CLINDAMYCIN HCL 300 MG CAPSULE (Generic Cleocin Hcl)

Uses Dosage and Administration Cautions Drug Interactions Pharmacokinetics

Uses

Clindamycin generally is used for the treatment of serious infections caused by susceptible gram-positive bacteria and for the treatment of serious infections caused by susceptible anaerobic bacteria. Because the risk of severe, potentially fatal Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) may be higher with clindamycin than with certain other anti-infectives, use of the drug should be limited to serious infections for which less toxic and/or more effective anti-infectives are not readily available. However, it should be noted that CDAD has been associated with the use of nearly all anti-infectives, being reported most frequently with clindamycin, cephalosporins, and ampicillin; second and third generation cephalosporins play an increasingly important role.Empiric therapy with clindamycin in infections that are highly likely to be nonbacterial in origin (e.g., many upper respiratory tract infections) should be avoided.(See Cautions: GI Effects.)

Prior to initiation of clindamycin therapy, the causative organism should be cultured and susceptibility tests conducted. Clindamycin therapy does not obviate incision, drainage, or certain other surgical procedures when indicated.

Because clindamycin does not distribute adequately into the CNS, the drug should not be used for the treatment of meningitis.

Gram-positive Aerobic Bacterial Infections

Clindamycin is used parenterally in the treatment of bone and joint infections (including acute hematogenous osteomyelitis) caused by Staphylococcus aureus and as an adjunct to surgery in the treatment of chronic bone and joint infections caused by susceptible organisms. Clindamycin also is used orally or parenterally in the treatment of serious respiratory tract infections, skin and skin structure infections, or septicemia caused by susceptible strains of S. aureus, Streptococcus pneumoniae, or other streptococci (except Enterococcus faecalis). However, clindamycin is not considered the drug of choice in infections caused by gram-positive aerobic cocci and its use in these infections should be reserved for penicillin-allergic patients or other patients for whom less toxic alternatives are contraindicated. Clindamycin should not be used for the treatment of minor bacterial skin or dental infections or for nonbacterial upper respiratory tract infections.

Anaerobic Bacterial Infections

Clindamycin is used orally or parenterally in the treatment of serious lower respiratory tract infections (including empyema, pneumonia, and lung abscess), serious skin and skin structure infections, septicemia, intra-abdominal infections (including peritonitis and intra-abdominal abscess), and gynecologic infections (including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infections) caused by susceptible anaerobic bacteria. Parenteral clindamycin also is used in the treatment of bone and joint infections (including acute hematogenous osteomyelitis) and as adjunctive therapy in the surgical treatment of chronic bone and joint infections caused by susceptible organisms. Most clinicians consider clindamycin to be a drug of choice for the treatment of infections caused by Bacteroides, including those caused by oropharyngeal strains of B. fragilis or B. melaninogenicus that often are penicillin resistant or do not respond to penicillin G. In the treatment of mixed aerobic-anaerobic bacterial infections, clindamycin has been used in conjunction with an IM or IV aminoglycoside. (See Drug Interactions: Aminoglycosides.)

Acute Otitis Media

Clindamycin is used as an alternative for treatment of acute otitis media (AOM) known or presumed to be caused by penicillin-resistant Streptococcus pneumoniae. Clindamycin is not considered a first-line agent for treatment of AOM, but the American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP) state that use of the drug may be considered in individuals with penicillin hypersensitivity who may have AOM caused by penicillin-resistant S. pneumoniae. If AOM persists after initial management with anti-infective agents, a course of clindamycin may be considered in individuals with type I penicillin hypersensitivity. If AOM persists after treatment with amoxicillin and clavulanate potassium or parenteral ceftriaxone, AAP and AAFP recommend use of tympanocentesis to make a bacteriologic diagnosis. If tympanocentesis is not available, a course of clindamycin may be considered.

For additional information regarding treatment of AOM, including information on diagnosis and management strategies, anti-infectives for initial treatment, duration of initial treatment, and anti-infectives for retreatment, .

Pharyngitis and Tonsillitis

Oral clindamycin is used as an alternative agent for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci). Although clindamycin usually is effective in eradicating S. pyogenes from the nasopharynx, it is not recommended as a drug of choice for treatment of streptococcal pharyngitis and tonsillitis. Clindamycin is reserved for use as an alternative in patients who cannot receive β-lactam anti-infectives and have infections caused by S. pyogenes resistant to macrolides. In addition, clindamycin is recommended as one of several possible alternatives for the treatment of symptomatic patients who have multiple, recurrent episodes of pharyngitis known to be caused by S. pyogenes.

Because penicillin has a narrow spectrum of activity, is inexpensive, and generally is effective, the US Centers for Disease Control and Prevention (CDC), AAP, AAFP, Infectious Diseases Society of American (IDSA), AHA, American College of Physicians (ACP), and others consider natural penicillins (i.e., 10 days of oral penicillin V or a single IM dose of penicillin G benzathine) the treatment of choice for streptococcal pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever, although oral amoxicillin often is used instead of penicillin V in small children because of a more acceptable taste. Other anti-infectives (e.g., oral cephalosporins, oral macrolides) generally are considered alternatives.

If there is recurrence of signs and symptoms of pharyngitis shortly after the initial recommended anti-infective regimen is completed (i.e., within a few weeks) and presence of S. pyogenes is detected, retreatment with the original regimen or another regimen of choice is indicated. If compliance with a 10-day oral regimen is a concern, IM penicillin G benzathine should be used for retreatment. Some clinicians suggest use of an alternative agent (e.g., amoxicillin and clavulanate, clindamycin, macrolide) for retreatment. However, if there are multiple, recurrent episodes of symptomatic pharyngitis within a period of months to years, it may be difficult to determine whether these are true episodes of S. pyogenes infection or whether the patient is a long-term streptococcal pharyngeal carrier who is experiencing repeated episodes of nonstreptococcal pharyngitis (e.g., viral pharyngitis) in whom treatment is not usually indicated. Continuous anti-infective prophylaxis (secondary prophylaxis) to prevent the recurrence of streptococcal pharyngitis is not recommended in these circumstances, unless the patient has a history of rheumatic fever. Instead, use of an alternative regimen is recommended by some clinicians. Although there are no controlled clinical studies evaluating efficacy, the IDSA suggests that symptomatic individuals with multiple, recurrent episodes of documented S. pyogenes pharyngitis receive a regimen of oral clindamycin, oral amoxicillin clavulanate, or IM penicillin G benzathine (with or without oral rifampin).

For additional information on treatment ofS. pyogenespharyngitis, see Pharyngitis and Tonsillitis under Gram-positive Aerobic Bacterial Infections: Streptococcus pyogenes Infections, in Uses in the Natural Penicillins General Statement 8:12.16.04.

Respiratory Tract Infections

Clindamycin is used for the treatment of serious respiratory tract infections (including pneumonia, empyema, lung abscess) caused by susceptible anaerobes, S. pneumoniae, other streptococci, or S. aureus.

For the treatment of community-acquired pneumonia (CAP) caused by anaerobes (including aspiration pneumonia), the IDSA and American Thoracic Society (ATS) recommend use of clindamycin or a β-lactam/β-lactamase inhibitor. The IDSA and ATS consider clindamycin an alternative agent for the treatment of CAP caused by S. pneumoniae or oxacillin-susceptible (methicillin-susceptible) S. aureus.

Acne

Oral clindamycin has been used for the treatment of inflammatory acne vulgaris. For information on use of topical clindamycin in the treatment of inflammatory acne vulgaris,

Actinomycosis

Clindamycin has been recommended for the treatment of actinomycosis caused by Actinomyces israelii. Some clinicians suggest that oral clindamycin is one of several options for long-term follow-up treatment (6-12 months) after initial parenteral treatment (4-6 weeks) with penicillin G or ampicillin.

Anthrax

Although limited clinical data are available regarding use of clindamycin in the treatment of anthrax, clindamycin was included in a multiple-drug regimen that was effective for the treatment of several patients in the US who developed anthrax during September and October 2001 following exposure to an intentional release of anthrax spores (biologic warfare, bioterrorism). At least 2 patients received a parenteral regimen of ciprofloxacin (400 mg every 8 hours), rifampin (300 mg every 12 hours), and clindamycin (900 mg every 8 hours) for treatment.

Because of the rapid course of symptomatic inhalational anthrax and high mortality rate, prompt recognition of symptoms and early initiation of anti-infective therapy is essential. The CDC and other experts (e.g., the US Working Group on Civilian Biodefense) recommend that treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism should be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 additional anti-infective agents predicted to be effective. Multiple-drug parenteral regimens also are recommended for the treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or lesions on the head and neck. Based on in vitro data, drugs that have been suggested as possibilities to augment ciprofloxacin or doxycycline in such multiple-drug regimens include chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, or ampicillin. Strains of Bacillus anthracis that were associated with cases of inhalational or cutaneous anthrax that occurred in the US (Florida, New York, District of Columbia) during September and October 2001 following bioterrorism-related anthrax exposures were susceptible to clindamycin in vitro. For information on treatment of anthrax and recommendations for prophylaxis following exposure to anthrax spores,

Babesiosis

A combination regimen of IV clindamycin and oral quinine is used for the treatment of babesiosis caused by Babesia microti.

