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LINCOMYCIN AND RELATED AGENTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Lincomycin and clindamycin are lincosamide antibiotics that act primarily as bacteriostatic agents.

Specific Substances

    A) LINCOMYCIN
    1) lincolnensin
    2) Cillimycin
    3) Jiemycin
    4) Lincolcina
    5) Lincomycin A
    6) Lyncomycin
    7) NSC-70731
    8) U 10,149 A
    9) NSC 70731
    10) U-10149
    11) CAS 154-21-2 (lincomycin)
    12) CAS 859-18-7 (lincomycin hydrochloride, anhydrous)
    13) CAS 7179-49-9 (lincomycin hydrochloride monohydrate)
    CLINDAMYCIN
    1) U-21251 (clindamycin)
    2) 7(S)-Chloro-7-deoxylincomycin
    3) 7-CDL
    4) 7-Chlorodeoxylincomycin
    5) 7-Chlorolincomycin
    6) Chlolincocin
    7) Cleocin
    8) Clindamycin
    9) Clinimycin
    10) Dalacin
    11) C Sobelin
    12) U-25179E (clindamycin palmitate hydrochloride)
    13) U-28508 (clindamycin phosphate)
    14) CAS 18323-44-9 (clindamycin)
    15) CAS 21462-39-5 (clindamycin hydrochloride, anhydrous)
    16) CAS 58207-19-5 (clindamycin hydrochloride monohydrate)
    17) CAS 36688-78-5 (clindamycin palmitate)
    18) CAS 25507-04-4 (clindamycin palmitate hydrochloride)
    19) CAS 24729-96-2 (clindamycin phosphate)

Available Forms Sources

    A) FORMS
    1) CLINDAMYCIN HYDROCHLORIDE: 75 mg, 150 mg, and 300 mg capsules (Prod Info CLEOCIN(R) oral capsules, 2009).
    2) CLINDAMYCIN PALMITATE HYDROCHLORIDE: 75 mg/5 mL oral powder for solution available in bottles of 100 mL for pediatric use (Prod Info CLEOCIN PEDIATRIC(R) oral solution, 2008).
    3) CLINDAMYCIN PHOSPHATE: Injection Solution: 150 mg/mL in 2 mL, 4 mL, and 6 mL vials (Prod Info CLEOCIN PHOSPHATE(R) IV, IM injection solution, 2007). Topical formulations: 1% Lotion, 1% gel, 1% foam, 1% solution, 1% topical pad, and 2% vaginal cream, 100 mg Vaginal Suppository (Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info EVOCLIN(R) topical foam, 2007; Prod Info clindamycin phosphate 2% vaginal cream , 2008; Prod Info clindamycin phosphate 1% topical solution, 2010; Prod Info CLEOCIN(R) vaginal ovules, 2005)
    4) CLINDAMYCIN/TRETINOIN COMBINATION: Contains clindamycin 1.2% and tretinoin 0.025% in 2, 30, or 60 gram tubes (Prod Info ZIANA(R) topical gel, 2008).
    5) CLINDAMYCIN/BENZOYL PEROXIDE COMBINATION: When reconstituted, this product contains either clindamycin 0.3 grams and benzoyl peroxide 19.7 grams in a 25 gram jar or 0.6 grams clindamycin and 39.4 grams of benzoyl peroxide in a 50 gram jar (Prod Info BENZACLIN(R) topical gel, 2009), or 10 grams of clindamycin and 40 grams of benzoyl peroxide in a 50 gram jar (Prod Info ACANYA(TM) topical gel, 2008).
    6) LINCOMYCIN HCl: 300 mg/mL in 2 or 10 mL vials (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    B) USES
    1) CLINDAMYCIN
    a) Clindamycin is a an antibiotic agent used to treat infections caused by anaerobic bacteria or susceptible strains of streptococci, pneumococci, and staphylococci for oral or IV use(Prod Info CLEOCIN(R) oral capsules, 2009)
    b) Clindamycin is applied topically for the treatment of acne vulgaris (Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info EVOCLIN(R) topical foam, 2007).
    2) LINCOMYCIN
    a) Lincomycin is an antibiotic agent approved for treatment of infections due to susceptible strains of streptococci, pneumococci, and staphylococci (Prod Info LINCOCIN(R) IM, IV injection, 2007).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Lincomycin and clindamycin are antibiotic agents approved for treatment of infections due to susceptible strains of streptococci, pneumococci, and staphylococci. Clindamycin is also used topically to treat acne vulgaris and bacterial vaginosis.
    B) PHARMACOLOGY: Clindamycin and lincomycin bind exclusively to the 50S bacterial ribosomal subunit and suppress bacterial protein synthesis.
    C) EPIDEMIOLOGY: Overdose from lincomycin and clindamycin is rare.
    D) WITH THERAPEUTIC USE
    1) Diarrhea has been reported following the administration of lincomycin and clindamycin. Pseudomembranous colitis is a widely reported adverse effect of lincomycin and clindamycin therapy when administered orally and/or parenterally. It may range in severity from mild to life-threatening. OTHER EFFECTS: Nausea, vomiting, abdominal pain, stomatitis, esophagitis, glossitis, tinnitus, vertigo, and dermatitis. RARE: Steven's-Johnson syndrome, toxic epidermal necrolysis, elevated liver enzymes, jaundice, acute allergic reactions, sideroblastic anemia, thrombocytopenia, granulocytopenia, and nephrotoxicity (eg, azotemia, oliguria, and proteinuria). Rapid administration of large doses has resulted in ventricular dysrhythmias, hypotension, and cardiac arrest.
    E) WITH POISONING/EXPOSURE
    1) Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses. A 12 gram bolus intravenous lincomycin dose produced cardiac arrest immediately following intubation.
    0.2.20) REPRODUCTIVE
    A) Systemic clindamycin is classified as FDA pregnancy category B. Systemic lincomycin and topical benzoyl peroxide/clindamycin are classified as FDA pregnancy category C. Topical and suppository clindamycin are classified as FDA pregnancy category B. Topical clindamycin phosphate/tretinoin gel is classified as FDA pregnancy category C. Clindamycin and lincomycin have been reported to cross the placental barrier. Clindamycin has been shown to pass into breast milk.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, the manufacturer does not report any human carcinogenic potential with lincomycin or clindamycin.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) Monitor vital signs, CBC with differential with platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Obtain an ECG, and institute continuous cardiac monitoring in patients with significant overdose.
    E) Monitor for clinical evidence of colitis and evaluate for Clostridium difficile toxin if colitis develops.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Acute toxicity, other than gastrointestinal discomfort, is not common. Rapid administration of large doses has resulted in hypotension. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. The primary toxic effects involve the gastrointestinal tract and may include severe diarrhea and pseudomembranous colitis. Metronidazole for mild to moderate disease and vancomycin for severe disease are recommended in the treatment of Clostridium difficile infection. Treat severe hypotension with IV fluids, dopamine, or norepinephrine. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is generally NOT necessary.
    2) HOSPITAL: Severe toxicity is not expected after an overdose. Gastrointestinal decontamination is not routinely warranted. Consider activated charcoal after extremely large ingestions or those involving toxic co-ingestants.
    D) AIRWAY MANAGEMENT
    1) Airway management is unlikely to be needed following an overdose; however, ensure adequate ventilation and perform endotracheal intubation early in patients with life-threatening cardiac dysrhythmias or severe allergic reactions.
    E) ANTIDOTE
    1) None.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patient with inadvertent ingestions who have minimal symptoms can be observed at home.
    2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a health care facility and monitored until symptoms resolve. Patients with unintentional ingestions who are symptomatic should be observed in a healthcare facility.
    3) ADMISSION CRITERIA: Patients who remain symptomatic despite adequate treatment should be admitted.
    4) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    G) ENHANCED ELIMINATION PROCEDURES
    1) In several studies, hemodialysis and peritoneal dialysis were not effective in reducing lincomycin or clindamycin levels significantly.
    H) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered.
    I) PHARMACOKINETICS
    1) CLINDAMYCIN: Tmax: parenteral, 1 to 3 hr; vaginal, 4 to 24 hr; oral, 45 min. Metabolism: (Injectable) rapid conversion; hydrolysis of phosphate to active form. Renal excretion: (topical) less than 0.2%. Elimination half-life: oral: 3.2 hr to 4 hr. Vaginal cream: 1.5 hr to 2.6 hr. LINCOMYCIN: Tmax: oral: 2 to 4 hr. Absorption: rapidly absorbed. Protein binding: about 72%. Vd: approximately 38 L. Elimination half-life: 5.1 hr (range, 4 to 6 hr).
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause severe diarrhea and pseudomembranous colitis, elevated liver enzymes, ventricular dysrhythmias, or acute renal failure.
    0.4.6) PARENTERAL EXPOSURE
    A) Refer to "ORAL OVERVIEW" for specific treatment information.

