(and dosage form):


TEQUIN tablets
contain 400 mg
TEQUIN injections contain 400 mg/40 mL gatifloxacin. The vehicle is water for injection.

A20.1.1 Broad and medium spectrum antibiotics

Gatifloxacin is an 8-methoxy fluoroquinolone with in vitro activity against a wide range of gram-negative and gram-positive aerobic and anaerobic microorganisms.
NOTE: Mycobacterium avium intracellulare complex organisms are commonly resistant to gatifloxacin.
NOTE: The activity of gatifloxacin against Treponema pallidum has not been evaluated; however, other quinolones are not active against Treponema pallidum.
The absolute bioavailability of gatifloxacin in volunteers is 96% relative to I.V. administration. Peak plasma concentrations of gatifloxacin occur 1-2 hours after oral dosing.
Serum protein binding of gatifloxacin is approximately 20%.
Gatifloxacin is widely distributed throughout the body into many body tissues and fluids such as alveolar macrophages, bronchial mucosa, lung epithelial lining fluid, lung parenchyma, sinus mucosa, sputum, middle ear mucosa, skin blister fluid, saliva, bile, prostate, prostatic fluid, seminal fluid, vagina, cervix, endometrium, myometrium, oviduct and ovary. Penetration into bone is moderate. Penetration into cerebrospinal fluid is poor.
Gatifloxacin undergoes limited biotransformation in humans with <1% of the dose excreted in the urine
More than 70% of an administered TEQUIN dose was recovered as unchanged drug in the urine within 48 hours following oral and I.V. administration, and 5% was recovered in the faeces.
Gatifloxacin is excreted as unchanged drug primarily via the kidney. The mean elimination half-life of gatifloxacin ranges from 7-14 hours and is independent of dose and route of administration. Gatifloxacin undergoes both glomerular filtration and tubular secretion.
In animal studies gatifloxacin freely crossed the placenta and appeared in breast milk.
Modest differences in the pharmacokinetics of gatifloxacin were noted in female subjects. Elderly females had a 21% increase inCmax and a 32% increase in AUC(0-¥) and slowerelimination compared to young females.
Pediatric: The pharmacokinetics of gatifloxacin in persons <18 years of age have not been established.
Renal Insufficiency: Clearance of gatifloxacin is reduced and systemic exposure increased in subjects with renal insufficiency. A reduced dosage of TEQUIN is recommended in patients with creatinine clearance <40 mL/min (see DOSAGE AND DIRECTIONS FOR USE Dosage Adjustment in Patients with Renal Insufficiency).

TEQUIN is indicated in patients >18 years of age for the treatment of the following infections when caused by susceptible bacteria (see MICROBIOLOGY):
Community acquired pneumonia caused by Streptococcus pneumonia, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Mycoplasma pneumonia, Chlamydia pneumonia, Legionella pneumophila, Staphylococcus aureus
Acute bacterial exacerbation of chronic bronchitis caused by Streptococcus pneumonia , Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Staphylococcus aureus, Enterobacter cloacae.
Acute sinusitis caused by Streptococcus pneumonia, Haemophilus influenzae, Moraxella catarrhalis.
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus, Acinetobacter spp.
Uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus saprophyticus.
Complicated urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Enterobacter spp.
Pyelonephritis caused by Escherichia coli.
Uncomplicated gonorrhea in males, and in females.

TEQUIN is contraindicated in persons with a history of hypersensitivity to gatifloxacin, quinolone antimicrobial agents, or any other components of this product.
Pregnancy and Nursing Mothers: Safety of use has not been established.
Pediatric Use
The safety and effectiveness of gatifloxacin in persons <18 years of age have not been established.

