Lincomycin - Darnitsa

General characteristics. Structure:

Active ingredient: lincomycin;

1 ml contains hydrochloride lincomycin in terms of lincomycin 300 mg;

excipients: dinatrium эдетат, sodium hydroxide, water for injections.

Pharmacological properties:

Pharmacodynamics. Lincomycin – an antibiotic of group of linkozamid, Streptomyces lincolniensis waste product. Suppresses proteinaceous synthesis of bacteria owing to reversible linkng with 50S-subunit of ribosomes, breaks formation of peptide bonds.

Depending on sensitivity of microorganisms and concentration of an antibiotic lincomycin can find both bacteriostatic, and bactericidal action. The range of activity of in vitro turns on a number of activators:

sensitive microorganisms (minimum overwhelming concentration (MOC) ≤ 2 mkg/ml):

anaerobic gram-positive bacteria, do not form disputes, including Propionibacterium spp, Eubacterim spp, and also Actinomyces spp;

anaerobic and mikroaerofilny gram-positive cocci, including Peptococcus spp, Peptostreptococcus spp. and mikroaerofilny streptococci;

aerobic gram-positive microorganisms, including staphylococcus, streptococci (except for S. faecalis) and pneumococci.

Microorganisms with moderate sensitivity (MPK makes 2-4 mkg/ml):
the anaerobic gram-negative bacteria which are not forming disputes, including Bacteroides spp, Fusobacterium spp;

the anaerobic gram-positive bacteria forming disputes, including Clostridium spp.
Resistant microorganisms or microorganisms with low sensitivity (MPK => 8 mkg/ml), including Streptococcus faecalis, Neisseria, the majority of strains of Haemophilus influenzae, Pseudomonas and other gram-negative microorganisms.

Though sort Shigella bacteria resistant in vitro to lincomycin (MPK is approximately equal to 200-400 mkg/ml), lincomycin is effective at this disease because in intestines very high level of lincomycin ( about 3000-7000 mkg/g of excrements) is reached.

Cross resistance of the dissociated in vitro type between lincomycin and clindamycin on the one hand and macroleads (erythromycin, Oleandomycinum and Spheromycinum) – with another was observed. Absolute cross resistance exists between lincomycin and clindamycin. In experiments of in vitro and in vivo bystry development of resistance of microorganisms to lincomycin was not observed. At stafilokokk resistance of in vitro to lincomycin or clindamycin develops slowly, gradually.

Pharmacokinetics. Absorption. Intramuscular introduction of a single dose of 600 mg allows to receive the maximum level in serum, equal 12-20 mkg/ml, in 0,5-1 hour, at the same time the concentration which is giving in to definition remains within 24 hours. At intravenous infusion of lincomycin on 600 mg lasting 2 hours it is possible to reach the maximum concentration in the serum equal of 20 mkg/ml within 30 minutes and to maintain the concentration equal of 1-2 mkg/ml, within 14 hours.

Distribution. On the basis of direct and indirect signs it is established that linkng with proteins decreases at increase in concentration in serum (the sating linkng with proteins of plasma). In fruit blood, in peritoneal and pleural liquids the concentration making 25-50% of level in blood can be reached, in maternal milk this indicator makes 50-100%, in a bone tissue – about 40% and in surrounding soft tissues – 75%.

At the same time, lincomycin slowly gets into cerebrospinal fluid (1-18% of level in blood), at a disease of meningitis level in liquor reaches 40% of level in blood.

Removal. A considerable part of drug is metabolized, metabolism happens preferential in a liver. Normal the serumal elimination half-life makes   5,4 ± 1 hour. However this period can be extended at an abnormal liver function and/or kidneys. In this regard it is necessary to consider need of reduction of frequency of administration of lincomycin by the patient with an abnormal liver function or kidneys.

After intramuscular introduction of 600 mg excretion bacteriological of active drug in urine makes 1,8-24,8% (on average – 17,3%), and in a chair – 4-14%. After intravenous administration of 600 mg within 2 hours excretion bacteriological of active drug in urine makes 4,9-30,3% (on average – 13,8%). The remains of drug are allocated in shape bacteriological inactive metabolites. The hemodialysis and peritoneal dialysis do not influence lincomycin excretion from blood.

