Unicure Lincomycin Hydrochloride Capsule

UNICURE LINCOMYCIN
Lincomycin Hydrochloride Capsule U.S.P. 500mg

 

Composition

Each capsule contains: Lincomycin (Iincomycin hydrochloride monohydrate) U.S.P. 500mg.

 

ORAL ADMINISTRATION

Capsules: Pack of 3 x4 ’s and 100 x 4’s Capsules.

 

Properties
Depending on the sensitivity of the micro-organism and the concentration of the antibiotic. Lincomycin may be either bactericidal or bacteriostatic. The in Vitro spectrum includes following micro-organisms:

1. Sensitivity micro-organism (MIC < 2mg/ml)

– Anaerobic non-sporulating, gram-positive bacteria a.o. Antinomyces spp., Propionibacterium spp. and Eubacterium spp. – anaerobic and micro – aerofilic gram – positive cocci, a.o. peptococcus spp. peptostreptococcus spp. and micro – aerofilic streptococci.

– Aerobic gram – positive micro – organisms a.o. staphylococci, streptococci (except S. faecalis) and pneumococci.

2. Moderately sensitive micro – organisms (MIC between 2 and 4 mg/ml) which are likely to response for higher dosages.

– Anaerobic non – sporulating gram – positive bacteria a.o. Clostridium spp.

3. Resistant micro -organisms or micro – organisms showing low sensitivity (MIC > 8ug /ml) a.o. Streptococcus faecalis, Neisseria, most Haemophilus influenzae strains. Pseudomonas and other gram – negative micro – organisms. Cross resistance of the dissociated type has been observed in Vitro between clindamycin and lincomycin on the one side and the macrolides (erythromiycin, oleandomycin, and spiramycin) on the other side. Absolute cross resistance exists between lincomycin and clindamycin. Micro-organisms have not developed resistance to UNICURE rapidly when tested by in Vitro or in vivo methods. Strapthyococci develop in Vitro resistance to lincomycin or clindamycin in a slow, stepwise manner.

 

PHARMACOKINETICS

Absorption: Reabsorption of orally, on an empty stomach, administered lincomycin is 20-35%. After an oral 500mg dose peak levels of circa 3ug /ml are reached in 2 to 4 hours, this value is diminished with about 50% in case the drug is administered with meals. For most gram-positive micro-organisms serum levels are maintained above the MIC (between 1 and 2 ug/ml) for 6 to 8 hours. Intramuscular administration of a single dose of 600 mg produces a peak serum level of 12- 20 ug /ml at 1/2 1 hour with detectable concentration as long as 24 hours. The intravenous infusion over a 2- hours interval of 600 mg of UNICURE results in a maximum serum concentration of 20 ug/ml at 30 minutes, yielding concentration of 1 to 2 ug/ml at 14 hours.

 

Distribution

Direct and indirect evidence suggests that protein binding decreases with higher serum concentration 5.471 (saturable plasma protein binding) in the foetal blood, the peritoneal and pleural liquid concentration of 25-50 % of the blood levels can be reached, in the mother milk 50 – 100%, in the bone tissues about 40% and in the surrounding softer tissues 75%. However lincomycin penetrates slowly, in the cerebrospinal fluid (1-18% of the blood level); in case of meningitis, liquor levels up to 40% of the blood levels have been observed.

 

Excretion

The relatively strong metabolism is mainly taking place through the liver. The Normal serum half-life time is 5, 4 + 1 hour. However, this time can be prolonged in case of disturbed liver and/or renal function. Therefore consideration should be given to decreasing the frequency of administration of lincomycin in patients with impaired hepatic or renal function.

After a signal oral dose 500 mg the excretion in microbiologically active form in the urine varies from 1 to 31% (average 4%) and in the faeces amounts to about 33%. Apparently the bile is an important route of excretion after oral demonstration, giving bile levels which are about 10 times higher than blood levels. After a 600 mg intramuscular dose the excretion of microbiologically active product in the urine is 1.8 to 24.8% (average 17.3%), in the faeces 4 to 14%. After intravenous administration of 600 mg over a 2 hours period, the excretion in microbiologically active product in the urine is 4.9 to 30.3% (average 13.8%). The reminder is being excreted as microbiologically non-active metabolities. There is no influence of hemodialysis and peritoneal dialysis on the excretion of lincomycin from the blood.

