitis, otitis media, and scarlet fever, if there is no response to primary antibiotics or if they cannot be used.
Infections of lower respiratory tract, such as bacterial bronchitis, pneumonia, empyema, lung abscess.
Difficult to treat skin and soft tissue infections, such as acne, furunculosis, cellulitis, impetigo, abscesses, wound infections, erysipelas, nail wall infections.
Bone and joint infections such as osteomyelitis and septic arthritis.
Gynaecological infections, such as endometritis, tubo-ovarian abscess, salpingitis, infections of the cervical area and inflammatory diseases of the pelvic area in combination with an antibiotic which is effective against gram-negative aerobic bacteria. In case of cervicitis caused by Chlamydia trachomatis clindamycin treatment can be given in monotherapy.
Intra-abdominal infections, such as peritonitis and abodominal abscess in combination with an antibiotic which is effective against gram-negative aerobic bacteria.
Dental infections, such as periodontal abscess and periodontitis.
In case of severe clinical status intravenous therapy is preferred to oral therapy .
Clindamycin is effective in many anaerobic infections (see Pharmacology: Pharmacodynamics under Actions). In aerobic infections, clindamycin is an alternative when other antimicrobial agents are not active or are contraindicated.
Consideration should be given to official/local guidance with regard to resistance to antibiotics and to the appropriate use of antibacterial agents.
Solution for Injection: Pneumonia, lung abscess, otitis media, pharyngitis, tonsillitis, bronchitis, sinusitis, scarlet fever, cellulites, peritonitis, intra-abdominal abscess, endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulites, postsurgical vaginal cuff infection, septicemia, furuncle, skin abscess, impetigo, acne pustule, cellulitis, wound infection.
Susceptible Strains: Bacteroides spp, Fusobacterium spp, Propionibacterium, Eubacterium actinomyces spp, Peptococcus spp, Peptostreptococci spp, Staphylococci, Streptococci (except Streptococcus faecalis), Pneumococci.
Dosage/Direction for Use
Capsule: Adults, adolescents over 14 years of age and older: 600-1800 mg/day divided into 3-4 equal doses.
For doses that cannot be reached by clindamycin, 450 mg or clindamycin 600 mg tablets other pharmaceutical forms with lower doses are available.
Children and adolescents: Depending on location and severity of infection children and adolescents (4 weeks to 14 years) take 8 to 25 mg clindamycin/kg bodyweight/day.
For this age group other pharmaceutical forms with lower doses are available.
Patients with hepatic impairment: Prolongation of clindamycin half-life has been observed in patients with mild to moderate hepatic impairment. However, pharmacokinetic studies have shown that accumulation occurs only rarely when clindamycin is administered every 8 hours.
In patients with severe liver insufficiency the blood level of clindamycin should be monitored carefully. Accordingly, dose reduction or prolongation of the dose interval can be necessary.
Patients with renal impairment: Prolongation of clindamycin half-life has been observed in patients with renal impairment. However, in patients with mild to moderate renal impairment dose reduction is not necessary.
In patients with severe renal insufficiency or anuria, the blood level of clindamycin should be monitored carefully. Accordingly, dose reduction or prolongation of the dosage interval to 8 or even 12 hours can be necessary.
Dosage in haemodialysis patients: Clindamycin cannot be removed by haemodialysis. No increase in dose is therefore required before or after dialysis.
Method and duration of treatment: To avoid oesophageal irritation the tablets should always be taken with full glass of water.
Treatment should last for at least 10 days in infections due to β-haemolytic streptococci.
Solution for Injection: Adult: Serious Infection: 600-1200 mg/day divided in 2-4 equal doses.
More Severe Infection: 1200-2700 mg/day divided in 2-4 equal doses.
Children (≥1 month): Serious Infection: 15-25 mg/kg/day in 3-4 equal doses.
More Severe Infection: 25-40 mg/kg/day in 3-4 equal doses.
Neonates (<1 month): 15-20 mg/kg/day in 3-4 equal doses. Lower dosage may be adequate for small premature infants. If it improves the condition as IV administration, it may be changed to oral dosing (capsule, syrup) by physician's opinion. In cases of β-hemolytic Streptococcal infections, treatment should continue for at least 10 days.
Administration: Clindamycin should not be injected intravenously undiluted as a bolus and should not be infused over at least 10-60 min as indicated as follows. Drug may be administered in the form of a single rapid infusion of the 1st dose followed by continuous IV infusion as follows, for maintaining serum clindamycin level. (See Table 3.)

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Overdosage
Capsule: Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
Contraindications
Capsule: Hypersensitivity to the active substance clindamycin, to lincomycin or to any of the excipients.
Solution for Injection: Hypersensitivity to clindamycin or lincomycin.