Pharmaceutical characteristics.

Main physical and chemical properties: transparent, colourless or slightly yellowish color liquid with a light specific smell.

Incompatibility.

Drug pharmaceutical is incompatible with Kanamycinum, ampicillin, barbiturates, theophylline, calcium a gluconate, heparin and magnesium sulfate.

Lincomycin is incompatible in one syringe or a dropper with Kanamycinum, novobiocin or Phenytoinum.

Indications to use:

Treatment of the infections caused by sensitive strains of gram-positive aerobic or anaerobic bacteria:

–       ENT organs, including tonsillitis, pharyngitis, average otitis, sinusitis, a mastoiditis; scarlet fevers, and also as auxiliary therapy at diphtheria;

–       respiratory tracts, including acute and chronic bronchitis, pneumonia;

–       skin and soft tissues, including a panniculitis, a furunculosis, abscess, impetigo, eels, infections of wounds, and also such diseases as an ugly face, lymphadenitis, a paronychia (felon), mastitis and gangrene of skin;

–       bones and joints, including osteomyelitis and septic arthritis;

–       septicaemia and endocarditis;

–       bacterial dysentery. Though Shigella is resistant to    in vitro lincomycin (the minimum inhibiting concentration – about 200-400 mkg/ml), lincomycin is effective for treatment of dysentery as in intestines very high levels of lincomycin are reached (about 3000-7000 mkg/g in excrements).

Route of administration and doses:

Before use of drug it is necessary to carry out a skin sensitivity test to Linkomitsin-Darnits.

Adults.

A. Intramuscular injections.

The usual dose makes:
1.600 mg intramusculary each 24 hours.
2. More severe forms of infections: on 600 mg intramusculary each 12 hours (or is more often) that is defined by weight of an infection.

B. Intravenous injections.

The usual dose makes:
1. From 600 mg to 1 g each 8-12 hours.
2. At heavier infections these doses can be raised.
3. At the states posing a threat for life, the daily dose for intravenous administration can make up to 8 g.

Children (is more senior than 1 month)

A. Intramuscular injections.

1)     10 mg of kg/days in the form of 1 injection.

2)     More severe forms of infections – to 10 mg/kg are each 12 hours or are more often.

B. Intravenous injections.

From 10 to 20 mg/kg/days depending on weight of an infection can be entered by several doses according to the described rules of cultivation and speed of infusion.
Dosage for patients with an abnormal liver function or kidneys. At patients with an abnormal liver function or kidneys the lincomycin elimination half-life from blood serum increases that is the basis for decrease in frequency of administration of lincomycin at patients with the broken function of a liver or kidneys. If therapy by lincomycin is necessary for patients with a considerable renal failure, the corresponding dose has to make from 25 to 30% of the dose recommended for patients with normal function of kidneys.

Duration of treatment is defined individually.

The infections caused by a β-hemolitic streptococcus. Treatment has to continue not less than 10 days.

Cultivation and speed of infusion.

The dose for introduction in the form of infusion is calculated as follows:
1 g of lincomycin gets divorced not less than in 100 ml of the corresponding solution for cultivation (0,9% chloride sodium solution), at the same time duration of infusion has to be not less than 1 hour.

Table 1.

 

Dose             Obem of solution for cultivation        infusion Duration
600                        mg 100 ml                                                are 1 hour
1                              g 100 ml                                                is 1 hour
2                              g 200 ml                                                there are 2 hours
3                              g 300 ml                                                there are 3 hours
4                              g 400 ml                                                there are 4 hours

The specified doses can be entered repeatedly, the frequency of introduction is defined as necessary, at the same time the daily dose should not exceed the maximum recommended dose of lincomycin, equal 8 g.

Note. There can be heavy reactions from cardiovascular and respiratory systems if the drug is administered in higher, than it is recommended, concentration and with greater speed.

Features of use:

Use during pregnancy or feeding by a breast.

Drug is not used to pregnant women except for cases, when necessary according to vital indications.

