C Tax-OF Tablets
Therapy Area
Anti Infective
1.0 Generic name
Cefixime & Ofloxacin Tablets
2.0 Qualitative and quantitative composition
Each film coated tablet contains:
Cefixime (as Trihydrate) IP equivalent to Anhydrous Cefixime 200 mg
Ofloxacin IP 200 mg
Excipients q.s.
Colours: Lake of Quinoline Yellow & Titanium Dioxide IP
3.0 Dosage form and strength
Film coated tablet
Cefixime (200mg) and Ofloxacin (200mg)
4.0 Clinical particulars
4.1 Therapeutic Indication
For the treatment of patients with typhoid fever and urinary tract infection in adults.
4.2 Posology and method of administration
C Tax-OF adult dose:
1 tablet two times daily.
4.3 Contraindications
- Persons with a history of hypersensitivity associated with the use of ofloxacin or any member of the quinolone group. Patients with known allergy to cefixime or other cephalosporins.
- Patients with a past history of tendinitis related to fluoroquinolone administration.
- Patients with a history of epilepsy or seizures.
- Children or growing adolescents and in pregnant or breast-feeding women, since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject
- Patients with latent or actual defects in G6PD activity
4.4 Special warnings and precautions for use
The drug may cause low blood sugar and mental health related side effects. Low blood sugar levels, also called hypoglycaemia, can lead to coma. The mental health side effects more prominent and more consistent across the systemic fluoroquinolone drug class. The mental health side effects to be added to or updated across all the fluoroquinolones are:
- Disturbances in attention
- Disorientation
- Agitation
- Nervousness
- Memory impairment
- Serious disturbances in mental abilities called delirium
| Condition | Description |
| Hypersensitivity and allergic reactions | Hypersensitivity, severe cutaneous ADRs such as TEN, Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in some patients. C Tax-OF should be discontinued and appropriate measures should be taken |
| Hypersensitivity to penicillins | As with other cephalosporins, C Tax-OF should be given with caution to patients with a history of hypersensitivity to penicillin, as there is some evidence of cross-allergenicity |
| Hemolytic anaemia | Drug-induced hemolytic anaemia has been seen with cephalosporins (as a class) |
| Renal impairment | It should be used with caution in patients with impaired renal function |
| G6PD deficiency | Patients with G6PD may be predisposed to hemolytic reactions if they are treated with quinolones. Therefore, if C Tax-OF has to be used in these patients, potential occurrence of haemolysis should be monitored |
| Impaired liver function | C Tax-OF should be used with caution in patients with impaired liver function |
| Myasthenia gravis | C Tax-OF is not recommended in patients with a known history of myasthenia gravis |
| Photosensitization | It is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays, during treatment and for 48 hours following treatment discontinuation |
| Superinfection | The prolonged use of C Tax-OF may result in overgrowth of non-susceptible organisms |
| Peripheral neuropathy | C Tax-OF should be discontinued if the patient experiences symptoms of neuropathy |
4.5 Drugs interactions
- Drugs known to prolong QT interval: C Tax-OF should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics).
- Antacids, Sucralfate, Metal Cations: Co-administered magnesium/aluminium antacids, sucralfate, zinc or iron preparations can reduce absorption. Therefore, ofloxacin should be taken 2 hours before such preparations.
- Theophylline, fenbufen or similar NSAIDs: A pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, NSAIDs, or other agents, which lower the seizure threshold. In case of seizures, treatment with C Tax-OF should be discontinued.
- Glibenclamide: Ofloxacin may cause a slight increase in serum concentrations of glibenclamide.
- Probenecid, cimetidine, furosemide and methotrexate: Caution should be exercised when ofloxacin is co-administered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.
- Vitamin K antagonists & Anticoagulants: Increased coagulation tests (PT/INR) and/or bleeding have been reported in patients treated with ofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests should be monitored in patients treated with Vitamin-K antagonists. Cefixime should be administered with caution to patients receiving coumarin-type anticoagulants, e.g. warfarin.
- Other forms of interaction: A false positive direct coombs test has been reported during treatment with cephalosporin antibiotics, therefore it should be recognised that a positive coombs test may be due to the drug.
4.6 Use in special populations
Pregnancy
C Tax-OF should not be used during pregnancy.
Lactation
Breast feeding should be discontinued during treatment with C Tax-OF because of the potential for arthropathy and other serious toxicity in the nursing infants.
Children
C Tax-OF is not indicated for use in children or growing adolescents.