Gatifloxacin has the potential to prolong the QTc interval of the electrocardiogram in some patients. Due to the lack of clinical experience, in patients with known prolongation of the QTc interval, patients with uncorrected hypokalemia, and patients receiving Class 1A (e.g. Quinidine, procainamide ) or Class 111 (e.g. amiodarone, sotalol) antiarrhythmic agents, Gatifloxacin should be avoided in these patient populations.
Pharmacokinetic studies between gatifloxacin and drugs that prolong the QTc interval such as cisapride, erythromycin, antipsychotics and tricyclic antidepressants have not been performed. Gatifloxacin should be used with caution when given concurrently with these medicines, as well as in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia.
The magnitude of QTc prolongation increases with increasing concentrations of the drug; therefore, the recommended dose should not be exceeded. QTc prolongation may lead to an increases risk for ventricular arrhythmias including torsade de pointes
During postmarketing surveillance , extremely rare cases of torsade de pointes have been reported in patients taking gatifloxacin. These cases have occurred in patients with underlying medical problems for which they were receiving concomitant medications; the contribution, if any, of gatifloxacin to the development of torsade de pointes in these patients is unknown.
Gatifloxacin has caused arthropathy and/or chondrodysplasia in immature rats and dogs. The relevance of these findings to the clinical use of gatifloxacin is unknown. (See Contra-indications)
Convulsions, increased intracranial pressure, and psychosis have been reported in patients receiving quinolones. Tequin may also cause central nervous system (CNS) stimulation, which may lead to tremors, restlessness, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, and insomnia. These reactions may occur following the first dose. If these reactions occur in patients receiving TEQUIN, the medicine should be discontinued and appropriate measures instituted.
Patients should be warned against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration may lead to accidents.
TEQUIN should be used with caution in patients with known or suspected central nervous system disorders, such as severe cerebral atherosclerosis, epilepsy, and other factors that predispose to seizures.
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones. These reactions may occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial oedema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnoea, urticaria, itching, and other serious skin reactions.
TEQUIN should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require emergency treatment.
Serious and sometimes fatal events, some due to hypersensitivity and some due to uncertain etiology, have been reported in patients receiving therapy with all antibiotics. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson Syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis, interstitial nephritis; acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anaemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.
Pseudomembranous colitis has been reported with TEQUIN and may range in severity from mild to life-threatening. It is important, therefore, to consider this diagnosis in patients who present with diarrhoea subsequent to the administration and antibacterial agent. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated.
Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving Tequin. TEQUIN should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been confidently excluded. Tendon rupture can occur during or after therapy with quinolones.
Antimicrobial agents used in high doses for short periods of time to treat gonorrhoea may mask or delay the symptoms of incubating syphilis. Gatifloxacin has not been shown to be effective in the treatment of syphilis.
Changes in Blood Glucose
Studies conducted in patients with diabetes mellitus controlled on oral hypoglycemic agents have demonstrated that TEQUIN is associated with transient disturbances in glucose homeostasis, including an increase in serum insulin and decrease in serum glucose following administration of the first dose, sometimes associated with symptomatic hypoglycemia. Increases in fasting serum glucose were also observed, usually after the third day of TEQUIN administration
During the postmarketing period, there have been reports of serious disturbances of glucose homeostasis in patients treated with TEQUIN. Hypoglycemic episodes, in some cases severe, have been reported in patients with diabetics mellitus treated with either sulfonylurea or non-sulfonylurea oral hypoglycemic medications. These events frequently occurred on the first day of therapy and usually within 3 days following the initiation of TEQUIN. Hyperglycemic episodes, in some cases severeand associated with hyperosmolar non-ketotic hyperglycemic coma, were reported in diabetic patients, mostly between 4 and 10 days following the initiation of TEQUIN therapy. Some of the hyperglycemic and hypoglycemic events were life-threatening and many required hospitalization, although these events were reversible when appropriately managed. Many of these patients had other underlying medical problems and were receiving concomitant medications that may have contributed to the glucose abnormality.
Episodes of hyperglycemia, including hyperosmolar non-ketotic hyperglycemic coma, occurred in patients not previously diagnosed with diabetes mellitus. Very elderly patients (>75 years of age) who may have unrecognized diabetes, age-related decrease in renal function, underlying medical problems, and/or are taking concomitant medications associated with hyperglycemia may be at particular risk for serious hyperglycemia.
The dose TEQUIN should be adjusted based on underlying renal function (see Dosage and directions for use). When TEQUIN is used in diabetic patients, blood glucose should be closely monitored. Signs and symptoms of hypoglycemia should be monitored, especially during the first 3 days of therapy, and signs and symptoms of hyperglycemia should be monitored in diabetics and patients who may be at risk for hyperglycemia, especially following the third day of therapy. If signs and symptoms of either hypoglycemia or hyperglycemia occur in any patient being treated with TEQUIN, appropriate therapy must be initiated immediately and TEQUIN should be discontinued.

