Pharmacological properties
Pharmacodynamics. Cefixime is a third-generation cephalosporin antibiotic for oral administration. In vitro, it exhibits significant bactericidal activity against a wide range of gram-positive and gram-negative microorganisms. Clinically effective in the treatment of infections caused by common pathogenic microorganisms, including streptococcus pneumoniae, streptococcus pyogenes, e.coli, proteus mirabilis, klebsiella species, haemophilus influenzae (beta-lactamase-positive and -negative), moraxella (branhamella) catarrhalis (beta-lactamase-positive and -negative) and enterobacter species. It exhibits a high degree of stability in the presence of beta-lactamases.
Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase-positive, coagulase-negative and methicillin-resistant strains) are resistant to cefixime. Most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to cefixime.
Pharmacokinetics. Absorption. The oral bioavailability of cefixime is 22-54%. Since the presence of food does not significantly affect absorption, cefixime can be administered without regard to meals. Cmax in plasma after taking the recommended doses for adults or children is from 1.5 to 3 μg/ml. With repeated dosing, there is little or no accumulation of cefixime. The pharmacokinetics of cefixime were compared in healthy elderly patients (aged 64 years) and young volunteers (aged 11-35 years) after taking 400 mg of cefixime once a day for 5 days. The mean Cmax and AUC values were slightly higher in the elderly. Elderly patients can be prescribed the same doses as adults.
Distribution: Cefixime is almost completely bound to albumin, with an average free fraction of approximately 30%.
Metabolism: Metabolites of cefixime have not been isolated from human plasma or urine.
Excretion: Cefixime is excreted mainly unchanged in the urine. The predominant mechanism is glomerular filtration.
There are no data on the penetration of cefixime into breast milk.
Indication
Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:
upper respiratory tract infections (including otitis media) and other upper respiratory tract infections (sinusitis, pharyngitis, tonsillitis of bacterial etiology) in case of known or suspected resistance of the pathogen to other commonly used antibiotics, or in case of risk of treatment failure;
lower respiratory tract infections (including acute bronchitis and exacerbation of chronic bronchitis);
urinary tract infections (including cystitis, cystourethritis, uncomplicated pyelonephritis).
Clinically effective in the treatment of infections caused by common pathogens, including Streptococcus pneumoniae, Streptococcus pyogenes, E. coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and -negative), Moraxella (Branhamella) catarrhalis (beta-lactamase positive and -negative) and Enterobacter species. Exhibits a high degree of stability in the presence of beta-lactamases.
Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase-positive, coagulase-negative and methicillin-resistant strains) are resistant to cefixime. Most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to cefixime.
Application
Food intake does not affect the absorption of cefixime. The duration of the course of treatment depends on the severity of the disease and is set individually. Usually the course of treatment is 7 days, if necessary - 14 days. In infections caused by streptococcus pyogenes, the course of treatment should be at least 10 days. In the treatment of uncomplicated cystitis, the course of treatment is 3 days.
Capsules. Adults and children over 12 years of age with a body weight of more than 50 kg: the recommended dose is 400 mg (1 capsule) once a day.
For the treatment of uncomplicated urethral or cervical gonococcal infection, a single dose of 400 mg is recommended.
Elderly patients: Administer at the recommended adult dose. Renal function should be monitored and the dose adjusted in severe renal impairment (see Renal impairment).
Renal insufficiency: cefixime should be administered with caution to patients with renal insufficiency. The dose is adjusted taking into account creatinine clearance (CC). If CC ≥60 ml/min, the standard dose is prescribed, if CC 21-60 ml/min or in patients on hemodialysis - 75% of the standard dose with maintaining the intervals between administration, if CC 20 ml/min or in patients on peritoneal dialysis, ½ of the standard dose with maintaining the intervals between administration. Neither hemodialysis nor peritoneal dialysis removes a significant amount of cefixime from the body.
If it is necessary to use the drug in a dose of 400 mg, it is recommended to prescribe the drug in another dosage form (for example, suspension).
Suspension. Children aged 6 months to 10 years with a body weight of up to 50 kg: the recommended dose is 8 mg/kg body weight per day in 1 dose or 4 mg/kg every 12 hours, depending on the severity of the disease.
Adults and children over 10 years of age (or weighing more than 50 kg): the recommended dose is 400 mg/day in 1 dose or 200 mg every 12 hours, depending on the severity of the disease.