Range Of Toxicity

    A) TOXICITY: The minimal toxic or lethal dose is not well established in the literature. Lincomycin- or clindamycin-induced diarrhea and pseudomembranous colitis have occurred following therapeutic doses. A 12 gram bolus of IV lincomycin produced cardiac arrest in an adult.
    B) THERAPEUTIC DOSES: Varies by indication. CLINDAMYCIN: ADULTS: Oral: varies by severity; 150 mg to 450 mg every 6 hours. Parenteral: 600 to 4800 mg/day IV in 2 to 4 equal doses. CHILDREN: Oral: 29 days and older: 8 to 40 mg/kg/day orally divided every 6 to 8 hours; maximum 600 mg/dose. Parenteral: greater than 1 month old: 20 to 40 mg/kg/day IV or IM in 3 or 4 equal doses, depending on the severity of infection. If dosed based on body surface area: 350 mg/m(2)/day to 450 mg/m(2)/day. Maximum dose: 2.7 g/day; up to 4.8 g/day has been used for life-threatening. LINCOMYCIN: ADULTS: IM: 600 mg every 12 to 24 hours; IV: 600 mg to 1 g every 8 to 12 hours to a maximum recommended dose of 8 g/day in life-threatening infections. CHILDREN (greater than 1 month old): IM: 10 mg/kg every 12 to 24 hours. IV: 10 to 20 mg/kg/day, depending on severity of infection, in divided doses.