Although several species of Babesia can infect humans, B. microti is the most common cause of babesiosis in the US.B. microti is transmitted by Ixodes scapularis ticks, which also may be simultaneously infected with and transmit Borrrelia burgdorferi (causative agent of Lyme disease) and Anaplasma phagocytophilum (causative agent of human granulocytotropic anaplasmosis [HGA, formerly known as human granulocytic ehrlichiosis]). Therefore, the possibility of coinfection with B. burgdorferi and/or A. phagocytophilum should be considered in patients who have severe or persistent symptoms despite appropriate anti-infective treatment for babesiosis.

The IDSA states that all patients with active babesiosis (i.e., symptoms of viral-like infection and identification of babesial parasites in blood smears or by polymerase chain reaction [PCR] amplification of babesial DNA) should receive anti-infective treatment because of the risk of complications; however, symptomatic patients whose serum contains antibody to babesia but whose blood lacks identifiable babesial parasites on smear or babesial DNA by PCR should not receive treatment. In addition, treatment is not recommended initially for asymptomatic individuals, regardless of the results of serologic examination, blood smears, or PCR, but should be considered if parasitemia persists for longer than 3 months.

When anti-infective treatment of babesiosis is indicated, the IDSA and other clinicians recommend that either a regimen of clindamycin and quinine or a regimen of atovaquone and azithromycin be used. The clindamycin and quinine regimen may be preferred in those with severe babesiosis. However, there is some evidence that, in patients with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the clindamycin and quinine regimen. Patients with moderate to severe babesiosis should be monitored closely during treatment to ensure clinical improvement. Exchange transfusions have been used successfully in asplenic patients with life-threatening babesiosis and should be considered, especially in severely ill patients with high levels of parasitemia (10% or more), significant hemolysis, or compromised renal, hepatic, or pulmonary function.

Bacillus cereus Infections

Clindamycin is used for the treatment of invasive disease caused by Bacillus cereus. Anti-infectives are not usually indicated for the treatment of gastroenteritis caused by B. cereus.

Bacterial Vaginosis

Oral clindamycin is used for the treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis). The drug also is used intravaginally as a vaginal cream or vaginal suppository for the treatment of bacterial vaginosis. Goals of treatment and recommended therapy differ for nonpregnant versus pregnant women. However, relief of signs and symptoms of infection is a principal goal of therapy, and all women with symptomatic bacterial vaginosis should be treated regardless of pregnancy status.

Nonpregnant Women

The CDC-recommended regimens for treatment of bacterial vaginosis in nonpregnant women are a 7-day regimen of oral metronidazole (500 mg twice daily); a 5-day regimen of intravaginal metronidazole gel; or a 7-day regimen of intravaginal clindamycin cream. Alternative regimens recommended by the CDC for these women are a 7-day regimen of oral clindamycin (300 mg twice daily) or a 3-day regimen of intravaginal clindamycin suppositories. (See Uses: Bacterial Vaginosis in or .) Intravaginal metronidazole results in clinical cure rates comparable to those of oral metronidazole therapy; intravaginal clindamycin appears to be less effective than the metronidazole regimens. Some clinicians prefer initial topical therapy because of the reduced risk of adverse systemic effects.

Regardless of the therapy chosen, relapse or recurrence of bacterial vaginosis is common, and some clinicians suggest that an alternative regimen (e.g., oral therapy when topical therapy was used initially) can be employed in such infections. A 7-day course of oral clindamycin (300 mg twice daily) may be used as an alternative regimen for the treatment of bacterial vaginosis in nonpregnant women (e.g., for treatment of relapse or recurrence following initial topical therapy, for initial therapy in patients in whom therapy with systemic metronidazole is contraindicated or not tolerated). However, experience with oral metronidazole is more extensive and studies of comparative efficacy with oral clindamycin are limited. The CDC suggests that intravaginal clindamycin is the preferred regimen for the treatment of bacterial vaginosis in women hypersensitive to metronidazole.

Pregnant Women

An increased risk of obstetric complications, including intraamniotic infection, chorioamnionitis, premature rupture of membranes, preterm delivery, and low-birthweight infants, is associated with the presence of bacterial vaginosis in pregnant women, and the organisms found in increased concentrations in the genital flora of women with bacterial vaginosis are frequently found in patients with postpartum or postcesarean endometritis. Evidence from randomized, controlled trials indicates that systemic treatment of bacterial vaginosis reduces the rate of preterm birth in pregnant women at high risk for complications of pregnancy.

Because of the increased risk of adverse pregnancy outcomes associated with the presence of bacterial vaginosis, the CDC recommends that all symptomatic pregnant women be treated for bacterial vaginosis. In addition, because there is evidence from randomized studies that treatment of bacterial vaginosis in asymptomatic pregnant women at high risk for complications of pregnancy (e.g., those who previously delivered of a premature infant) has reduced preterm delivery, some experts recommend that all women at high risk be screened and treated for bacterial vaginosis. Screening for bacterial vaginosis (if conducted) and treatment should be performed at the first prenatal visit. The preferred regimens for the treatment of bacterial vaginosis in pregnant women are a 7-day course of oral metronidazole (500 mg twice daily or 250 mg 3 times daily) or a 7-day course of oral clindamycin (300 mg twice daily).

Because recurrence of bacterial vaginosis is not unusual, and the treatment of this condition may prevent adverse pregnancy outcomes, particularly in women at high risk for complications of pregnancy, follow-up at 1 month after treatment to assess for cure and evaluate the need for additional treatment should be considered. If bacterial vaginosis persists, some clinicians suggest that additional therapy (e.g., second course of oral therapy in a pregnant woman at high risk for preterm delivery) may be used to treat relapsed or recurrent disease.

HIV-infected Women

Recommendations for treatment and preferred regimens for bacterial vaginosis in patients with concurrent human immunodeficiency virus (HIV) infection are the same as those for patients without HIV infection.

Sexual Contacts

Results of several randomized, double-blind, placebo-controlled trials indicate that concurrent treatment of male sexual contacts of a woman with symptomatic bacterial vaginosis generally does not appear to affect the clinical cure rate, including the risk of relapse or recurrence of the syndrome, in the woman. Therefore, routine treatment of male sexual contacts currently is not recommended. Further study is needed to elucidate the possible role, if any, of sexual transmission in bacterial vaginosis.

Capnocytophaga Infections

Clindamycin is used as an alternative to penicillin G for the treatment of infections caused by Capnocytophaga canimorsus.

Clostridium Infections

Clindamycin is used as an alternative to penicillin G for the treatment of clostridial myonecrosis (gas gangrene) caused by Clostridium perfringens or other Clostridium. Anti-infectives are not usually indicated for the treatment of gastroenteritis caused by C. perfringens.

Malaria

Treatment of Uncomplicated Malaria

Oral clindamycin is used in conjunction with oral quinine sulfate for the treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria or when the plasmodial species has not been identified. Clindamycin is not effective when used alone for the treatment of malaria.

The CDC and other clinicians state that the treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine sulfate in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of oral atovaquone and proguanil. The CDC states that use of mefloquine for treatment of chloroquine-resistant P. falciparum malaria should be reserved for circumstances when the treatments of choice cannot be used. When a quinine sulfate regimen is used, concomitant use with doxycycline or tetracycline generally is preferable to use with clindamycin because more efficacy data exist regarding regimens that include tetracyclines. However, for pregnant women with uncomplicated malaria caused by chloroquine-resistant P. falciparum infection, prompt treatment with quinine sulfate and clindamycin is recommended. Although tetracyclines generally are contraindicated in pregnant women, in rare circumstances (e.g., if other treatment options are not available or are not tolerated) quinine sulfate may be used in conjunction with doxycycline or tetracycline if the benefits outweigh the risks.

Because doxycycline and tetracycline generally are contraindicated in children younger than 8 years of age, children in this age group with chloroquine-resistant P. falciparum malaria may receive a regimen of oral quinine sulfate alone for a full 7 days (regardless of geographic area where infection was acquired), oral quinine sulfate in conjunction with oral clindamycin, or oral atovaquone and proguanil. Mefloquine may be considered in these children if these other antimalarial agents are unavailable. In rare circumstances when other treatment options are unavailable or are not tolerated, CDC states that doxycycline or tetracycline may be used in conjunction with quinine sulfate in children younger than 8 years of age if the benefits of tetracycline therapy outweigh the risks.