In a research on rats at peroral administration of lincomycin in a dose to 1000 mg/kg (that exceeds by 7,5 times the maximum dose for the person of 8 g/days) undesirable impacts on survival of posterity are not registered (for the period from the birth before completion of maternal feeding). Also teratogenic effects in researches on rats to whom the lincomycin dose exceeding the highest recommended dose for the person of 8 g/days more than by 55 times was entered are not revealed.

At the person lincomycin gets through a placenta and is defined in serum of umbilical blood at the level of 25% of level in blood serum of mother. Considerable accumulation of drug in amniotic liquid was not observed. Controlled researches at pregnant women were not conducted; however at children of 302 patients accepting lincomycin on different durations of gestation increase in frequency of congenital anomalies or delay of development in comparison with control group at observation to seven-year age was not observed. It is necessary to appoint lincomycin during pregnancy only in case of need.

Lincomycin was found in breast milk of the person in concentration from 0,5 to 2,4 mkg/ml therefore at use of lincomycin of feeding by a breast it is necessary to stop temporarily.

Children.

Linkomitsin-Darnitsa apply to children is more senior than 1 month in the recommended doses.

As well as at use of almost all antibiotics, at use of lincomycin colitis with a possible lethal outcome can develop. Symptoms of colitis can vary from a scanty watery chair to the heavy long diarrhea which is followed by a leukocytosis, fever, strong colicy pains in a stomach, availability of blood and slime in a chair, and when progressing these symptoms peritonitis, shock and toxic megacolon can develop.

The diagnosis of the colitis connected with an antibioticotherapia usually is made on the basis of clinical symptoms. The diagnosis is confirmed by data of an endoscopic research at which pseudomembranous colitis is shown, and further the calla on existence of Clostridium difficile with use of the selection environments, and also test researches a calla on availability of the toxins produced by C. difficile can be confirmed with a cultural research. Development of the colitis connected with an antibioticotherapia happens during treatment or in 2-3 weeks after the end of treatment by antibiotics.

This complication is most probable at a serious illness at elderly people, and also at the weakened patients. If against the background of therapy not heavy colitis develops, then administration of lincomycin is recommended to be stopped. It is recommended to carry out treatment with use of holestiraminovy and holestipolovy pitches as in vitro these substances connect toxins. Holestiramin is recommended to apply on 4 g 3-4 times a day, and холестипол – on 5 g 3 times a day. If the colitis connected with an antibioticotherapia develops, then treatment is shown by administration of liquid, electrolytes and protein. Researches also show what toxins which are produced by Clostridium (especially C. difficile) is the main direct reason for the colitis connected with an antibioticotherapia. It is possible to apply bacitracin to treatment inside on 25 000 ME 4 times a day within 7-10 days. It is impossible to apply medicines which cause intestinal стаз.

Patients should appoint lincomycin with care with digestive tract diseases in the anamnesis, especially with colitis.

Though it is established that lincomycin gets through a blood-brain barrier, lincomycin level in cerebrospinal fluid can be insufficient for treatment of meningitis. Therefore this drug at treatment of meningitis should not be used.
When performing long antibiotic treatment by lincomycin it is regularly necessary to conduct researches of function of a liver and kidneys. At use of lincomycin the excess growth of microorganisms, especially yeast, insensitive to this antibiotic, is possible.

Lincomycin should not be entered in the form of intravenous bolyusny not divorced injections, infusion has to last not less than 60 minutes as it is specified in the section "Route of Administration and Doses". It is necessary to appoint lincomycin with care the patient with an atopy.
By the patient with the serious illness of a liver and/or kidneys which are followed by serious violations of metabolism, it is necessary to carry out selection of a dose with care (to reduce a single dose of lincomycin on 1/3-1/2 and to increase an interval between introductions), and at therapy by high doses it is necessary to carry out monitoring of level of lincomycin in blood serum.

Reception of antibacterial drugs can lead to the overgrowth of insensitive organisms, in particular barmy fungi.

