Metaxalone Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: diet pills/appetite suppressants (such as diethylpropion), drugs for attention deficit disorder (such as atomoxetine, methylphenidate), apraclonidine, bupropion, buspirone, carbamazepine, cyclobenzaprine, deutetrabenazine, a certain combination product (dextromethorphan/quinidine), levodopa, maprotiline, methyldopa, metoclopramide, certain opioid pain relievers (such as fentanyl, meperidine, methadone, tapentadol), certain drugs for Parkinson’s disease (such as entacapone, tolcapone), certain supplements (such as tryptophan, tyramine), tetrabenazine, tricyclic antidepressants (such as amitriptyline, doxepin), valbenazine.

The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/”ecstasy,” St. John’s wort, certain antidepressants (including mirtazapine, SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), tramadol, certain “triptans” used to treat migraine headaches (such as rizatriptan, sumatriptan, zolmitriptan), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.

Some products can interact with metaxalone if you take them together, or even if you take them weeks before or after taking metaxalone. Tell your doctor or pharmacist if you take anything in the list of products that may interact with this drug, or any of the products that increase serotonin, within 2 weeks before or after taking metaxalone. Also tell them if you have taken fluoxetine within 5 weeks before starting metaxalone. Ask your doctor how much time to wait between starting or stopping any of these drugs and starting metaxalone.

Taking other MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Do not take any other MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.

Before using metaxalone, report the use of drugs that may increase the risk of extremely high blood pressure (hypertensive crisis) when combined with metaxalone, including herbal products (such as ephedra/ma huang), nasal decongestants (such as phenylephrine, pseudoephedrine), and stimulants (such as amphetamines, ephedrine, epinephrine, phenylalanine). Metaxalone should not be used with any of these medications. Talk to your doctor or pharmacist for more details.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), other muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This medication may interfere with certain lab tests (such as certain urine glucose tests), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

Does Metaxalone interact with other drugs you are taking?

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Metaxalone – LiverTox – NCBI Bookshelf

Last Update: September 13, 2021.

OVERVIEW

Introduction

Metaxalone is a centrally acting skeletal muscle relaxant that has been in use for more than 40 years. Metaxalone has not been associated with serum aminotransferase elevations during therapy or with clinically apparent hepatic injury.

Background

Metaxalone (me tax’ a lone) acts centrally as a skeletal muscle relaxant, but its efficacy and precise mechanism of action are not well documented. Metaxalone was approved for use in the United States in 1962 and has been a widely used muscle relaxant, but its use recently has declined. Current indications include the treatment of pain from acute musculoskeletal conditions and muscle spasms. The recommended dosage is 800 mg orally three to four times daily. Metaxalone is available by prescription only in 400 and 800 mg tablets in generic forms as well as under the commercial name Skelaxin. Sparse data are available regarding metaxalone safety. Side effects are not common, but can include drowsiness, dizziness, headache, nausea, and dry mouth. When combined with other serotonergic medications (such as serotonin reuptake inhibitors, tricyclic antidepressants, triptans, opiates and others), metaxalone can cause acute serotonin syndrome marked by agitation, confusion, hallucinations, tachycardia, hyperthermia, incoordination, neuromuscular rigidity, nausea and abdominal pain.

Hepatotoxicity

According to the product brochure, metaxalone may cause jaundice, although there are no specific case reports of hepatotoxicity from metaxalone in the literature and no prospective trials with routine monitoring of aminotransferase levels. Given its long history, metaxalone appears to be without significant hepatotoxicity.

Likelihood score: E (Unlikely cause of clinically apparent liver injury).

Drug Class: Muscle Relaxants

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 13 September 2021

• Zimmerman HJ. Muscle spasmolytics. In, Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. 2nd Ed. Philadelphia: Lippincott, 1999. p. 544-45.

  (Expert review of hepatotoxicity published in 1999; dantrolene, chlorzoxazone and baclofen are discussed; mentions that metaxalone has been cited as causing jaundice but that no such case reports have appeared in the literature).

• Hibbs RE, Zambon AC. Agents acting at the neuromuscular junction and autonomic ganglia. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s The pharmacological basis of therapeutics, 12th ed. New York: McGraw-Hill, 2011. p. 255-76.

