Non-proprietary name: lincomycin hydrochloride Chemical Name: Lincomycin hydrochloride consists mainly of the monohydrate of methyl 6,8-dideoxy-6-[(2S,4R)-1-methyl-4-propylpyrrolidine-2-carboxamido]-1-thio-D-erythro--D- galacto-octopyranoside hydrochloride. CAS Number: 7179-49-9 The structure of lincomycin hydrochloride is:
LINCOCIN (lincomycin hydrochloride) is the monohydrated salt of lincomycin, a substance produced by the growth of a member of the lincolnensis group of Streptomyces lincolnensis (fam. Streptomycetaceae). It is a white, or practically white, crystalline powder and is odourless or has a faint odour. Its solutions are acid and are dextrorotatory. LINCOCIN is freely soluble in water, soluble in dimethylformamide and very slightly soluble in acetone. LINCOCIN Injection is a clear, colourless or almost colourless solution, practically free from particles.
In vitro studies indicate that the following organisms are usually sensitive to concentrations achieved normally in the serum following recommended doses: Staphylococcus aureus, Staphylococcus epidermidis, beta-haemolytic Streptococcus, Streptococcus viridans, Streptococcus pneumoniae, Clostridium tetani, Clostridium perfringens, Corynebacterium diphtheriae.
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The drug is not active against most strains of Enterococcus faecalis, nor against Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae or other gram-negative organisms or yeasts. Some strains of Clostridium perfringens and strains of some less common human pathogens of Clostridia may be lincomycin-resistant. Depending on the sensitivity of the organism and concentration of the antibiotic, it may be either bactericidal or bacteriostatic. Cross resistance has not been demonstrated with penicillin, chloramphenicol, ampicillin, cephalosporins or the tetracyclines. Despite chemical differences, LINCOCIN exhibits antibacterial activity similar but not identical to the macrolide antibiotics (e.g. erythromycin). Some cross-resistance (with erythromycin) including a phenomenon known as dissociated cross-resistance or macrolide effect has been reported. Microorganisms have not developed resistance to LINCOCIN rapidly when tested by in vitro or in vivo methods. Staphylococci develop resistance to LINCOCIN in a slow step-wise manner based on in vitro serial subculture experiments. Studies indicated that LINCOCIN does not share antigenicity with penicillin compounds.
LINCOCIN is absorbed rapidly after a 500 mg oral dose, reaching peak serum levels of 2-3 micrograms/mL in 2 to 4 hours, which then diminish to approximately 1 micrograms/mL in a further 4-8 hours. Doubling the dose increases but does not double the peak serum levels. Food in the stomach reduces total absorption as well as peak serum levels. Urinary recovery of drug in a 24-hour period ranges from 1.0 to 31 percent (mean: 4.0) after a single oral dose of 500 mg. Bile is an important route of excretion. Significant levels have been demonstrated in the majority of body tissues. Although the drug is not present in significant amounts in the spinal fluid of normal volunteers, it has been demonstrated in the spinal fluid of one patient with pneumococcal meningitis. Intramuscular administration of a single dose of 600 mg produces a peak serum level of approximately 9-11.5 micrograms/mL at 30 minutes with detectable levels persisting for 24 hours. Urinary excretion after this dose ranges from 1.8 to 24.8 percent (mean: 17.3). The intravenous infusion over a 2-hour interval of 600 mg of LINCOCIN in 500 mL of 5 percent glucose in water yields therapeutic levels for 14 hours. Urinary excretion ranges from 4.9 to 30.3 percent (mean: 13.8). The excretion of lincomycin in urine and bile does not account for all the administered dose and a substantial proportion of the drug appears to be inactivated in the body, presumably in the liver. The biological half-life, after oral, intramuscular or intravenous administration is 5.4 + 1.0 hours. Haemodialysis and peritoneal dialysis do not effectively remove lincomycin from the blood.
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LINCOCIN is indicated in the treatment of serious infections due to susceptible strains of gram-positive aerobes such as streptococci, pneumococci and staphylococci. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgement of the physician, a penicillin is inappropriate. Because of the risk of colitis (see PRECAUTIONS), before selecting lincomycin the physician should consider the nature of infection and the suitability of less toxic alternatives (e.g. erythromycin). LINCOCIN has been demonstrated to be effective in the treatment of staphylococcal infections resistant to other antibiotics and susceptible to lincomycin. Staphylococcal strains resistant to LINCOCIN have been recovered; culture and susceptibility studies should be done in conjunction with LINCOCIN therapy. In the case of macrolides, partial but not complete cross resistance may occur. The drug may be administered concomitantly with other antimicrobial agents with which it is compatible when indicated (see PRECAUTIONS). The specific infections for which LINCOCIN is indicated are as follows:
Upper respiratory infections including tonsillitis, pharyngitis, otitis media, sinusitis, scarlet fever and as adjuvant therapy for diphtheria. Effectiveness in the treatment of mastoiditis would be anticipated.
