Medaxone - instructions for use, dose, side effects, contraindications

Ceftriaxone is a third generation generic cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits the synthesis of the cell wall, in vitro suppresses the growth of most gram-positive and gram-negative microorganisms. Resistant to the action of most beta-lactamases of gram-negative and gram-positive microorganisms. It is active against the following microorganisms:

Gram-positive - Staphylococcus aureus (including strains producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans.

Literate - Acinetobacter calcoaceticus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella spp. (incl. Klebsiella pneumoniae), Moraxella catarrhalis, (including beta-lactamase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including beta-lactamase-producing strains), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (incl. Serratia marcescens), Borrelia burgdorferi, individual strains Pseudomonas aeruginosa are also sensitive.

Anaerobes - Bacteroides fragilis, Clostridium spp. (Besides Clostridium difficile), Peptostreptococcus spp. Possesses activity in vitro at respect majority strains the following microorganismbasics: Citrobacter diversus, Citrobacter freundii, Providencia spp. (at t.h. Providencia rettgeri), Salmonella spp. (including Salmonella typhi), Shigella spp., Streptococcus agalactiae, Bacteroides bivius, Bacteroides melaninogenicus. Methicillin-resistant staphylococci are resistant to cephalosporins, incl. to ceftriaxone. Many strains of group streptococci D and enterococci, incl. Enterococcus faecalis, also resistant to ceftriaxone.

Pharmacokinetics:

Bioavailability of ceftriaxone is 100%. The maximum concentration (Оmах) after the / m administration of 1 g is achieved after 2-3 hours and averages 76 μg / ml, and Omax after iv injection of 1 g of ceftriaxone is reached at the end of the infusion and is 151 μg / ml.

Ceftriaxone penetrates well into tissues and body fluids (including the lungs, heart, bile ducts, liver, tonsils, middle ear and nasal mucosa, bones, as well as spinal, pleural and synovial fluids and the secretion of the prostate) and reaches a concentration ,significantly exceeding the minimum inhibitory concentrations (MIC), which are maintained for 24 hours.

With iv introduction ceftriaxone rapidly diffuses into the interstitial fluid, where it exhibits bactericidal action against sensitive microorganisms within 24 hours. In adults, 2-24 hours after administration at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid (CSF) is many times greater than the MIC for the most common pathogens of meningitis. In neonates and children, in the case of bacterial meningitis, an average of 17% of the concentration of the drug in the blood serum diffuses into the cerebrospinal fluid, which is approximately 4 times greater than in aseptic meningitis. After intravenous administration of ceftriaacon in a dose of 50-100 mg / kg body weight, the concentration of the drug in the CSF is 18 μg / ml achieved on average after 4 hours and maintained at the MIC level for 24 hours.

Ceftriaxone reversibly binds to albumin (83-96%). The volume of distribution of ceftriaxone is 0.12-0.14 l / kg (5.78-13.5 l), in children 0.3 l / kg, plasma clearance 0.58-1.45 l / h and renal - 0,32-0,73 l / h.

The half-life period (T1 / 2) of ceftriaxone in adult healthy subjects after IM is 5.8-8.7 hours, in children with meningitis after iv injection at a dose of 50-75 mg / kg, 4.3-4 , 6 hours, in patients,(for CC) from 0 to 5 ml / min - 14.7 hours, with SC from 5 to 15 ml / min-15.7 h, with a QC of 16 to 30 ml / min - 11, 4 hours and at a CS from 31 to 60 ml / min-12.4 hours.

Ceftriaxone does not undergo systemic metabolism, but turns into inactive metabolites under the influence of intestinal flora.

33-67% of ceftriaxone is unchanged through the kidneys, and 40-50% - in unchanged form with bile in the intestine, where the inactivation occurs. About 70% of the drug is excreted through the kidneys in newborn infants. In infants during the first 8 days of life, as well as in people older than 75 years, the half-life is on average two or three times higher than in young adults.