  (Textbook of pharmacology and therapeutics)

• Toth PP, Urtis J. Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone. Clin Ther. 2004;26:1355–67. [PubMed: 15530999]

  (A review of safety and efficacy of muscle relaxants which states “Although rare instances of hepatic enzyme elevation and anemia have been reported [with metaxalone], this association appears to be based on a false-positive hepatic assay using the cephalin flocculation test. “).

• Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28:140–75. [PubMed: 15276195]

  (Thorough review of the pharmacology, efficacy and side effects of the muscle relaxants).

• Moore KA, Levine B, Fowler D. A fatality involving metaxalone. Forensic Sci Int. 2005;149:249–51. [PubMed: 15749367]

  (54 year old woman found dead in whom postmortem analysis indicated metaxalone overdose; liver reported as being normal).

• Poklis JL, Ropero-Miller JD, Garside D, Winecker RE. Metaxalone (Skelaxin)-related death. J Anal Toxicol. 2004;28:537–41. [PubMed: 15516312]

  (21 year old woman found dead in whom postmortem analysis indicated metaxalone overdose; no mention of liver abnormalities, although highest levels of drug were present in liver).

• Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl. 2004;10:1018–23. [PubMed: 15390328]

  (Among ~50,000 liver transplants done in the US between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, but none were attributed to muscle relaxants).

• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, one was attributed to chlorzoxazone, but none to metaxalone).

• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were due to metaxalone or other muscle relaxants).

• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the General population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to metaxalone or other muscle relaxants).

• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–1352. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 5 [0.7%] were attributed to muscle relaxants, one of which was possibly related to metaxalone).

• Li Y, Delcher C, Reisfield GM, Wei YJ, Brown JD, Winterstein AG. Utilization patterns of skeletal muscle relaxants among commercially insured adults in the United States from 2006 to 2018. Pain Med. 2021:pnab088. Epub ahead of print. [PubMed: 33690860]

  (Analysis of utilization of skeletal muscle relaxants in the US over a 12 year period demonstrated an increasing use of cyclobenzaprine [65% of prescriptions], baclofen and tizanidine but decreasing use of metaxalone and carisoprodol).

Medakson – instructions and analogues of the drug

Instructions for use

Contents of instructions

Composition

active ingredient: 1 bottle contains ceftriaxone sodium in terms of ceftriaxone 1 g.

Dosage form

Powder for solution for injection.

Pharmacotherapeutic group

Antibacterial agents for systemic use. Cephalosporins. Ceftriaxone. ATC code J01D D04.

Indications

Treatment of infections susceptible to ceftriaxone:

Preoperative prophylaxis of infections in gastrointestinal, biliary, urinary and gynecological surgery, but only in cases of potential or known contamination.

When prescribing the drug, it is necessary to follow official recommendations for antibiotic therapy and recommendations for the prevention of antibiotic resistance.

Contraindications

Hypersensitivity to cephalosporins, penicillins or other β-lactam antibiotics in history, to lidocaine or other amide local anesthetic drugs (when administered – to lidocaine).

Hyperbilirubinemia in neonates and premature infants. Ceftriaxone can displace bilirubin from its association with serum albumin, which may lead to the risk of developing bilirubin-induced encephalopathy.

The use of the drug is contraindicated in preterm infants under 41 weeks of gestational age (gestational age + age after birth) and in newborns ≤ 28 days of age (see section “Children”).

Never use ceftriaxone with calcium-containing solutions (Ringer’s solution). Calcium-containing solutions should not be administered within 48 hours after the last administration of ceftriaxone.

Dosage and administration

Adults and children over 12 years of age: Usually, 1-2 g of Medaxone should be given once a day (every 24 hours). In severe infections or infections with only moderate sensitivity to ceftriaxone, the daily dose may be increased up to 4 g.

Children

Neonates (up to 2 weeks): 20-50 mg/kg body weight once a day. Given the underdevelopment of the enzyme system, the daily dose should not exceed 50 mg/kg of body weight. When determining the dose of full-term and premature babies, there are no differences.