Treatment of Severe Malaria

Oral or IV clindamycin is used in conjunction with IV quinidine gluconate for the treatment of severe chloroquine-resistant Plasmodium falciparum malaria in adults and children. The CDC recommends that severe malaria be treated with IV quinidine gluconate therapy in conjunction with a 7-day course of doxycycline, tetracycline, or clindamycin administered orally or IV as tolerated. After parasitemia is reduced to less than 1% and the patient can tolerate oral therapy, IV quinidine gluconate can be discontinued and oral quinine sulfate initiated to complete 3 or 7 days of total quinidine and quinine therapy as determined by the geographic origin of the infecting parasite (3 days if malaria was acquired in Africa or South America or 7 days if acquired in Southeast Asia).

For additional information on treatment of severe malaria,

Pelvic Inflammatory Disease

The CDC and other clinicians suggest IV clindamycin in conjunction with an IV or IM aminoglycoside (e.g., gentamicin) as one possible parenteral regimen for the treatment of acute pelvic inflammatory disease (PID) in adults and adolescents. PID is a polymicrobial infection most frequently caused by N. gonorrhoeae and/or Chlamydia trachomatis; however, organisms that can be part of the normal vaginal flora (e.g., anaerobic bacteria, Garnerella vaginalis, H. influenzae, enteric gram-negative bacilli, S. agalactiae) or mycoplasma (e.g., Mycoplasma hominis, Ureaplasma urealyticum) also may be involved. PID is treated with an empiric regimen that provides broad-spectrum coverage. The regimen should be effective against N. gonorrhoeae and C. trachomatis and also probably should be effective against anaerobes. In addition, women with PID often have bacterial vaginosis concurrently, a polymicrobial infection that includes anaerobes.(See Uses: Bacterial Vaginosis.)

The optimum regimen for the treatment of PID has not been identified. A variety of parenteral and oral regimens have been recommended by the CDC and other clinicians. The clindamycin- aminoglycoside regimen is one of the recommended parenteral regimens. The parenteral regimen may be discontinued 24 hours after the patient improves clinically and then an oral regimen of either doxycycline (100 mg twice daily) or clindamycin (450 mg 4 times daily) is used to complete 14 days of therapy. If tubo-ovarian abscess is present, many clinicians prefer clindamycin for follow-up oral therapy since it provides more effective coverage against anaerobes than doxycycline. Another recommended regimen for the treatment of PID consists of IV cefoxitin and oral doxycycline. However, if this regimen is used when tubo-ovarian abscess is present, many clinicians recommend use of clindamycin or metronidazole with doxycycline for follow-up oral therapy (instead of oral doxycycline alone) to provide more effective anaerobic coverage.

For additional information on treatment of PID, see Uses: PID in Ceftriaxone Sodium 8:12.06.12.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment

Clindamycin is used in conjunction with primaquine for the treatment of mild to moderately severe Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) in HIV-infected adults and adolescents. Clindamycin is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition.

Co-trimoxazole is the initial drug of choice for the treatment of PCP in most adults, adolescents, and children, including HIV-infected patients. A regimen of clindamycin and primaquine appears to be an effective alternative to co-trimoxazole, at least in those with mild to moderately severe PCP, and can be considered for adults and adolescents who have had an inadequate response to co-trimoxazole or when co-trimoxazole is contraindicated or not tolerated.

Results of clinical studies indicate that clindamycin administered IV (1.8-3.6 g given in 3 or 4 divided doses daily) or orally (1.2-3.6 g in 3 or 4 divided doses daily [in some cases oral clindamycin was administered after initial IV administration]) in conjunction with oral primaquine (15 or 30 mg daily) for a total 21 days of therapy is effective for the treatment of PCP in HIV-infected adults. Most patients exhibit clinical improvement within 2-7 days, and the combination generally appears to be well tolerated.

Prevention of Recurrence

While a regimen of clindamycin and primaquine has been used as an alternative to usual regimens for prevention of recurrence (secondary prophylaxis or chronic maintenance therapy) of PCP in a limited number of AIDS patients, the Prevention and Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) generally does not recommend this combination for prophylaxis of PCP in HIV-infected individuals because current data are insufficient to determine efficacy of the regimen. Instead, the USPHS/IDSA states that a regimen of clindamycin and primaquine can be considered for primary or secondary prophylaxis of PCP in unusual situations when the usually recommended agents (co-trimoxazole, dapsone, dapsone with pyrimethamine and leucovorin, aerosolized pentamidine, atovaquone) cannot be administered. Clindamycin is designated an orphan drug by the FDA for use in this condition.

Toxoplasmosis

Treatment

A regimen of clindamycin and pyrimethamine has been used with some success for the treatment of cerebral and/or ocular toxoplasmosis in immunocompromised patients (e.g., those with AIDS) who are unable to tolerate the regimen of choice (combination therapy with pyrimethamine and sulfadiazine) or who relapse or fail to respond to treatment with the pyrimethamine and sulfadiazine regimen. Leucovorin usually is added to pyrimethamine and clindamycin therapy to prevent pyrimethamine-induced adverse hematologic effects.

The CDC, National Institutes of Health (NIH), IDSA, and others state that a regimen of pyrimethamine and leucovorin in conjunction with sulfadiazine is the regimen of choice for initial treatment of toxoplasmosis, including toxoplasmosis in immunocompromised patients (e.g., HIV-infected individuals). A regimen of clindamycin in conjunction with pyrimethamine and leucovorin is the preferred alternative when the regimen of choice cannot be used. Although relative efficacy has not been determined, other alternative regimens that have been used for treatment of toxoplasmosis in adults and adolescents include pyrimethamine and leucovorin in conjunction with atovaquone, atovaquone alone or in conjunction with sulfadiazine, or pyrimethamine and leucovorin in conjunction with azithromycin. When a parenteral regimen is required for initial treatment in severely ill adults or adolescents, some experts suggest use of oral pyrimethamine in conjunction with parenteral co-trimoxazole or parenteral clindamycin.

Pyrimethamine and leucovorin in conjunction with sulfadiazine also is the regimen of choice for the treatment of acquired CNS, ocular, or systemic toxoplasmosis in HIV-infected children and for the treatment of congenital toxoplasmosis (especially when the disease is moderate to severe or occurs in HIV-infected neonates). The preferred alternative for treatment of toxoplasmosis in neonates, infants, and children with sulfonamide sensitivity is pyrimethamine and leucovorin in conjunction with clindamycin; other alternative regimens that have been used in adults and adolescents have not been adequately studied in children. Infants born to women who had symptomatic toxoplasmosis during pregnancy should be treated empirically for congenital toxoplasmosis, regardless of whether the mother received treatment for toxoplasmosis during the pregnancy.

Prevention of Recurrence

Because recurrence of toxoplasmosis has been reported commonly following initial recovery and/or discontinuance of anti-infective therapy in immunocompromised patients, prolonged anti-infective therapy usually is necessary for the treatment of acute toxoplasmosis in such patients; long-term suppressive therapy may be necessary.

The USPHS/IDSA, CDC, NIH, and others recommend combination therapy with pyrimethamine and sulfadiazine as the regimen of choice for long-term suppressive therapy (secondary prophylaxis or chronic maintenance therapy) to prevent relapse of toxoplasmosis in HIV-infected adults, adolescents, infants, and children. When this regimen cannot be used (e.g., in patients who cannot tolerate sulfonamides), a regimen of pyrimethamine and leucovorin in conjunction with clindamycin or a regimen of atovaquone with or without pyrimethamine and leucovorin is recommended for long-term suppressive therapy to prevent relapse. In a prospective, randomized study in HIV-infected patients with initial episodes of toxoplasmic encephalitis, the relapse rate was higher in patients who received initial and maintenance therapy with clindamycin in conjunction with pyrimethamine than in those who received a regimen of sulfadiazine in conjunction with pyrimethamine. In addition, only the pyrimethamine/sulfadiazine regimen appears to provide protection against both toxoplasmosis and Pneumocystis jiroveci (formerly known as Pneumocystis carinii) pneumonia.

Long-term suppressive therapy to prevent relapse or recurrence of toxoplasmosis in HIV-infected individuals generally is continued for life, unless immune recovery has occurred as the result of potent antiretroviral therapy. Limited data indicate that HIV-infected adults and adolescents who have successfully completed initial therapy for toxoplasmic encephalitis remain asymptomatic with respect to toxoplasmic encephalitis and have CD4 T-cell counts greater than 200/ mm as the result of potent antiretroviral therapy that have been sustained for 6 months or longer are at low risk for recurrence of toxoplasmic encephalitis. Based on these data and more extensive cumulative data on safety of discontinuing secondary prophylaxis for other opportunistic infections, the USPHS/IDSA, CDC, and others state that it is reasonable to consider discontinuing secondary toxoplasmosis prophylaxis in adults and adolescents meeting these criteria. Some experts would obtain a magnetic resonance image of the brain as part of their evaluation to determine whether or not discontinuance of prophylaxis is appropriate and might be reluctant to stop secondary prophylaxis if any mass lesion or contrast enhancement persists. The USPHS/IDSA, CDC, and others state that secondary prophylaxis against toxoplasmosis should be restarted in adults and adolescents if CD4 T-cell counts decrease to less than 200/ mm. The safety of discontinuing secondary toxoplasmosis prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.