Hemodialysis is ineffective.

Ceftriaxone passes through the placental barrier and in small concentrations enters the breast milk.

Indications:

Bacterial infections caused by microorganisms sensitive to ceftriaxone: bacterial meningitis, bacterial septicemia, lower respiratory tract infections (including pneumonia, lung abscess, pleural empyema), acute otitis media, urinary tract infections (complicated and uncomplicated), infections of small organs pelvis, abdominal cavity organs (peritonitis, inflammatory diseases of the digestive tract, bile ducts, incl.cholangitis, empyema of the gallbladder), infections of bones and joints, skin and soft tissues (including infected wounds and burns), uncomplicated gonorrhea, Lyme disease.

Infectious diseases in patients with weakened immunity.

Prevention of postoperative infections.

Contraindications:

Hypersensitivity to cephalosporins, penicillins, carbapenems; premature newborns under the "expected" age of 41 weeks (including the term of intrauterine development and age); term infants with hyperbilirubinemia, acidosis or hypoalbuminemia; term infants who are shown intravenous administration of calcium-containing solutions.

Carefully:

Renal / hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs.

Pregnancy and lactation:

In pregnancy, use the drug only in those cases where the intended use for the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, the question of abolishing breastfeeding should be resolved.

Dosing and Administration:

The drug is used intramuscularly and intravenously (struino and drip). Do not use solutions containing calcium for dilution of the preparation!

Newborns: 20-50 mg / kg body weight once a day. In connection with the immaturity of the enzyme system of the newborn is not recommended to exceed the daily dose.

With bacterial meningitis in children The initial dose is 100 mg / kg (but not more than 4 g) once a day, then 100 mg / kg / day (but not more than 4 g) once a day or divided into 2 divided doses (every 12 hours). The duration of treatment is from 7 to 14 days.

Infection of the skin and soft tissues: daily dose in children - 50-75mg / kg, divided into 2 doses (every 12 hours). The total daily intake for children should not exceed 2 g.

Acute otitis media: children are recommended a single intravenous injection of the drug at a dose of 50 mg / kg (not more than 1.0 g).

When treating other infections in children the recommended daily dose is 50-75 mg / kg, divided into 2 doses (every 12 hours). The total daily intake for children should not exceed 2 g.

In children younger than 12 years with a body weight of 50 kg and above, doses for adults are used.

Adults and children over 12 years of age: the initial daily dose, depending on the type and severity of the infection, is 1-2 g once a day or divided into 2 doses (every 12 hours). The total daily dose should not exceed 4 g.

Gonorrhea uncomplicated: 250 mg Medaxone intramuscularly once.

Lyme disease: 50 mg / kg (the highest daily dose is 2 g) for adults and children, once a day for 14 days.

Prevention of postoperative infections: depending on the degree of infectious risk Medaxone is administered in a dose of 1 g once for 30 minutes - 2 hours before the operation. In operations on the colon and rectum, it is recommended to additionally administer (separately) a drug from the group of 5-nitroimidazoles.

In patients with chronic renal failure (creatinine clearance less than 10 ml / min) the daily dose of Medaxone should not exceed 2 g. Hemodialysis and peritoneal dialysis do not significantly affect the pharmacokinetics of ceftriaxone.

Therefore, patients on hemodialysis do not require an additional dose after the hemodialysis session. However, it is necessary to monitor the concentration of ceftriaxone in the plasma, so that if necessary, adjust the dose in a timely manner, since the rate of its elimination in these patients can be slowed down.

In patients with renal-hepatic failure, the daily dose should not exceed 2 g without monitoring the concentration of the drug in the blood plasma.

Duration of treatment: depends on the nature and severity of the disease. Usually it is 4-14 days; with complicated infections, a longer duration of administration may be required. The course of treatment for infections caused by Streptococcus pyogenes, must be at least 10 days. As always with antibiotic therapy, the drug should be administered to the patient for another 48 hours after the temperature normalization, the disappearance of the symptoms of the infection and / or confirmation of the eradication of the pathogen.

