Refix

Cefixime trihydrate.

Capsule: Cefixime 200 mg capsule is available as off-white to light yellow fine crystalline powder encapsulated in slightly soft and slightly brittle empty gelatin capsule size #1 with yellow cap and yellow body.
Each capsule contains: Cefixime (as trihydrate), USP 200 mg.
Granules for oral suspension: Each 5 mL of reconstituted suspension contains: Cefixime (as Trihydrate), USP 100 mg.
Cefixime is a third generation cephalosporin which has antibacterial activity similar to penicillin, carbacephems and cephamycins. It has a vinyl group at the 3 position and a carboxymethoxylimino group at the 7 position of 7-aminocephalosporanic acid.

Pharmacology: Pharmacodynamics: Capsule: Cefixime is a third generation cephalosporin with antibacterial activity similar to penicillins, carbacephems and cephamycins.
Cefixime exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It binds to specific penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves completion of the cross-linking of the terminal glycine residue of the pentaglycine bridge to the fourth residue of the pentapeptide. The transpeptidase that catalyzes this step is inhibited by cephalosporins. Thus, inhibition of the transpeptidase interrupts peptidoglycan synthesis, causing formulation of defective cell walls and osmotically unstable spheroplasts and lysis of the bacteria.
Pharmacokinetics: Capsule: About 30% to 50% of a single oral dose of cefixime is absorbed. Food decreases the rate but generally does not affect the extent of drug absorption. Peak serum concentrations (C_max) after a single, oral 200 or 400 mg dose of cefixime as capsule, tablet or oral suspension are attained between 2 to 6 hours. Although there are differences in pharmacokinetic parameters between the formulations, results of controlled, cross-over studies in healthy adults indicate that the capsules are essentially bioequivalent to tablets. However, oral suspension is more completely absorbed than tablets; thus, tablets theoretically should not be substituted for oral suspension.
Peak serum concentrations of cefixime are about 15 to 50% higher when the drug is administered as an oral suspension rather than as tablets. When 200 and 400 mg doses of cefixime are administered as an oral suspension, peak serum concentrations average 3 to 3.4 mcg/mL and 4.6 mcg/mL, respectively. Areas under the concentration-time curves (AUCs) of 100 to 400 mg cefixime oral suspension are approximately 10 to 25% higher than cefixime tablets. This lack of bioequivalence between dosage forms should be considered if the oral suspension is to be substituted for tablets.
When cefixime oral suspension at a single dose of 4, 6, or 8 mg per kg body weight was administered to children 6 months to 6 years old or older, mean serum concentrations (C_max) attained to 3.5 to 4.5 hours after the dose were 2.18 to 2.44, 3.55 to 4.07, and 3.4 to 3.91 mcg/mL, respectively. Serum concentrations of cefixime are not directly dose proportional at doses of 4 to 8 mg/kg body weight in children. Little or no accumulation of cefixime occurs after multiple dosing.
After oral administration, cefixime is distributed into bile, sputum, tonsils, maxillary sinus mucosa, middle ear discharge, blister fluid, and prostatic fluid. Sputum concentrations may be 2% to 10% of concurrent serum concentrations; in one study, a single 200 mg oral dose of cefixime resulted in sputum concentrations of 0.03 to 0.12 mcg/mL. It is not known whether cefixime is distributed into CSF after oral administration.
About 65% to 75% of cefixime is bound to serum proteins, principally albumin, and such binding is not concentration-dependent over the range of 0.5 to 30 mcg/mL. The fraction of free cefixime in plasma may be slightly greater in patients with renal impairment than in those with normal renal function.
Cefixime crosses the placenta and is distributed in low concentrations into amniotic fluid and cord serum; cord serum concentrations may be 15% to 50% of concurrent maternal plasma concentrations. No data are available on secretion of cefixime into human milk.
The half-life of cefixime is about 3 to 4 hours is not dose-dependent. It is excreted renally via glomerular filtration and to a lesser extent by tubular secretion. Metabolites of cefixime have not been isolated from human serum or urine. About 7% to 41% of a single oral dose of the drug is excreted unchanged in urine within 24 hours. The remainder of the dose (up to 60%) is eliminated by nonrenal mechanism. In animal studies, it was noted that up to 10% of a single oral dose of cefixime is excreted unchanged in bile.
Cefixime is not removed to a significant degree by either hemodialysis or peritoneal dialysis.
Granules for oral suspension: Only 40% to 50% of an oral dose of cefixime is absorbed from the gastrointestinal tract, whether taken before or after meals, although the rate of absorption may be decreased in the presence of food. Cefixime is better absorbed from oral suspension than from tablets. Absorption is fairly slow. Peak plasma concentrations of 2 to 3 μg per mL and 3.7 to 4.6 μg per mL have been reported between 2 and 6 hours after single doses of 200 and 400 mg, respectively. The plasma half-life is usually about 3 to 4 hours and may be prolonged when there is renal impairment. About 65% of cefixime in the circulation is bound to plasma proteins. Information on the distribution of cefixime in body tissues and fluids is limited. It crosses the placenta. Relatively high concentrations may be achieved in bile and urine. About 20% of an oral dose (or 50% of an absorbed dose) is excreted unchanged in the urine within 24 hours. Up to 60% may be eliminated by non renal mechanisms; there is no evidence of metabolism but some is probably excreted into the faeces from bile. It is not substantially removed by dialysis.
Antimicrobial Action: Cefixime is a bactericidal antibiotic and stable to hydrolysis by many beta-lactamases. It has a mode of action and spectrum of activity similar to those of the third-generation cephalosporin cefotaxime, but some Enterobacteriaceae are less susceptible to cefixime. Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis) and Neisseria gonorrhoea are sensitive, including penicillinase producing strains. Of the Gram-positive bacteria, streptococci are sensitive to cefixime but most strains of staphylococci, enterococci, and Listeria spp. are not.