Lower respiratory infections including acute and chronic bronchitis and pneumonia.
Skin and skin structure infections including cellulitis, furuncles, abscesses, impetigo, acne and wound infections. Conditions such as erysipelas, lymphadenitis, paronychia (panaritium), mastitis and cutaneous gangrene should, if caused by susceptible organisms, respond to lincomycin therapy.
Bone and joint infections including osteomyelitis and septic arthritis.
Septicaemia and endocarditis. Selected cases of septicaemia and/or endocarditis due to susceptible organisms have responded well to lincomycin. However, bactericidal drugs are often preferred for these infections.
Bacillary Dysentery. Although Shigella is resistant to lincomycin in vitro (MIC approximately 200-400 micrograms/mL), lincomycin has been effective in its treatment due to the very high levels of lincomycin attained in the bowel (approximately 3000-7000 micrograms/gram of stool).
This drug is contraindicated in patients previously found to be hypersensitive to lincomycin or clindamycin. It is not indicated in the treatment of minor bacterial infections or viral infections. Lincomycin is not indicated in the newborn.
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LINCOCIN Injection contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. The use of lincomycin can lead to the development of severe colitis. Fatalities have been reported. Therefore LINCOCIN should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS section. It should not be used in patients with non-bacterial infections such as most upper respiratory tract infections. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with the use of antibiotics, including parenteral lincomycin. Symptoms may occur up to several weeks after cessation of antibiotic therapy. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone, however, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against C. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis (e.g. opiates and diphenoxylate with atropine [LOMOTIL(r)]) may prolong and/or worsen the condition and should not be used. Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhoea less well. When LINCOCIN is indicated in these patients, they should be carefully monitored for change in bowel frequency.
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Carefulmedical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. LINCOCIN should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. LINCOCIN, like any drug, should be used with caution in patients with a history of asthma or significant allergies. The use of antibiotics occasionally results in overgrowth of nonsusceptible organisms - particularly yeasts. Should superinfections occur, appropriate measures should be taken. When patients with pre-existing monilial infections require LINCOCIN therapy, concomitant antimonilial treatment should be given.
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During prolonged LINCOCIN therapy, periodic liver function and renal studies and blood counts should be performed. In patients with impaired hepatic or renal function, the serum half-life of lincomycin is increased. Consideration should be given to decreasing the frequency and dose of lincomycin administered in patients with impaired hepatic or liver function. Since adequate data are not yet available in patients with pre-existing liver disease, its use in such patients is not recommended at this time unless special clinical circumstances so indicate. Although lincomycin appears to diffuse into cerebrospinal fluid, levels of lincomycin in the CSF may be inadequate for the treatment of meningitis. Thus, the drug should not be used in the treatment of meningitis. LINCOCIN is incompatible with novobiocin, kanamycin and phenytoin. Lincomycin should not be injected IV as a bolus but should be infused as described in the DOSAGE AND ADMINISTRATION section.
:
In humans, lincomycin crosses the placenta and results in cord serum levels about 25% of the maternal serum levels. No significant accumulation occurs in the amniotic fluid. There are no controlled studies in pregnant women; however, the progeny of 302 patients treated with lincomycin at various stages of pregnancy showed no increases in congenital anomalies or delayed development compared to a control group for up to 7 years after birth. Lincomycin should be used during pregnancy only if clearly needed. Lincomycin is not indicated in the newborn (see CONTRAINDICATIONS).
LINCOCIN has been reported to appear in breast milk in ranges of 0.5 to 2.4 micrograms/mL. It should not, therefore, be used during lactation unless alternative arrangements can be made for feeding the baby.
LINCOCIN has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.
Antagonism has been demonstrated between lincomycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.
Gastrointestinal:
Glossitis, stomatitis, nausea, vomiting, abdominal distress, persistent diarrhoea, enterocolitis (see PRECAUTIONS). With oral preparations, oesophagitis.
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Haemopoietic:
Neutropenia, leucopenia, agranulocytosis and thrombocytopenic purpura have been reported. There have been rare reports of aplastic anaemia and pancytopenia in which LINCOCIN could not have been ruled out as the causative agent.
Hypersensitivity Reactions:
Hypersensitivity reactions such angioneurotic oedema, serum sickness and anaphylaxis have been reported, some of these in patients known to be sensitive to penicillin. Rare instances of erythema multiforme, some resembling Stevens-Johnson Syndrome, have been associated with LINCOCIN. If an allergic reaction should occur, the drug should be discontinued and the usual agents (adrenalin, corticosteroids, antihistamines) should be available for emergency treatment.