Right-hander cooking and introducing solutions.

Use only freshly prepared solutions.

For intramuscular injection: to reduce pain when injected, it is preferable to dissolve 1 g of the drug in 3.5 ml of a 1% solution of lidocaine and injected deeply into the gluteal muscle. To check up absence of hit of a needle in a blood vessel by return movement of the piston of a syringe and to enter no more than 1 g of a preparation in a muscle.

For intravenous injection dissolve 1 g of the drug in 10 ml of water for injection and enter intravenously slowly for 2-4 minutes.

Solutions containing lidocaine. can not be administered intravenously!

Intravenous infusion

To prepare the solution, dilute 2 g of the drug in 40 ml of one of the following infusion solutions that do not contain calcium ions (0.9% sodium chloride solution, 5-10% solution of dextrose, 5% solution of levulose (fructose), 5% dextrose + 0.9% sodium chloride, 5% dextrose + 0.45% sodium chloride). Doses of 50 mg / kg or more should be injected intravenously into the capillary for at least 30 minutes.

It is preferable to use the freshly prepared solution.

The shelf life of the finished solution depends on the nature of the solvent, its concentration and storage temperature.

For intramuscular injection:

Solvent	Concentration,	Room	Storage in
	mg / ml	temperature, 25 ° С	fridge, 4 ° С
Water for injections	100	2 days	10 days
	250, 350	24 hours	3 days
0.9% Sodium chloride	100	2 days	10 days
	250,350	24 hours	3 days
5% dextrose	100	2 days	10 days
	250,350	24 hours	3 the day
Bacteriostatic water +	100	24 days	10 days
0.9% Benzyl alcohol	250,350	24 days	3 days
1% Lidocaine without epinephrine	100	24 days	10 days
	250,350	24 days	3 days

For intravenous administration in a concentration of 10,20,40 mg / ml:

Solvent	Room temperature, 25 ° С	Storage in the refrigerator, 4 ° С
Water for injections	2 days	10 days
0.9% Sodium chloride	2 days	10 days
5% Dextrose	2 days	10 days
10% Dextrose	2 days	10 days
5% Dextrose + 0.9% Sodium chloride *	2 days	-
5% Dextrose + 0.45% Sodium chloride	2 days	-

* Applicable for solutions with a concentration of 10-40 mg / ml only in PVC bottles.

Side effects:

Allergic reactions: chills or fever, rash, itching, urticaria, polymorphic exudative erythema, Stevens-Johnson syndrome, angioedema, allergic dermatitis, Lyell's syndrome.

From the nervous system: headache, dizziness.

From the digestive system: nausea, vomiting, taste disorder, diarrhea or constipation, pseudomembranous colitis, glossitis, stomatitis.

From the hematopoiesis: anemia (including hemolytic), leukopenia, lymphopenia, neutropenia, thrombocytopenia, thrombocytosis, eosinophilia.

From the genitourinary system: candidiasis of the vagina, vaginitis, oliguria.

Local reactions: with iv introduction - phlebitis, tenderness, compaction along the way intys; with the / m introduction - soreness, sensation of warmth, tightness or condensation at the injection site.

Laboratory indicators: increase (decrease) prothrombin time, increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, hyperaemia, the presence of sediment in the urine.

Other: increased sweating, "tides" of blood.

Undesirable reactions with a frequency of less than 0.1%: abdominal pain, agranulocytosis, hypersensitivity pneumonitis, anaphylactic shock, basophils, cholelithiasis, bronchospasm, colitis, dyspepsia, nasal bleeding, bloating, "sludge-phenomenon" of the gallbladder, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations , serum sickness, convulsions.

Overdose:Hemodialysis and peritoneal dialysis are not effective. Symptomatic measures are recommended for the treatment of overdose cases. There is no specific antidote.

