Lomecomb (Isoniazid,Lomefloxacin,Pyrazinamide,Ethambutol,Pyridoxine Hydrochloride) Uses, Dosage, Side Effects and more

Ethambutol appears to inhibit the synthesis of 1 or more metabolites in susceptible bacteria resulting in impairment of cellular metabolism, arrest of multiplication, and cell death. It is active against susceptible bacteria only when they are undergoing cell division.

Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. It has a long duration of action as it is administered daily, and a moderate therapeutic window. Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.

Isoniazid inhibits the synthesis of mycoloic acids in susceptible bacteria which results in loss of acid-fastness and disruption of bacterial cell wall. At therapeutic levels, it is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.

Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly.

Lomefloxacin, a difluorinated quinolone derivative, is a bacterial gyrase inhibitor, effective against gram positive and gram negative bacteria. The acute toxicity of Lomefloxacin following systemic and topical ophthalmic application is low. Lomefloxacin interferes with bacterial DNA related processes like initiation, elongation, and termination phases of replication, transcription, DNA repairing, recombination, transposition, supercoiling and relaxation of DNA. The target molecule for quinolones is the A-subunit of bacterial enzyme gyrase (topoisomerase II). The forming of a stable complex between the quinolone and the whole gyrase teramer A2B2 leads to impaired enzyme functions, resulting in a rapid killing of sensitive bacteria.

Cross-resistance has only been reported with other quinolones, but not with any other group of antibiotics. No clinical studies are available about the efficacy in cases of infections with chlamydia.

Lomefloxacin is a fluoroquinolone antibiotic used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.

Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. Its activity appears to partly depend on conversion of the drug to pyrazinoic acid (POA), which lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to POA, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity.

Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.

Attribute	Details
Trade Name	Lomecomb (Isoniazid,Lomefloxacin,Pyrazinamide,Ethambutol,Pyridoxine Hydrochloride)
Generic	Ethambutol + Isoniazid + Lomefloxacin + Pyrazinamide + Pyridoxine Hydrochloride
Type
Therapeutic Class
Manufacturer
Available Country	Russia
Last Updated:	January 7, 2025 at 1:49 am

Uses

Ethambutol is used for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug. Selection of the companion drug should be based on clinical experience, considerations of comparative safety, and appropriate in vitro susceptibility studies. In patients who have not received previous antituberculous therapy, ie, initial treatment, the most frequently used regimens have been the following:

• Ethambutol plus isoniazid
• Ethambutol plus isoniazid plus streptomycin.

In patients who have received previous antituberculous therapy, mycobacterial resistance to other drugs used in initial therapy is frequent. Consequently, in such retreatment patients, Ethambutol should be combined with at least one of the second line drugs not previously administered to the patient and to which bacterial susceptibility has been used by appropriate in vitro studies. Antituberculous drugs used with Ethambutol have included cycloserine, ethionamide, pyrazinamide, viomycin and other drugs. Isoniazid, aminosalicylic acid, and streptomycin have also been used in multiple drug regimens. Alternating drug regimens have also been utilized.

Isoniazid is used for the treatment of all forms of tuberculosis in which organisms are susceptible.

Lomefloxacin oral preparation is used for the treatment of:

• Uncomplicated urinary tract infections.
• Complicated including recurrent and pyelonephritis, urinary tract infections.
• Acute exacerbation of chronic bronchitis.
• Skin and skin structure infections.

Prevention/Prophylaxis: Lomefloxacin is used preperatively to prevent postoperative urinary tract infections in patients undergoing transurethral surgical procedures.

Lomefloxacin ophthalmic preparation is used for the bacterial infections, including conjunctivitis, blepharitis, blepharoconjunctivitis which are due to Lomefloxacin susceptible germs and Staphylococcus aureus- induced corneal ulcers.

Pyrazinamide is used for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.

• The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and Pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months
• Patients with drug-resistant disease should be treated with regimens individualized to their situation. Pyrazinamide frequently will be an important component of such therapy.
• In patients with concomitant HIV infection, the physician should be aware of current recommendation of CDC. It is possible these patients may require a longer course of treatment

It is also used after treatment failure with other primary drugs in any form of active tuberculosis.

Pyrazinamide should only be used in conjunction with other effective antituberculous agents.