Skin and Mucous Membranes:
Skin rashes, pruritus including pruritus ani, urticaria and vaginitis and rare instances of exfoliative and vesiculobullous dermatitis have been reported.
Liver:
Although no direct relationship of LINCOCIN to liver dysfunction has been established, jaundice and abnormal liver function tests (particularly elevations of serum transaminase) have been observed in a few instances.
Renal:
Although no direct relationship of lincomycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.
Cardiovascular:
Instances of hypotension following parenteral administration have been reported, particularly after too rapid intravenous administration. Rare instances of cardiopulmonary arrest have been reported after too rapid intravenous administration.
Special Senses:
Tinnitus and vertigo have been reported occasionally.
Local Reactions
: Local irritation, pain induration and sterile abscess formation have been seen with intramuscular injection. Thrombophlebitis has been reported with intravenous injection. These reactions can be minimised by deep intramuscular injection and avoidance of indwelling intravenous catheters.
If significant diarrhoea occurs during therapy, this antibiotic should be discontinued (see PRECAUTIONS).
With beta-haemolytic streptococcal infections, treatment should continue for at least 10 days to diminish the likelihood of subsequent rheumatic fever or glomerulonephritis.
Adults: Serious infections - 600 mg (2 mL) intramuscularly every 24 hours. More serious infections - 600 mg (2 mL) intramuscularly every 12 hours or more often, as determined by the severity of the infection.
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Children over 1 month of age: Serious infections - one intramuscular injection of 10 mg/kg/day. More serious infections - one intramuscular injection of 10 mg/kg every 12 hours or more often.
Intravenous doses are given on the basis of 1 g LINCOCIN diluted in not less than 100 mL of appropriate solution and infused over a period of not less than one hour. Note: Severe cardiopulmonary reactions have occurred when this drug has been given at greater than the recommended concentration and rate. Adults: Serious infections - 600 mg to 1 g given every 8-12 hours. More severe infections - the above doses may be increased. In life-threatening situations, daily intravenous doses of as much as 8 g have been given. Children over 1 month of age: Depending on the severity of the infection, 10-20 mg/kg/day may be infused in divided doses as described in the table below.
| Dilution and Infusion Rates | ||
| Dose | Vol. Diluent | Time |
| 600 mg | 100 mL | 1 hr |
| 1 g | 100 mL | 1 hr |
| 2 g | 200 mL | 2 hr |
| 3 g | 300 mL | 3 hr |
| 4 g | 400 mL | 4 hr |
These doses may be repeated as often as required to the limit of the maximum recommended daily dose of 8 g. The following infusion solutions have been found to be physically compatible with LINCOCIN: Glucose Intravenous Infusion 5%, Glucose Intravenous Infusion 10%, Sodium Chloride 0.9% and Glucose 5% Intravenous Infusion, Sodium Chloride 0.9% and Glucose 10% Intravenous Infusion, Compound Sodium Lactate Intravenous Infusion, Sodium Lactate 1/6 Molar and Dextran 70 Intravenous Infusion. Please note that these compatibility determinations are physical observations only, not chemical determinations. Adequate clinical evaluation of the safety and efficacy of these combinations has not been performed.
When LINCOCIN therapy is required in individuals with severe impairment of renal function, an appropriate dose is 25 to 30% of that recommended for patients with normal renal function.
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The minimal toxic or lethal dose is not well established. At therapeutic doses, the primary toxic effects may involve the gastrointestinal tract and may include severe diarrhoea and pseudomembranous colitis that may result in death. Rapid administration of large doses has resulted in ventricular dysrhythmias, hypotension and cardiac arrest. Dermatitis, nephrotoxicity, hepatotoxicity, and various haematological abnormalities are toxic effects that occur less frequently. No specific antidote is known. Support respiratory and cardiac function. In cases of overdose, drug levels of lincomycin are not clinically useful. However, monitoring serum concentrations in patients with markedly reduced renal and hepatic function may be indicated during high-dose therapy. Monitor full blood count in patients with significant exposure as lincomycin may produce abnormalities of the haematopoietic system. Because lincomycin may cause hepatotoxicity, monitor liver function tests in patients with significant exposure. Haemodialysis and peritoneal dialysis are not effective in removing lincomycin from the serum. Contact the Poisons Information Centre for advice on the management of an overdose.
LINCOCIN Injection is available as 5 x 2 mL vials. Each mL contains lincomycin hydrochloride equivalent to lincomycin base 300 mg; also benzyl alcohol, 9.45 mg; water for injections, q.s.
Store below 25oC Protect from light. Do not freeze.
Prescription Medicine
LINCOCIN Injection is available as 5 x 2 mL vials
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Pfizer New Zealand Limited PO Box 3998 Auckland New Zealand Toll free number: 0800 736 363
29 December 2010
(r) Registered Trademark
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