 

Indications

Lincomycin has been shown to be effective in the treatment of the following infections when caused by susceptible strain of gram-positive aerobes such as streptococci, pneumococci and staphylococci, or by susceptible anaerobic bacteria.

1. 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.

2. Lower respiratory infections including acute bronchitis and pneumonia.

3. Skin and soft tissue infections including cellulitis, furuncles abscesses, impetigo, acne and wound infections, conditions like erysipelas, lymphadenitis, paronychia (panaritium), mastitis and cutaneous gangrene should, if caused by susceptible organisms, have responded well to lincomycin therapy.

4. Bone and joints infections including osteomyelitis and septic arthritis.

5. Septicemia and endocarditis. Selected cases of septicemia and/or endocarditis due to susceptible organisms have responded well to lincomycin. However, bactericidal drug are often preferred for these infections.

6. Bacillary dysentery -although Shigella is resistant to lincomycin in vitro (MIC approximately 200- 400ug /ml), lincomycin has been effective in its treatment due to the very high levels of lincomycin attained in the bowel (approximately 3000-7000ug /grams of stool).

 

Dosage and administration

ADULTS

A. Oral

1. Serious infections due to susceptible organisms: 500 mg t.i.d. (q8h).

2. More severe infections: 500 mg q6h or q. i. D.

B. Intramuscular Injection

1. Serious infections: 600 mg I. M. every 24 hours.

2. More severe infections: 600 mg I. M. 12 hours (or more often) as determined by the severity of the infection.

C. Intravenous injection (see dilution and infusion rates)

1. Serious Infections: 600 mg to 1 gram every 8 to 12 hours.

2. For more severe Infections these doses may have to be increased.

3. In life threatening situations, daily intravenous doses of as much as 8 grams have been given.

CHILDREN (over 1 month of age)

A. Oral

1. Serious infections: 30mg/kg/day divided into 3 to 4 equal doses.

2. More severe infections: 60 mg/kg/day divided into 3 to 4 equal doses.

B. Intramuscular injection

1. Serious infections: 10mg/kg/day as 1 intramuscular injection.

2. More severe infections: 10mg/kg given every 12 hours or more often.

C. intravenous injection

10 to 20 mg/kg/day depending on the severity of the injection may be infused in divided doses as described in the section on dilution and infusion rates. When therapy with lincomycin is required in individuals with severe impairment of renal function, an appropriate dose is 25 to 30% of that recommended for patients with normally functioning kidneys.

In cases of beta-hemolytic streptococcal injection, treatment should be continued for at least 10 days. For optimal absorption it is recommended that nothing be given by mouth for a period of one to two hours before and after oral administration of lincomycin.

 

DILUTION AND INFUSION RATES

Intravenous doses are given on the basis of 1 gram of lincomycin diluted in not less than 100 ml of appropriate solution and infused over a period of not less than one hour.

Doses Volume diluents Time
600 mg 100 ml 1 hour
1 gram 100 ml 1 hour
2 grams 200 ml 2 hours
3 grams 300 ml 3 hours
4 grams 400 ml 4 hours

These doses may be repeated as often as required to the maximum recommended daily of 8 grams of lincomycin.

Note:

Severe cardiopulmonary reactions have occurred when this drug has been given at greater than the recommended concentration and rate.

 

Contraindication

Lincomycin is contraindicated in patients previously found sensitive to lincomycin or clindamycin.

 

Adverse reactions
1. Gastrointestinal – Nausea, vomiting, abdominal distress and persistent diarrhea (see SPECIAL PRECAUTIONS) and, with oral preparations, esophagitis.

2. Hematopoietic – Neutropenia, leukopenia, agranlocytosis and thrombocytopenic purpura have been reported. There have been rare reports of aplastic anemia and pancytopenia in which lincomycin could not be ruled out as the causative agent.

3. Hypersensitivity reactions – Hypersensitivity reactions such as angioneurotic edema, serum sickness and anaphylaxis have been reported, some of these in patients sensitive to penicillin. Rare instance of erythema, some resembling Stevens- Johnson syndrome, have been associated with lincomycin administration.

4. Skin and mucous membranes – Pruritus, skin rashes, urticaria, vaginitis and rare instance of exfoliative and vesiculobullous dermatitis have been reported.

5. Liver – Jaundice and abnormal liver functions tests (particularly elevation of serum transaminase) have been observed during lincomycin thereapy.