Lomecomb (Isoniazid,Lomefloxacin,Pyrazinamide,Ethambutol,Pyridoxine Hydrochloride) is also used to associated treatment for these conditions: Mycobacterium Infections, Mycobacterium avium complex infection, Pulmonary Tuberculosis (TB)Active Tuberculosis, Mycobacterium kansasii infection, Late phase TuberculosisAcute Bacterial Conjunctivitis, Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Blepharoconjunctivitis, Urinary Tract Infection, Bacterial blepharitisActive Tuberculosis, Pulmonary Tuberculosis (TB)

How Lomecomb (Isoniazid,Lomefloxacin,Pyrazinamide,Ethambutol,Pyridoxine Hydrochloride) works

Ethambutol diffuses into Mycobacterium cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells.

Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.

Lomefloxacin is a bactericidal fluoroquinolone agent with activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.

Pyrazinamide diffuses into active M. tuberculosis that express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids. This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I.

It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria.

Dosage

Ethambutol should not be used alone, in initial treatment or in retreatment. Ethambutol should be administered on a once every 24-hour basis only.Absorptionis not significantly altered by administration with food. Therapy, in general, should be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred.

Ethambutol is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.

Initial Treatment:In patients who have not received previous antituberculous therapy, administer Ethambutol 15 mg/kg of body weight, as a single oral dose once every 24 hours. In the more recent studies, isoniazid has been administered concurrently in a single, daily, oral dose.

Retreatment:In patients who have received previous antituberculous therapy, administer Ethambutol 25 mg/kg of body weight, as a single oral dose once every 24 hours. Concurrently administer at least one other antituberculous drug to which the organisms have been demonstrated to be susceptible by appropriatein vitrotests. Suitable drugs usually consist of those not previously used in the treatment of the patient. After 60 days of Ethambutol administration, decrease the dose to 15 mg/kg of body weight, and administer as a single oral dose once every 24 hours.

During the period when a patient is on a daily dose of 25 mg/kg, monthly eye examinations are advised.

Renal Impairment: Dose adjustment may be needed as determined by blood levels of ethambutol.

Adult:

• Active tuberculosis: 5 mg/kg/day. Max: 300 mg/day or 15 mg/kg up to 900 mg/day, 2 or 3 times wkly.
• Latent tuberculosis: 300 mg/day for 6 mth. Nontuberculous mycobacterial infections 5 mg/kg/day for at least 12 mth of culture-negative sputum. Max: 300 mg/day.

Child:10-15 mg/kg/day, max 300 mg/day q 12-24 hourlyWith directly observed biweekly therapy, dosage is 20-30 mg/kg, max 900 mg/dose twice weekly

Typhoid fever: 400 mg once daily or 200 mg b.i.d 10-14 days. UTI infections:

• Uncomplicated:400 mg once daily or 200 mg b.i.d 3 days.
• Complicated:400 mg once daily or 200 mg b.i.d 10-14 days.

Bacterial Diarrhea: 400 mg once daily or 200 mg b.i.d 5-7 days.

Acute exacerbation of chronic bronchitis: 400 mg once daily 7-10 days.

Skin and skin structure infections: 400 mg once daily 10-14 days.

Prophylaxis of UTI following surgery: 400 mg Single dose 2-6 hours prior to transurethral surgery.

Adults and children (above 1 year of age): Instill 2-3 times daily 1 drop into the lower conjunctival sac. At the beginning of the treatment application should be more frequent, apply 5 drops within 20 minutes or 1 drop every hour during 6-10 hours. Duration of the treatment: 7 to 9 days.

Usual Adult Dose for Tuberculosis: Active:

15 to 30 mg/kg (up to 2 g) orally once a day in combination with three other antituberculous drugs for the initial 2 months of a 6-month or 9-month treatment regimen, until drug susceptibility tests are known. An alternate dosing regimen of 50 to 75 mg/kg (up to 3 g) orally twice a week may be used after 2 weeks of daily therapy to increase patient compliance.

Alternatively, the CDC, The American Thoracic Society, and the Infectious Diseases Society of America suggest the following dosing based on estimated lean body weight:

Daily dosing:

• 40 to 45 kg: 1000 mg
• 56 to 75 kg: 1500 mg
• 76 to 90 kg: 2000 mg

Twice weekly dosing:

• 40 to 55 kg: 2000 mg
• 56 to 75 kg: 3000 mg
• 76 to 90 kg: 4000 mg

Thrice weekly dosing:

• 40 to 55 kg: 1500 mg
• 56 to 75 kg: 2500 mg
• 76 to 90 kg: 3000 mg

Usual Adult Dose for Tuberculosis: Latent:

A public health expert should be consulted prior to the use of the combination regimen with rifampin.

15 to 20 mg/kg, based on actual body weight (lean), orally once daily (maximum 2 g) for 2 months. Alternatively, a dosage of 50 mg/kg may be administered orally twice-weekly (maximum 4 g).

