Dalacin C (Clindamycin)

Dalacin C (Clindamycin)

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Dalacin C (Clindamycin)

Clindamycin belongs to the class of medications called antibiotics. It is used to treat infections caused by certain types of bacteria. It is also used before dental procedures or surgery to prevent infections in people who have heart conditions that put them at greater risk of infection. Clindamycin kills bacteria by preventing the growth of the bacteria, so they cannot reproduce.

Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin.
Clindamycin phosphate is a water soluble ester of clindamycin and phosphoric acid. The chemical name of clindamycin phosphate is [(2R,3R,4S,5R,6R)-6-[(1S,2S)-2-chloro-1-[[(2S,4R)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate.

The molecular formula is C18H34ClN2O8PS and the molecular weight is 504.96.

Capsule: Each capsule contains Clindamycin hydrochloride hydrate equivalent to 150 mg and 300 mg of Clindamycin respectively.
Clindamycin hydrochloride is the hydrated hydrochloride salt of clindamycin. The chemical name for clindamycin hydrochloride 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 monohydrochloride.

Oral Solution: When reconstituted with water, each 5 mL (1 teaspoonful) of solution contains clindamycin palmitate HCl equivalent to 75 mg of clindamycin.
Clindamycin palmitate hydrochloride is a water soluble salt of the ester of clindamycin and palmitic acid. The chemical name for clindamycin palmitate hydrochloride 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-palmitate monohydrochloride.

Sterile Solution for Injection: Each mL contains clindamycin phosphate equivalent to 150 mg of clindamycin. Contains 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as preservative in each mL.

Mechanism of action

Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. At usual doses, clindamycin exhibits bacteriostatic activity in vitro.

Therapeutic indications

Clindamycin has been shown to be effective in the treatment of the following infections when caused by susceptible anaerobic bacteria; susceptible strains of the gram-positive aerobic bacteria eg, streptococci, staphylococci and pneumococci; and susceptible strains of Chlamydia trachomatis.

  • Upper respiratory infections including tonsillitis, pharyngitis, sinusitis, otitis media and scarlet fever.
  • Lower respiratory infections including bronchitis, pneumonia, emphysema and lung abscess.
  • Skin and soft tissue infections including acne, furuncles, cellulites, impetigo, abscesses and wound infections. For specific skin and soft tissue infections eg, erysipelas and paronychia (panaritium), it would seem logical that these conditions would respond very well to Dalacin C therapy.
  • Bone and joint infections including osteomyelitis and septic arthritis.
  • Gynecological infections including endometritis, cellulites, vaginal cuff infection, tubo-ovarian abscess, salpingitis and pelvic inflammatory disease when given in conjunction with an antibiotic of appropriate gram-negative aerobic spectrum in cases of cervicitis due to Chlamydia trachomatis, single drug therapy with clindamycin has been shown to be effective in eradicating the organism.
  • Intra-abdominal infections including peritonitis and abdominal abscesses when given in conjunction with an antibiotic of appropriate gram-negative spectrum.
  • Septicemia and Endocarditis: The effectiveness of Dalacin C in the treatment of selected cases of endocarditis has been documented when Dalacin C is determined to be bactericidal to the infecting organism by in vitro testing of appropriate achievable serum concentrations.
  • Dental infections eg, periodontal abscess and periodontitis.
  • 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.
  • Pneumocystis jiroveci (previously classified as 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.
  • Malaria including multi-resistant Plasmodium falciparum, in combination with quinine.
  • Prophylaxis of endocarditis in patients sensitive/allergic to penicillin(s).
  • Prophylaxis of infection in neck and head surgery. Clindamycin phosphate diluted in normal saline is used as an intraoperative irritant of the surgical field.
  • Clindamycin phosphate when used concurrently with an aminoglycoside antibiotic eg, gentamycin or tobramycin has been shown effective in preventing peritonitis or intra-abdominal abscess after bowel perforation and bacterial contamination secondary to trauma.

Resistance

Resistance to clindamycin is most often due to mutations at the rRNA antibiotic binding site or methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit. These alterations can determine in vitro cross resistance to macrolides and streptogramins B (MLSB phenotype). Resistance is occasionally due to alterations in ribosomal proteins. Resistance to clindamycin may be inducible by macrolides in macrolide-resistant bacterial isolates. Inducible resistance can be demonstrated with a disk test (D-zone test) or in broth. Less frequently encountered resistance mechanisms involve modification of the antibiotic and active efflux.

There is complete cross resistance between clindamycin and lincomycin. As with many antibiotics, the incidence of resistance varies with the bacterial species and the geographical area. The incidence of resistance to clindamycin is higher among methicillin-resistant staphylococcal isolates and penicillin-resistant pneumococcal isolates than among organisms susceptible to these agents.