4.7 Effects on ability to drive and use machines
There have been occasional reports of drowsiness/somnolence, impairment of skills, dizziness/vertigo and visual disturbances, which may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery), patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.
In the case of side effects such as encephalopathy (which may include convulsion, confusion, impairment of consciousness, movement disorders), the patient should not operate machines or drive a vehicle.
4.8 Undesirable effects
Cefixime:
- Acute generalized exanthematous pustulosis and Mouth Ulceration has been reported with Cefixime use.
- The most commonly seen adverse reactions reported were gastrointestinal events (30%) in adult patients
- Individual adverse reactions included Diarrhea-16%, Loose or frequent stools- 6%, Abdominal pain-3%, Nausea-7%, Dyspepsia-3%, Flatulence 4%
Ofloxacin:
- Stevens-Johnson syndrome (SJS)/ Toxic epidermal necrolysis (TEN) has been reported with Ofloxacin use.
- The most frequently reported adverse events were nausea- 10%, headache- 9%, insomnia- 7%, external genital pruritus in women- 6%, Dizziness-5%, Vaginitis-5%, Diarrhea-4%, Vomiting 4%
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com
Website: https://www.zuventus.com/drug-safety-reporting
By reporting side effects, you can help provide more information on the safety of this medicine.
4.9 Overdose
Ofloxacin
Important signs of acute over dosage: CNS symptoms such as confusion, dizziness, impairment of consciousness and seizures, increases QT interval, GIT reactions e.g. nausea and mucosal erosions.
In the case of overdose steps to remove any unabsorbed ofloxacin e.g. gastric lavage, administration of adsorbants and sodium sulphate are recommended; antacids are recommended for protection of the gastric mucosa. A fraction of ofloxacin may be removed from the body with haemodialysis.
No specific antidote exists. Elimination of ofloxacin may be increased by forced diuresis. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
Cefixime There is no experience with overdoses with Cefixime. Cefixime is not removed from the circulation in significant quantities by dialysis. No specific antidote exists. General supportive measures are recommended.
5.0 Pharmacological properties
5.1 Pharmacodynamic Properties
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. Bactericidal action of cefixime results from inhibition of cell-wall synthesis.
- Active against most isolates of the following bacteria both in vitro and in clinical infections:
- Gram-positive bacteria- Streptococcus pneumonia, Streptococcus pyogenes
- Gram-negative bacteria - Haemophilus influenza, Moraxella catarrhalis, Escherichia coli, Proteus mirabilis, Neisseria gonorrhoeae
- In vitro bactericidal activity is seen against isolates of the following microorganisms.
- Gram-positive bacteria- Streptococcus agalactiae
- Gram-negative bacteria- Haemophilus parainfluenzae, Proteus vulgaris, Klebsiella pneumonia, Klebsiella oxytoca, Pasteurella multocida, Providencia species, Salmonella species, Shigella species, Citrobacter amalonaticus, Citrobacter diversus, Serratia marcescens
Ofloxacin
- Is a quinolone-carboxylic acid derivative with a wide range of antibacterial activity against both gram negative and gram positive organisms.
- The primary mode of action of the quinolones is the specific inhibition of bacterial DNA gyrase. This enzyme is required for DNA replication, transcription, repair and recombination. Its inhibition leads to expansion and destabilisation of the bacterial DNA and hence to cell death.
- Active against most isolates of the following bacteria both in vitro and in clinical infections.