Perioperative Prophylaxis

IV clindamycin is used perioperatively to reduce the incidence of infections in patients undergoing clean, contaminated head and neck surgery. While perioperative prophylaxis does not appear to reduce the rate of infection in patients undergoing clean procedures involving the head and neck (e.g., parotidectomy, thyroidectomy, submandibular-gland excision), there is evidence that antimicrobial prophylaxis decreases the incidence of postoperative infection following head and neck surgery involving an incision through oral or pharyngeal mucosa. The preferred regimens for perioperative prophylaxis in patients undergoing clean, contaminated head or neck surgery are IV clindamycin (with or without IV gentamicin) or, alternatively, IV cefazolin.

IV clindamycin also has been used for perioperative prophylaxis in patients undergoing certain GI procedures such as appendectomy. Although cephalosporins (cefazolin, cefoxitin, or cefotetan) usually are the preferred anti-infectives for perioperative prophylaxis in patients undergoing GI procedures (e.g., esophageal and gastroduodenal surgery, biliary tract surgery, colorectal surgery, nonperforated appendectomy), some clinicians suggest that a regimen of clindamycin and gentamicin, ciprofloxacin, levofloxacin, or aztreonam can be used for perioperative prophylaxis in patients hypersensitive to cephalosporins.

A cephalosporin (cefazolin, cefoxitin, or cefotetan) usually is recommended for perioperative prophylaxis in patients undergoing gynecologic and obstetric surgery (vaginal, abdominal, or laparoscopic hysterectomy); however, some clinicians suggest that a regimen of clindamycin and gentamicin, ciprofloxacin, levofloxacin, or aztreonam can be used for perioperative prophylaxis in patients hypersensitive to cephalosporins.

Although a regimen of cefoxitin or cefotetan usually is recommended for perioperative prophylaxis in patients with ruptured abdominal viscus, some clinicians suggest that a regimen of clindamycin and gentamicin, ciprofloxacin, levofloxacin, or aztreonam can be used as an alternative for perioperative prophylaxis in contaminated or dirty surgery involving a perforated abdominal viscus in patients hypersensitive to cephalosporins. When indicated in this situation, anti-infective therapy is continued postoperatively for about 5 days and is considered treatment rather than prophylaxis. Ruptured viscus in postoperative setting (dehiscence) requires anti-infectives that include coverage for nosocomial pathogens.

Prevention of Bacterial Endocarditis

Clindamycin is used as an alternative agent for prevention of α-hemolytic (viridans group) streptococcal bacterial endocarditis in penicillin-allergic adults and children with certain cardiac conditions who are undergoing certain dental procedures (i.e., procedures that involve manipulation of gingival tissue, the periapical region of teeth, or perforation of oral mucosa) or certain invasive respiratory tract procedures (i.e., procedures involving incision or biopsy of respiratory mucosa).

The American Heart Association (AHA) generally recommends routine use of prophylactic anti-infectives prior to certain procedures only in patients with cardiac conditions that are associated with the highest risk of adverse outcome from endocarditis, including congenital heart disease, prosthetic heart valves, cardiac valvulopathy after cardiac transplant, and previous bacterial endocarditis. The AHA no longer recommends prophylaxis against bacterial endocarditis based solely on an increased lifetime risk of acquisition of infective endocarditis. When selecting anti-infectives for prophylaxis of bacterial endocarditis, the current recommendations published by the AHA should be consulted.

Prevention of Perinatal Group B Streptococcal Disease

IV clindamycin is used as an alternative to parenteral penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease in certain women who are hypersensitive to penicillins. Pregnant women who are colonized with GBS in the genital or rectal areas can transmit GBS infection to their infants during labor and delivery resulting in invasive neonatal infection that can be associated with substantial morbidity and mortality. Intrapartum anti-infective prophylaxis for prevention of early-onset neonatal GBS disease is administered selectively to women at high risk for transmitting GBS infection to their neonates.

When intrapartum prophylaxis is indicated in the mother, penicillin G is the regimen of choice and ampicillin is the preferred alternative. When intrapartum prophylaxis to prevent GBS in the neonate is indicated in women who are hypersensitive to penicillins, the CDC recommends a regimen of IV clindamycin or IV erythromycin for those allergic to penicillins who are at high risk for anaphylaxis (e.g., those with a history of immediate penicillin hypersensitivity, such as anaphylaxis, angioedema, or urticaria; those with a history of asthma or other conditions that would make anaphylaxis more dangerous or difficult to treat, including individuals receiving β-adrenergic blocking agents). For those allergic to penicillins who are not at high risk for anaphylaxis, the CDC states that a regimen of IV cefazolin should be used since this cephalosporin has a narrow spectrum of activity and is associated with high intraamniotic concentrations.

The fact that S. agalactiae (group B streptococci) with in vitro resistance to clindamycin and erythromycin have been reported with increasing frequency should be considered when choosing an alternative to penicillins. When use of erythromycin or clindamycin is being considered in a women hypersensitive to penicillin, in vitro susceptibility testing of clinical isolates obtained during GBS prenatal screening should be performed whenever possible to determine if the isolates are susceptible to these drugs. Strains of GBS resistant to erythromycin often are resistant to clindamycin, although this may not be evident in results of in vitro testing. If in vitro susceptibility testing is not possible, results are unknown, or isolates are found to be resistant to erythromycin or clindamycin, a regimen of vancomycin should be used for intrapartum prophylaxis in women with penicillin allergy who are at high risk for anaphylaxis.

For additional information on prevention of perinatal GBS disease, see Uses: Prevention of Perinatal Group B Streptococcal Disease, in the Natural Penicillins General Statement 8:12.16.04.

Topical Uses

For topical uses of clindamycin,

Dosage and Administration

Reconstitution and Administration

Clindamycin hydrochloride and clindamycin palmitate hydrochloride are administered orally. Clindamycin phosphate is administered by IM injection or by intermittent or continuous IV infusion.

Oral Administration

Clindamycin hydrochloride capsules and clindamycin palmitate hydrochloride oral solution can be administered without regard to food. To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules should be administered orally with a full glass of water.

Clindamycin palmitate hydrochloride oral solution is reconstituted by adding 75 mL of water to the 100-mL bottle; a large portion of the 75 mL should be added initially and the bottle shaken vigorously, and then the remainder of the water should be added and the bottle shaken until the solution is uniform. The resulting solution contains 75 mg of clindamycin per 5 mL.

Parenteral Administration

Prior to IV administration, clindamycin phosphate injection (including that contained in ADD-Vantage vials) must be diluted with a compatible IV solution to a concentration not exceeding 18 mg/mL. For intermittent IV infusion, the diluted solution should be infused over a period of at least 10-60 minutes and at a rate not exceeding 30 mg/minute; the drug should not be administered IV undiluted as a bolus. The manufacturers suggest that 300- or 600-mg doses of the drug be diluted in 50 mL of diluent and infused over 10 or 20 minutes, respectively, 900-mg doses of the drug be diluted in 50-100 mL of diluent and infused over 30 minutes, or that 1.2-g doses be diluted in 100 mL of diluent and infused over 40 minutes. No more than 1.2 g of the drug should be given by IV infusion in a single 1-hour period. Rapid IV administration of clindamycin phosphate should be avoided. As an alternative to intermittent IV infusion, clindamycin may be given by continuous IV infusion after the first dose of the drug has been given by rapid IV infusion.(See Parenteral Dosage in Dosage and Administration: Dosage.)

The commercially available injections of clindamycin phosphate in 5% dextrose are administered by IV infusion. The container should be checked for minute leaks by firmly squeezing the bag. Clindamycin phosphate in 5% dextrose injection should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit. The injection should be discarded if the container seal is not intact or leaks are found or if the solution is not clear. Additives should not be introduced into the injection container. The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

The clindamycin phosphate pharmacy bulk packages are not intended for direct IV infusion; doses of the drug from the bulk package must be further diluted in a compatible IV infusion solution prior to administration. The bulk package is intended for use only in a laminar flow hood. Entry into the vial should be made using a sterile transfer set or other sterile dispensing device, and the contents dispensed in aliquots using appropriate technique; multiple entries with a syringe and needle are not recommended because of the increased risk of microbial and particulate contamination. The date and time when the pharmacy bulk package was opened initially should be recorded on the pharmacy bulk vial. After entry into a bulk package vial, the entire contents of the Cleocin Phosphate pharmacy bulk package vial should be used promptly; any unused portion should be discarded within 24 hours after initial entry into the vial. The manufacturer of another clindamycin phosphate pharmacy bulk package (Gensia) states that the contents should be used as soon as possible after initial entry, but within 4 hours; if not used immediately, the vial should be stored at room temperature under the laminar flow hood during this period.