Renal impairment: Cefixime can be used in cases of renal impairment. Patients with creatinine clearance ≥20 ml/min should be given the usual dose and dosing regimen. In patients with creatinine clearance <20 ml/min, a 50% reduction in the daily dose is recommended. This also applies to patients on chronic ambulatory peritoneal dialysis or hemodialysis.
Method of preparation of suspension. Before preparation, it is necessary to invert and shake the bottle to loosen the powder. Add boiled cold water to the line (mark) indicated on the bottle, in 2 doses, shaking the bottle each time until a homogeneous suspension is formed.
The suspension can be taken no earlier than 5 minutes after preparation.
The prepared suspension should be shaken thoroughly before each administration.
Contraindication
Confirmed hypersensitivity to cephalosporin antibiotics or other components of the drug; hypersensitivity to penicillins; porphyria.
Side effects
Side effects caused by cefixime are minor and occur rarely. The following disorders are possible:
from the nervous system: headache, dizziness, dysphoria, hyperactivity;
From the side of the organs of hearing and vestibular apparatus: hearing loss;
Respiratory system: dyspnea;
from the blood and lymphatic system: eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, thrombocytosis, neutropenia, hemolytic anemia, hypoprothrombinemia (bleeding and bruising without apparent cause), thrombophlebitis, prolongation of thrombin and prothrombin time, agranulocytosis;
from the digestive tract: stomach and intestinal cramps, abdominal pain, diarrhea *, nausea, vomiting, candidiasis of the oral mucosa, pseudomembranous colitis, dry mouth, dyspepsia, flatulence, dysbacteriosis, rarely - stomatitis, glossitis;
Metabolic: anorexia;
from the hepatobiliary system: hepatitis, cholestasis, transient increase in liver transaminases and LF activity, hyperbilirubinemia, cholestatic jaundice, icteric sclerae, icteric skin;
Kidney and urinary system: acute renal failure, including interstitial nephritis as the main pathological condition, hematuria;
Immune system and skin and subcutaneous tissue disorders: hypersensitivity reactions, including rash, pruritus, angioedema, anaphylactic shock, anaphylactic reaction; serum sickness-like reactions; drug rash with eosinophilia and systemic symptoms (DRESS), facial oedema, skin hyperemia, urticaria, erythema multiforme or Stevens-Johnson syndrome, serum sickness, purpura, arthralgia, fever, maculopapular and vesicular rashes, fungal dermatitis, epithelial desquamation, dry skin, hair loss, sunburn, toxic epidermal necrolysis;
infections and infestations: vaginal candidiasis (vaginal itching or discharge).
Cases of diarrhea following cefixime use may be associated with Clostridium difficile.
Laboratory data: Most laboratory changes are transient and have no clinical significance. Increased urea, increased serum creatinine, false-positive Coombs test results, and positive urine ketones in nitroprusside tests but not nitrofurantoin may occur. Cefixime may cause false-positive urine glucose tests, so enzyme tests, liver function tests, and kidney function tests should be used.
General disorders: sweating, fatigue, weakness, inflammation of the mucous membrane.
* Diarrhea is usually associated with high doses. Moderate to severe diarrhea has been reported; discontinuation of therapy is warranted in such cases. Cefixime should be discontinued if severe diarrhea occurs.
Special instructions
Severe cutaneous adverse reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), have been reported in some patients with cefixime. If severe cutaneous adverse reactions occur, cefixime should be discontinued and appropriate treatment should be initiated.
Cases of drug-induced hemolytic anemia, including severe cases with fatal outcome, have been described with cephalosporins. Hemolytic anemia has also been reported after repeated use of cephalosporins (including cefixime).
Effects on renal function: Cefixime should be used with caution in patients with significant renal impairment (see Dosage and Administration).
As with other cephalosporins, cefixime may cause acute renal failure, including tubulointerstitial nephritis as the underlying pathological condition. If acute renal failure occurs, cefixime should be discontinued and appropriate therapy and/or measures should be taken.
Hypersensitivity reactions. Due to cross-reactivity of hypersensitivity, before starting treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cephalosporins or penicillins. Cefixime should be administered with particular caution to patients with hypersensitivity to penicillin, since there is a risk of anaphylactic reactions. If an allergic reaction to cefixime develops, the drug should be discontinued. Allergic reactions (especially anaphylaxis) observed with the use of beta-lactam antibiotics can be severe and in some cases fatal (see Adverse Reactions).