Capsule: For the treatment of the following infections due to susceptible microorganisms: Acute bronchitis, acute exacerbations of chronic bronchitis, bronchiectasis with infection, secondary infections in chronic respiratory tract diseases, pneumonia.
Urinary tract infections including pyelonephritis, cystitis and cystourethritis.
Uncomplicated gonorrhea (cervical/urethral).
Cholecystitis, cholangitis.
Scarlet fever.
Sinusitis, tonsillitis, pharyngitis, otitis media.
Typhoid fever (enteric fever) including multi-drug resistant typhoid fever.
Granules for oral suspension: Used in the treatment of susceptible infections, including gonorrhea, otitis media, pharyngitis, lower respiratory tract infections such as bronchitis, and urinary tract infections.

Capsule: Cefixime may be given without regard to meals. (See Tables 1 & 2).

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Click on icon to see table/diagram/image

Dosage in Adults with Renal Impairment: Adult patients whose creatinine clearance is between 20 and 40 mL/min should be given 75% of the standard dosage (i.e., 300 mg/day at the usual dosing interval). Patients whose creatinine clearance is less than 20 mL/min and those patients who are maintained on chronic ambulatory peritoneal dialysis or hemodialysis should be given 50% of the standard dosage (i.e., 200 mg/day at the usual dosing interval).
Maximum dose: 400 mg/day.
Usual Duration of Treatment: Most infections: 7 to 14 days.
Infections due to Streptococcus pyogenes: at least 10 days.
Or, as prescribed by a physician.
Granules for oral suspension: Children over 6 months and under 50 kg may be given 8 mg/kg daily, as a single dose or in two divided doses. Or as prescribed by the physician.
Direction for Reconstitution: To make 60 mL reconstituted suspension, add approximately 40 mL of water. Shake well until the powder are evenly suspended. The suspension is stable for 7 days at temperatures not exceeding 30°C and 14 days under refrigeration (2-8°C).

Capsule: Limited information is available on the acute toxicity of cefixime in humans. In healthy adults who received cefixime in single doses up to 2 g, adverse effects were similar to those seen with usual doses of the drug and included mild to moderate adverse GI effects.
There is no specific antidote for cefixime toxicity. In case of acute overdosage, gastric lavage may be indicated. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis.
Granules for oral suspension: Gastric lavage may be indicated; otherwise, no specific antidote exists. Cefixime is not removed in significant quantities from the circulation by hemodialvsis or peritoneal dialysis. Adverse reactions in small numbers of healthy adult volunteers receiving single doses up to 2 g of cefixime did not differ from the profile seen in patients treated at the recommended doses.