Clinical Effects

Summary Of Exposure

    A) USES: Lincomycin and clindamycin are antibiotic agents approved for treatment of infections due to susceptible strains of streptococci, pneumococci, and staphylococci. Clindamycin is also used topically to treat acne vulgaris and bacterial vaginosis.
    B) PHARMACOLOGY: Clindamycin and lincomycin bind exclusively to the 50S bacterial ribosomal subunit and suppress bacterial protein synthesis.
    C) EPIDEMIOLOGY: Overdose from lincomycin and clindamycin is rare.
    D) WITH THERAPEUTIC USE
    1) Diarrhea has been reported following the administration of lincomycin and clindamycin. Pseudomembranous colitis is a widely reported adverse effect of lincomycin and clindamycin therapy when administered orally and/or parenterally. It may range in severity from mild to life-threatening. OTHER EFFECTS: Nausea, vomiting, abdominal pain, stomatitis, esophagitis, glossitis, tinnitus, vertigo, and dermatitis. RARE: Steven's-Johnson syndrome, toxic epidermal necrolysis, elevated liver enzymes, jaundice, acute allergic reactions, sideroblastic anemia, thrombocytopenia, granulocytopenia, and nephrotoxicity (eg, azotemia, oliguria, and proteinuria). Rapid administration of large doses has resulted in ventricular dysrhythmias, hypotension, and cardiac arrest.
    E) WITH POISONING/EXPOSURE
    1) Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses. A 12 gram bolus intravenous lincomycin dose produced cardiac arrest immediately following intubation.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CASE REPORT: A 44-year-old man was mistakenly injected intraocularly with 300 mg of lincomycin during a lens extraction procedure. Twenty- four hours later, the patient presented with swelling of the eyelids and chemosis of the conjunctiva. Signs and symptoms resolved within two weeks, following treatment with methylprednisolone, dexamethasone, and atropine (Tabbara & Salamoun, 1972).
    3.4.4) EARS
    A) WITH THERAPEUTIC USE
    1) Tinnitus has occasionally been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Supraventricular and ventricular premature beats and hypotension in a 42-year-old man, following an intravenous lincomycin infusion at a dose of 200 mg/kg of body weight. Other ECG abnormalities were observed, including ST segment depression and marked reduction of voltage in the limb leads. The symptoms began to recede 30 minutes after the infusion was finished. The patient's condition normalized in the course of 24 hours (Vacek et al, 1970)
    b) CASE REPORT: A 76-year-old woman, with no history of cardiac complaints, developed bradycardia that progressed to ventricular fibrillation approximately 3 weeks after beginning clindamycin therapy, 300 mg three times daily, for treatment of an infected left knee prosthesis. The ventricular fibrillation was immediately discontinued within seconds by a precordial thump. A temporary intravenous pacemaker was inserted for the patient's complete AV block. An echocardiogram revealed ventricular hypertrophy and an ECG showed QT interval prolongation. The QT interval decreased to normal values following discontinuation of clindamycin therapy, with no further occurrence of dysrhythmic events (Gabel et al, 1999).
    B) CARDIAC ARREST
    1) WITH THERAPEUTIC USE
    a) Rapid parenteral administration of large doses of clindamycin and lincomycin have resulted in cardiac arrest within minutes following injection of the drug (Prod Info CLEOCIN HCl(R) oral capsules, 2011; Prod Info LINCOCIN(R) injection, 2007).
    b) The patient may experience intraventricular conduction disturbances which then progresses to arrest (Waisbren, 1968; Daubeck et al, 1974; Aucoin et al, 1982).
    2) WITH POISONING/EXPOSURE
    a) A 12 gram bolus intravenous lincomycin dose produced cardiac arrest immediately following intubation (Daubeck et al, 1974).
    C) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Rare instances of hypotension have been reported after intravenous lincomycin was administered too rapidly (Prod Info LINCOCIN(R) injection, 2007).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) VERTIGO
    1) WITH THERAPEUTIC USE
    a) Vertigo has occasionally been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    B) FLACCID PARALYSIS
    1) WITH THERAPEUTIC USE
    a) Lincomycin and clindamycin may augment pancuronium-induced neuromuscular blockade (Booij et al, 1978; Fogdall & Miller, 1974) as well as produce neuromuscular blockade when administered alone (Best et al, 1999).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 58-year-old woman, who was admitted for wrist arthrodesis, was given succinylcholine and tubocurarine prior to the surgery, as well as an inadvertent overdose administration of intravenous clindamycin (2400 mg instead of 600 mg). After the end of the surgery, the patient made no attempt at spontaneous ventilation and was unresponsive to painful stimuli, indicating the development of prolonged neuromuscular blockade. The patient's neuromuscular function gradually returned approximately 9 hours later (Ahdal & Bevan, 1995).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PARALYSIS FLACCID
    a) RABBITS: Neuromuscular blockade was observed in rabbit nerve-muscle preparations following administration of lincomycin and during stimulation with high frequencies of intermittent tetanic shocks. The neuromuscular blocking effect was not reversed by the administration of neostigmine methylsulfate (Straw et al, 1965; Tang & Schroeder, 1968). The neuromuscular blocking effect appeared to be dose- related.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea has been reported following the administration of lincomycin and clindamycin. Discontinuation of the drug usually results in the resolution of symptoms (Prod Info CLEOCIN HCl(R) oral capsules, 2011; Prod Info LINCOCIN(R) injection, 2007; Dallos, 1975; Decoux et al, 1979; Leigh et al, 1980; Jacobson et al, 1992; Pear et al, 1994; Prod Info CLEOCIN(R) oral capsules, 2009; Prod Info CLEOCIN PEDIATRIC(R) oral solution, 2008).
    b) A double-blind randomized study showed that diphenoxylate-atropine, when used to treat lincomycin-caused diarrhea, actually increased the incidence of diarrhea in patients as compared to patients receiving a placebo.(Novak et al, 1976).
    c) CASE SERIES: Two patients who had received diphenoxylate-atropine to treat their lincomycin-induced diarrhea, experienced a recurrence of more severe diarrhea following the cessation of the diphenoxylate-atropine. (Pittman & Pittman, 1970).
    d) Decreased intestinal motility after diphenoxylate-atropine therapy may increase the contact time between the lincomycin or its metabolites or some developing toxic substances and the mucosal epithelium, causing the occurrence of more severe diarrhea (Novak et al, 1976).
    e) Clostridium difficile-associated diarrhea occurred in a 32-year-old woman approximately 3 days after beginning treatment of vaginitis with 2% clindamycin phosphate vaginal cream. Although the patient also experienced abdominal pain, malaise, and nausea, a colonoscopy was not performed; therefore, a diagnosis of colitis could not be confirmed, but C difficile toxin was present in stool samples. The patient recovered following treatment with metronidazole (Vikenes et al, 1999).
    B) ANTIBIOTIC ENTEROCOLITIS
    1) WITH THERAPEUTIC USE
    a) Pseudomembranous colitis is a widely reported adverse effect of lincomycin and clindamycin therapy when administered orally and/or parenterally. It may range in severity from mild to life-threatening. Symptoms of pseudomembranous colitis may present during or up to two months after administration of antibiotic treatment (Prod Info CLEOCIN HCl(R) oral capsules, 2011; Prod Info LINCOCIN(R) injection, 2007; Ecker et al, 1970; Anon, 1974; Tully & Feinberg, 1974; Lemos et al, 1976; Marrie, 1978; Davies & Beck, 1981; Parry & Rha, 1986; Herman et al, 1992; Boaz et al, 2000).
    b) The colitis usually presents with loose stools or diarrhea that may be bloody. In cases of more severe disease, patients may have fever, leukocytosis, nausea and vomiting, tenesmus, and abdominal tenderness or cramping (Sneddon, 1974; Wells, 1974) Lefrock et al, 1975; (Munk et al, 1976; Causey, 1976; Smart et al, 1976; Finegold, 1986; Boaz et al, 2000).
    c) If pseudomembranous colitis is present, these diagnostic procedures may reveal erythematous, friable mucosa covered with small, raised, yellowish-white plaques, and the formation of pseudomembranes (Stanley et al, 1974; Tedesco et al, 1974; Tully & Feinberg, 1974) Loells, 1974; (Ramirez-Ronda & Sanford, 1975; Sumner & Tedesco, 1975); (Finegold, 1986; Boaz et al, 2000).
    d) Protein-losing enteropathy, toxic megacolon, and perforation of the colon occur occasionally and are serious complications that may lead to shock and death (Munk & Breen, 1975; Ramirez-Ronda & Sanford, 1975; Dane & King, 1976; Totten et al, 1978; Finegold, 1986).
    e) CASE REPORT: A 61-year-old woman ingested oral 150 mg of clindamycin every 6 hours, to treat a superficial skin infection. Sixteen days later, the patient experienced a sudden onset of diarrhea, nausea and vomiting, right-sided abdominal pain, and pyrexia. A colectomy was performed, revealing the mucosal appearances of pseudomembranous colitis affecting the dilated colon and rectal stump (Wise et al, 1974).
    f) CASE REPORT: A 61-year-old woman was given clindamycin 150 mg intramuscularly every 6 hours for 4 days, to treat a wound infection. Six days after cessation of antibiotic therapy, the patient experienced nausea, abdominal cramps, and increasingly severe diarrhea. A proctoscopy revealed ulceration in the mucosa with inflammatory changes and a pseudomembrane. Due to the severity of the colitis, a subtotal colectomy with an ileostomy was performed to avoid further complications of colonic necrosis, perforation, or hemorrhage (Levine et al, 1976).