Medaxone is contraindicated in neonates ≤ 28 days of age in case of need (or expected need) for treatment with intravenous solutions containing calcium, including intravenous infusions containing calcium, such as parenteral nutrition, due to the risk of precipitation of ceftriaxone calcium salts.

Children aged 15 days to 12 years 20-80 mg/kg body weight once a day. Children weighing more than 50 kg are prescribed doses as for adults.

Intravenous doses of 50 mg/kg or higher should be given by infusion over at least 30 minutes.

Do not exceed 80 mg/kg body weight due to increased risk of biliary precipitation.

Elderly patients

Elderly patients do not need dose adjustment.

Duration of treatment

The duration of treatment depends on the course of the disease. Patients should continue taking Medaxone for at least 48-72 hours after the temperature has returned to normal and tests show the absence of pathogens.

Combination therapy

Studies have shown that synergism exists between ceftriaxone and aminoglycosides for many Gram-negative bacteria. Although the increased effectiveness of such combinations cannot always be foreseen, it should be considered in the presence of severe, life-threatening infections caused by Pseudomonas aeroginosa. Due to the physical incompatibility of ceftriaxone and aminoglycosides, they should be administered separately at the recommended doses.

Dosing in special cases

Meningitis

For bacterial meningitis in children aged 15 days to 12 years, treatment begins with a dose of 100 mg / kg (but not more than 4 g) 1 time per day. Once the pathogen has been identified, its sensitive dose can be reduced accordingly. The best results were achieved with this duration of treatment:

Lyme borreliosis

Adults and children – 50 mg / kg (highest daily dose – 2 g) 1 time per day for 14 days.

Gonorrhea

For the treatment of gonorrhea (caused by strains that produce or do not form penicillinase), a single dose of 250 mg intramuscularly is recommended.

Prevention of infections in surgery

For the prevention of postoperative infections in surgery, it is recommended, depending on the degree of infection risk, to administer a single dose of 1-2 g of Medaxone 30-90 minutes before the start of the operation. In operations on the colon and rectum, the simultaneous (but separate) administration of the drug and one of the 5-nitroimidazoles, such as ornidazole, has proven itself well.

Renal and hepatic insufficiency

In patients with impaired renal function, there is no need to reduce the dose if liver function remains normal. Only in case of renal insufficiency in the pre-terminal stage (creatinine clearance less than 10 ml / min), the daily dose should not exceed 2 g. .

Patients on hemodialysis do not need additional administration of the drug after dialysis. Serum concentrations of ceftriaxone should, however, be monitored for possible dose adjustments, as the elimination rate may decrease in such patients. The daily dose of Medaxone in patients on hemodialysis should not exceed 2 g.

Prepare solutions immediately before their use.

Freshly prepared solutions retain their physical and chemical stability for 6 hours at room temperature (or 24 hours at 2-8°C). Depending on the concentration and duration of storage, the color of the solutions may vary from pale yellow to amber. This property of the active substance does not affect the efficacy or tolerability of the drug.

Injection

For intramuscular injection dissolve 1 g in 3.5 ml of 1% lidocaine solution; injection to do deep into the gluteal muscle. It is recommended to enter no more than 1 g in one buttock. If a dose greater than 1 g is indicated, it should be divided and administered as several injections.

Solution containing lidocaine must not be administered intravenously.

Intravenous injection

For intravenous injection, dissolve 1 g in 10 ml of sterile water for injection; enter intravenously slowly (2-4 minutes).

Injection

Infusion must last at least 30 minutes. To prepare an infusion solution, dissolve 2 g of Medaxone in 40 ml of one of the following infusion solutions free of calcium ions: 0.9% sodium chloride, 0.45% sodium chloride + 2. 5% glucose, 5% glucose, 10% glucose , 6% dextran in glucose solution 5%, 6-10% hydroxyethyl starch, water for injection. Due to possible incompatibilities, solutions containing ceftriaxone should not be mixed with solutions containing other antibiotics, both when preparing and when administered.

