Triolev-200/Triolev

Triolev-200: White to off white coloured, round, biconvex and plain on both sides and film coated tablet.
Each film-coated tablet contains: Cefixime (as Trihydrate) USP equivalent to Anhydrous Cefixime 200 mg.
Triolev: Off white free flowing granular powder filled in 60 mL white HDPE bottle which gives off white color suspension after constitution with water.
Each 5 mL of the reconstituted suspension contains: Cefixime Trihydrate eq. to Anhydrous Cefixime USP 100 mg.

Triolev-200: Pharmacotherapeutic group: Third generation cephalosporin.
Pharmacology: Pharmacodynamics: Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms. Clinical efficacy has been demonstrated in infections caused by commonly occurring pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative strains), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. It is highly stable in the presence of beta-lactamase enzymes. Most strains of Enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase positive and negative strains and methicillin-resistant strains) are resistant to Cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to Cefixime.
Pharmacokinetics: The absolute oral bioavailability of Cefixime is in the range of 22-54%. Absorption is not significantly modified by the presence of food. Cefixime may therefore be given without regard to meals. From in vitro studies, serum or urine concentrations of 1 mcg/mL or greater were considered to be adequate for most common pathogens against which Cefixime is active. Typically, the peak serum levels following the recommended adult or pediatric doses are between 1.5 and 3 mcg/mL. Little or no accumulation of Cefixime occurs following multiple dosing.
The pharmacokinetics of Cefixime in healthy elderly (age >64 years) and young volunteers (11-35). Compared the administration of 400 mg doses once daily for 5 days. Mean Cmax and AUC values were slightly greater in the elderly. Elderly patients may be given the same dose as the general population. Cefixime is predominantly eliminated as unchanged drug in the urine. Glomerular filtration is considered the predominant mechanism. Metabolites of Cefixime have not been isolated from human serum or urine. Serum protein binding is well characterised for human and animal sera; Cefixime is almost exclusively bound to the albumin fraction, the mean free fraction being approximately 30%. Protein binding of Cefixime is only concentration dependent in human serum at very high concentrations which are not seen following clinical dosing.
Transfer of 14C-labelled Cefixime from lactating rats to their nursing offspring through breast milk was quantitatively small (approximately 1.5% of the mothers' body content of Cefixime in the pup). No data are available on secretion of Cefixime in human breast milk. Placental transfer of Cefixime was small in pregnant rats dosed with labelled Cefixime.
Triolev: Pharmacotherapeutic group: Antibacterial for systemic use, belonging to the class of cephalosporins.
Pharmacology: Pharmacodynamics: Mode of action: Cefixime is an antibiotic belonging to the third generation cephalosporin group. Like other cephalosporins, cefixime exerts antibacterial activity by binding to and inhibiting the action of penicillin-binding proteins involved in the synthesis of bacterial cell walls. This leads to bacterial cell lysis and cell death.
Mechanism of resistance: Bacterial resistance to cefixime may be due to one or more of the following mechanisms: Hydrolysis by extended-spectrum beta-lactamases and/or by chromosomally-encoded (AmpC) enzymes that may be induced or de-repressed in certain aerobic gram negative bacterial species; Reduced affinity of penicillin-binding proteins; Reduced permeability of the outer membrane of certain gram-negative organisms restricting access to penicillin-binding proteins; Drug efflux pumps.
More than one of these mechanism of resistance may co-exist in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express cross-resistance to several or all beta-lactams and/or antibacterial drugs of other classes.
Pharmacokinetics: Cefixime, given orally is about 40% to 50% absorbed whether administered with or without food; however, time for maximal absorption is increased approximately 0.8 hours when administered with food without alteration in other pharmacokinetic parameters. A single 200 mg tablet of Cefixime produces an average peak serum concentration of approximately 2.7 mcg/mL. No biologically active metabolites of Cefixime have been discovered. It is approximately 70% protein bound. Very high concentration is found in bile and hence used in biliary tract infections. The mean elimination half life is 3 hours. Urinary excretion accounts for between 12% to 34% of orally administered dose. The biliary recovery of Cefixime in 24 hours is 5% of orally administered dose.
The t_1/2 is prolonged in patients with severely impaired renal function. Hence dosage adjustment is necessary in severe renal impairment i.e. Creatinine clearance <20 mL/min. Peak serum concentration following oral administration of the absorbed dose is excreted unchanged in the urine in 24 hours.

Triolev-200: Cefixime is indicated for the treatment of the following infections when caused by susceptible microorganisms.
Upper Respiratory Tract Infections: e.g., bacterial pharyngitis, tonsilitis, otitis media, sinusitis.
Lower Respiratory Tract Infections: e.g., acute bronchitis.
Urinary Tract Infections: e.g., acute uncomplicated cystitis and urethritis.
Uncomplicated gonorrhea.
Triolev: Cefixime is indicated for the treatment of following infections when caused by susceptible organisms: Sequential treatment after initial I.V. Chemotherapy with parenteral cephalosporin, respiratory tract infections, otitis media, urinary tract infections, gonorrhoea, typhoid fever.