In some cases the septicaemia and/or an endocarditis caused by sensitive microorganisms well give in to therapy by lincomycin. However at these diseases preference is given to use of bactericidal drugs.

To prevent development of an aseptic necrosis, intramuscular introductions carry out deeply to a muscle.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

During treatment it is necessary to refrain from control of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the central nervous system: headache, dizziness.

From digestive tract: a glossitis, stomatitis, nausea, heartburn, vomiting, discomfort and pain in a stomach and persistent diarrhea, colitis (including pseudomembranous), candidiasis, an itch in the field of an anus, a loss of appetite.

From the hemopoietic system: cases of a neutropenia, a leukopenia, an agranulocytosis and a Werlhof's disease are noted. There are separate messages on aplastic anemia and a pancytopenia at which it is impossible to exclude lincomycin influence as the reason of side reaction.

Allergic reactions: the Quincke's disease, a serum disease and an acute anaphylaxis, some of them developed at patients with hypersensitivity to penicillin. Seldom also cases of a multiformny erythema and similar to Stephens-Johnson's syndrome, connected with administration of lincomycin were registered.

From skin and mucous membranes: an itch, skin rash (vesicular, makulezny, rozeolezny, punctulate, urtikarny, spotty), a small tortoiseshell, a vaginitis, it is rare – exfoliative and vezikulo-violent dermatitis.

From a liver: jaundice and change of indicators of hepatic tests (especially increase in level of transaminases in serum) can be also observed at therapy by lincomycin.
From cardiovascular system: it is reported about episodes of arterial hypotension after parenteral administration of drug, especially at too bystry introduction. Also episodes of oppression of cordial activity and function of respiratory system, tachycardia, dizziness, an adynamy, relaxation of skeletal muscles were seldom observed, up to cardiopulmonary shock after too bystry introduction.

From urinogenital system: renal failure (azotemia, oliguria, proteinuria), vaginitis.

From sense bodys: sonitus, вертиго.

Local reactions: at intramuscular injections perhaps local irritation (a hyperemia, an itch), morbidity, hypostasis, formation of hardening and sterile abscess. At intravenous administration developing of thrombophlebitis is possible. The probability of these reactions can be minimized at administration of drug in the form of deep intramuscular injections at refusal of use of constant intravenous catheters.

Interaction with other medicines:

At simultaneous use with penicillin, cephalosporins, chloramphenicol or erythromycin antagonism of antimicrobic action is possible.

At simultaneous use with aminoglycosides an action synergism is possible.

At simultaneous use with means for an inhalation anesthesia or muscle relaxants of peripheral action and opioid analgetics strengthening of neuromuscular blockade is noted, up to development of an apnoea.

Reception of antidiarrheal drugs reduces effect of lincomycin.

Pharmaceutical it is incompatible with Kanamycinum, ampicillin, barbiturates, theophylline, calcium a gluconate, heparin and magnesium sulfate.

Lincomycin is incompatible in one syringe or a dropper with Kanamycinum or novobiocin.

Contraindications:

Hypersensitivity to components of drug or to clindamycin in the anamnesis. Pregnancy (except for cases, when necessary according to vital indications). Heavy liver and/or renal failure. Breastfeeding period. Children's age up to 1 month. Serious fungus diseases of skin, mucous membrane of an oral cavity, vagina. Myasthenia. Colitis, diarrhea of not clear origin.

Overdose:

In case of overdose emergence of secondary gastrointestinal frustration, including an abdominal pain, nausea, vomiting and diarrhea is possible. Heavy reactions from cardiopulmonary system after too bystry introduction not of divorced high doses are described. Such reactions did not arise if drug was divorced according to recommendations.

Treatment of overdose is possible by means of gastric lavage or provoking of vomiting. The specific antidote is unknown.

The hemodialysis and peritoneal dialysis are inefficient for a lincomycin conclusion from blood.

Storage conditions:

Period of validity. 2 years. To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C. Not to freeze.

Issue conditions:

According to the recipe

Packaging:

On 1 ml or on 2 ml in an ampoule; on 10 ampoules in a box; on 5 ampoules in a blister strip packaging; on the 2nd blister strip packagings in a pack.