Interaction:

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

Pharmaceutically incompatible with solutions containing calcium (including Hartman and Ringer's solution, calcium containing solutions for parenteral nutrition), as well as with aminoglycosides, amsacrine, vancomycin and fluconazole.

Due to the absence of the N-methylthiotetrazole group, the interaction with ethanol does not lead to the development of disulfiram-like reactions and bleeding inherent in some cephalosporins.

In connection with the possibility of ceftriaxone to increase prothrombin time, the simultaneous administration of it with indirect anticoagulants can lead to bleeding.

Special instructions:

When concomitant severe renal and hepatic failure, as well as in patients on hemodialysis, should be regularly to determine the concentration of drug in plasma.

With long-term treatment, it is necessary to regularly monitor the picture of peripheral blood, indicators of the functional state of the liver and kidneys.

In rare cases, with ultrasound of the gallbladder, blackouts are observed that disappear after the drug is discontinued (even if this phenomenon is accompanied by pain in the right upper quadrant, it is recommended to continue the prescription of the antibiotic and conduct symptomatic treatment). With the development of the symptoms or signs indicating the possible gallbladder disease, or in the presence of ultrasound signs "sludge phenomenon" is recommended to stop administering the drug.

Despite the detailed history, which is the rule for other cephalosporin antibiotics, one can not exclude the possibility of developing an anaphylactic shock that requires immediate therapy - first intravenously injected epinephrine, then glucocorticosteroids.

In vitro studies have shown that, like other cephalosporin antibiotics, ceftriaxone It is able to displace bilirubin from bonding with albumins.

In the literature, rare cases of prothrombin time change are described.

Patients with vitamin K deficiency (impaired synthesis, eating disorders) may need to monitor prothrombin time and prescribe vitamin K (10 mg / week) with an increase in prothrombin time before or during therapy.

Rare cases of fatal reactions as a result of deposition of ceftriaxone-calcium precipitates in the lungs and kidneys of newborns are described. Theoretically there is a probability of interaction of ceftriaxone with calcium (Ca²⁺) -containing preparations with both IV and oral administration and in other age groups. therefore ceftriaxone should not be administered concomitantly with Ca-containing drugs. Theoretically, based on the calculation of 5 T_1/2 ceftriaxone interval between the administration of ceftriaxone and Ca²⁺containing solutions should be at least 48 hours. Data on the possible interaction of ceftriaxone with oral "Ca²⁺ -containing preparations, as well as ceftriaxone for the / m introduction with Ca²⁺ -containing drugs (in / in and oral) are absent.

When the drug is used, rare cases of pancreatitis, which develops, possibly due to obstruction of the biliary tract, are described. Most patients had risk factors for congestion of the biliary tract (previous drug therapy, severe co-morbidities, completely parenteral nutrition). At the same time, it is impossible to exclude the starting role of precipitate formation in the biliary tract under the influence of ceftriaxone.

In the treatment of ceftriaxone, false-positive results of Coombs test, a test for galactosemia, glucose in urine (glucosuria is recommended to be determined only by enzyme method).

Effect on the ability to drive transp. cf. and fur:Does not cause drowsiness and does not affect the ability to drive vehicles and control mechanisms that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1.0 g.

Packaging:

1 g is placed in glass vials of type I (EP). The bottles are sealed with rubber stoppers and crimped with aluminum caps.

1 bottle or 100 bottles (for hospitals), along with instructions for use in a cardboard pack.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N015208 / 01-2003

Date of registration:15.08.2008

Expiration Date:Unlimited

The owner of the registration certificate:Medocemi Co., Ltd.Medocemi Co., Ltd. Cyprus

Manufacturer: & nbsp

MEDOCHEMIE, Ltd. Cyprus

Representation: & nbspMEDOKEMI LTD. MEDOKEMI LTD. Cyprus

Information update date: & nbsp26.04.2018

Illustrated instructions

Instructions

Medaxon (Medaxon)