Dosage

Dosage is expressed in terms of clindamycin and depends on the severity of the infection and the susceptibility of the infecting organism. In the treatment of serious anaerobic infections, parenteral clindamycin is usually used initially and oral clindamycin may be substituted when the condition of the patient warrants; however, in clinically appropriate circumstances, treatment may be initiated or continued with oral clindamycin. The duration of clindamycin therapy depends on the type and severity of infection. If clindamycin is used in infections caused by group A β-hemolytic streptococci, therapy should be continued for at least 10 days. At least 6 weeks of therapy may be required for serious infections such as endocarditis or osteomyelitis.

Oral Dosage

General Adult Dosage

The usual adult oral dosage of clindamycin is 150-300 mg every 6 hours for serious infections or 300-450 mg every 6 hours for more severe infections.

General Dosage for Neonates

When clindamycin oral solution is used in pediatric patients, the manufacturer recommends 8-12 mg/kg daily for serious infections, 13-16 mg/kg daily for severe infections, and 17-25 mg/kg daily for more severe infections. Daily dosage is given in 3 or 4 equally divided doses. In pediatric patients weighing 10 kg or less, the manufacturer recommends a minimum dosage of 37.5 mg 3 times daily.

The American Academy of Pediatrics (AAP) recommends that neonates younger than 1 week of age receive oral clindamycin in a dosage of 5 mg/kg every 12 hours if they weigh 2 kg or less or 5 mg/kg every 8 hours if they weigh more than 2 kg.

The AAP recommends that neonates 1-4 weeks of age receive oral clindamycin in a dosage of 5 mg/kg every 12 hours if they weigh less than 1.2 kg, 5 mg/kg every 8 hours if they weigh 1.2-2 kg, and 5-7.5 mg/kg every 6 hours if they weigh more than 2 kg.

General Dosage for Infants and Children

When clindamycin capsules are used in pediatric patients, the manufacturer recommends 8-16 mg/kg daily given in 3 or 4 equally divided doses for serious infections or 16-20 mg/kg daily given in 3 or 4 equally divided doses for more severe infections. When the oral solution is used, the manufacturer recommends 8-12 mg/kg daily for serious infections, 13-16 mg/kg daily for severe infections, and 17-25 mg/kg daily for more severe infections; daily dosage is given in 3 or 4 equally divided doses. In pediatric patients weighing 10 kg or less, the manufacturer recommends a minimum dosage of 37.5 mg 3 times daily.

For the treatment of mild to moderate infections in infants and children older than 1 month of age, the AAP recommends an oral clindamycin dosage of 10-20 mg/kg daily given in 3 or 4 equally divided doses. The AAP states that oral clindamycin is inappropriate for the treatment of severe infections in these children.

Acute Otitis Media

If oral clindamycin is used as an alternative for treatment of acute otitis media (AOM), the AAP and American Academy of Family Physicians (AAFP) recommend a dosage of 30-40 mg/kg daily given in 3 divided doses.

Pharyngitis and Tonsillitis

If oral clindamycin is used for the treatment of symptomatic patients who have multiple, recurrent episodes of pharyngitis known to be caused by Streptococcus pyogenes (group A β-hemolytic streptococci) (see Uses: Pharyngitis and Tonsillitis), the Infectious Diseases Society of America (IDSA) recommends that children receive a 10-day regimen of oral clindamycin in a dosage of 20-30 mg/kg daily given in 3 divided doses. Adults should receive a 10-day regimen of oral clindamycin in a dosage of 600 mg daily given in 2-4 divided doses; the IDSA states that this dosage has not been specifically studied in adults and was extrapolated from the pediatric dosage.

Acne

In adults, inflammatory acne vulgaris has been treated with 150 mg of oral clindamycin twice daily.

Bacterial Vaginosis

When oral clindamycin is used as an alternative regimen for the treatment of bacterial vaginosis in nonpregnant women, the US Centers for Disease Control and Prevention (CDC) and other clinicians recommend a dosage of 300 mg twice daily for 7 days. The same dosage is recommended by the CDC and others when oral clindamycin is used for the treatment of bacterial vaginosis in pregnant women.

Malaria

If clindamycin is used in conjunction with quinine sulfate for the treatment of uncomplicated malaria caused by chloroquine-resistant Plasmodium falciparum, CDC and other clinicians recommend that adults receive oral clindamycin in a dosage of 20 mg/kg daily in 3 equally divided doses given for 7 days in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Children with uncomplicated chloroquine-resistant P. falciparum malaria (e.g., those younger than 8 years of age who should not receive tetracyclines) can receive oral clindamycin in a dosage of 20 mg/kg daily in 3 equally divided doses given for 7 days in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

If clindamycin is used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) for treatment of severe malaria caused by P. falciparum and if the patient is intolerant of oral therapy, treatment may be initiated in adults and children with a 10-mg/kg loading dose of IV clindamycin followed by 5 mg/kg IV every 8 hours continued until treatment can be switched to oral clindamycin (given in dosages recommended for uncomplicated malaria). The total duration of clindamycin therapy should be 7 days.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

If a regimen of clindamycin and primaquine is used for the treatment of mild to moderate P. jiroveci (formerly P. carinii) pneumonia, the CDC, National Institutes of Health (NIH), HIV Medicine Association of the IDSA, and other clinicians recommend that adults and adolescents receive clindamycin in a dosage of 300-450 mg orally every 6-8 hours (or 600-900 mg IV every 6-8 hours) for 21 days in conjunction with oral primaquine (15-30 mg once daily for 21 days).

Toxoplasmosis

For the treatment of CNS toxoplasmosis in HIV-infected patients who cannot receive sulfadiazine, clindamycin has been given in a dosage of 1.8-2.4 g daily in divided doses in conjunction with pyrimethamine (200-mg loading dose followed by 50-100 mg daily). The CDC, NIH, and IDSA recommend that adults and adolescents with T. gondii encephalitis (TE) receive oral (or IV) clindamycin in a dosage of 600 mg every 6 hours in conjunction with oral pyrimethamine (200-mg loading dose followed by 50-75 mg once daily) and oral leucovorin (10-20 mg once daily; higher dosage may be needed). For the treatment of acquired CNS, ocular, or systemic toxoplasmosis in HIV-infected children, the CDC, NIH, and IDSA recommend an oral (or IV) clindamycin dosage of 5-7.5 mg/kg (up to 600 mg) 4 times daily in conjunction with oral pyrimethamine (2 mg/kg once daily for 3 days followed by 1 mg/kg once daily) and oral leucovorin (10-25 mg once daily). The treatment regimen should be continued for at least 6 weeks; a longer duration may be appropriate if clinical or radiologic disease is extensive or there is an incomplete response at 6 weeks.

For long-term suppressive therapy or chronic maintenance therapy (secondary prophylaxis) to prevent relapse of toxoplasmosis in HIV-infected patients when the regimen of first choice (pyrimethamine and sulfadiazine) cannot be used, the Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA), CDC, NIH, and others recommends that adults and adolescents receive oral clindamycin in a dosage of 300-450 mg given every 6-8 hours with pyrimethamine (25-50 mg once daily) and leucovorin (10-25 mg once daily; higher dosage may be needed). For long-term suppressive therapy to prevent relapse of toxoplasmosis in HIV-infected infants and children, the USPHS/IDSA recommends an oral clindamycin dosage of 20-30 mg/kg daily given in 4 divided doses with oral pyrimethamine (1 mg/kg once daily) and oral leucovorin (5 mg once every 3 days). Long-term suppressive therapy for prophylaxis against relapse of toxoplasmosis in HIV-infected individuals generally is continued for life, unless immune recovery has occurred as the result of potent antiretroviral therapy.(See Uses: Toxoplasmosis.)

Prevention of Bacterial Endocarditis

For prophylaxis of bacterial endocarditis in penicillin-allergic patients with certain cardiac conditions who are undergoing certain dental procedures or respiratory tract procedures (see Uses: Prevention of Bacterial Endocarditis), the American Heart Association (AHA) currently recommends that adults receive a single 600-mg dose of clindamycin and that children receive a single 20-mg/kg dose of the drug 30-60 minutes before the procedure. Pediatric dosage should not exceed adult dosage.