The recommended dosages for TEQUIN tablets or TEQUIN injection are shown in the following table. Doses of TEQUIN are administered once every 24 hours. These recommendations apply to patients with creatinine clearance >40 mL/min; for patients with creatinine clearance <40 mL/min, see Dosage Adjustment in Patients with Renal Insufficiency. TEQUIN can be administered without regard to food, including milk and dietary supplements containing calcium.
Community-acquired pneumonia 400 mg 7-14 days
Acute Bacterial Exacerbation of Chronic Bronchitis 400 mg 5 days
Acute Sinusitis 400 mg 10 days
Skin and Skin Structure Infections, Uncomplicated 400 mg 7-10 days
Uncomplicated Urinary Tract Infections (cystitis) 400 mg
200 mg
Single dose (400 mg)
3 days (200 mg)
Complicated Urinary Tract Infections 400 mg 7-10 day
Acute pyelonephritis 400 mg 7-10 days
Uncomplicated Gonorrhea in Males and Females 400 mg Single dose
*        For either the oral or IV route of administration.
When switching from I.V. to oral dose administration, no dosage adjustment is necessary. Patients whose therapy is started with TEQUIN injection may be switched to TEQUIN tablets when clinically indicated at the discretion of the physician.
TEQUIN injection should be administered by INTRAVENOUS infusion only. It is not intended for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. Single-use vials contain a concentrated solution of gatifloxacin and require dilution prior to administration (see PREPARATION FOR INTRAVENOUS ADMINISTRATION).
TEQUIN injection should be administered by intravenous infusion over a period of 60 minutes. CAUTION: TEQUIN injection IS NOT FOR RAPID OR BOLUS INJECTION.

Interactions. Oral doses of TEQUIN should be administered at least 2 hours before or 2 hours after the administration of ferrous sulfate and dietary supplements containing zinc, magnesium, or iron (such as multivitamin products). Oral doses of TEQUIN should be administered at least 4 hours prior to the administration of an aluminum/magnesium-containing antacid. (See Interactions )

Dosage Adjustment in Patients with Renal Insufficiency
Since gatifloxacin is eliminated primarily by renal excretion , the dosage of TEQUIN should be modified in patients with creatinine clearance <40 mL/min, including patients on haemodialysis and on chronic ambulatory peritoneal dialysis (CAPD). The recommended dosage of TEQUIN in this population is 400 mg each on Days 1 and 2, no dose on Day 3, then 400 mg every 48 hours from Day 4 onward. For patients on haemodialysis, the dose should be administered after a dialysis session.
No dosage adjustment is necessary for single dose regimens (400 mg single dose for treatment of uncomplicated urinary tract infection and gonorrhoea) or for the 3-day 200 mg once daily regimen for the treatment of uncomplicated urinary tract infection.
Chronic Hepatic Disease
No adjustment in the dosage of TEQUIN is necessary in patients with hepatic impairment

Single-Use Vials
TEQUIN injections supplied in single-use 400 mg/40 mL vials contain a concentrated solution of gatifloxacin (10 mg/mL in 5% dextrose solution). THESE VIALS MUST BE FURTHER DILUTED WITH AN APPROPRIATE SOLUTION PRIOR TO INTRAVENOUS ADMINISTRATION (see Compatible Intravenous Solutions). The concentration of the resulting diluted solution should be 2 mg/mL prior to administration. Doses should be prepared according to the following chart:
400 mg 40 mL 160 mL 200 mL 2 mg/mL

Compatible Intravenous Solutions and Stability Following Dilution:
Because a hypotonic solution results, water for injection should not be used as a diluent when preparing a 2 mg/mL solution from the concentrated solution of gatifloxacin (10 mg/mL)
Any of the following intravenous solutions may be used to dilute gatifloxacin from the single-use vials prior to administration:
  Glucose 5% Intravenous Solution
  Sodium Chloride 0,9% Intravenous Solution
  Ringer-Lactate Solution for Injection
Once diluted, the compound, gatifloxacin, is physically and chemically stable for 14 days at room temperature (250C) or under refrigeration (20- 80C). Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution.
Single-Use Vials
Solutions should be inspected visually for particulate matter prior to dilution and administration. Do not use if the solution appears cloudy or if a precipitate is present. If leaks are found, or if seals are not intact, discard the solution, as the sterility may be compromised. Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. The vials are for single-use only; any unused portion should be discarded.
Since only limited data are available on the compatibility of gatifloxacin intravenous injection with other intravenous substances, additives or other medications should neither be added to TEQUIN injection nor infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of other drugs, the line should be flushed before and after infusion of TEQUIN injection with a solution compatible with TEQUIN injection and other drugs administered via this common line.