    g) Several cases of patients who received lincomycin or clindamycin intravenously, and subsequently developed symptoms ranging from mild diarrhea to fulminant diarrhea, nausea and vomiting, and abdominal cramps have been reported. Colonoscopies or necropsies showed a dilated colon with granularity, inflammation, and pseudomembranes(Totten et al, 1978).
    h) Severe pseudomembranous colitis in a father and his two children has been observed. Two of the affected family members received lincomycin prior to onset of their symptoms, suggesting a possible genetic predisposition to antibiotic-induced pseudomembranous colitis(Harrod et al, 1975).
    i) Topical clindamycin, used to treat facial acne, has been reported to cause pseudomembranous colitis. The signs and symptoms of the colitis are the same as when the antibiotic is administered systemically (Milstone et al, 1981; Parry & Rha, 1986).
    j) Recurrent pseudomembranous colitis was reported in the same patient following twice daily applications of topical clindamycin. Symptoms resolved following oral administration of vancomycin hydrochloride, 500 mg four times daily for 10 days (Parry & Rha, 1986).
    k) CASE REPORT: A case of a 30-year-old man who presented with a two-week history of severe diarrhea, sometimes bloody, following the ingestion of clindamycin phosphate, 150 mg three times daily for a total of 2.4 grams has been reported. Abdominal x-rays showed a toxic megacolon and a proctosigmoidoscopy revealed pseudomembranous colitis (Axelrod et al, 1975).
    l) CASE REPORT: A fatality due to pseudomembranous colitis was reported in a case of a patient who experienced severe diarrhea following the intravenous administration of clindamycin 500 mg every 8 hours, for a total of 13 grams. The patient subsequently developed pseudomembranous colitis with toxic megacolon; a total colectomy with ileostomy was performed after which the patient developed irreversible shock and died (Wehmeyer et al, 1976).
    m) CASE REPORT:A 61-year-old man presented with a 2-week history of severe diarrhea and a 2-day history of nausea, vomiting, and severe left-lower abdominal pain, following the ingestion of clindamycin 300 mg three times daily for 2 weeks. The patient also developed anasarca, ascites, and noncardiogenic pulmonary edema. A sigmoidoscopy revealed a rare condition of fulminant pseudomembranous colitis without a toxic megacolon. The patient recovered following supportive treatment and oral vancomycin and cholestyramine therapy (Herman et al, 1992).
    n) CASE SERIES: A prospective study was conducted of 200 patients receiving clindamycin. Twenty-one percent of the patients developed diarrhea and ten percent developed pseudomembranous colitis. The colitis was more commonly associated with orally administered clindamycin (13 of 80 patients) than with clindamycin administered parenterally (3 of 74 patients) (Tedesco et al, 1974).
    o) CASE REPORT: A patient developed pseudomembranous colitis with acute migratory polyarthritis following ingestion of clindamycin hydrochloride, 150 mg four times daily, a total of 7.2 grams. Severe diarrhea began six days after termination of the antibiotic and the migratory polyarthritis began 27 days after termination of the antibiotic when the gastrointestinal symptoms were most severe. The arthritis resolved as the colitis improved(Rollins & Moeller, 1976).
    p) Early evidence suggested that colitis may be due to an enterotoxin-forming clostridia (Rifkin et al, 1977).
    q) Analyzed data from 62 patients whose feces contained clostridium difficile toxin revealed a significant correlation between a toxin titer of 6400 or more and the presence of pseudomembranous colitis(Burdon et al, 1981).
    C) COLITIS
    1) WITH THERAPEUTIC USE
    a) Non-specific colitis is an uncommon adverse effect of lincomycin and clindamycin therapy.
    b) The symptoms of non-specific colitis are very similar to pseudomembranous colitis including bloody diarrhea, tenesmus, abdominal pain, and fever. The difference with non-specific colitis is that there are no pseudomembranes present during proctoscopic examinations and rectal biopsies show non-specific inflammatory changes (Cohen et al, 1973; Cohen et al, 1974). Symptoms resolved following discontinuation of the antibiotic and initiation of supportive treatment. Severe cases respond well to steroid therapy.
    c) CASE SERIES: Three patients showing symptoms of bloody diarrhea, abdominal pain, and fever following lincomycin or clindamycin therapy have been reported. The non-specific colitis resolved following treatment with antispasmodics, asulfadine, and steroid enemas, and withdrawal of the antibiotic. (Manashil & Kern, 1973).
    d) CASE REPORT: A patient who had similar symptoms of colitis beginning several days after initiation of clindamycin therapy, 150 mg orally four times daily. Symptoms gradually disappeared within 12 days of the onset of the illness(Theodoropoulos et al, 1975).
    D) ESOPHAGITIS
    1) WITH THERAPEUTIC USE
    a) Esophagitis has been reported with clindamycin hydrochloride use (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    b) CASE REPORT: A case of esophagitis occurred following the second day of oral clindamycin treatment for a staphylococcal infection. The esophagitis resolved 5 days later, following supportive care (Froese, 1979).
    E) STOMATITIS
    1) WITH THERAPEUTIC USE
    a) Stomatitis has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    F) GLOSSITIS
    1) WITH THERAPEUTIC USE
    a) Glossitis has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    G) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting have been reported in patients treated with lincomycin and clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011; Prod Info LINCOCIN(R) injection, 2007).
    H) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) Abdominal pain has been reported with all dosage forms of clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Elevated liver enzymes and jaundice have been reported with oral and parenteral clindamycin therapy (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    b) Lincomycin has been reported infrequently to cause jaundice and an elevation of liver function tests (Prod Info LINCOCIN(R) IM, IV injection, 2007). Although no direct relationship has been established.
    c) CASE REPORT: One patient developed hepatotoxicity, including elevated liver enzyme and bilirubin levels and hepatocyte swelling and necrosis, following intravenous clindamycin therapy, 900 mg every 6 hours infused over 30 minutes, to treat staphylococcal endocarditis. The hepatotoxicity resolved following discontinuation of clindamycin therapy(Elmore et al, 1974).
    B) CHOLESTATIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 67-year-old man presented with jaundice, pale stools, dark urine, and pruritus 7 days after completing a 10-day course of clindamycin for treatment of a skin abscess. Liver enzyme levels and bilirubin levels were also elevated. A liver biopsy, performed 10 days after the onset of jaundice, revealed severe cholestasis with duct injury and reduced numbers of bile ducts. Several months after discontinuation of the clindamycin, the jaundice and cholestasis resolved, but a liver biopsy continued to show duct injury and reduced numbers of bile ducts (Altraif et al, 1994).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) INTERSTITIAL NEPHRITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A patient developed interstitial nephritis 4 days following initiation of therapy with gentamicin 80 mg intravenously every 8 hours, and lincomycin 300 mg intramuscularly every 6 hours for treatment of possible bacteremia and intra- abdominal abscess. The interstitial nephritis promptly resolved following withdrawal of the gentamicin and lincomycin. It is not known whether the interstitial nephritis was caused by the drugs acting singly or in combination (Bell & Thompson, 1980).
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) Signs of nephrotoxicity (eg, azotemia, oliguria, and proteinuria) have been rarely observed with oral and parenteral administration of clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    b) CASE SERIES: Three patients who developed acute renal failure following combination therapy with gentamicin and clindamycin. Renal function gradually returned to normal in all three patients after discontinuation of gentamicin and clindamycin therapy. Because gentamicin is a known nephrotoxic drug, it has been suggested that clindamycin may enhance the nephrotoxicity of gentamicin (Butkus et al, 1976).
    C) VAGINITIS
    1) WITH THERAPEUTIC USE
    a) Vaginitis has been reported with clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011) and lincomycin use (Prod Info LINCOCIN(R) injection, 2007).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) SIDEROBLASTIC ANEMIA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: One patient developed sideroblastic anemia following therapy with lincomycin 300 mg 4 times daily. The anemia was completely reversible after the termination of lincomycin and the introduction of pyridoxine (Kokkini et al, 1983).
    B) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenic purpura has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    b) Thrombocytopenia has been reported with clindamycin hydrochloride administration (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    c) CASE REPORT: A 56-year-old alcoholic man was given intravenous lincomycin, 6 g/day, to treat aspiration pneumonia. Three days later spontaneous epistaxis and petechiae appeared. The patient's platelet count decreased from 34,000/mm(3) to 30,000/mm(3). Discontinuation of lincomycin resulted in a platelet count increase of 125,000/mm(3) on day 6 and 170,000/mm(3) on day 8 (Raff, 1973).
    C) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) Leukopenia has been reported in patients treated with lincomycin and clindamycin (Prod Info LINCOCIN(R) injection, 2007; Fleming & Crowe, 1976).