Usual Pediatric Dose for Tuberculosis: Active:

(Used as part of a multidrug regimen. Treatment regimens consist of an initial 2-month phase, followed by a continuation phase of 4 or 7 additional months. Frequency of dosing may differ depending on phase of therapy)

Infants, Children less than 40 kg and Adolescents 14 years and younger and less than 40 kg:Non-HIV patients:

• Daily therapy: 15 to 30 mg/kg/dose (maximum: 2 g/dose) once daily
• Directly observed therapy (DOT): 50 mg/kg/dose (maximum: 2 g/dose) twice weekly

HIV-exposed/infected patients:

• Daily therapy: 20 to 40 mg/kg/dose once daily (maximum: 2 g/day)

Should be taken with food.

Side Effects

Retrobulbar neuritis with reduction in visual acuity, constriction of visual field, central or peripheral scotoma and green-red colour blindness of 1 or both eyes. Reduced renal clearance of urate and may precipitate acute gout. Confusion, disorientation, hallucinations, headache, dizziness, malaise, jaundice or transient liver dysfunction, peripheral neuropathy, thrombocytopenia, pulmonary infiltrates, eosinophilia and GI disturbances (e.g. nausea, vomiting, anorexia, abdominal pain). Rarely, retinal haemorrhage, hypersensitivity reactions including rashes, pruritus, leucopenia, fever, and joint pains.

Peripheral neuropathy (dose-related incidence, 10-20% incidence with 10 mg/kg/d), Loss of appetite, Nausea, Vomiting, Stomach pain, Weakness 1-10%, Dizziness, Slurred speech, Lethargy, Progressive liver damage (increases with age; 2.3% in pts > 50 yo), Hyperreflexia, Agranulocytosis, Anemia, Megaloblastic anemia, Thrombocytopenia, Systemic lupus erythematosus, Seizure

Common side effects are Nausea, headache, photosensitivity, dizziness, diarrhea, dry mouth, fatigue, convulsions, CNS stimulation which may lead to tremors, restlessness, light headedness, confusion hallucinations and pseudomembranous colitis.

Slight and transient burning immediately after instillation of the eye drops has been reported in 4.7% of users. Although phototoxicity has not been reported after ophthalmic use, photosensitization is possible. Since the following allergic reactions have been reported after systemic use of Lomefloxacin, they can not be excluded after topical ophthalmic use: allergic reactions, asthma, dyspnoea, urticaria, erythema, pruritus, and hypersensitization.

General: Fever, porphyria and dysuria have rarely been reported. Gout.

Gastrointestinal: The principal adverse effect is a hepatic reaction. Hepatotoxicity appears to be dose related, and may appear at any time during therapy. GI disturbances including nausea, vomiting and anorexia have also been reported.

Hematologic and Lymphatic: Thrombocytopenia and sideroblastic anemia with erythroid hyperplasia, vacuolation of erythrocytes and increased serum iron concentration have occurred rarely with this drug. Adverse effects on blood clotting mechanisms have also been rarely reported.

Other: Mild arthralgia and myalgia have been reported frequently. Hypersensitivity reactions including rashes, urticaria, and pruritis have been reported. Fever, acne, photosensitivity, porphyria, dysuria and interstitial nephritis have been reported rarely.

Toxicity

Patients experiencing a chronic overdose of ethambutol may present with disturbances in colour vision and reduced visual acuity as symptoms of optic neuropathy. In these cases, ethambutol should be stopped. Data regarding acute overdose of ethambutol are not readily available. Patients experiencing an acute overdose of ethambutol may be experience an increased risk and severity of adverse effects such as pruritus, joint pain, gastrointestinal upset, abdominal pain, malaise, headache, dizziness, mental confusion, disorientation, and possible hallucinations. Patients should be treated with symptomatic and supportive measures.

LD₅₀ 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.

Adverse reactions include peripheral neuropathy, nervousness, agitation, anxiety, and phototoxic events (rash, itching, burning) due to sunlight exposure.

Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.

Precaution

Patient with ocular defects (e.g. cataracts, recurrent ocular inflammatory conditions, diabetic neuropathy). Renal impairment. Pregnancy and lactation.

Renal or hepatic impairment; convulsive disorders; history of psychosis; patients at risk of neuropathy or pyridoxine deficiency eg, diabetic, alcoholic, malnourished, uraemic, infected with HIV. Careful monitoring of hepatic function is necessary for black and hispanic women. Check hepatic function before and during treatment. Pregnancy and lactation.