Parenteral Dosage

General Adult Dosage

The usual adult IM or IV dosage of clindamycin is 600 mg to 2.7 g daily administered in 2-4 equally divided doses, depending on the type and severity of infection. Single IM doses should not exceed 600 mg, and no more than 1.2 g should be administered by IV infusion in a 1-hour period. In the treatment of life-threatening infections, the adult IV dosage may be increased to a maximum of 4.8 g daily.

To maintain serum clindamycin concentrations of 4-5 mcg/mL in adults, clindamycin may be infused IV at an initial rate of 10 mg/minute for 30 minutes followed by continuous IV infusion at a rate of 0.75 mg/minute. Alternatively, initial IV infusion of the drug at a rate of 15 mg/minute for 30 minutes followed by continuous IV infusion at 1 mg/minute will maintain serum concentrations of 5-6 mcg/mL, or initial IV infusion at a rate of 20 mg/minute for 30 minutes followed by continuous IV infusion at 1.25 mg/minute will maintain serum concentrations greater than 6 mcg/mL.

General Dosage for Neonates

The manufacturer recommends that neonates younger than 1 month of age receive IM or IV clindamycin in a dosage of 15-20 mg/kg daily given in 3 or 4 equally divided doses. The lower dosage may be adequate for small, premature neonates.

The AAP recommends that neonates younger than 1 week of age receive IM or IV clindamycin in a dosage of 5 mg/kg every 12 hours if they weigh 2 kg or less or 5 mg/kg every 8 hours if they weigh more than 2 kg. The AAP recommends that neonates 1-4 weeks of age receive IM or IV clindamycin in a dosage of 5 mg/kg every 12 hours if they weigh less than 1.2 kg, 5 mg/kg every 8 hours if they weigh 1.2-2 kg, and 5-7.5 mg/kg every 6 hours if they weigh more than 2 kg.

General Dosage for Infants and Children

The IM or IV dosage of clindamycin recommended by the manufacturer for infants and children 1 month of age or older is 20-40 mg/kg daily administered in 3 or 4 equally divided doses, depending on the type and severity of infection. Alternatively, the manufacturer states that these infants and children may receive 350 mg/m daily for the treatment of serious infections or 450 mg/m daily for the treatment of more severe infections.

For infants and children 1 month of age or older, the AAP recommends an IM or IV dosage of 15-25 mg/kg daily for mild to moderate infections and 25-40 mg/kg daily for severe infections. Daily dosage is given in 3 or 4 equally divided doses.

Anthrax

Although the optimum regimen for the treatment of inhalational anthrax remains to be established, several patients who developed inhalational anthrax in the context of an intentional release of anthrax spores (biologic warfare, bioterrorism) were treated successfully with a multiple-drug regimen that included IV clindamycin (900 mg every 8 hours), IV ciprofloxacin (400 mg every 8 hours), and IV rifampin (300 mg every 12 hours).(See Uses: Anthrax.)

Babesiosis

For the treatment of babesiosis caused by Babesia microti, the IDSA recommends that adults receive a clindamycin dosage of 300-600 mg IV every 6 hours or 600 mg orally every 8 hours in conjunction with quinine (650 mg orally every 6-8 hours) given for 7-10 days. Some clinicians recommend that adults receive a regimen of clindamycin given in a dosage of 1.2 g IV twice daily or 600 mg orally 3 times daily for 7-10 days in conjunction with oral quinine (650 mg 3 times daily for 7-10 days).

For the treatment of babesiosis in pediatric patients, the IDSA recommends a clindamycin dosage of 7-10 mg/kg (up to 600 mg) IV or orally every 6-8 hours in conjunction with oral quinine (8 mg/kg [up to 650 mg] every 8 hours) given for 7-10 days. Other clinicians recommend an oral clindamycin dosage of 20-40 mg/kg daily given in 3 divided doses for 7-10 days in conjunction with oral quinine (25 mg/kg daily given in 3 divided doses for 7-10 days).

Patients with mild to moderate babesiosis should have clinical improvement within 48 hours after treatment is initiated; symptoms should resolve completely within 3 months. Patients with severe babesiosis should receive IV clindamycin rather than oral clindamycin. Some patients may have persistent low-grade parasitemia for months after anti-infective treatment. Regardless of the presence or absence of symptoms, the IDSA suggests that retreatment be considered if babesial parasites or amplifiable babesial DNA are detected in blood 3 months or longer after initial treatment.

Pelvic Inflammatory Disease

For the treatment of acute pelvic inflammatory disease (PID) when a parenteral regimen is indicated, adolescents and adults may receive 900 mg of clindamycin IV every 8 hours. Gentamicin sulfate should be administered IV or IM concomitantly; an initial IV or IM gentamicin dose of 2 mg/kg followed by 1.5 mg/kg every 8 hours is recommended in adolescents and adults with normal renal function; alternatively, single-daily dosing of gentamicin may be employed. Dosage of gentamicin (dose and/or dosing interval) should be adjusted according to serum gentamicin concentrations. Both parenteral drugs can be discontinued after there is clinical improvement and therapy then continued with oral clindamycin in a dosage of 450 mg 4 times (every 6 hours) daily to complete 14 days of therapy. Alternatively, oral doxycycline (100 mg twice daily) can be given to complete 14 days of therapy.

Patients with PID who do not demonstrate substantial clinical improvement (e.g., defervescence; reduction in direct or rebound abdominal tenderness; reduction in uterine, adnexal, and cervical motion tenderness) within 72 hours of initiating oral or parenteral therapy usually require additional diagnostic tests and/or surgical intervention.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

If a regimen of clindamycin and primaquine is used for the treatment of mild to moderate Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia, the CDC, NIH, IDSA, and other clinicians recommend that adults and adolescents receive clindamycin in a dosage of 600-900 mg IV every 6-8 hours (or 300-450 mg orally every 6-8 hours) for 21 days in conjunction with oral primaquine (15-30 mg once daily for 21 days).

Toxoplasmosis

For the treatment of CNS toxoplasmosis in patients with human immunodeficiency virus (HIV) infection who cannot receive sulfadiazine, clindamycin has been given in a dosage of 1.8-2.4 g daily in divided doses in conjunction with pyrimethamine (200-mg loading dose followed by 50-100 mg daily). The CDC, NIH, and IDSA recommend that adults and adolescents with Toxoplasma gondii encephalitis (TE) receive IV (or oral) clindamycin in a dosage of 600 mg every 6 hours in conjunction with oral pyrimethamine (200-mg loading dose followed by 50-75 mg once daily) and oral leucovorin (10-20 mg once daily; higher dosage may be needed). For the treatment of acquired CNS, ocular, or systemic toxoplasmosis in HIV-infected children, the CDC, NIH, and IDSA recommend an IV (or oral) clindamycin dosage of 5-7.5 mg/kg (up to 600 mg) 4 times daily in conjunction with oral pyrimethamine (2 mg/kg once daily for 3 days followed by 1 mg/kg once daily) and oral leucovorin (10-25 mg once daily). The treatment regimen should be continued for at least 6 weeks; a longer duration may be appropriate if clinical or radiologic disease is extensive or there is an incomplete response at 6 weeks.

Perioperative Prophylaxis

If clindamycin is used for perioperative prophylaxis in patients undergoing head and neck surgery involving incisions through oral or pharyngeal mucosa, some clinicians recommend a dose of 600-900 mg of clindamycin IV in conjunction with IV gentamicin (1.5 mg/kg) immediately prior to surgery. During prolonged procedures (longer than 4 hours) or if major blood loss occurs, some clinicians suggest that additional intraoperative doses of clindamycin may be given every 3-6 hours. Postoperative doses of prophylactic drugs generally are unnecessary.

Prevention of Bacterial Endocarditis

For prophylaxis of bacterial endocarditis in penicillin-allergic patients with certain cardiac conditions who are undergoing certain dental procedures or respiratory tract procedures (see Uses: Prevention of Bacterial Endocarditis) who cannot receive an oral regimen, the AHA currently recommends that adults receive a single 600-mg dose of clindamycin and that children receive a single 20-mg/kg dose of the drug given IM or IV 30-60 minutes before the procedure. Pediatric dosage should not exceed adult dosage.

Prevention of Perinatal Group B Streptococcal Disease

If clindamycin is used for intrapartum anti-infective prophylaxis to prevent perinatal group B streptococcal (GBS) disease in women with penicillin hypersensitivity who should not receive a β-lactam anti-infective, the CDC recommends that 900 mg of clindamycin be given IV every 8 hours until delivery. When indicated, such prophylaxis is initiated at the time of labor or rupture of membranes.Streptococcus agalactiae (group B streptococci) with resistance to clindamycin have been reported with increasing frequency. Therefore, clinical isolates obtained during GBS prenatal screening should be tested for in vitro susceptibility to clindamycin whenever use of the drug is being considered for prevention of perinatal GBS disease in women hypersensitive to penicillin.(See Uses: Prevention of Perinatal Group B Streptococcal Disease.)