    b) CASE REPORT: Granulocytopenia developed in a patient after receiving lincomycin, 2 grams/day. After a total dose of 2 grams, the lincomycin was stopped because the white blood cell (WBC) count was 1150/cubic millimeter. Three days after discontinuation of lincomycin, the WBC count increased to 21,200/cubic millimeter. The patient had a severe infection that can depress bone marrow and may give rise to leukopenia. Therefore, the association of lincomycin with granulocytopenia, in this case, may be coincidental and unrelated (Brown & Cunningham, 1965).
    c) CASE REPORT: A 44-year-old man developed granulocytopenia several days after therapy with clindamycin 150 mg every 6 hours for 6 days, for treatment of septic finger. The patient was also experiencing diarrhea, aching legs, lightheadedness, coughing, and fever. His white blood cell (WBC) count, at the height of his illness, was 2500/cubic millimeter of which 2% were neutrophils. Subsequently, the WBC count improved so that nine days after discontinuation of clindamycin, the WBC count was 9200/cubic millimeter of which 68% were neutrophils. Treatment was continued with penicillin (Fleming & Crowe, 1976).
    D) NEUTROPENIA
    1) WITH THERAPEUTIC USE
    a) Neutropenia has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007) and clindamycin use (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    E) APLASTIC ANEMIA
    1) WITH THERAPEUTIC USE
    a) Rare reports of aplastic anemia in which lincomycin could not be ruled out as the causative agent have been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    F) AGRANULOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Agranulocytosis has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007) and clindamycin use (Prod Info CLEOCIN HCl(R) oral capsules, 2011).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) STEVENS-JOHNSON SYNDROME
    1) WITH THERAPEUTIC USE
    a) Rare cases of Stevens-Johnson syndrome have been associated with lincomycin (Prod Info LINCOCIN(R) injection, 2007) and clindamycin use (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    b) CASE REPORT: A case of Stevens-Johnson syndrome that occurred 4 days after the completion of a 10-day course of clindamycin, 150 mg four times daily has been reported. The patient presented with erythematous skin lesions, conjunctivitis, and stomatitis. Her symptoms rapidly improved following prednisone therapy (Fulghum & Catalano, 1973).
    B) LYELL'S TOXIC EPIDERMAL NECROLYSIS, SUBEPIDERMAL TYPE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 50-year-old man developed a generalized erythematous rash, fever, malaise, and arthralgia approximately 7 days after beginning oral clindamycin therapy for treatment of a foot infection. Histology of a dermal biopsy specimen showed a perivascular mononuclear infiltrate and a subepidermal blister of necrotic keratinocytes, consistent with a diagnosis of toxic epidermal necrolysis. The patient recovered following supportive care (Paquet et al, 1995).
    C) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Rare instances of exfoliative and vesiculobullous dermatitis have been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    b) CASE REPORT: A 37-year-old woman topically administered a 50-50 mixture of lincomycin hydrochloride and 6-methyl-prednisolone to treat chronic otitis in her left ear. Twelve days later the patient developed intense pruritus on her left ear lobule and exudative lesions that extended and disseminated over her face, neck, trunk, and extremities. The patient recovered in 10 days, following treatment with systemic steroids. The patient later tested positive to lincomycin hydrochloride and clindamycin hydrochloride (1% aqueous) as allergens (Conde-salazar et al, 1985) .
    c) CASE SERIES: Two cases of contact dermatitis resulting from contact with a lincomycin-spectinomycin antibiotic have been reported. Both patients experienced intense pruritus, erythema, and papules. The patients recovered following treatment with topical corticosteroids and oral antihistamines, and discontinuation of the antibiotic. (Vilaplana et al, 1991).
    d) Clindamycin 1% (in the hydrochloride and phosphate salt forms) has been reported to cause contact dermatitis in patients who have been tested positive to clindamycin as an allergen. Patients developed pruritus, erythema, and papules or pustules following contact with clindamycin (De Kort & De Groot, 1989; Yokoyama et al, 1991; Vejlstrup & Menne, 1995).
    e) CASE REPORT: A 53-year-old man developed pruritus, maculopapular eruptions, and facial edema two days after initiation of intravenous clindamycin therapy, 600 mg four times daily. The patient recovered in seven days following withdrawal of clindamycin and treatment with high-dose corticosteroids. Six hours after a rechallenge of intravenous clindamycin 300 mg, the patient presented with the same symptoms. He recovered following administration of corticosteroids and antihistamines (Vidal et al, 1991).
    f) CASE REPORT: A 38-year-old man developed a generalized pruritic maculopapular rash with lip edema and facial edema after 10 days of treatment with oral clindamycin phosphate and amoxicillin. The patient recovered following cessation of antibiotic therapy and treatment with corticosteroids and antihistamines. Two months later, patch tests were performed with penicillin, amoxicillin, ampicillin, and clindamycin phosphate. Only clindamycin phosphate was positive. An oral challenge with clindamycin phosphate was also performed which resulted in the recurrence of the rash, accompanied by lip and facial edema. The rash again resolved following administration of antihistamines and corticosteroids.(Vicente & Fontela, 1999).
    D) ACNE
    1) WITH THERAPEUTIC USE
    a) Several cases of comedone development following several months of therapy using 5% lincomycin hydrochloride monohydrate (in 70% isopropyl alcohol) to treat acne vulgaris have been reported (Scherzer, 1978)
    E) LYMPHADENOPATHY
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 54-year-old woman, receiving ciprofloxacin, gentamicin, and clindamycin to treat osteomyelitis, developed a fever, and pain and swelling of her neck several days after beginning antibiotic therapy. According to the patient, the acute pains occurred in the same area of the neck in association with each dose of clindamycin. An MRI of the neck and upper thorax showed lymphadenopathy without suppuration. The patient recovered approximately 7 to 10 days after discontinuation of the clindamycin. A rechallenge with a single dose of clindamycin administered intravenously again resulted, 1 hour later, in a fever and severe pain involving the same area of the neck (Southern, 1997).
    F) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) Rare cases of erythema multiforme have been associated with lincomycin (Prod Info LINCOCIN(R) injection, 2007) and clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    G) URTICARIA
    1) WITH THERAPEUTIC USE
    a) Urticaria has been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    H) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Skin rashes have been reported in patients treated with lincomycin (Prod Info LINCOCIN(R) injection, 2007).
    b) Rash has been observed with all dosage forms of clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    I) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) Pruritus has been reported with all dosage forms of clindamycin (Prod Info CLEOCIN HCl(R) oral capsules, 2011).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RESTLESS LEGS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A case report described severe restless leg syndrome (RLS) in a 38-year-old woman following oral clindamycin use (300 mg/day) for acne vulgaris. Symptoms appeared on the third day of therapy that supported an RLS diagnosis using the International Restless Leg Syndrome Study Group criteria. These symptoms included nocturnal discomfort confined to the legs that worsened with rest and was relieved by movement. Physical and neurological examinations were normal, and serum iron and ferritin were within normal limits. Resolution of RLS symptoms occurred three days after discontinuation of clindamycin (Coco & Cannizzaro, 2008).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions such as angioneurotic edema, serum sickness and anaphylaxis have been reported with lincomycin use (Prod Info LINCOCIN(R) injection, 2007).
    b) Hypersensitivity reactions, including anaphylactoid reactions, have been reported with clindamycin hydrochloride (Prod Info CLEOCIN HCl(R) oral capsules, 2011).
    c) CASE REPORT: A 25-year-old man developed Drug Rash with Eosinophilia and Systemic Symptoms syndrome (DRESS) after completing a 10-day course of clindamycin and methylprednisolone to treat strep throat with peritonsillar abscess that developed shortly after a diagnosis of mononucleosis. The patient presented with a morbilliform rash that, over one week, had spread from the abdomen, antecubital fossae, and neck to his lower extremities, chest, and face, along with 3 days of 102-degree F spiking fevers. Tests for infection were negative. Complement (C3 and C4) levels were normal and antinuclear antibody was negative. However, AST and ALT levels were 44 units/L and 55 units/L, respectively. Lymph nodes in the neck were palpable, with evidence of leukocytosis and eosinophilia. The patient did not develop any visceral involvement, and his fever and rash resolved after 4 days of prednisone treatment. Should visceral involvement occur with DRESS, consider monitoring the affected organ system for several months, along with 3 to 6 months of thyroid monitoring (Tian et al, 2010).
    d) CASE REPORT: One patient developed nasal passage swelling and lip edema following intravenous administration of 600 mg of clindamycin. The swelling began 10 minutes following the start of the infusion. At the end of the infusion (approximately 20 minutes), the patient's lips were extremely swollen and his nasal passages were completely closed off secondary to the swelling. The patient completely recovered twenty-four hours later following the discontinuation of clindamycin therapy(Segars & Threlkeld, 1993).