Colitis/overgrowth of non-susceptible microorganisms. Adverse reactions from the digestive tract may occur when using the drug, therefore cefixime should be prescribed with caution to patients with a history of bleeding, digestive tract diseases, especially ulcerative colitis, regional colitis or enteritis, as well as with impaired liver function.
Prolonged use of cefixime may lead to overgrowth of non-susceptible microorganisms, including disruption of the normal intestinal microflora, which may lead to overgrowth of Candida albicans and the development of oral candidiasis (see Side effects).
Pseudomembranous colitis: Broad-spectrum antibiotics, especially when used long-term, can cause pseudomembranous colitis. Symptoms of pseudomembranous colitis may develop during or after antibiotic treatment is stopped.
The occurrence of severe diarrhea during treatment may be a consequence of the development of pseudomembranous colitis. In these cases, cefixime should be discontinued and appropriate investigation should be performed.
Effects on the blood system: Neutropenia and agranulocytosis may occur with beta-lactam antibiotics, especially with prolonged treatment. Cefixime should be discontinued if neutropenia develops.
With prolonged use of the drug (more than 10 days), blood tests should be monitored.
Effect on serological tests: Cefixime may cause false-positive Coombs' test results. Cefixime may also cause false-positive urine glucose tests (see Adverse Reactions).
Spectrum of antibacterial activity. For infections caused by group A beta-hemolytic streptococcus, the course of treatment should be at least 10 days to prevent acute rheumatic fever.
Interaction with alcohol. Cephalosporins increase the toxicity of alcohol, so it is not recommended to drink alcoholic beverages during treatment with cefixime.
Use during pregnancy and breastfeeding. There are no data on the use of the drug during pregnancy. Cefixime crosses the placenta. The use of cefixime during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus.
Children. The drug in capsule form is not used in children under 12 years of age. The drug in oral suspension is used in children from 6 months of age. The safety and efficacy of cefixime in children under 6 months of age have not been established, therefore the use of cefixime in this category of patients is not recommended.
The ability to influence the reaction rate when driving vehicles or other mechanisms. In general, there is no effect, but the possibility of adverse reactions from the central nervous system (for example, dizziness) should be taken into account, which can cause a decrease in the speed of psychomotor reactions, in which case you should refrain from driving vehicles or working with other mechanisms.
Interactions
As with other cephalosporins, increases in prothrombin time have been reported in some patients, so caution should be exercised in individuals receiving anticoagulant therapy.
Cefixime should be used with caution in patients receiving coumarin-type anticoagulants, such as warfarin potassium. Since cefixime may potentiate the effects of anticoagulants, an increase in prothrombin time with or without clinical bleeding may occur.
Blockers of tubular secretion (allopurinol, probenecid, diuretics) increase C max of cefixime in blood plasma, slowing down the excretion of cefixime by the kidneys, which may lead to symptoms of overdose.
When cefixime is used in combination with potentially nephrotoxic substances (aminoglycosides, colistin, polymyxin, viomycin) or potent diuretics (ethacrynic acid, furosemide), there is an increased risk of developing renal failure.
Salicylic acid increases the level of free cefixime by 50% due to displacement of cefixime from protein binding sites. This effect is concentration-dependent.
Carbamazepine may cause an increase in cefixime plasma concentrations, so it is advisable to monitor this indicator.
Nifedipine increases the bioavailability of cefixime, but the clinical interaction has not been determined.
Potentially, like other antibiotics, the use of the drug may result in a decrease in estrogen reabsorption and a decrease in the effectiveness of combined oral contraceptives.
Cephalosporin antibiotics may cause a false-positive direct Coombs test. It should be noted that a positive Coombs test may be caused by this drug.
Overdose
Symptoms: increased manifestations of adverse reactions, such as dizziness, nausea, vomiting, diarrhea.
Treatment: gastric lavage, use of antihistamines and glucocorticoids; oxygen therapy. Hemodialysis or peritoneal dialysis only slightly contribute to the removal of cefixime from the body. Therapy is symptomatic.
There is no specific antidote for the treatment of overdose.
Storage conditions
Capsules and dry powder - at a temperature not exceeding 25 °C, the finished suspension - in the refrigerator (use within 14 days).