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to dissolve the drug in vials or to dilute the reconstituted solution for intravenous administration due to the possibility of precipitation of ceftriaxone calcium salts. The occurrence of precipitation of calcium salts of ceftriaxone can also occur when Medaxone is mixed with solutions containing calcium in the same infusion system for intravenous administration. Medaxone must not be administered simultaneously with solutions containing calcium, including long-term infusions containing calcium, such as parenteral nutrition (see “Interaction with other medicinal products and other types of interactions”).

Adverse reactions

Infections: genital tract mycosis, secondary fungal infections and infections caused by resistant microorganisms.

From the blood and lymphatic system: eosinophilia, neutropenia, leukopenia, granulocytopenia, anemia, including hemolytic anemia, thrombocytopenia, increased prothrombin time, coagulation disorders. Very rarely, cases of agranulocytosis (<500/mm3) have been observed, predominantly after a total dose of 20 g or more. During long-term treatment, the blood picture should be regularly monitored. A slight prolongation of prothrombin time has been reported.

From the digestive tract: diarrhea, nausea, vomiting, stomatitis, glossitis; pancreatitis, possibly due to obstruction of the bile ducts. Most of these patients had risk factors for biliary congestion, such as a history of treatment, severe illness, and total parenteral nutrition, and a role for ceftriaxone-induced biliary tract precipitates in the development of pancreatitis cannot be ruled out; pseudomembranous enterocolitis has been reported.

From the digestive system: precipitates of ceftriaxone calcium salt in the gallbladder with corresponding symptoms in children, reverse cholelithiasis in children. The specified phenomena were seldom observed at children; often – an increase in the level of liver enzymes in the blood serum (AST, ALT, alkaline phosphatase).

From the side of the skin and subcutaneous tissue: skin rash, allergic dermatitis, itching, urticaria, edema, exanthema; exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

From the urinary system: oliguria, hematuria, glucosuria; formation of kidney stones, mainly in children aged 3 years and older who received large daily doses of the drug (≥ 80 mg / kg per day), or cumulative doses of more than 10 g, and who had additional risk factors (restricted fluid intake, bed rest). The formation of calculi in the kidneys may be asymptomatic or manifest clinically, may cause renal failure, which disappears after discontinuation of treatment with ceftriaxone.

General disorders: headache and dizziness, fever, chills, anaphylactic or anaphylactoid reactions. In isolated cases, inflammatory reactions of the vein wall are observed. They can be avoided by applying a slow injection (2-4 minutes).

Local reactions: with intravenous administration – phlebitis, pain along the vein; with intramuscular injection – pain at the injection site. Injection without lidocaine is painful.

Interaction with calcium

Medaxone must not be given simultaneously or mixed with calcium-containing solutions, even when using separate infusion systems. Described a small number of deaths due to the formation of precipitates of calcium salts of ceftriaxone in the lungs and kidneys of newborns. In some cases, venous accesses and administration of ceftriaxone and calcium-containing solutions were different.

Laboratory findings

Rarely, patients treated with ceftriaxone may experience false positive Coombs results. Like other antibiotics, ceftriaxone can cause false positive galactosemia. False-positive results can also be obtained when determining glucose in the urine, therefore, during treatment with the drug, glucosuria, if necessary, should be determined only by the enzyme method.

Overdose

In case of overdose, the manifestations of adverse reactions may increase.

Hemodialysis or peritoneal dialysis will not reduce drug levels. There is no specific antidote. Treatment of overdose is symptomatic.

Use during pregnancy or lactation

Ceftriaxone crosses the placental barrier. The safety of ceftriaxone in women during pregnancy has not been studied.

In small concentrations, ceftriaxone passes into breast milk, therefore, when ceftriaxone is prescribed, breastfeeding should be discontinued.

Children

Use the drug in children according to the dosage indicated in the section “Method of administration and doses”.

The drug is contraindicated in premature infants up to 41 weeks of gestation (gestational age + age after birth).

In full-term newborns (up to 28 days of life) with jaundice or hypoalbumineria, acidosis, the level of binding of bilirubin to blood proteins is reduced, the risk of bilirubin encephalopathy.

The drug is contraindicated in neonates ≤ 28 days of age for use when necessary (or expected to be needed) for treatment with intravenous solutions containing calcium, including intravenous infusions containing calcium, such as parenteral nutrition, due to the risk of precipitation of calcium salts of ceftriaxone (see . section “Method of administration and doses”).