Reproductive

    3.20.1) SUMMARY
    A) Systemic clindamycin is classified as FDA pregnancy category B. Systemic lincomycin and topical benzoyl peroxide/clindamycin are classified as FDA pregnancy category C. Topical and suppository clindamycin are classified as FDA pregnancy category B. Topical clindamycin phosphate/tretinoin gel is classified as FDA pregnancy category C. Clindamycin and lincomycin have been reported to cross the placental barrier. Clindamycin has been shown to pass into breast milk.
    3.20.2) TERATOGENICITY
    A) PLACENTAL BARRIER
    1) LINCOMYCIN: Lincomycin can cross the placental barrier in therapeutic concentrations without any significant accumulation of lincomycin after repeated doses and without toxic reactions in any of the infants (Duignan et al, 1973).
    2) CLINDAMYCIN: In one study, clindamycin crossed the placental barrier, and fetal tissue levels of clindamycin increased as therapy continued (Philipson et al, 1973). In another study, cord serum concentrations were up to half the maternal serum concentration (Weinstein et al, 1976).
    B) FETAL GASPING SYNDROME
    1) CLINDAMYCIN: Clindamycin solutions contain benzyl alcohol, which can cross the placenta and has been associated with fatal gasping syndrome in premature infants (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014).
    C) LACK OF EFFECT
    1) CLINDAMYCIN
    a) In clinical trials, there was no increased frequency of congenital abnormalities associated with systemic administration of clindamycin during the second and third trimesters in pregnant women (Prod Info Cleocin(R) vaginal cream, 2014; Prod Info Cleocin(R) Vaginal Ovules vaginal suppositories, 2014; Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014).
    2) LINCOMYCIN
    a) In a 3-part study, women were given lincomycin in each trimester of pregnancy to treat symptomatic cervicitis and vaginitis. The doses of lincomycin were 2 g/day, in divided doses, for 7 days. The children from these mothers were monitored, from birth until they were 6.5 to 7.5 years old for any drug-related abnormalities (physical, mental, or developmental). The results of the study showed that the children had no physical, mental, or developmental anomalies related to the administration of lincomycin (Mickal & Panzer, 1975).
    D) ANIMAL STUDIES
    1) CLINDAMYCIN
    a) There was no evidence of teratogenic effects of clindamycin given to rats and mice following oral and parenteral doses up to 600 mg/kg/day (62 and 25 times, respectively, the maximum human exposure based on body surface area) (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014; Prod Info Cleocin(R) vaginal cream, 2014; Prod Info Cleocin(R) Vaginal Ovules vaginal suppositories, 2014) or subQ doses up to 250 mg/kg/day (0.9- and 0.5-fold the highest recommended adult human dose based on mg/m2, respectively) (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014).
    2) MICE, RATS: No teratogenicity was seen in mice and rats following oral doses of clindamycin of up to 600 mg/kg/day (480 and 240 times, respectively, the recommended clinical dose based on body surface area), or with subcutaneous doses of up to 180 mg/kg/day (140 and 70 times, respectively, the recommended clinical dose based on body surface area) (Prod Info VELTIN(TM) topical gel, 2010).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified clindamycin injection as FDA pregnancy category B (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014). The manufacturers have classified lincomycin injection and topical benzoyl peroxide/clindamycin as FDA pregnancy category C (Prod Info LINCOCIN(R) injection, 2007; Prod Info BENZACLIN(R) topical gel, 2009). Topical and suppository clindamycin are classified as FDA pregnancy category B (Prod Info Cleocin(R) vaginal cream, 2014; Prod Info Cleocin(R) Vaginal Ovules vaginal suppositories, 2014).
    2) The manufacturer has classified topical clindamycin phosphate/tretinoin gel as FDA pregnancy category C (Prod Info VELTIN(TM) topical gel, 2010).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Lincomycin and clindamycin have been reported to pass into the breast milk of nursing mothers. The degree of toxicity to the infant has not yet been established (Medina, 1963; Smith et al, 1975; Mann, 1980). Lincomycin has been reported to appear in human milk in concentrations of 0.5 to 2.4 mcg/mL (Prod Info LINCOCIN(R) injection, 2007). .
    2) CLINDAMYCIN: Although clindamycin is considered compatible with breastfeeding by the American Academy of Pediatrics (Anon, 2001), the World Health Organization recommends avoiding clindamycin while nursing. They additionally recommend that exposed infants be monitored for diarrhea or bloody stools (Anon, 2002).
    3) CLINDAMYCIN IV: Clindamycin, dosed 150 mg to 600 mg IV, was detected in breast milk in concentrations of 0.7 to 3.8 mcg/mL (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014). Clindamycin may have been a contributing factor in the development of bloody stools in an infant. The infant had been nursing from his mother who had been given gentamicin, 80 mg IV every 8 hours, and clindamycin, 600 mg IV every 6 hours for a possible endometrial infection (Mann, 1980).
    4) SUPPOSITORY CLINDAMYCIN: It is unknown if vaginally administered clindamycin is excreted into human breast milk (Prod Info Cleocin(R) Vaginal Ovules vaginal suppositories, 2014).
    5) TOPICAL CLINDAMYCIN/BENZOYL PEROXIDE: It is not known whether benzoyl peroxide/clindamycin phosphate is excreted in human milk after topical application (Prod Info BENZACLIN(R) topical gel, 2009).
    6) TOPICAL CLINDAMYCIN/TRETINOIN: Orally and parenterally administered clindamycin has appeared in human milk. It is recommended that clindamycin use or nursing be discontinued due to potentially serious adverse reactions in the nursing infant (Prod Info VELTIN(TM) topical gel, 2010).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) RATS: Doses of oral clindamycin 300 mg/kg/day (1.1-fold the highest recommended clinical dose based on body surface area) did not impact mating or fertility in rats (Prod Info CLEOCIN PHOSPHATE(R) intramuscular injection, intravenous injection, 2014).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, the manufacturer does not report any human carcinogenic potential with lincomycin or clindamycin.
    3.21.4) ANIMAL STUDIES
    A) LACK OF INFORMATION
    1) No animal studies have been conducted evaluating the carcinogenic potential of lincomycin (Prod Info LINCOCIN(R) IM, IV injection, 2007), or topical clindamycin with tretinoin gel (Prod Info ZIANA(R) topical gel, 2008), or other topical formulations of clindamycin (Prod Info clindamycin phosphate 2% vaginal cream , 2008; Prod Info CLEOCIN(R) vaginal ovules, 2005; Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010).
    B) KERATOACANTHOMA
    1) In 2-year dermal carcinogenicity study, the use of clindamycin 1% and benzoyl peroxide 5%, at doses of 100 mg, 500 mg, and 2000 mg/kg/day, resulted in a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats. However, in a study involving male mice given clindamycin 1% and benzoyl peroxide 5% at does of 900 mg, 2700 mg, and 15,000 mg/kg/day (1.8, 5.4, and 30 times the highest recommended adult human dose of 2.5 grams based on mg/m(2), respectively), no carcinogenicity was observed (Prod Info ACANYA(TM) topical gel, 2008).
    2) In a photocarcinogenicity study in hairless mice, clindamycin 1% gel caused a statistically significant shortening of the median time to tumor onset in a study with hairless mice in which tumors were induced with simulated sunlight (Prod Info EVOCLIN(R) topical foam, 2007). The incidence of skin tumors was increased following exposure to ultraviolet radiation when clindamycin was combined with high doses of benzoyl peroxide (5000 and 10,000 mg/kg/day, 5 days a week) (Prod Info ACANYA(TM) topical gel, 2008).

Genotoxicity

    A) Genotoxic effects of topical clindamycin were negative in the human lymphocyte chromosome aberration test (Prod Info ACANYA(TM) topical gel, 2008) and when evaluated with a rat micronucleus test and an Ames test (Prod Info EVOCLIN(R) topical foam, 2007; Prod Info clindamycin phosphate 2% vaginal cream , 2008; Prod Info CLEOCIN(R) vaginal ovules, 2005).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) Monitor vital signs, CBC with differential with platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Obtain an ECG, and institute continuous cardiac monitoring in patients with significant overdose.
    E) Monitor for clinical evidence of colitis and evaluate for Clostridium difficile toxin if colitis develops.
    4.1.2) SERUM/BLOOD
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) Monitor vital signs, CBC with differential with platelet count, renal function, and liver enzymes in symptomatic patients.
    4.1.4) OTHER
    A) OTHER
    1) OTHER
    a) Proctoscopy, sigmoidoscopy, or barium-contrast studies are very helpful in the definitive diagnosis of lincomycin- or clindamycin-associated colitis. These procedures may be indicated for those patients that develop diarrhea following lincomycin or clindamycin administration (Tedesco et al, 1974; Tully & Feinberg, 1974; Kabins & Spira, 1975; Ramirez-Ronda & Sanford, 1975; Hoberman et al, 1976).
    2) FECAL
    a) Assay stool for the presence of Clostridium difficile toxin in patients with diarrhea associated with clindamycin of lincomycin (Burdon et al, 1981)
    b) Fecal occult blood test may be indicated in patients who develop diarrhea in association with clindamycin (Hoberman et al, 1976).

Methods

    A) IMMUNOASSAY
    1) A radioimmunoassay was developed for measuring clindamycin in serum extracts. This assay measures only clindamycin and not the microbiologically active metabolite, N-demethylclindamycin.
    2) The sensitivity of this procedure for clindamycin in serum is about 0.1 mg/liter. The sensitivity can increase depending on the specific activity of 3(H) clindamycin (Gilbertson & Stryd, 1976).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who remain symptomatic despite adequate treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patient with inadvertent ingestions who have minimal symptoms can be observed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with deliberate self-harm ingestions should be evaluated in a health care facility and monitored until symptoms resolve. Patients with unintentional ingestions who are symptomatic should be observed in a healthcare facility.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    C) Monitor vital signs, CBC with differential with platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Obtain an ECG, and institute continuous cardiac monitoring in patients with significant overdose.
    E) Monitor for clinical evidence of colitis and evaluate for Clostridium difficile toxin if colitis develops.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is generally NOT necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Severe toxicity is not expected after an overdose. Gastrointestinal decontamination is not routinely warranted. Consider activated charcoal after extremely large ingestions or those involving toxic co-ingestants.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    3) Monitor vital signs, CBC with differential with platelet count, renal function, and liver enzymes in symptomatic patients.
    4) Obtain an ECG, and institute continuous cardiac monitoring in patients with significant overdose.
    5) Monitor for clinical evidence of colitis. Evaluate for C difficile toxin if colitis develops.
    B) DIARRHEA
    1) Lincomycin or clindamycin therapy by any route is frequently associated with diarrhea which can progress to pseudomembranous colitis. Discontinuation of the drug usually results in improvement of the diarrhea (Ramirez-Ronda & Sanford, 1975; Decoux et al, 1979).
    2) CLOSTRIDIUM DIFFICILE INFECTION
    a) Patients with severe symptoms of Clostridium difficile infection (CDI) should be started on empiric treatment as soon as the diagnosis is suspected (Cohen et al, 2010) and laboratory samples have been obtained (Bartlett & Gerding, 2008).
    b) Metronidazole for mild to moderate disease and vancomycin for severe disease are recommended in the treatment of CDI. Antibiotics thought to be causing the disease should be discontinued (Cohen et al, 2010).
    c) TREATMENT OF MILD TO MODERATE CDI: Metronidazole: Adults: 500 mg orally 3 times a day for 10 to 14 days (Cohen et al, 2010). Children: Pediatrics: 30 mg/kg/day orally every 6 hours (Gunn et al, 2002).
    d) TREATMENT OF SEVERE CDI: Vancomycin: Adults: 125 mg orally 4 times a day for 10 to 14 days (Cohen et al, 2010). Children: 40 to 50 mg/kg/day orally in divided doses every 6 hours for 7 to 10 days; maximum 500 mg daily (Gunn et al, 2002).
    e) TREATMENT OF COMPLICATED OR FULMINANT CDI: Adults: Metronidazole 500 mg IV every 8 hours AND vancomycin 500 mg orally 4 times a day. If complete ileus, rectal instillation of vancomycin may be added (Cohen et al, 2010).
    C) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) In several studies, hemodialysis and peritoneal dialysis were not effective in reducing lincomycin or clindamycin levels significantly (Kaplan & Weinstein, 1968; Eastwood & Gower, 1974; Malacoff et al, 1975; Peddie et al, 1975).