Alterations of the dosage regimen is recommended for patients with impairment of renal function (CrCl <40 ml/min/1.73 m2). Avoid exposure to excessive sunlight or artificial UV light. Phototoxicity reaction may occur if undue exposure occurs. Safety and efficacy of Lomefloxacin has not been established in children, pregnant and lactating women.

Some isolated cases of phototoxicity have been reported after systemic but not after topical ophthalmic use of Lomefloxacin. Nevertheless, during treatment with Lomefloxacin intensive exposure to sunlight or UV-radiation should be avoided

Pyrazinamide is contraindicated in patients with severe hepatic disease and with acute gout.

Patients started on pyrazinamide should have baseline serum uric acid and liver function test results. Liver function should be monitored closely during therapy. Patients with preexisting liver disease or those at increased risk of drug related hepatitis should be monitored closely.

Pyrazinamide should be discontinued and not restarted if signs of hepatocellular damage or hyperuricemia with an acute gouty arthritis appear.

Polyarthralgias have been reported in patients. The pain may respond to aspirin or other nonsteroidal anti-inflammatory agents.

Caution should be used in patients with a history of diabetes mellitus, as management of the disease may be more difficult.

Primary resistance of Mycobacterium tuberculosis to pyrazinamide is not common. In cases with known or suspected drug resistance, in vitro susceptibility tests with recent cultures of Mycobacterium tuberculosis against pyrazinamide and the usual primary drugs should be conducted. There are few reliable in vitro tests for pyrazinamide resistance. A reference laboratory capable of performing these tests must be utilized.

Clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal or hepatic function, and of concomitant disease or other drug therapy.

Interaction

Delayed or reduced absorption with aluminium hydroxide.

Inhibit the hepatic metabolism of antiepileptics (e.g. carbamazepine, ethosuximide, primidone, phenytoin), benzodiazepines (e.g. diazepam, triazolam), chlorzoxazone, theophylline, disulfiram, sometimes leading to increased toxicity. Increased metabolism of enflurane, resulting in potentially nephrotoxic levels of fluoride. Increased concentrations and enhanced effects or toxicity of clofazimine, cycloserine and warfarin. Reduced absorption with Al-containing antacids. Increased risk of peripheral neuropathy with zalcitabine and stavudine.

Lomefloxacin does not alter theophylline clearance and concentration. No change of caffeine is reported. Sucralfate and antacid containing magnesium and aluminium interfere with its bioavailability. Enhances effects of warfarin. Probenecid slows renal elimination of Lomefloxacin.

In order to avoid reduction of efficacy, no ophthalmic preparations containing heavy metals, such as zinc, should be used during 15 minutes preceding and following application of Lomefloxacin. Bacteriostatic ophthalmic antibiotics should not be used concomitantly with Lomefloxacin eye drops.

Antagonises the effect of uricosuric agents (e.g. probenecid, sulfinpyrazone). May reduce the contraceptive effect of oestrogens. May inactivate oral typhoid vaccine. May increase the serum concentration of ciclosporin. May enhance the hepatotoxic effect of rifampicin.

Volume of Distribution

Patients coinfected with tuberculosis and HIV have an estimated ethambutol volume of distribution of 76.2 L.

Elimination Route

Oral ethambutol is approximately 75-80% orally bioavailable. A 25 mg/kg oral dose of ethambutol reaches a C_max of 2-5 µg/mL, with a T_max of 2-4 hours. In a separate study, the AUC_0-8 varied from 6.3 ± 5.5 h*mg/L to 10.8 ± 7.6 h*mg/L depending on CYP1A2 genetic polymorphisms.

Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.

Rapid and nearly complete with approximately 95% to 98% of a single oral dose being absorbed.

Rapidly and well absorbed from the gastrointestinal tract.

Half Life

Ethambutol has a half life of 3.3 hours in patients with normal renal function. In patients with renal failure, the half life could be 7 hours or longer.

Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.

8 hours

9-10 hours (normal conditions)

Clearance

Patients coinfected with tuberculosis and HIV have an estimated ethambutol oral clearance of 77.4 L/h.

• 271 mL/min/1.73 m2 [creatinine clearance of 110 mL/min/1.73 m2]
• 31 mL/min/1.73 m2 [creatinine clearance of 0 mL/min/1.73 m2]

Elimination Route

Ethambutol is 50% eliminated in the urine as the unmetabolized parent compound and 8-15% as inactive metabolites. 20-22% of a dose is eliminated unchanged in the feces.

From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.

The urinary excretion of lomefloxacin was virtually complete within 72 hours after cessation of dosing, with approximately 65% of the dose being recovered as parent drug and 9% as its glucuronide metabolite.