In newborns and premature infants, cases of precipitates in the lungs and kidneys, resulting in a fatal outcome, have been described with the simultaneous administration of ceftriaxone and calcium preparations. In some of these cases, the same infusion systems were used for administration of ceftriaxone and solutions containing calcium, and precipitation was observed in some infusion systems for administration.

Application considerations

When prescribing ceftriaxone, official recommendations for antibiotic therapy and, in particular, recommendations for the prevention of antibiotic resistance should be followed.

As with other cephalosporins, cases of fatal anaphylactic reactions have been reported with ceftriaxone, even if there are no relevant references in the detailed history. If allergic reactions occur, Medaxon should be immediately canceled and appropriate treatment prescribed.

Ceftriaxone should be used with caution in patients with a tendency to allergic diathesis.

Ceftriaxone may increase prothrombin time. In this regard, if vitamin K deficiency is suspected, it is necessary to determine the prothrombin time.

With the use of almost all antibacterial drugs, including ceftriaxone, diarrhea associated with Clostridium difficile, from mild severity to fatal colitis, may occur. Antibacterial drugs alter the normal flora of the large intestine, leading to an overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which contribute to the development of diarrhea associated with Clostridium difficile. Excessive toxin-producing strains of Clostridium difficile cause increased morbidity and mortality because these infections may be resistant to antimicrobials and require colectomy. Clostridium difficile-associated diarrhea should be excluded in all patients during antibiotic use. A detailed medical history should be taken, as Clostridium difficile-associated diarrhea may occur up to 2 months after the end of antibiotic use.

If diarrhea associated with Clostridium difficile is suspected or confirmed, antibiotic therapy that does not affect Clostridium difficile should be discontinued. Appropriate amounts of fluids and electrolytes, protein supplements, antibiotic therapy to which Clostridium difficile is susceptible, and surgical examination should be given as clinically indicated.

During long-term use of ceftriaxone, it may be difficult to control non-susceptible organisms. In this regard, careful monitoring of patients is necessary. If superinfection occurs, appropriate measures must be taken.

After the use of ceftriaxone, usually at doses higher than the standard recommended doses, shadows that are mistaken for gallstones may be observed on ultrasound of the gallbladder. These are precipitates of the calcium salt of ceftriaxone, which disappear after completion or discontinuation of ceftriaxone therapy. Such changes are rarely accompanied by any symptoms. But even in such cases, only conservative treatment is recommended. If these phenomena are accompanied by clinical symptoms, then the decision to cancel the drug is made by the doctor.

Patients treated with ceftriaxone have experienced isolated cases of pancreatitis, possibly due to obstruction of the biliary tract. Most of these patients had risk factors for biliary congestion, such as a history of treatment, severe disease, and total parenteral nutrition. At the same time, the role of precipitates in the development of pancreatitis, formed under the action of ceftriaxone in the biliary tract, cannot be ruled out.

Ceftriaxone may displace bilirubin from its association with serum albumin. In this regard, the use of ceftriaxone in newborns with hyperbilirubinemia is contraindicated (see Section “Contraindications”).

Caution should be exercised when administering ceftriaxone to patients with renal insufficiency who are simultaneously receiving aminoglycosides and diuretics.

Ceftriaxone should not be mixed or administered simultaneously with calcium-containing solutions, even when the drugs are administered through different infusion systems. In newborns and premature babies, there are cases of precipitates in the lungs and kidneys that caused a fatal outcome with the simultaneous administration of ceftriaxone and calcium preparations. In this regard, calcium-containing solutions for intravenous administration should not be used in newborns and patients of other age groups for at least 48 hours after the last dose of ceftriaxone (see Section “Contraindications”).

Cases of intravascular precipitates following concomitant use of ceftriaxone with intravenous calcium-containing solutions have also been reported in patients of other age groups.

Immune-mediated hemolytic anemia has been observed in patients receiving cephalosporins, including ceftriaxone. Cases of severe hemolytic anemia, including fatal cases, have been reported in adult and pediatric patients. With the development of anemia with the use of ceftriaxone, it is necessary to exclude anemia caused by ceftriaxone and stop the drug until the etiology of anemia is established.