- Gram-Positive Microorganisms- Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pneumoniae (penicillin-susceptible), Streptococcus pyogenes
- Gram-Negative Microorganisms- Citrobacter koseri, Enterobacter aerogenes, Escherichia coli, Haemophilus influenza, Klebsiella pneumonia, Neisseria gonorrhoeae, Proteus mirabilis, Pseudomonas aeruginosa,
- Other Microorganisms- Chlamydia trachomatis
- In vitro bactericidal activity is seen against isolates of the following microorganisms
- Gram-positive microorganisms- Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus saprophyticu, Streptococcus pneumonia,
- Gram-Negative Microorganisms- Acinetobacter calcoaceticus, Bordetella pertussis, Pasteurella multocida, Enterobacter cloacae, Haemophilus ducreyi, Klebsiella oxytoca, Moraxella catarrhalis, M. morganii, Proteus vulgaris, Providencia rettgeri, P. stuartii, Serratia marcescens
- Other microorganisms- Chlamydia pneumoniae, Gardnerella vaginalis, Legionella pneumophila, Mycoplasma pneumoniae, Ureaplasma urealyticum,
- Anaerobic Microorganisms- Clostridium perfringes
5.2 Pharmacokinetic properties
| Parameter | Cefixime | Ofloxacin |
| Oral bioavailability | 40% to 50% | Approximately 98% |
| Tmax | 2 and 5 hours | 1 to 2 hours |
| Cmax | 2 mcg/mL (range 1 to 4 mcg/mL) | 2.2 mcg/mL |
| Plasma protein binding | Approx. 65%. | Approx. 32% |
| AUC | 34.9 ± 12.2 to 49.5 ± 19.1 mg.h/L | 14.1 mcg.h/mL |
| Half life | Averages 3 to 4 hours but may range up to 9 hours in some healthy volunteers. | Biphasic elimination. Following multiple oral doses at steady-state administration, the half-lives are approximately 4 to 5 hours and 20 to 25 hours. However, the longer half-life represents less than 5% of the total AUC. Accumulation at steady-state can be estimated using a half-life of 9 hours |
| Elimination | Approx. 50% of the absorbed dose is cefixime is also excreted in the bile in excess of 10% of the administered dose. | Mainly by renal excretion |
| Renal impairment | In severe renal impairment (CrCl- 5 to 20 ml/min), the half-life increased to an average of 11.5 hrs. | Dosage adjustment is necessary for elderly and patients with impaired renal function. |
6.0 Nonclinical properties
6.1 Animal Toxicology or Pharmacology
Preclinical effects in conventional studies of safety pharmacology, acute toxicity, repeated dose toxicity, reproductive studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Joint toxicity was observed at exposure in the human therapeutic range in juvenile rats and dogs. Ofloxacin exhibits a neurotoxic potential and causes reversible testicular alterations at high doses.
Mutagenicity studies showed no evidence for mutagenicity of ofloxacin. However, like some other quinolones Ofloxacin is phototoxic in animals at exposure in the human therapeutic range. The phototoxic, photomutagenic and photocarcinogenic potential of ofloxacin is comparable with that of other gyrase inhibitors.
Preclinical data from conventional genotoxicity studies reveal no special hazard to humans, carcinogen potential has not been investigated.
Reproduction toxicity
Ofloxacin has no effect on fertility, peri- or postnatal development, and therapeutic doses did not lead to any teratogenic or other embryotoxic effects in animals. Ofloxacin crosses the placenta and levels reached in the amniotic fluid are about 30% of the maximal concentrations measured in maternal serum.
7.0 Description
Cefixime is a semisynthetic, cephalosporin antibacterial for oral administration. Ofloxacin tablets are a synthetic broad-spectrum antimicrobial agent for oral administration.
Cefixime
Chemical Name: (6R,7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 72-(Z)- [O-(carboxy methyl) oxime] trihydrate
Chemical Formula: C16H15N5O7S2.3H2O
Molecular Weight: 507.50
Structure:
Ofloxacin
Chemical Name: (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine6-carboxylic acid
Chemical Formula: C18H20FN3O4
Molecular Weight: 361.4
Structure:
8.0 Pharmaceutical particulars
8.1 Incompatibilities
None
8.2 Shelf-life
Refer on the pack
8.3 Packaging information
A blister strip of 10 tablets.
8.4 Storage and handing instructions
Store below 25°C. Protect from light
Keep out of reach of children.
9.0 Patient Counselling Information
- Counsel patients that antibacterial drugs should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When C Tax-OF is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by C Tax- OF or other antibacterial drugs in the future.
- Advise patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue C Tax-OF treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants;
- Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.
- Advise patients that peripheral neuropathies have been associated with ofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, they should discontinue treatment and contact their physicians
- photosensitivity/phototoxicity has been reported in patients receiving quinolone antibiotics. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.
- if they are diabetic and are being treated with insulin or an oral hypoglycemic drug, to discontinue ofloxacin immediately if a hypoglycemic reaction occurs and consult a physician
- convulsions have been reported in patients taking quinolones, including ofloxacin, and to notify their physician before taking this drug if there is a history of this condition
- if they are diabetic and are being treated with insulin or an oral hypoglycemic drug, to discontinue C Tax-OF immediately if a hypoglycemic reaction occurs and consult a physician
- Patients are advised to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any class IA (quinidine, procainamide), or class III (amiodarone, sotalol) antiarrhythmic agents. Patients should notify their physicians f they have any symptoms of prolongation of the QTc interval including prolonged heart palpitations or a loss of consciousness.
- Tell the patients if they get any side effects, talk to the doctor. This includes any possible side effects not listed in this leaflet. Advice patients if they have any further questions, ask the doctor or pharmacist.
12.0 Date of revision of text
05-07-2024