Abstracts

Case Reports

    A) ADULT
    1) A 55-year-old man was given clindamycin hydrochloride 150 mg orally 4 times daily for a total of 12 days to treat non-specific sialadenitis. The patient developed several watery, non-bloody stools per day six days after completion of clindamycin therapy. Twenty-one days later, the patient also developed polyarthritis when his gastrointestinal symptoms were most severe. A sigmoidoscopy revealed pseudomembranous colitis. The patient rapidly improved following the administration of steroid enemas followed by oral prednisone (Rollins & Moeller, 1976).

Range Of Toxicity

Summary

    A) TOXICITY: The minimal toxic or lethal dose is not well established in the literature. Lincomycin- or clindamycin-induced diarrhea and pseudomembranous colitis have occurred following therapeutic doses. A 12 gram bolus of IV lincomycin produced cardiac arrest in an adult.
    B) THERAPEUTIC DOSES: Varies by indication. CLINDAMYCIN: ADULTS: Oral: varies by severity; 150 mg to 450 mg every 6 hours. Parenteral: 600 to 4800 mg/day IV in 2 to 4 equal doses. CHILDREN: Oral: 29 days and older: 8 to 40 mg/kg/day orally divided every 6 to 8 hours; maximum 600 mg/dose. Parenteral: greater than 1 month old: 20 to 40 mg/kg/day IV or IM in 3 or 4 equal doses, depending on the severity of infection. If dosed based on body surface area: 350 mg/m(2)/day to 450 mg/m(2)/day. Maximum dose: 2.7 g/day; up to 4.8 g/day has been used for life-threatening. LINCOMYCIN: ADULTS: IM: 600 mg every 12 to 24 hours; IV: 600 mg to 1 g every 8 to 12 hours to a maximum recommended dose of 8 g/day in life-threatening infections. CHILDREN (greater than 1 month old): IM: 10 mg/kg every 12 to 24 hours. IV: 10 to 20 mg/kg/day, depending on severity of infection, in divided doses.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) CLINDAMYCIN
    a) ORAL: The usual oral dose is 150 mg to 300 mg every 6 hours. For more severe infections, 300 mg to 450 mg every 6 hours (Prod Info CLEOCIN(R) oral capsules, 2009).
    b) PARENTERAL: The usual parenteral dose is 600 to 1200 mg/day in 2 to 4 equal doses. For more severe infections, 1200 to 2700 mg/day in 2 to 4 equal doses. In life-threatening situations, 4800 mg/day IV may be given. Single IM injections of greater than 600 mg are NOT recommended (Prod Info CLEOCIN PHOSPHATE(R) IV, IM injection solution, 2007).
    c) TOPICAL: Topical formulations are applied to the affected area once or twice daily (Prod Info clindamycin phosphate 1% topical solution, 2010; Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info EVOCLIN(R) topical foam, 2007; Prod Info ZIANA(R) topical gel, 2008; Prod Info ACANYA(TM) topical gel, 2008; Prod Info BENZACLIN(R) topical gel, 2009).
    d) VAGINAL CREAM: The usual recommended dose is one applicatorful of cream or one ovule intravaginally once nightly at bedtime (Prod Info CLEOCIN(R) vaginal cream, 2005; Prod Info CLEOCIN(R) vaginal ovules, 2005).
    2) LINCOMYCIN
    a) INTRAMUSCULAR (IM): The usual IM dose is 600 mg every 24 hours. For more severe infections, 600 mg every 12 hours or more often (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    b) INTRAVENOUS (IV): The usual IV dose is 600 mg to 1 g every 8 to 12 hours to a maximum recommended dose of 8 g/day in life-threatening infections (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    c) For intravenous administration, 1 g of lincomycin should be diluted in not less than 100 mL of solution and infused over a period of not less than one hour (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    d) SUBCONJUNCTIVAL INJECTION: The usual subconjunctival injection dose is 75 mg (0.25 mL) (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    7.2.2) PEDIATRIC
    A) CLINDAMYCIN
    1) ORAL
    a) 29 days and older: 10 to 30 mg/kg/day orally divided every 6 to 8 hours; Maximum 600 mg/dose (Prod Info CLEOCIN PEDIATRIC(R) oral solution, 2008; Prod Info CLEOCIN HCL(R) oral capsules, 2007; Kaplan, 2006; Martinez-Aguilar et al, 2003; Kaplan et al, 1982). The usual dose of clindamycin hydrochloride is 8 to 16 mg/kg/day in 3 or 4 equal doses. For more severe infections, 16 to 20 mg/kg/day in 3 or 4 equal doses (Prod Info CLEOCIN(R) oral capsules, 2009). For clindamycin palmitate, the usual oral dose is 8 to 12 mg/kg/day in 3 or 4 equal doses. For severe infections, 13 to 25 mg/kg/day in 3 or 4 equal doses. In children weighing 10 kg or less, the minimum dose is 37.5 mg 3 times daily (Prod Info CLEOCIN PEDIATRIC(R) oral solution, 2008).
    b) Doses as high as 40 mg/kg/day orally divided every 6 hours have been used to treat S. aureus osteomyelitis (Peltola et al, 2009; Peltola et al, 1997).
    c) ACUTE OTITIS MEDIA, PENICILLIN-ALLERGIC
    1) 30 to 40 mg/kg/day orally divided every 8 hours for 5 to 7 days (6 years and older with mild to moderate disease) or 10 days (less than 6 years of age or severe illness) (American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media, 2004). Maximum 600 mg/dose.
    d) BABESIOSIS
    1) 7 to 10 mg/kg orally; maximum 600 mg/dose every 6 to 8 hours in combination with quinine 8 mg/kg orally every 8 hours; maximum 650 mg/dose for 7 to 10 days (Wormser et al, 2006).
    e) COMMUNITY-ACQUIRED METHICILLIN-RESISTANT S. AUREUS
    1) 40 mg/kg/day orally divided every 6 to 8 hours (Liu et al, 2011). Maximum 600 mg/dose.
    f) INFECTIVE ENDOCARDITIS, PROPHYLAXIS; PENICILLIN-ALLERGIC
    1) 20 mg/kg orally 30 to 60 minutes prior to dental, respiratory, or infected skin/skin structure or musculoskeletal procedures. Maximum 600 mg/dose (Wilson et al, 2007).
    g) STREPTOCOCCAL PHARYNGITIS, PENICILLIN-ALLERGIC
    1) 20 mg/kg/day orally divided every 8 hours for 10 days. Maximum 600 mg/dose (Gerber et al, 2009).
    2) PARENTERAL
    a) For children greater than 1 month old, the usual dose is 20 to 40 mg/kg/day IV or IM in 3 or 4 equal doses, depending on the severity of infection. If children are dosed based on body surface area, the usual dose is 350 mg/m(2)/day and, for more severe infections, 450 mg/m(2)/day (Prod Info CLEOCIN PHOSPHATE(R) IV, IM injection solution, 2007). Maximum dose: 2.7 g/day; up to 4.8 g/day has been used for life-threatening infections (St Peter et al, 2008; Prod Info CLEOCIN PHOSPHATE(R) IV, IM injection solution, 2007; Kaplan, 2006; Martinez-Aguilar et al, 2003; Emil et al, 2003; Collins et al, 1998; Dougherty et al, 1995; Schropp et al, 1991; Kaplan et al, 1982).
    b) For infants less than 1 month old, the usual parenteral dose is 15 to 20 mg/kg/day in 3 or 4 equal doses (Prod Info CLEOCIN PHOSPHATE(R) IV, IM injection solution, 2007).
    c) BABESIOSIS
    1) Severe: 7 to 10 mg/kg IV; Maximum 600 mg/dose every 6 to 8 hours in combination with quinine 8 mg/kg orally every 8 hours; Maximum 650 mg/dose for 7 to 10 days (Wormser et al, 2006)
    d) COMMUNITY-ACQUIRED METHICILLIN - RESISTANT S. AUREUS
    1) 40 mg/kg/day IV divided every 6 to 8 hours (Liu et al, 2011). Maximum 600 mg/dose.
    e) INFECTIVE ENDOCARDITIS, PROPHYLAXIS; PENICILLIN-ALLERGIC
    1) 20 mg/kg IV or IM 30 to 60 minutes prior to dental, respiratory, or infected skin/skin structure or musculoskeletal procedures. Maximum 600 mg/dose (Wilson et al, 2007).
    f) SURGICAL PROPHYLAXIS, BETA-LACTAM ALLERGIC PATIENTS
    1) 10 to 15 mg/kg IV within 60 minutes before incision. Repeat intraoperatively within 2 half-lives (3 to 6 hours) if the operation is still in progress. Maximum 600 mg/dose (Milstone et al, 2008; Bratzler & Houck, 2004; Emil et al, 2003; None Listed, 1999; Dellinger et al, 1994).
    2) Generally, surgical prophylaxis should be discontinued within 24 hours after the end of surgery. For cardiovascular surgery, prophylaxis for 24 to 48 hours is recommended. Controversy remains on whether to continue prophylaxis until all lines and drains are removed (Bratzler & Houck, 2004; Dellinger et al, 1994).
    3) TOPICAL
    a) Use in children under 12 years of age has not been studied. In children older than 12 years, topical formulations are applied to the affected area once or twice daily (Prod Info clindamycin phosphate 1% topical solution, 2010; Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info EVOCLIN(R) topical foam, 2007; Prod Info ZIANA(R) topical gel, 2008; Prod Info ACANYA(TM) topical gel, 2008; Prod Info BENZACLIN(R) topical gel, 2009; Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info CLINDETS(R) pads, 2000).
    b) ACNE VULGARIS: 12 years of age and older: apply thin film of solution, lotion, or gel topically twice daily to affected areas (Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010; Prod Info CLINDETS(R) pads, 2000). For foam, apply topically to entire affected area once daily (Prod Info EVOCLIN(R) topical foam, 2010).
    c) VAGINAL: Safety and efficacy have not been established (Prod Info CLEOCIN(R) vaginal cream, 2005) in premenarchal females (Prod Info CLEOCIN(R) vaginal ovules, 2005). Bacterial vaginosis: vaginal ovule, postmenarchal girls: 1 ovule intravaginally at bedtime for 3 days in non-pregnant women (Prod Info CLEOCIN(R) vaginal ovules, 2005).
    B) LINCOMYCIN
    1) INTRAMUSCULAR (IM): For children greater than 1 month old, the usual IM dose is 10 mg/kg every 24 hours. For more severe infections, 10 mg/kg every 12 hours or more often (Prod Info LINCOCIN(R) IM, IV injection, 2007).
    2) INTRAVENOUS (IV): For children greater than 1 month old, the usual IV dose is 10 to 20 mg/kg/day, depending on severity of infection, in divided doses (Prod Info LINCOCIN(R) IM, IV injection, 2007).