Dosage in Renal and Hepatic Impairment

Although reduced clindamycin dosage may be required in patients with severe renal or hepatic impairment, modification of dosage is not necessary in those with mild or moderate renal or hepatic disease.

Cautions

GI Effects

Adverse GI effects frequently occur with oral, IM, or IV clindamycin and may be severe enough to necessitate discontinuance of the drug. Adverse GI effects of clindamycin include nausea, vomiting, diarrhea, abdominal pain, and tenesmus. In addition, flatulence, bloating, anorexia, weight loss, and esophagitis have occurred. An unpleasant or metallic taste has occurred occasionally following IV administration of high doses of the drug. Nonspecific colitis and diarrhea, as well as potentially fatal Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis), have also occurred in patients receiving clindamycin.

Diarrhea and Colitis

CDAD induced by clindamycin is usually characterized by severe diarrhea and abdominal cramps and/or distension and may be associated with the passage of blood or mucus; endoscopic examination is necessary to reveal the presence of pseudomembranes. This diarrhea and colitis frequently is accompanied by fever and leukocytosis; rarely, reactive polyarthritis and protein-losing enteropathy (in geriatric patients) have been reported in patients with pseudomembranous colitis. Data from animal and clinical studies indicate that CDAD is caused by toxin-producing clostridia resistant to the antibiotic being administered. Although the role of these bacteria in antibiotic-associated diarrhea in the absence of colitis is unclear, some evidence suggests that the organism may be the principal pathogen in 15-25% of cases of diarrhea associated with anti-infective use. Antibiotic-associated diarrhea of unknown cause is far more common than C. difficile-associated diarrhea and/or colitis. If colitis occurs, symptoms usually develop 2-9 days following initiation of clindamycin therapy, but may not occur until several weeks after the drug has been discontinued.

CDAD occurs predominately in institutionalized patients, principally in hospitals, as the result of nosocomial transmission. The infection rarely occurs in a community (outpatient) setting. The principal reservoirs for the infection are infected humans, both those who are symptomatic and those who are asymptomatic carriers. Patients with symptomatic intestinal infections probably serve as the principal reservoir, but asymptomatic colonization appears to be common in institutions with a high prevalence of symptomatic disease. Health-care workers do not appear to provide a major reservoir for the infection but contribute to transmission because of transient hand carriage of the organism. Environmental surface contamination with, and persistence of, C. difficile spores (which can be highly resistant to cleaning and disinfection measures) have been well documented in hospitals, although the extent to which such contamination contributes to transmission is unclear. Direct patient exposure to contaminated items (e.g., commodes, bedpans, rectal thermometers, enteral feedings) within the hospital also appears to contribute to transmission. As a result, infection control procedures aimed at reducing horizontal spread of the infection may be important in managing an institutional outbreak. However, in one reported institutional outbreak, educational measures, enforcement of barrier precautions, and increased attention to environmental cleaning did not affect the rate of CDAD; only after clindamycin use within the hospital was restricted did the outbreak resolve.

Patients admitted to a hospital generally are considered at negligible risk of developing CDAD until they are exposed to anti-infective therapy; thus, while they may be continually at risk of exposure to the organism while hospitalized, they appear to become vulnerable only after exposure to anti-infective therapy. Exposure to a single prophylactic surgical dose of an anti-infective may be sufficient to place a patient at risk. The risk of becoming infected with C. difficile increases with an increasing duration of stay within a hospital.

Mild cases of CDAD may respond to discontinuance of the drug alone, but diagnosis and management of moderate to severe cases should include appropriate bacteriologic and other (e.g., identification of clostridial toxins) studies, and treatment with fluid, electrolyte, and protein supplementation as indicated; sigmoidoscopy (or other appropriate endoscopic examination) usually is reserved for special situations. Isolation of the patient may also be advisable. Other causes of colitis should be considered.

If CDAD is moderate to severe or is not relieved by discontinuance of clindamycin, appropriate anti-infective therapy (e.g., oral metronidazole or oral vancomycin) should be administered. Most experts and clinicians state that in order to decrease the incidence of vancomycin-resistant enterococci and also ), metronidazole therapy should be used first in patients with CDAD, reserving vancomycin therapy for seriously ill patients (i.e., those with severe or potentially life-threatening colitis), patients in whom metronidazole-resistant C. difficile is suspected, patients in whom metronidazole therapy is contraindicated or not tolerated, or those who do not respond to metronidazole. Oral metronidazole therapy also generally is preferred because of cost considerations. Cholestyramine and colestipol hydrochloride have been shown to bind clostridia-produced toxin(s) in vitro; however, an established benefit of this approach is lacking, and the resins have also been shown to bind vancomycin in vitro. The manufacturers state that systemic corticosteroids and corticosteroid retention enemas may help relieve colitis; however, antiperistaltic and antidiarrheal agents such as opiates and diphenoxylate may prolong and/or worsen the condition. For additional information on the management of this colitis,

Dermatologic and Sensitivity Reactions

Generalized mild to moderate morbilliform rash is the most frequently reported adverse reaction to clindamycin. Maculopapular rash, urticaria, pruritus, fever, hypotension, and rarely polyarthritis have also occurred. A few anaphylactoid reactions have been reported in patients receiving clindamycin. Rarely, erythema multiforme, sometimes resembling Stevens-Johnson syndrome, has occurred with the drug.

Local Effects

Thrombophlebitis, erythema, and pain and swelling have occurred with IV administration of clindamycin. IM administration of clindamycin has caused pain, induration, sterile abscess, and reversible increases in serum creatine kinase (CK, creatine phosphokinase, CPK) concentrations. Local reactions can be minimized by giving deep IM injections or avoiding the prolonged use of indwelling IV catheters.

Other Adverse Effects

Other reported adverse effects of clindamycin include transient increases in serum bilirubin, alkaline phosphatase, and AST (SGOT) concentrations; transient leukopenia; neutropenia; eosinophilia; thrombocytopenia; and agranulocytosis. The relationship of liver function and hematologic abnormalities to clindamycin is not known. Polyarthritis has been reported rarely, and rare occurrences of cardiopulmonary arrest and hypotension have been reported following too rapid IV administration of the drug. Although renal damage has not been directly attributed to clindamycin, renal dysfunction manifested as azotemia, oliguria, and/or proteinuria has been observed rarely in patients receiving the drug. Polyarthritis also has been reported rarely with clindamycin.

Precautions and Contraindications

Clindamycin is contraindicated in patients who are hypersensitive to clindamycin or lincomycin.

If clinically important or persistent diarrhea occurs during clindamycin therapy, the drug should be discontinued or, if necessary, continued only with close observation of the patient. Appropriate therapy should be instituted if necessary. (See Cautions: GI Effects.) In addition to antibiotic-associated pseudomembranous colitis, other causes of colitis should be considered in these patients. Experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well than other patients; when clindamycin is indicated in such patients, they should be monitored carefully for changes in bowel movement and/or frequency.

During prolonged clindamycin therapy, liver and renal function tests and blood cell counts should be performed periodically.

To reduce development of drug-resistant bacteria and maintain effectiveness of clindamycin and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy. Patients should be advised that antibacterials (including clindamycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold). Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with clindamycin or other antibacterials in the future.

The use of clindamycin may cause overgrowth of nonsusceptible organisms, particularly fungi. If superinfection occurs, appropriate measures should be taken.

Prior to initiation of clindamycin, the patient should be questioned regarding prior hypersensitivity to drugs and other allergens. Use clindamycin with caution in atopic individuals.

If a hypersensitivity reaction occurs during clindamycin therapy, the drug should be discontinued and appropriate therapy (e.g. antihistamines, epinephrine, oxygen, corticosteroids) instituted as necessary.

Cleocin HCl 75- and 150-mg capsules contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin.

Clindamycin should be used with caution in patients with a history of GI disease, particularly colitis.

Clindamycin should be used with caution in patients with severe renal and/or hepatic impairment; serum clindamycin concentrations should be monitored during high-dose therapy in these patients.

Because clindamycin does not distribute adequately into the CNS, the drug should not be used for the treatment of CNS infections.

Pediatric Precautions

When clindamycin is administered to pediatric patients (birth to 16 years of age), organ system functions should be monitored.

Each mL of clindamycin phosphate injection contains 9.45 mg of benzyl alcohol. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100-400 mg/kg daily) of benzyl alcohol in these neonates. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.

Geriatric Precautions

Clinical studies of clindamycin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently from younger patients. Clinical experience indicates that C. difficile-associated diarrhea and colitis (see GI Effects: Diarrhea and Colitis, in Cautions) seen in association with anti-infective agent therapy may occur more frequently and be more severe in geriatric patients (i.e., patients older than 60 years of age). Therefore, geriatric patients receiving clindamycin should be carefully monitored for the development of diarrhea (e.g., changes in bowel frequency).

