Clindamycin palmitate hydrochloride for oral solution, USP For pediatric use

Serious respiratory tract infections such as empyema, anaerobic pneumonitis and lung abscess; serious skin and soft tissue infections; septicemia; intra-abdominal infections such as peritonitis and intra-abdominal abscess (typically resulting from anaerobic organisms resident in the normal gastrointestinal tract); infections of the female pelvis and genital tract such as endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis and postsurgical vaginal cuff infection.

Serious respiratory tract infections; serious skin and soft tissue infections.

Serious respiratory tract infections; serious skin and soft tissue infections.

Serious respiratory tract infections. Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin palmitate HCl and other antibacterial drugs, clindamycin palmitate HCl 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.

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin palmitate HCl, 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.

Anaphylactic shock and anaphylactic reactions have been reported (see ADVERSE REACTIONS).

Severe hypersensitivity reactions, including severe skin reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS), some with fatal outcome, have been reported (see ADVERSE REACTIONS).

In case of such an anaphylactic or severe hypersensitivity reaction, discontinue treatment permanently and institute appropriate therapy.

A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.

Clindamycin is potentially nephrotoxic and cases with acute kidney injury have been reported. Consider monitoring of renal function particularly in patients with pre-existing renal dysfunction or those taking concomitant nephrotoxic drugs. In case of acute kidney injury, discontinue clindamycin palmitate HCl when no other etiology is identified.

Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.

Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency.

Clindamycin palmitate HCl should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Clindamycin palmitate HCl should be prescribed with caution in atopic individuals.

Indicated surgical procedures should be performed in conjunction with antibiotic therapy.

The use of clindamycin palmitate HCl occasionally results in overgrowth of nonsusceptible organisms-particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation.

Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of clindamycin half-life has been found. However, it was postulated from studies that when given every eight hours, accumulation should rarely occur. Therefore, dosage modification in patients with liver disease may not be necessary. However, periodic liver enzyme determinations should be made when treating patients with severe liver disease.

Prescribing clindamycin palmitate HCl in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Patients should be counseled that antibacterial drugs including clindamycin palmitate HCl should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When clindamycin palmitate HCl is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by clindamycin palmitate HCl or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

During prolonged therapy, periodic liver and kidney function tests and blood counts should be performed.

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 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 increase plasma concentrations of clindamycin and inducers of these isoenzymes may reduce plasma concentrations of clindamycin. In the presence of strong CYP3A4 inhibitors, monitor for adverse reactions. 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.

Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.6 times the highest recommended adult human oral dose based on mg/m²) revealed no effects on fertility or mating ability.

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. Clindamycin should be used during the first trimester of pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed.

Reproduction studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (3.2 and 1.6 times the highest recommended adult human dose based on mg/m², respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (1.3 and 0.7 times the highest recommended adult human dose based on mg/m², respectively) revealed no evidence of teratogenicity.

Limited published data based on breast milk sampling reports that clindamycin appears in human breast milk in the range of less than 0.5 to 3.8 mcg/mL. Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. 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. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

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 breast-fed child from clindamycin or from the underlying maternal condition.

When clindamycin palmitate HCl is administered to the pediatric population (birth to 16 years), appropriate monitoring of organ system functions is desirable.

Clinical studies of clindamycin did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger patients. However, other reported clinical experience indicates that antibiotic-associated colitis and diarrhea (due to Clostridioides difficile) seen in association with most antibiotics occur more frequently in the elderly (>60 years) and may be more severe. These patients should be carefully monitored for the development of diarrhea.

Pharmacokinetic studies with clindamycin have shown no clinically important differences between young subjects (18–39 years) and elderly subjects (61–79 years) with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration.

When reconstituted with water as follows, each 5 mL (teaspoon) of solution contains clindamycin palmitate HCl equivalent to 75 mg clindamycin.

Reconstitute bottles of 100 mL with 75 mL of water. Add a large portion of the water and shake vigorously; add the remainder of the water and shake until the solution is uniform.

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Do NOT refrigerate the reconstituted solution; when chilled, the solution may thicken and be difficult to pour. The solution is stable for 2 weeks at room temperature.