During long-term treatment, the blood picture should be monitored regularly.

In rare cases, patients treated with ceftriaxone may experience false positive Coombs test results. Like other antibiotics, ceftriaxone can cause false positive galactosemia. False positive results can also be obtained when determining glucose in the urine, therefore, during treatment with ceftriaxone, glucosuria, if necessary, should be determined only by the enzyme method.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms

There is no data on the effect of ceftriaxone on the reaction rate, but due to the possibility of dizziness, the drug may affect the ability to drive vehicles or work with complex mechanisms.

Interaction with other medicinal products and other types of interactions

Under no circumstances should the drug be used with calcium-containing solutions (Ringer’s solution).

Calcium-containing solutions should not be administered within 48 hours of the last administration of ceftriaxone.

In neonates and premature infants, cases of precipitates in the lungs and kidneys, resulting in death, have been described with the simultaneous administration of ceftriaxone and calcium preparations.

Co-administration of high doses of ceftriaxone and potent diuretics such as furosemide has not shown renal dysfunction. There is no indication that ceftriaxone increases the nephrotoxicity of aminoglycosides. After taking alcohol immediately after taking ceftriaxone, no effects similar to those of disulfiram (teturam) were observed.

Ceftriaxone does not contain an N-methylthiotetrazole group that could cause ethanol intolerance and bleeding associated with some other cephalosporins. Probenecid does not affect the excretion of ceftriaxone.

Antagonism between ceftriaxone and chloramphenicol has been found in vitro.

Calcium-containing diluents, such as Ringer’s solution or Hartmann’s solution, should not be used to dissolve ceftriaxone in vials or to dilute the reconstituted solution for intravenous administration due to the possibility of precipitation of ceftriaxone calcium salts. Precipitation of ceftriaxone calcium salts can also occur when ceftriaxone is mixed with solutions containing calcium in the same intravenous infusion set. Ceftriaxone should not be co-administered with solutions containing calcium, including long-term infusions containing calcium, such as parenteral nutrition. In vitro studies have shown that infants have an increased risk of precipitated calcium salts of ceftriaxone.

Ceftriaxone has been reported to be incompatible with amzacrine, vancomycin, fluconazole and aminoglycosides.

Bacteriostatic agents may interfere with the bactericidal action of cephalosporins.

Ceftriaxone may reduce the effectiveness of hormonal oral contraceptives. In this regard, it is recommended to use additional (non-hormonal) methods of contraception during treatment and for 1 month after its completion.

There are no reports of interactions between ceftriaxone and oral products containing calcium, and interactions between ceftriaxone by intramuscular injection and products containing calcium (intravenous or oral), because this information is indicated in the instructions for medical use.

Pharmacological properties

Pharmacodynamics.

Ceftriaxone is a long-acting parenteral cephalosporin antibiotic of the third generation.

The bactericidal activity of ceftriaxone is due to the inhibition of cell wall synthesis. Ceftriaxone is active in vitro against most Gram-negative and Gram-positive microorganisms. Ceftriaxone is characterized by very high resistance to most b-lactamases (both penicillinases and cephalosporinases) of gram-positive and gram-negative bacteria. Ceftriaxone is active against these microorganisms in vitro and in clinical infections: 9Ol000 Litical, group B), Streptococcus Viridans, Streptococcus Pneumoniae.

Note. Methicillin-resistant Staphylococcus spp., as well as most strains of Enterococcus (eg Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes) show resistance to cephalosporins, including ceftriaxone;

Gram-negative aerobes:

Acinetobacter lwoffi, Acinetobacter anitratus (mainly A. baumanii)*, Aeromonas spp., Alcaligenes faecalis, Alcaligenes spp., Alkagen-like bacteria, Borrelia burgdorferi, Capnocytophaga spp. , Citrobacter diversus (including C. amalonaticus), Citrobacter spp. *, Escherichia coli, Enterobacter aerogenes *, Enterobacter cloacae *, Enterobacter spp (others) *, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae **, Moraxella catarrhalis (formerly Branhamella catarrhalis), Mor axella osloensis, Moraxella spp. (Others), Morganella morganii, Neisseria gonorrhoea, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri *, Proteus vulgaris *, Pseudomonas fluorescens *, Pseudomonas spp. (Others) *, Providentia rettgeri * Providentia spp. (Others), Salmonella typhi, Salmonella spp. (Nontyphoids), Serratia marcescens *, Serratia spp. (Others) *, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (Other).