Studies to date have not revealed any clinically important differences in the pharmacokinetics of oral or parenteral clindamycin between younger adults and geriatric patients with normal hepatic function and normal (age-adjusted) renal function.

Mutagenicity and Carcinogenicity

Clindamycin was not mutagenic in a rat micronucleus test or the Ames Salmonella reversion test. Long-term studies in animals have not been performed to date to evaluate the carcinogenic potential of clindamycin.

Pregnancy, Fertility, and Lactation

Pregnancy

Safe use of clindamycin in pregnant women has not been established. Reproduction studies in rats and mice using oral and parenteral dosages of clindamycin up to 600 mg/kg daily (2.1 and 1.1 times, respectively, the maximum recommended human parenteral dosage or 3.2 and 1.6 times, respectively, the maximum human oral dosage on a mg/m basis) or subcutaneous doses of clindamycin up to 250 mg/kg daily (0.9-1.3 and 0.5-0.7 times, respectively, the maximum recommended human dosage on a mg/m basis) have not revealed evidence of harm to the fetus. While cleft palates were observed in fetuses in one mouse strain, this was considered to be a strain-specific effect since it was not observed in other mouse strains or in other species studied. There are no adequate and controlled studies to date using clindamycin in pregnant women. Because animal reproduction studies are not always predictive of human response, clindamycin should be used during pregnancy only when clearly needed.

The US Centers for Disease Control and Prevention (CDC) recommends that screening and/or treatment for bacterial vaginosis in pregnant women as clinically indicated should be conducted at the first prenatal visit. For the treatment of bacterial vaginosis and reduction in the incidence of adverse pregnancy outcomes associated with bacterial vaginosis (e.g., preterm birth), particularly in pregnant women at high risk for complications of pregnancy, a 7-day regimen of oral metronidazole or a 7-day course of oral clindamycin is recommended.

Fertility

Fertility studies in rats treated with oral clindamycin doses up to 300 mg/kg daily (about 1.1-1.6 times the maximum recommended human dose on a mg/m basis) have not revealed evidence of impaired fertility or mating ability.

Lactation

Clindamycin is distributed into milk, achieving breast milk concentrations of 0.7-3.8 mcg/mL at dosages of 150 mg orally to 600 mg IV. Because of the potential for serious adverse reactions from clindamycin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Drug Interactions

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the neuromuscular blocking action of other agents (e.g., ether, tubocurarine, pancuronium). Clindamycin should be used with caution in patients receiving such agents, and such patients should be observed for prolongation of neuromuscular blockade.

Aminoglycosides

Clindamycin has been reported to antagonize the bactericidal activity of aminoglycosides in vitro, and some clinicians recommend that these drugs not be used concomitantly. However, in vivo antagonism has not been demonstrated, and clindamycin has been administered successfully in conjunction with an aminoglycoside with no apparent decrease in activity.

Erythromycin

There is in vitro evidence of antagonism between erythromycin and clindamycin.

Pharmacokinetics

Absorption

Approximately 90% of an oral dose of clindamycin hydrochloride is rapidly absorbed from the GI tract. Prior to absorption, oral clindamycin palmitate hydrochloride is hydrolyzed in the GI tract to active clindamycin. Clindamycin is not inactivated by gastric acidity. Serum concentrations of clindamycin appear to be predictable, increasing linearly with increased doses. The extent of absorption and peak serum concentrations of clindamycin are not appreciably affected when either clindamycin hydrochloride capsules or clindamycin palmitate hydrochloride oral solution is administered with food, although peak serum concentrations may be delayed. Following oral administration of a single 150-mg dose of clindamycin hydrochloride to healthy fasting adults, peak serum concentrations of clindamycin average 1.9-3.9 mcg/mL and are attained within 45-60 minutes; serum concentrations of clindamycin average 1.5 mcg/mL at 3 hours and 0.7 mcg/mL at 6 hours. Oral doses of clindamycin palmitate hydrochloride produce serum concentrations of clindamycin similar to those achieved with oral clindamycin hydrochloride. In a study in healthy children, oral administration of clindamycin palmitate hydrochloride 2, 3, or 4 mg/kg every 6 hours produced mean peak serum clindamycin concentrations of 1.24, 2.25, and 2.44 mcg/mL, respectively, 1 hour after the first dose. After the fifth dose, peak serum concentrations of the drug averaged 2.46, 2.98, and 3.79 mcg/mL, respectively.

Following IM or IV administration, clindamycin phosphate is rapidly hydrolyzed in plasma to active clindamycin. Following IM administration of clindamycin phosphate, peak serum concentrations occur within 3 hours in adults and 1 hour in children. In healthy adult males, IM doses of 300 mg of clindamycin phosphate every 8 hours result in average peak serum clindamycin concentrations of 6 mcg/mL. IV doses of 600 mg of clindamycin phosphate infused over 20 minutes every 8 hours in healthy adult males result in average peak serum clindamycin concentrations of 10 mcg/mL. In a study in children with infections, single IV or IM doses of 5-7 mg/kg resulted in average peak serum clindamycin concentrations of 10 or 8 mcg/mL, respectively.

Distribution

Clindamycin is distributed into many body tissues and fluids including saliva, ascites fluid, pleural fluid, synovial fluid, bone, and bile. However, even in the presence of inflamed meninges, only small amounts of the drug diffuse into CSF. The concentration of clindamycin in synovial fluid and bone is reported to be 60-80% of concurrent serum concentrations of the drug; the degree of penetration does not appear to be affected by joint inflammation. Clindamycin readily crosses the placenta, and cord blood concentrations of the drug have been reported to be 46% of concurrent maternal blood concentrations. Clindamycin is distributed into milk.

At a concentration of 1 mcg/mL, clindamycin is approximately 93% bound to serum proteins.

Elimination

The serum half-life of clindamycin is 2-3 hours in adults and children with normal renal function. The serum half-life is increased slightly in patients with markedly reduced renal or hepatic function. In neonates, the serum half-life depends on gestational and chronologic age and body weight. The serum half-life of clindamycin reportedly averages 8.7 and 3.6 hours in premature and full-term neonates, respectively, and about 3 hours in infants 4 weeks to 1 year of age; serum half-life was longer in infants weighing less than 3.5 kg than in heavier infants. Serum concentrations of the drug are not appreciably affected by hemodialysis, peritoneal dialysis, or prolonged administration in patients (including neonates and infants) with normal renal function.

Clindamycin is partially metabolized to bioactive and inactive metabolites. The major bioactive metabolites are clindamycin sulfoxide and N-demethyl- clindamycin which are excreted in urine, bile, and feces. Within 24 hours, approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in feces as active drug and metabolites; the remainder is excreted as inactive metabolites. Probenecid has no effect on clindamycin excretion.

clindamycin hcl 300 mg capsule (generic cleocin hcl)

Uses

Gram-positive Aerobic Bacterial Infections

Anaerobic Bacterial Infections

Acute Otitis Media

Pharyngitis and Tonsillitis

Respiratory Tract Infections

Acne

Actinomycosis

Anthrax

Babesiosis

Bacillus cereus Infections

Bacterial Vaginosis

Nonpregnant Women

Pregnant Women

HIV-infected Women

Sexual Contacts

Capnocytophaga Infections

Clostridium Infections

Malaria

Treatment of Uncomplicated Malaria

Treatment of Severe Malaria

Pelvic Inflammatory Disease

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment

Prevention of Recurrence

Toxoplasmosis

Treatment

Prevention of Recurrence

Perioperative Prophylaxis

Prevention of Bacterial Endocarditis

Prevention of Perinatal Group B Streptococcal Disease

Topical Uses

Dosage and Administration

Reconstitution and Administration

Oral Administration

Parenteral Administration

Dosage

Oral Dosage

General Adult Dosage

General Dosage for Neonates

General Dosage for Infants and Children

Acute Otitis Media

Pharyngitis and Tonsillitis

Acne

Bacterial Vaginosis

Malaria

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Toxoplasmosis

Prevention of Bacterial Endocarditis

Parenteral Dosage

General Adult Dosage

General Dosage for Neonates

General Dosage for Infants and Children

Anthrax

Babesiosis

Pelvic Inflammatory Disease

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Toxoplasmosis

Perioperative Prophylaxis

Prevention of Bacterial Endocarditis

Prevention of Perinatal Group B Streptococcal Disease

Dosage in Renal and Hepatic Impairment

Cautions

GI Effects

Diarrhea and Colitis

Dermatologic and Sensitivity Reactions

Local Effects

Other Adverse Effects

Precautions and Contraindications

Pediatric Precautions

Geriatric Precautions

Mutagenicity and Carcinogenicity

Pregnancy, Fertility, and Lactation

Pregnancy

Fertility

Lactation

Drug Interactions

Neuromuscular Blocking Agents

Aminoglycosides