Adverse events occurring in more than >3% in clinical trials include:
In patients who were treated with either I.V. alone or I.V. followed by oral therapy, the incidence of adverse events was similar to those who received oral treatment. Local injection site reactions (redness at injection site) were noted in 5% of patients.
Other Tequin related adverse events that occurred in >0,1% to <3% of patients:
Body as a Whole: allergic reaction, Asthenia, chills, fever, back pain, chest pain. Face oedema
Cardiovascular: palpitation, hypertension
Digestive: abdominal pain ,anorexia, dyspepsia, constipation, glossitis, oral moniliasis, stomatitis, mouth ulcer, flatulence, vomiting, gastritis
Metabolic: peripheral oedema thirst, hyperglycemia
Nervous System: abnormal dreams, paresthesia, tremor, vasodilatation, vertigo, agitation, anxiety, confusion, insomnia, nervousness, somnolence
Respiratory: dyspnea, pharyngitis.
Skin/Appendages: rash, sweating , dry skin, pruritis
Special Senses: abnormal vision, tinnitus, taste perversion
Urogenital: dysuria,
Musculoskeletal system: Arthralgia, leg cramp

Rare adverse events: abnormal thinking, alcohol intolerance, arthritis, asthma (bronchospasm), ataxia, bone pain, bradycardia, breast pain, cheilitis, colitis, convulsion, cyanosis, depersonalization, depression, diabetes mellitus, dysphagia, ear pain, ecchymosis, oedema, epistaxis, euphoria, eye pain, eye photosensitivity, gastrointestinal hemorrhage, generalised oedema, gingivitis, halitosis, hallucination, haematemesis, hematuria, hostility, hyperesthesia, hyperglycemia, hypertonia, hyperventilation, hypoglycemia, lymphadenopathy, maculopapular rash, metrorrhagia, migraine, mouth oedema, myalgia, myasthenia, neck pain, panic attack, paranoia, parosmia, photophobia, pseudomembranous colitis, psychosis, ptosis, rectal hemorrhage, stress, substernal chest pain, tachycardia, taste loss, thirst, tongue edema, vesiculobullous rash.

Laboratory Test Abnormalities
These included the following: neutropenia, increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, bilirubin, and serum amylase, and electrolyte abnormalities.
Postmarketing Adverse Event Reports
Cases with the following events have been reported very rarely during post approval use of Tequin
Acute allergic reaction including anaphylactic reaction and angioneurotic edoema, abnormal renal function (including acute renal failure) increased International Normalized Ratio (INR)/prothrombin time, Severe hyperglycemia, (including hyperosmolar nonketotic hyperglycemia), severe hypoglycemia (including hypoglycaemic coma), hypotension, pancreatitis, Stevens-Johnson syndrome, syncope, hepatitis, torsade de pointes, thrombocytopenia and tendon rupture

Patients with Renal Insufficiency
Administer TEQUIN with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of gatifloxacin may be reduced. In patients with a calculated creatinine clearance <40 mL/min, adjustment of the dosage regimen is necessary to avoid the accumulation of gatifloxacin due to decreased clearance. (See DOSAGE AND ADMINISTRATION).
Glucose Homeostasis: No clinically significant changes in glucose tolerance (via measurement of oral glucose challenge) and glucose homeostasis (via measurement of fasting serum glucose, serum insulin and c-peptide) were observed following single or multiple intravenous infusion doses of 200 to 800 mg TEQUIN in healthy volunteers, or 400-mg oral doses of TEQUIN for 10 days in patients with type 2 diabetes (non-insulin-dependent diabetes mellitus). Transient modest increases inserum insulin and decreases in glucose concentrations were noted with the first dose of intravenous or oral gatifloxacin. Following multiple oral doses of TEQUIN in patients with type 2 non-insulin-dependent diabetes mellitus controlled with a sulphonylureas, decreases in serum insulin concentrations were noted following oral glucose challenge; however, these decreases were not accompanied by statistically significant changes in serum glucose levels. (See WARNINGS) . In this study, modest increases in fasting glucose (average increases of 40 mg/dL) were also noted by day 4, although these changes did not reach statistical significance.