Capsule: Known hypersensitivity to cefixime or other cephalosporins, to penicillins or any component of the product.
Granules for oral suspension: History of allergy to any ingredient in this product or other cephalosporins.
History of hypersensitivity to penicillins.

Capsule: Hypersensitivity Reactions: Careful inquiry should be made prior to cefixime therapy to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs. Use with caution in penicillin-sensitive patients since cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of allergy to penicillin. In case of an allergic reaction to cefixime, the drug should be discontinued. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures including oxygen, intravenous (IV) fluids, IV antihistamines, corticosteroids, pressor amines and airway management as clinically indicated.
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions including toxic epidermal necrolysis, Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in some patients on cefixime. When severe cutaneous adverse reactions occur, cefixime should be discontinued and appropriate treatment and/or measures should be taken.
Clostridium difficile-associated diarrhea (CDAD): This has been reported with the use of nearly all antibacterial agents, including cefixime, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea following administration of antibacterial agents.
Hemolytic Anemia: Cefixime should not be used in patients with a history of cephalosporin-associated hemolytic anemia since the recurrence of hemolysis is much more severe.
An immune-mediated hemolytic anemia has been observed in patients receiving cephalosporin antibiotics, including cefixime. Severe cases of hemolytic anemia including fatalities, have been reported with cephalosporins in both adults and children if a patient develops anemia anytime during or within 2 to 3 weeks following the administration of cefixime. The diagnosis of a cephalosporin-associated anemia should be considered and the drug discontinued until the etiology is determined.
Periodic monitoring of signs and symptoms of hemolytic anemia, including measurement of hematological parameters or drug-induced antibody testing, where appropriate is recommended.
Acute Renal Failure: As with other cephalosporins, cefixime may cause acute renal failure including tubulointerstitial nephritis. In case of renal failure, cefixime should be discontinued and appropriate therapy instituted.
Prothrombin Time: Cephalosporins may be associated with a fall in prothrombin activity. Patients who are at risk are those with kidney or liver impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated.
Seizures: These have been reported with several cephalosporins (e.g., cefuroxime, ceftazidime), particularly in patients with renal impairment in whom dosage of the drug was not reduced. If seizures occur during treatment with a cephalosporin, the drug should be discontinued and anticonvulsant therapy initiated as clinically indicated.
Other Precautions: As with other broad-spectrum antibiotics, cefixime should be given with caution in individuals with a history of colitis. The safety and efficacy of cefixime have not been established in patients with gastrointestinal malabsorption.
Prescribing cefixime in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of antibiotic resistance.
As with other antibacterial drugs, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi.
Abnormal Laboratory Tests: Positive Coombs' test, pancytopenia, transient increase in gamma-glutamyl transferase, decreased serum albumin and/or total protein.
Granules for oral suspension: Should not be given to patients who are hypersensitive to it or to other cephalosporins. About 10% of penicillin-sensitive patients may also be allergic to cephalosporins although the true incidence is uncertain; great care should be taken if cefixime is to be given to such patients. Care is also necessary in patients with a history of allergy.

Pregnancy: (Pregnancy Category B).
Capsule: Reproduction studies performed in mice and rats up to 400 times the human dose have not revealed evidence of harm to the fetus. There are no adequate and well-controlled studies in pregnant women, and the drug should be used during pregnancy only when clearly needed.
Granules for oral suspension: There are no adequate and well-controlled studies in pregnant women. Potential benefit should justify the potential risk when cefixime is used during pregnancy.
Labor and Delivery: The effect of cefixime in labor and delivery is unknown.
Lactation: It is not known whether cefixime is excreted in human milk. Consideration should be given discontinuing breastfeeding temporarily during treatment with cefixime.