* Some isolates of these species are resistant to ceftriaxone mainly due to the formation of

chromosomally encoded β-lactamases;

** Some isolates of these species are resistant to ceftriaxone due to the production of a number of plasmid-mediated β-lactamases.

Note. Many of the strains of the above microorganisms, which have multiple resistance to antibiotics such as aminopenicillins and ureidopenicillins, first and second generation cephalosporins, aminoglycosides, are sensitive to ceftriaxone.

Treponema pallidum is sensitive to ceftriaxone in vitro. Clinical studies show that ceftriaxone is effective for the treatment of primary and secondary syphilis, except for clinical strains of P. aeruginosa that are resistant to ceftriaxone;

anaerobes:

Bacteroides spp. (Bile sensitive) *, Clostridium spp. (Except C. difficile), Fusobacterium nucleatum, Fusobacterium spp. (Others), Gaffkia anaerobica (formerly Peptococcus), Peptostreptococcus spp.

* Some isolates of these species are resistant to ceftriaxone due to the formation of β-lactamases.

Note. Many of the b-lactamase producing strains of Bacteroides spp. (particularly B. fragilis) are resistant to ceftriaxone. Resistant Clostridium difficile.

Pharmacokinetics.

The pharmacokinetics of ceftriaxone is non-linear. All major pharmacokinetic parameters based on total drug concentrations, with the exception of the half-life, are dose dependent.

Absorption

The maximum plasma concentration after a single injection of 1 g of the drug is 81 mg / l and is reached 2-3 hours after administration. The area under the plasma concentration curve after intravenous administration is equal to that after administration. This means that the bioavailability of ceftriaxone after intramuscular administration is 100%.

Distribution

The volume of distribution of ceftriaxone is 7-12 liters. After administration at a dose of 1-2 g, ceftriaxone penetrates well into tissues and body fluids. For more than 24 hours, its concentrations far exceed the minimum inhibitory concentrations for most infectious agents in more than 60 tissues and fluids (including the lungs, heart, biliary tract, liver, tonsils, middle ear and nasal mucosa, bones, and spinal cord, pleural and synovial fluids, in the secretion of the prostate).

After administration, ceftriaxone rapidly penetrates into the cerebrospinal fluid, where bactericidal concentrations against susceptible microorganisms persist for 24 hours.

Protein binding

Ceftriaxone binds reversibly to albumin, and the degree of binding decreases with increasing concentration, for example, it decreases from 95% at a plasma concentration of less than 100 mg / l to 85% at a concentration of 300 mg / l. Due to the low concentration of albumin in tissue fluid, the proportion of free ceftriaxone in it is higher than in blood plasma.

Penetration into certain tissues

Ceftriaxone penetrates through inflamed meninges in children, incl. newborns. 24 hours after the administration of ceftriaxone at a dose of 50-100 mg/kg body weight (newborns and infants, respectively), ceftriaxone concentrations in the cerebrospinal fluid exceed 1.4 mg/l. The maximum concentration in the cerebrospinal fluid is reached approximately 4 hours after administration and averages 18 mg/l. With bacterial meningitis, the average concentration of ceftriaxone in the cerebrospinal fluid is 17% of the concentration in blood plasma, with aseptic meningitis – 4%. In adult patients with meningitis, after a dose of 50 mg / kg body weight, ceftriaxone concentrations in the cerebrospinal fluid are achieved after 2-24 hours, which are many times higher than the minimum inhibitory concentrations for the most common pathogens of meningitis.

Ceftriaxone crosses the placental barrier and passes into breast milk in low concentrations.

Metabolism

Ceftriaxone is metabolized systemically and converted to inactive metabolites by intestinal flora.

Conclusion

Total plasma clearance of ceftriaxone is 10-22 ml/min. Renal clearance cos

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