No significant interactions with milk or calcium carbonate have been observed when administered to healthy volunteers concomitantly with TEQUIN. No significant pharmacokinetic interactions occurred when TEQUIN was administered to healthy volunteers concomitantly with drugs metabolized by the cytochrome P450 (CYP) system, i.e., cimetidine, midazolam, theophylline, warfarin, or when administered to diabetic subjects concomitantly with glyburide; however, pharmacodynamic changes have been seen with concomitant glyburide use. These results and the data from in vitro studies suggest that gatifloxacin is unlikely to significantly alter the metabolic clearance of drugs metabolized by CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2D6 isoenzymes. No dosage adjustments are necessary when these drugs are administered concomitantly with TEQUIN.
Concomitant administration of TEQUIN and digoxin did not produce significant alteration of the pharmacokinetics of gatifloxacin; however, an increase in digoxin concentrations was observed in 3 of 11 subjects. Patients taking digoxin should, therefore, be monitored for signs and/or symptoms of digoxin toxicity. In patients who display signs and/or symptoms of digoxin intoxication, serum digoxin concentrations should be determined, and digoxin dosage should be adjusted as appropriate.
Systemic exposure to gatifloxacin is increased following the concomitant administration of TEQUIN and probenecid, and is reduced by the concomitant administration of TEQUIN and ferrous sulfate or antacids containing aluminum or magnesium salts.
Ferrous sulfate: When TEQUIN (400 mg single oral dose) was administered concomitantly with ferrous sulfate (325 mg single oral dose), bioavailability of gatifloxacin was significantly reduced (54% reduction in mean Cmax and 35% reduction in mean AUC).
Aluminium/magnesium-containing antacid. When administered 2 hours before, concomitantly, or 2 hours after an aluminium/magnesium-containing antacid, there were respective reductions in gatifloxacin C
max of 15%, 69%, and 48%, and in gatifloxacin AUC of 17 %, 64%, and 40%.
Oral doses of TEQUIN should be administered at least 2 hours before or 2 hours after the administration of ferrous sulfate and dietary supplements containing zinc, magnesium, or iron (such as multivitamin products). Oral doses of TEQUIN should be administered at least 4 hours prior to the administration of an aluminium/magnesium-containing antacid.

In the event of acute oral overdose of gatifloxacin, the stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed and given symptomatic and supportive treatment. Adequate hydration should be maintained. Gatifloxacin is not efficiently removed from the body by haemodialysis (approximately 14% recovered over 4 hours) or by CAPD (approximately 11% recovered over 8 days).

White to off-white, almond shaped, biconvex, film-coated tablets debossed with “BMS”on one side and “TEQUIN”and “400”on the other side.
TEQUIN INJECTION The appearance of the I.V. solution may range from light yellow to light greenish yellow in color. The color does not affect nor is it indicative of product stability.

are available in blister packs of 7 tablets.
TEQUIN CONCENTRATE FOR INTRAVENEOUS INFUSION is available in 400 mg/40 mL single-use, clear flint glass vials. The size is 50 mL. The contents are at a concentration of 10 mg/mL intended for dilution prior to administration as a sterile, preservative-free solution of gatifloxacin in 5% dextrose solution with a pH range of 3,5 –5,5. The vials are packed individually in a carton.

Store at room temperature not exceeding 25°C.
Keep out of reach of children.
Concentrate for Intravenous Infusion:
Store at room temperature not exceeding 25°C. Do not freeze.
Store vials in the carton until required for use.
Diluted solution:
Once diluted in the appropriate intravenous fluid, gatifloxacin, the compound, is stable for 14 days at room temperature (25°C) or in the fridge (2-8°C).

TEQUIN 400 mg tablets:         34/20.1.1/0134
TEQUIN 400 mg injection:         34/20.1.1/0136

Bristol-Myers Squibb (Pty) Ltd
47 van Buuren Road

March 2004.

Licensed from Kyorin Pharmaceutical Company Limited
Tokyo, JAPAN

Updated on this site: June 2005
Source: Pharmaceutical Industry

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