Capsule: Most adverse effects reported with cefixime were similar to those reported with other oral cephalosporins and were usually mild and transient in nature.
Gastrointestinal (GI): Abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, flatulence, loose or frequent stools/stool changes, nausea, vomiting, pseudomembranous colitis, pruritus ani.
Dermatologic/Hypersensitivity Reactions: Anaphylactic/anaphylactoid reactions (including shock and fatalities), angioedema, arthralgia, drug fever, erythema multiforme, facial edema, pruritus, skin rashes, serum sickness-like reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), urticaria.
Hepatic: Transient elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, bilirubin, and lactate dehydrogenase (LDH); hepatitis, jaundice (cholestatic and/or hepatocellular).
Renal/Genitourinary: Transient elevations in blood urea nitrogen (BUN) and serum creatinine levels; acute renal failure including tubulointerstitial nephritis; dysuria, pyuria, genital pruritus, vaginitis, vaginal candidiasis.
Nervous System: Dizziness, headache, fatigue, insomnia, malaise, nervousness, seizures, somnolence.
Hematologic: Transient thrombocytopenia, thrombocytosis, leucopenia, leukocytosis, neutropenia, agranulocytosis, eosinophilia, and hypereosinophilia, immune hemolytic anemia; prolonged prothrombin time, prolonged partial thromboplastin time, decreased hemoglobin concentration and hematocrit.
Abnormal Laboratory Test: Hyperbilirubinemia.
Other Adverse Effects: Increased serum amylase concentrations; dyspnea, respiratory distress.
In addition to the adverse reactions listed previously which have been observed in patients treated with cefixime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics.
Allergic reactions, hypersensitivity reactions including chills, joint pain or inflammation, hypotension; renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis; aplastic anemia, epistaxis or hemorrhage, thrombocythemia, granulocytosis, monocytosis, lymphocytopenia, basophilia, hypoprothrombinemia (with or without bleeding), menstrual irregularities, tenesmus, epigastric pain, glossitis, candidiasis (oral thrush), taste alteration, decreased salivation, heartburn, colitis, nightmares, vertigo, chest pain, pleural effusion, pulmonary infiltrate, cough and rhinitis, increased or decreased serum glucose concentration; superinfection.
Granules for oral suspension: The most common are hypersensitivity reactions, including skin rashes, urticaria, eosinophilia, fever, reactions resembling serum sickness, and anaphylaxis. There may be a positive response to the Coombs' test although haemolytic anaemia rarely occurs. Neutropenia and thrombocytopenia have occasionally been reported. Agranulocytosis has been associated rarely with some cephalosporins. Bleeding complications related to hypoprothrombinaemia and/or platelet dysfunction have occurred especially with cephalosporins and cephamycins having a methylthiotetrazole side-chain, including cefamandole, cefbuperazone, cefmenoxime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotetan, cefpiramide, and latamoxef. The presence of a methylthiadiazolethiol side-chain, as in cefazolin, or a methylthiotriazine ring, as in ceftriaxone, might also be associated with such bleeding disorders.

Capsule: Carbamazepine: Elevated carbamazepine levels have been reported when administered concomitantly with cefixime. Drug monitoring when these drugs are given together is advised.
Chloramphenicol: In vitro and in vivo antagonism have been noted between cephalosporins and chloramphenicol against a variety of Gram-positive and Gram-negative bacteria; therefore, it is recommended that combined therapy with chloramphenicol and cephalosporin be avoided particularly when bactericidal activity is considered important.
Nifedipine: Concomitant administration of cefixime and nifedipine increases oral bioavailability of cefixime as a result of higher C_max and AUC.
Probenecid: Concomitant administration of probenecid reportedly increases C_max and AUC of cefixime and decreases renal clearance and volume of distribution of the drug.
Salicylates: Concomitant administration of 650 mg oral dose and 400 mg oral dose of cefixime in healthy adult men may result in a 20 to 25% decrease in C_max and AUC of cefixime but did not affect protein binding, serum t_1/2, or renal clearance. This effect may not be clinically important since serum concentrations of cefixime remained higher than the MIC values reported for most susceptible organisms. However, some clinicians state that this effect may be clinically important in certain infections.
Warfarin and other anticoagulants: Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is given concomitantly.
Granules for oral suspension: Care should be exercised in patients receiving anticoagulants and cefixime due to the possibility that cefixime may increase prothrombin times.

Store at temperatures not exceeding 30°C.

Cephalosporins

J01DD08 - cefixime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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