Triolev-200: Adults: The recommended dose of Cefixime is 400 mg daily. This may be given as 400 mg once daily or as 200 mg every 12 hours. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended.
Children: The recommended dose is 8 mg/kg/day. This may be administered as a single dose or may be given in two divided doses as 4 mg/kg every 12 hours. In typhoid, the dose is 15 to 20 mg/kg/day given as a single dose or divided into two equal doses every 12 hours for 7 to 14 days. In the treatment of infections due to S. pyogenes, a therapeutic dosage of Cefixime should be administered for at least 10 days, or as directed by the physician.
Triolev: For children, the recommended dose is 8 mg/kg/day of the suspension. This may be administered as a single dose or in two divided doses is recommended, as 4 mg/kg every 12 hours. In typhoid dose is 20 mg/kg/day in two divided doses or as a single dose in the treatment of infections due to S. pyogenes, a therapeutic dosage of Cefixime should be administered for at least 10 days.
Or as prescribed by the physician.

Triolev-200: There is a risk of encephalopathy in cases of administration of beta-lactam antibiotics, including Cefixime, particularly in case of overdose or renal impairment.
Adverse reactions seen at dose levels up to 2 g Cefixime in normal subjects did not differ from the profile seen in patients treated at the recommended doses. Cefixime is not removed from the circulation in significant quantities by dialysis.
No specific antidote exists. General supportive measures are recommended.
Triolev: There is no experience with overdoses with Cefixime.
Adverse reactions seen at dose levels up to 2 g cefixime in normal subjects did not differ from the profile seen in patients treated at the recommended doses. Gastric lavage may be indicated in overdosage. No specific antidote exists. Cefixime is not removed from the circulation in significant quantities by dialysis.

Triolev-200: Hypersensitivity to cephalosporin antibiotics or to any of the excipients. Cefixime is contraindicated in patients with renal impairment with creatine clearance below 60 mL/min.
Triolev: Patients with known hypersensitivity to cefixime, other cephalosporin antibiotics or to any of the excipients.
Cefixime is also contraindicated in patients with previous, immediate and/or severe hypersensitivity to penicillin or any beta-lactam antibiotics and preterm and term newborn infants (0-27 days).

Triolev-200: Cefixime should be given with caution to patients who have shown hypersensitivity to other medicines. Cephalosporins should be given with caution to penicillin-sensitive patients as there is some evidence of partial cross allergenicity between the penicillins and the cephalosporins. Patients have had severe reactions (including anaphylaxis) to both classes of drugs. If an allergic effect occurs with Cefixime the drug should be discontinued and the patient treated with appropriate agents if necessary. Cefixime should be administered with caution in patients with markedly impaired renal function. Prolonged use of Cefixime may result in the overgrowth of non-susceptible organisms. Cefixime has been shown to alter the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate a toxin(s) produced by Clostridium difficile is the primary cause of antibiotic associated pseudomembranous colitis. The product should be discontinued if diarrhea occurs.