Warnings
Solution for Injection: Clindamycin may be associated with severe colitis which may end fatally. Therefore, it should be reserved for serious infections where other antimicrobial agents are inappropriate.
It should not be used in patients with nonbacterial upper respiratory or mild bacterial infections. The colitis is usually characterized by severe, persistent diarrhea and severe abdominal pain and may be associated with the passage of blood and mucus. Endoscopic examination may reveal pseudomembranous colitis. When significant diarrhea occurs, the drug should be discontinued or, if necessary, continued only with close observation of the patient. Large bowel endoscopy has been recommended. Diarrhea, colitis and pseudomembranous colitis has been observed after several weeks following cessation of therapy with clindamycin.
Peldacyn should not be used in the treatment of meningitis, since it does not penetrate into the cerebrospinal fluid.
Clindamycin should not be used in the treatment of nonbacterial upper respiratory tract infection or patients with mild bacterial infections.
Special Precautions
Capsule: Severe hypersensitivity reactions, including severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrom (SJS), toxic epidermal necrolysis (TEN), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients received clindamycin therapy. If a hypersensitivity or severe skin reaction occurs, clindamycin should be discontinued and appropriate therapy should be initiated (see Contraindications and Adverse Reactions).
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile. This has been reported with the use of nearly all antibacterial agents, including clindamycin. Clostridium difficile produced toxins A and B which contribute to the development of Clostridium difficile associated diarrhea (CDAD) and is primary cause of "antibiotic-associated colitis".
It is important to consider the diagnosis of CDAD in patients who present with diarrhoea subsequent to the administration of antibacterial agents. This may progress to colitis, including pseudomembranous colitis (see Adverse Reactions), which may range from mild to fatal colitis. If antibiotic-associated diarrhea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including clindamycin, should be discontinued and adequate therapeutic measures should be initiated immediately. Medicinal products inhibiting peristalsis are contraindicated in this situation.
Caution should be used when prescribing clindamycin to individuals with a history of gastro-intestinal disease, especially colitis.
Since clindamycin does not diffuse adequately into cerebrospinal fluid, the medicinal product should not be used in the treatment of meningitis.
If therapy is prolonged, renal and hepatic function tests should be performed.
The use of clindamycin may result in overgrowth of non-susceptible organisms, particularly yeasts.
Treatment with clindamycin is possibly an alternative treatment in case of penicillin allergy (penicillin hypersensitivity). An allergic cross-reaction between clindamycin and penicillin is not known and not expected because of the structural differences of both substances. However, (in isolated cases) anaphylaxis has been observed after clindamycin treatment of patients with existing penicillin allergy. This should be taken into consideration before treating penicillin allergic patients with clindamycin.
Effects on ability to drive and use machines: Clindamycin has no or negligible influence on the ability to drive and use machines.
Solution for Injection: Patients with history of colitis, renal or hepatic disease, hypersensitivity to drugs or allergic antigen; dysphagia and atopic individuals. Elderly, neonate, foetus immaturus.
General Precautions: In order to prevent appearance of resistant strains, susceptibility should be tested prior to treatment and should be used as short as therapeutic period needed.
Mild colitis could be covered by drug discontinuance. Moderate to severe cases should be managed with fluid, electrolyte and protein supplementation as indicated. Antiperistaltic agents eg, opiates and diphenoxylate with atropine may prolonged and/or worsen the condition.
Vancomycin has been found to be effective in the treatment of pseudomembranous colitis associated with antibiotics produced by Clostridium difficile. The usual adult dosage is vancomycin 500 mg to 2 g/day orally in 3-4 divided doses administered for 7-10 days.
The use of clindamycin occasionally results in overgrowth of nonsusceptible organisms, particularly yeast.
Use in Newborn and Infants: When clindamycin is administered to newborns or infants, appropriate monitoring of organ system is advised.
Use In Pregnancy & Lactation
Capsule: Pregnancy: Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations.
In clinical trails with pregnant women, the systematic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.
Clindamycin should be used in pregnancy only if clearly needed.
Oral and subcutaneous reproductive toxicity studies in rats and rabbits revealed no evidence of impaired fertility or harm to the foetus due to clindamycin, except at doses that caused maternal toxicity. Animal reproduction studies are not always predictive of human response.
Lactation: Orally and parenterally administered clindamycin has been reported to appear in human breast milk in ranges from 0.7 to 3.8 μg/mL. Because of the potential for serious adverse reactions in nursing infants, clindamycin should not be taken by nursing mothers.
Fertility: Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability.
Solution for Injection: Use in Pregnancy: Safety for use in pregnancy has not been established.
Use in Lactation: Since clindamycin has been reported to be excreted in breast milk in ranges of 0.7-3.8 mcg/mL, it should not be used during lactation.