Approximately 70% of an oral dose is excreted in the urine, mainly by glomerular filtration within 24 hours

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Lactation: distributed into milk but safe for nursing infants

Pregnancy Category C. Reproductive function studies have been performed in rats at doses up to 8 times the recommended human dose based on mg/m² (34 times the recommended human dose based on mg/kg), and no impaired fertility or harm to the fetus was reported due to lomefloxacin. Increased incidence of fetal loss in monkeys has been observed at approximately 3 to 6 times the recommended human dose based on mg/m² (6 to 12 times the recommended human dose based on mg/kg). No teratogenicity has been observed in rats and monkeys at up to 16 times the recommended human dose exposure. In the rabbit, maternal toxicity and associated fetotoxicity, decreased placental weight, and variations of the coccygeal vertebrae occurred at doses 2 times the recommended human exposure based on mg/m². There are, however, no adequate and well-controlled studies in pregnant women. Lomefloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing mothers: It is not known whether lomefloxacin is excreted in human milk. However, it is known that other drugs of this class are excreted in human milk and that lomefloxacin is excreted in the milk of lactating rats. Because of the potential for serious adverse reactions from lomefloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy Category C. Animal reproduction studies have not been conducted with Pyrazinamide. It is also not known whether Pyrazinamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pyrazinamide should be given to a pregnant woman only if clearly needed.

Nursing Mothers: Pyrazinamide has been found in small amounts in breast milk. Therefore, it is advised that Pyrazinamide be used with caution in nursing mothers taking into account the risk-benefit of this therapy.

Contraindication

Ethambutol is contraindicated in patients who are known to be hypersensitive to this drug. It is also contraindicated in patients with known optic neuritis unless clinical judgment determines that it may be used. Ethambutol is contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision.

Acute liver disease or history of hepatic damage during INH therapy; hypersensitivity.

Lomefloxacin is contraindicated in patients with a history of hypersensitivity to Lomefloxacin or to other quinolones. Lomefloxacin like other drugs in its class, cause arthropathy in juvenile animals. Therefore, its use in children, growing adolescents, and pregnant women is not recommended.

Pyrazinamide is contraindicated in persons:

• With severe hepatic damage.
• Who have shown hypersensitivity to it.
• With acute gout.

Special Warning

Pediatric use: The safety and effectiveness of lomefloxacin in pediatric patients and adolescents less than 18 years of age have not been established. Lomefloxacin causes arthropathy in juvenile animals of several species.

Geriatric use: Of the total number of subjects in clinical studies of lomefloxacin, 25% were ≥65 years and 9% were ≥ 75 years. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Usage in Children: Pyrazinamide regimens employed in adults are probably equally effective in children. Pyrazinamide appears to be well tolerated in children.

Geriatric Use: Clinical studies of Pyrazinamide did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function, and of concomitant disease or other drug therapy.It does not appear that patients with impaired renal function require a reduction in dose. It may be prudent to select doses at the low end of the dosing range, however.

Renal Dose Adjustments: The manufacturer recommends to start therapy at low end of dosage range and monitor patient closely.For the treatment of active tuberculosis, the CDC, ATS, and IDSA recommend against daily dosing. For patients with CrCl less than 30 mL/min or patients receiving hemodialysis the recommended dose is 25 to 35 mg/kg per dose three times per week.

Liver Dose Adjustments: Monitor patients closely.

Dose Adjustments: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function, and of concomitant disease or other drug therapy.

If organism is susceptible to isoniazid and rifampin, pyrazinamide is continued for the first 2 months of a 6-month course of therapy (9-months if HIV positive). If primary drug resistance is shown, drug regimens should be adjusted as needed and continued for at least 6 months, or 3 months beyond culture conversion (9 months, or 6 months beyond culture conversion if HIV positive). If multiple-drug resistance is demonstrated, therapy should be continued for 12 to 24 months following culture conversion.

Acute Overdose

Practically there is no risk of adverse effects due to accidental oral ingestion, since a bottle of 5 ml eye drop solution contains only 15 mg Lomefloxacin. This corresponds to 3.75% of the recommended oral daily dose for adults of 400 mg Lomefloxacin.

Overdosage experience is limited. In one case report of overdose, abnormal liver function tests developed. These spontaneously reverted to normal when the drug was stopped. Clinical monitoring and supportive therapy should be employed. Pyrazinamide is dialyzable.

Storage Condition

Store between 20-25°C. Protect from light, moisture and excessive heat.

Should be stored in cool and dry place

Store between 15-30° C.

Innovators Monograph