Minimum Lethal Exposure

    A) ANIMAL DATA
    1) Convulsions, depression and significant mortality were observed in mice when given an IV dose of clindamycin 855 mg/kg. Significant mortality alone was observed in rats when given oral or subcutaneous doses of clindamycin 2618 mg/kg (Prod Info CLEOCIN(R) oral capsules, 2009).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) In one study, the highest tolerated single dose of lincomycin intravenously was 214 mg/kg. The highest tolerated daily dose was 420 mg/kg. The only complaints noted during the study were slight transient hypotension during the infusion and transient blurred vision (Vacek et al, 1970).
    2) A 23-year-old was given a 200 mg/kg of lincomycin, infused at a rate of 50 mg/kg/hour, and developed the same transient symptoms without any signs of adverse cardiac reactions (Vacek et al, 1970).
    3) A study observed the effects of high-dose intravenous administration of lincomycin on 32 healthy volunteers. Only 2 of the 32 volunteers had troublesome side effects. One patient, who received 1200 mg of lincomycin, reported loose stools on day 8. The 2nd patient, who received 2100 mg of lincomycin, reported mild and transient dizziness. On the basis of this study, it appears that if large doses of lincomycin are intravenously administered, with adequate dilution and given over a reasonably extended period of time, cardiovascular changes do not occur (Novak et al, 1971).
    4) A 50-year-old woman was given 600 mg of undiluted clindamycin phosphate injected over several minutes into a central intravenous line. She immediately developed ventricular arrhythmias progressing to complete heart block (Aucoin et al, 1982).
    5) A lincomycin dose of 200 mg/kg of body weight, infused over 2 hours and 20 minutes, produced nausea, vomiting, dyspnea, severe hypotension, and ECG abnormalities (Vacek et al, 1970).
    6) A 12 gram bolus intravenous lincomycin dose produced cardiac arrest immediately following intubation (Daubeck et al, 1974).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) CLINDAMYCIN
    a) ORAL: A single oral dose of clindamycin 150 mg produced average serum levels 1.51 mcg/mL at 3 hours and 0.7 mcg/mL at 6 hours after administration (Prod Info CLEOCIN(R) oral capsules, 2009).
    b) TOPICAL: Following multiple administrations of topical solution of 10 mg/mL, very low serum levels of 0 to 3 ng/mL have been observed (Prod Info clindamycin phosphate 1% topical solution, gel, lotion, suspension, 2010).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) CLINDAMYCIN
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 361 mg/kg (Budavari, 1996)
    2) LD50- (ORAL)MOUSE:
    a) 2618 mg/kg (Budavari, 1996)
    B) LINCOMYCIN
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1 g/kg (Budavari, 1996)
    2) LD50- (ORAL)MOUSE:
    a) 4 g/kg (Budavari, 1996)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 1 g/kg (Budavari, 1996)
    4) LD50- (ORAL)RAT:
    a) 4 g/kg (Budavari, 1996)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Clindamycin is a semisynthetic antibiotic created from the parent compound lincomycin (Prod Info CLEOCIN(R) oral capsules, 2009).
    1) Clindamycin and lincomycin bind exclusively to the 50S bacterial ribosomal subunit and suppress bacterial protein synthesis (Sande & Mandell, 1990; Prod Info CLEOCIN(R) oral capsules, 2009).

Physicochemical

Physical Characteristics

    A) Is monobasic.

Ph

    A) CLINDAMYCIN
    1) CLINDAMYCIN HYDROCHLORIDE: 3.0 to 5.0 (10% aqueous solution) (S Sweetman , 2001)
    2) CLINDAMYCIN PALMITATE HYDROCHLORIDE: 2.8 to 3.8 (1% aqueous solution) (S Sweetman , 2001)
    3) CLINDAMYCIN PHOSPHATE: 3.5 to 4.5 (1% aqueous solution) (S Sweetman , 2001).
    B) LINCOMYCIN
    1) LINCOMYCIN HYDROCHLORIDE: 3.5 to 5.5 (10% aqueous solution) (S Sweetman , 2001).

Molecular Weight

    A) CLINDAMYCIN
    1) 424.99 (Budavari, 1996)
    B) LINCOMYCIN
    1) 406.54 (Budavari, 1996)

References

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    116) Product Information: CLEOCIN(R) vaginal cream, clindamycin phosphate vaginal cream. Pharmacia & Upjohn Company, New York, NY, 2005.
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    129) Product Information: clindamycin phosphate 2% vaginal cream , clindamycin phosphate 2% vaginal cream . Greenstone LLC, Peapack, NJ, 2008.
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