Adverse Reactions
Capsule: The list as follows shows the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. The frequency grouping is defined using the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very Rare (<1/10,000); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 4.)

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Solution for Injection: Local Reactions: Pain, insensibility and sterile abscess have been reported after IM injection and thrombophlebitis after IV injection. Reactions can be minimized or avoided by giving deep IM injections and avoiding prolonged use of indwelling IV catheters.
Gastrointestinal: Pseudomembranous colitis, diarrhea, nausea, vomiting, anorexia, glossitis, stomatitis, abdominal pain and esophagitis may occur.
Shock: Patients should be closely observed during therapy because shock may occur infrequently. Medication should be discontinued when cyanosis, dyspnea, shortness of breath, hypotension occurs.
Hypersensitivity: Maculopapular rash, urticaria and edema may occur during therapy. If hypersensitivity reaction occurs, the drug should be discontinued and in serious cases, the usual emergency treatment agents (epinephrine, corticosteroids, antihistamines) should be available.
Skin: Patients should be closely observed since Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, erythema multiforme may occur and medication should be discontinued when these occur.
Liver: Jaundice and increase in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) may occur.
Kidney: Renal dysfunction as azotomia, oliguria, proteinuria has been observed.
Musculoskeletal: Instances of polyarthritis have been rarely been reported.
Cardiovascular: Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid IV administration.
Hematopoietic: Neutropenia, leukopenia, agranulocytosis, thrombocytopenic purpura, aplastic anemia may occur.
Nervous System: Tinnitus, dizziness may occur during drug therapy.
Others: Facial flush, bitter taste, fever, headache, fatigue may occur.
Inform physician of any adverse effect suffered from using Peldacyn.
Drug Interactions
Capsule: 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.
Antagonism in vitro has been observed between clindamycin and erythromycin. Due to possible clinical significance the two medicinal products should not be administered concurrently.
Clindamycin is metabolised predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmehtylclindamycin. Therefore, inhibitors of CYP3A4 and CYP3A5 may reduce clindamycin clearance and inducers of these isoenzymes may increase clindamycin clearance. In the presence of strong CYP3A4 inducers such as rifampicin, monitor for loss of effectiveness.
In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYPC19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4. Therefore, clinically important interactions between clindamycin and co-administered drugs metabolised by these CYP enzyme are unlikely.
Cross-resistance between clindamycin and lincomycin has been observed.
Vitamin K antagonists: Increased coagulation tests (PT/INR) and/or bleeding, have been reported in patients with clindamycin in combination with a vitamin K antagonists (e.g. warfarin, acenocoumarol and fluindione).
Coagulation tests, therefore, should be frequently monitored in patients treated with Vitamin K antagonists.
Solution for Injection: Clindamycin may enhance the action of peripheral muscle relaxant eg, suxametonium chloride, tubocurarine chloride, therefore, it should be used with caution in patients receiving such agents.
Antagonism has been demonstrated between clindamycin and erythromycin in vitro, therefore, the 2 drugs should not be administered concurrently.
Caution For Usage
Capsule: Incompatibilities: Not applicable.
Solution for Injection: Dilution and Infusion Rates: Clindamycin phosphate must be diluted prior to IV administration. The concentration of clindamycin in diluent for infusion should not exceed 18 mg/mL, infusion rates should not exceed 30 mg/min. The usual infusion dilutions and rates are shown in Table 5. (See Table 5.)

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Dilution and Compatibility: Physical and biological compatibility studies for 24 hrs at room temperature have demonstrated no activation or incompatibility with use of clindamycin phosphate in IV solutions containing sodium chloride, glucose, calcium, potassium and solutions containing vitamin B complex in concentrations usually used clinically. No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamycin, penicillin or carbenicillin.
The following drugs are physically incompatible with clindamycin phosphate: Ampicillin, phenytoin, barbiturates, aminophylline, calcium gluconates and magnesium sulfate.
Precautions during application: After solution, it should be used as soon as possible. Store at room temperature and should be used within 48 hrs.
Pain and hardness at injection site may occur.
It should not be injected direct-IV because cardiac arrest may occur after directly rapid IV administration.
Storage
Capsule: Store at temperatures not exceeding 25°C.
Solution for Injection: Store at temperatures not exceeding 30°C.
MIMS Class
Other Antibiotics
ATC Classification
J01FF01 - clindamycin ; Belongs to the class of lincosamides. Used in the systemic treatment of infections.
Presentation/Packing
Cap 300 mg (brown hard gelatin, size 0, filed with homogenous white powder) x 30's. Soln for inj 150 mg/mL (colorless and transparent liquid) x 2 mL x 1's, 10's; 4 mL x 1's, 10's.
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