Dosage and directions for use

  • Inpatient Treatment of Pelvic Inflammatory Disease: Clindamycin phosphate 900 mg (IV) every 8 hours daily plus an antibiotic with an appropriate gram-negative aerobic spectrum administered IV, e.g., gentamicin 2.0 mg/kg followed by 1.5 mg/kg every 8 hours 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 450-600 mg q6h daily to complete 10-14 days total therapy.
  • Treatment of Chlamydia trachomatis Cervicitis: Clindamycin hydrochloride capsules orally 450-600 mg 4 times daily for 10-14 days.
  • Treatment of Toxoplasmic Encephalitis in Patients with AIDS: Clindamycin phosphate IV or clindamycin hydrochloride orally 600-1200 mg every 6 hours for 2 weeks followed by 300-600 mg orally every 6 hours. The usual total duration of therapy is 8 to 10 weeks. The dose of pyrimethamine is 25 to 75 mg orally each day for 8 to 10 weeks. Folinic acid 10 to 20 mg/day should be given with higher doses of pyrimethamine.
  • Treatment of 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 orally every 6 hours for 21 days and Primaquine 15 to 30 mg dose orally once daily for 21 days.
  • Treatment of Acute Streptococcal Tonsillitis/Pharyngitis:Clindamycin hydrochloride capsules 300 mg orally twice daily for 10 days.
  • Treatment of Malaria:Clindamycin hydrochloride capsules or clindamycin palmitate solution (oral administration).
  • Uncomplicated Malaria/P. falciparum: Adults: Quinine sulfate: 650 mg orally three times daily for 3 or 7 days plus clindamycin: 20 mg base/kg/day orally divided three times daily for 7 days.
  • Children: Quinine sulfate: 10 mg/kg orally three times daily for 3 or 7 days plus clindamycin: 20 mg base/kg/day orally divided three times daily for 7 days.
  • Prophylaxis of Endocarditis in Patients Sensitive to Penicillin:Clindamycin hydrochloride capsules or clindamycin palmitate solution (oral administration). Adults: 600 mg 1 hour before procedure; children: 20 mg/kg 1 hour before procedure. Alternatively, when parenteral administration is required: clindamycin phosphate 600 mg IV 1 hour before procedure.
  • Prophylaxis of Infection in Head and Neck Surgery: Clindamycin phosphate 900 mg diluted in 1000 mL normal saline for use as an intraoperative irrigant in contaminated head and neck surgery prior to wound closure.

Contraindications

Dalacin C is contra-indicated in patients previously found to be sensitive to clindamycin, lincomycin or to any of the excipients

Special warnings and precautions for use

Severe hypersensitivity reactions, including severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients receiving clindamycin therapy. If a hypersensitivity or severe skin reaction occurs, clindamycin should be discontinued and appropriate therapy should be initiated

Dalacin C should only be used in the treatment of serious infections. In considering the use of the product, the practitioner should bear in mind the type of infection and the potential hazard of the diarrhoea which may develop, since cases of colitis have been reported during, or even two or three weeks following, the administration of clindamycin.

Studies indicate a toxin(s) produced by clostridia (especially Clostridium difficile) is 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 mg to 500 mg of vancomycin are administered orally four times a day for 7 – 10 days, there is a rapid observed disappearance of the toxin from faecal samples and a coincident clinical recovery from the diarrhoea. (Where the patient is receiving cholestyramine in addition to vancomycin, consideration should be given to separating the times of administration).

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.

Precautions: Caution should be used when prescribing Dalacin C to individuals with a history of gastro-intestinal disease, especially colitis.

Periodic liver and kidney function tests should be carried out during prolonged therapy. Such monitoring is also recommended in neonates and infants.

Prolonged administration of Dalacin C, as with any anti-infective, may result in super-infection due to organisms resistant to clindamycin.

Care should be observed in the use of Dalacin C in atopic individuals.

Drug interactions

Vitamin K antagonists

Increased coagulation tests (PT/INR) and/or bleeding, have been reported in patients treated with clindamycin in combination with a vitamin K antagonist (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests, therefore, should be frequently monitored in patients treated with vitamin K antagonists.

Co-administration of clindamycin with inhibitors of CYP3A4 and CYP3A5

Clindamycin is metabolized predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmethylclindamycin. 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, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4. Therefore, clinically important interactions between clindamycin and co-administered drugs metabolized by these CYP enzymes are unlikely.

Fertility, pregnancy and lactation

Pregnancy

There was evidence of maternal toxicity and embryofetal toxicity in animal studies (see section 5.3).

Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations.

In clinical trials with pregnant women, the systemic 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.

Breast-feeding

Orally and parenterally administered clindamycin has been reported to appear in human breast milk in ranges from <0.5 to 3.8µg/mL.

Clindamycin has the potential to cause adverse effects on the breastfed infant’s gastrointestinal flora such as diarrhoea or blood in the stool, or rash. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin and any potential adverse effects on the breastfed child from clindamycin or from the underlying maternal condition.

Fertility

Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability.

Overdose

In cases of overdosage no specific treatment is indicated.

The serum biological half-life of clindamycin is 2.4 hours. Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.

If an allergic adverse reaction occurs, therapy should be with the usual emergency treatments, including corticosteroids, adrenaline and antihistamines.

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