6. Cardiovascular – Instance of hypertension following parenteral administration have been reported, particularly after too rapid administration. Rare instance of cardiopulmonary arrest have been reported after too rapid intravenous administration (see DOSAGE & ADMINISTRATION).

7. Local reactions – Local irritation, pain, induration and sterile abscess formation have been seen with I.M. injection. Thrombophlebitis has been reported with l.V. injection. These reactions can be minimized by deep I.M. injection and avoidance of indwelling I.V. Catheters.

 

Special precautions

The injectable form of this product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal ‘gasping syndrome’ in premature infants. As is the case for almost all antibiotic therapies the lincomycin therapy has been associated with severe colitis, which may end fatally. The clinical spectrum varies from mild, watery diarrhea to severe, persistent diarrhea, leukocytosis, fever, severe abdominal cramps which may be associated with the passage of blood and mucus which, if allowed to progress, may produce peritonitis, shock and toxic megacolon.

The diagnosis of antibiotic – associated colitis is usually made by the recognition of the clinical symptoms. It can be substantiated by endoscopic demonstration of pseudomembrance colitis and may be further confirmed by culture of the stool for Clostridium difficile on selective media and assay of the stool specimen for the toxin(s)
C. Difficile: Onset of antibiotic – associated colitis has occurred during the administration or even or two or three weeks following administration of the antibiotic. The disease is likely to take a more severe course in order patients or in patients who are debilitated.
In case of occurrence of mild colitis, discontinuance of lincomycin is recommended. Treatment with cholestyramine and colestipol resins is recommended as these products have been shown to blind the toxin in vitro. The recommended dosage for cholestyramine is 4 grams given 3 to 4 times daily/and for colestipol, 5 grams given 3 times daily. When severe antibiotic- associated colitis occurs this has been treated with appropriate fluid electrolyte and protein supplementation.

Studies have also indicated that a toxin(s) produced by Clostridia (especially C. difficile) is (are) the principal direct cause of antibiotic associated colitis. These studies also indicate that this toxigenic Clostridium is usually sensitive in vitro to vancomycin, when 125 to 500 mg rapid observed disappearance of the toxin from faecal sample and a coincident clinical recovery from the diarrhea. In some cases colitis may reoccur after cessation blind vancomycin treatment. Chloestyramine or colestipol resins blind vancomycin in vitro. If both a resin and vancomycin are to be administered concurrently, it may be advisable to separate the time of administration of each drug. As an alternative therapy oral bacitracin 25,000 units q. i. d. for 7-10 days could be considered. Drugs which cause bowel stasis should be avoided.

Caution should be exercised in prescribing lincomycin doses in patients with a history of GI disease, particularly colitis. 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 used in the treatment of meningitis.

Antagonism has been demonstrated between lincomycin and erythromycin in vitro, because of possible clinical significance, these two drugs should not be administered concurrently.

If lincomycin antibiotic therapy is prolonged, liver and kidney function tests should be performed.

The use of lincomycin may result in overgrowth of non-susceptible organisms, particularly yeasts.

Lincomycin should not be injected intravenously undiluted as a bolus, but should be infused over at least 10-60 minutes as directed in the DOSAGE AND ADMINISTRATION section. Lincomycin has been known 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. Lincomycin should be administered with caution in atopic individuals. Patients with very severe renal disease and/or very severe hepatic disease accompanied by severe metabolic aberrations should be dosed with caution, and serum lincomycin levels monitored during high dose -therapy.

 

Incompatibilities

The following drugs are physically incompatible with lincomycin: novobiocin, kanamycin.

 

Pregnancy and lactation

Safety for use in pregnancy has not been established. Lincomycin has been reported to appear in breast milk in ranges from 0.5 to 2.4 ug/mI.

 

Interactions

Cross resistance has been demonstrated between clidamycin and lincomycin.

 

Storage

Store at controlled room temperature (150 – 30°C).

Store in a cool, dry and dark place. Protect from light.

Keep all medicines out of reach of children.

 

Dosage

As directed by the Physician.

 

Manufactured by

GREENFIELD PHARMACEUTICAL (JIANG SU) CO., LTD.

NO. 38, TAI JIU ROAD, TAI ZHOU, JIANG SU PROVINCE, P.R. CHINA

 

Marketed by

UNICURE PHARMACEUTICAL CO., LTD.

Ikofa Village, Lagos-Benin Expressway, Ijebu-Ode,

Ogun State, Nigeria