Triolev-200: Encephalopathy: Beta-lactams, including Cefixime, predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment.
Severe cutaneous adverse reactions: Severe cutaneous adverse reactions such as 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 therapy and/or measures should be taken. Cefixime should be given with caution to patients who have shown hypersensitivity to other drugs.
Hypersensitivity to penicillins: As with other cephalosporins, Cefixime should be given with caution to patients with a history of hypersensitivity to penicillin, as there is some evidence of partial cross-allergenicity between the penicillins and cephalosporins. Patients have had severe reactions (including anaphylaxis) to both classes of drugs. If an allergic effect occurs with Cefixime, the drug should be discontinued and the patient treated with appropriate agents if necessary.
Hemolytic anaemia: Drug-induced hemolytic anaemia, including severe cases with a fatal outcome, has been described for cephalosporins (as a class). The recurrence of hemolytic anaemia after re-administration of cephalosporins in a patient with a history of cephalosporin (including Cefixime) associated hemolytic anemia has also been reported.
Acute renal failure: As with other cephalosporins, Cefixime may cause acute renal failure including tubulointerstitial nephritis as an underlying pathological condition. When acute renal failure occurs, Cefixime should be discontinued and appropriate therapy and/or measures should be taken.
Renal impairment: Cefixime should be administered with caution in patients with markedly impaired renal function.
Use in children: Safety of Cefixime in premature or newborn infant has not been established.
Treatment with broad spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated diarrhea. Pseudomembranous colitis is associated with the use of broad-spectrum antibiotics (including macrolides, semi-synthetic penicillins, lincosamides and cephalosporins); it is therefore important to consider its diagnosis in patients who develop diarrhea in association with the use of antibiotics. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment.
Management of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriologic studies, fluids, electrolytes and protein supplementation. If the colitis does not improve after the drug has been discontinued, or if the symptoms are severe, oral vancomycin is the drug of choice for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be excluded.
Triolev: Cefixime should be given with caution to patients who have shown hypersensitivity to other drugs. Cephalosporins should be given with caution to penicillin-sensitive patients, as there is some evidence of partial cross-allergenicity between penicillin and cephalosporins. Patients have had severe reactions (including anaphylaxis) to both classes of drugs. Special care is indicated in patients who have experienced any allergic reaction to penicillins or any beta-lactam antibiotics as cross-reactions may occur.
If severe hypersensitivity reactions or anaphylactic reactions occur after administration of Cefixime, the medicine should be discontinued immediately and appropriate emergency measures should be initiated.
Prolonged use of cefixime may result in the overgrowth of non-susceptible organisms. Treatment with a broad spectrum of antibiotics alters the normal flora of the colon and may permit the overgrowth of Clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause for antibiotic-associated diarrhoea.
Pseudomembranous colitis is associated with the use of broad-spectrum antibiotics (including macrolides, semi-synthetic penicillins, lincosamides and cephalosporins). It is therefore important to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics.
In patients who develop severe diarrhoea during or after use of cefixime, the risk of life threatening pseudo-membranous colitis should be taken into account. The use of cefixime should be discontinued and appropriate treatment measures should be established. Management of pseudomembranous colitis should include symptomatic therapy, appropriate bacteriologic studies, fluids, electrolytes and protein supplementation. If the colitis does not improve after the drug has been discontinued or if the symptoms are severe, oral vancomycin is the drug of choice for antibiotic associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be excluded. The use of medicinal products inhibiting the intestinal peristalsis is contraindicated.
Cefixime contains sucrose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use of Nifedipine, a calcium channel blocker, may increase bioavailability of Cefixime up to 70%.
Renal insufficiency: Cefixime should be administered with caution in adult patients with creatinine clearance <20 mL/min. There are insufficient data regarding use of cefixime in the pediatric and adolescent age group in the presence of renal insufficiency; the use of cefixime in these patient-groups is not recommended.

Triolev-200: Fertility, Pregnancy and Lactation: Reproduction studies have been performed in mice and rats at doses up to 400 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Cefixime. In the rabbits, at doses up to 4 times the human dose, there was no evidence of a teratogenic effect; there was a high incidence of abortion and maternal death which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in the population of the microflora of the intestine. There are no adequate and well-controlled studies in pregnant women. Cefixime should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.
Triolev: Pregnancy: For cefixime, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Caution should be exercised when prescribing to pregnant women. Cefixime should not be used in pregnant mothers unless considered essential by the physician.
Lactation: It is unknown whether cefixime is excreted in human milk and non-clinical studies have shown excretion of cefixime in animal milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with cefixime should be made taking into account the benefit of breast-feeding to the child and the benefit of cefixime therapy to the woman. However, until further clinical experience is available, cefixime should not be prescribed to breast-feeding mothers.

Gastrointestinal Disturbances: The most frequent side effects seen with Cefixime are diarrhea and stool changes. Moderate to severe diarrhea has been reported; this has occasionally warranted cessation of therapy. Cefixime should be discontinued if marked diarrhoea occurs. Other gastrointestinal side effects seen less frequently are nausea, abdominal pain, dyspepsia, vomiting and flatulence.
Pseudomembranous colitis has been reported.
Central Nervous System: Headache and dizziness.
Hypersensitivity Reactions: Allergies in the form of rash, pruritus, urticaria, drug fever and arthralgia have been observed. These reactions usually subsided upon discontinuation of therapy.
Hematological and Clinical Chemistry: Thrombocytopenia, leukopenia and eosinophilia have been reported. These reactions were infrequent and reversible. Changes in liver and renal function tests have been observed.
Triolev-200mg: Miscellaneous: Other possible reactions includes genital pruritus and vaginitis.
Triolev: Cefixime is generally well tolerated. The majority of adverse reactions observed in clinical trials were mild and self limiting in nature.

Triolev-200: Anticoagulants: In common with other cephalosporins, increases in prothrombin times have been noted in a few patients. Care should therefore be taken in patients receiving anticoagulation therapy.
Cefixime should be administered with caution to patients receiving coumarin-type anticoagulants, e.g. warfarin potassium. Since Cefixime may enhance effects of the anticoagulants, prolonged prothrombin time with or without bleeding may occur.
Other forms of interaction: A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.
A false positive direct Coombs test has been reported during treatment with cephalosporin antibiotics, therefore it should be recognized that a positive Coombs test may be due to the drug.
Triolev: Care should be exercised in patients receiving anticoagulants and cefixime due to possibility that cefixime may increase prothrombin times.

Triolev: Direction for Reconstitution: Add boiled and cooled water up to the mark on the bottle and shake well. Adjust the volume up to the mark by adding more water if necessary. The reconstituted suspension should be stored in a cool place and used within 7 days.

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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