Moxifloxacin HCl Imedco Djaja

Moxifloxacin.

Biconvex red-brown tablet, with "IMEDCO" embossing on the top side and a straight line on the bottom side.
Each film-coated caplet contains: Moxifloxacin HCl equivalent to Moxifloxacin 400 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose, polyvinyl pyrrolidone, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, coating agent (hypromellose, titanium dioxide, polyethylene glycol 400, talc, red iron oxide).

Pharmacology: Moxifloxacin is an antibiotic of the fluoroquinolone class. In vitro, moxifloxacin exhibits activity against both Gram-positive and Gram-negative pathogenic bacteria. It works by interfering with topoisomerase II (DNA gyrase) and IV. Topoisomerase is an essential enzyme that plays an important role in bacterial DNA replication, transcription, and repair. Topoisomerase IV is also known to influence bacterial chromosome division. Kinetically, the bactericidal effect of moxifloxacin depends on its concentration. The Minimum Bacterial Concentration (MBC) is a range of the Minimum Inhibitory Concentration (MIC).
Interference with Culture Tests: Moxifloxacin therapy may cause false-negative culture results for Mycobacterium spp. by inhibiting mycobacterium growth.
Effect on Normal Flora in the Human Gastrointestinal Tract: A decrease in the following normal flora in the digestive tract was observed in volunteers given moxifloxacin: E. coli, Bacillus spp., Enterococci, and Klebsiella spp. decreased, as well as anaerobic bacteria Bacteroides vulgatus, Bifidobacterium, Eubacterium, and Peptostreptococcus. B. fragilis increased. These changes returned to normal within two weeks. Moxifloxacin is not indicated for the treatment of Clostridium difficile.
Prevalence of Resistance patterns can vary geographically and this depend on time for the certain species and it needs the information of resistance in local area, especially when treating severe infections.
Resistance: Resistance mechanisms of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines do not interfere with the antibacterial activity of moxifloxacin. Other resistance mechanisms such as permeation inhibition (a common example in Pseudomonas aeruginosa) and efflux mechanisms, however, also affect the sensitivity of bacteria to moxifloxacin. There is no cross-resistance between moxifloxacin and these compounds. Plasmid-mediated resistance has not been observed. Laboratory studies of the development of moxifloxacin resistance in gram-positive bacteria have shown that resistance develops slowly, with multiple mutations, and is mediated by modification of target sites (such as topoisomerases II and IV) and efflux mechanisms. The frequency of resistance development is low (rates of 10-7-10-10). Parallel resistance has been reported with other quinolones. However, because moxifloxacin inhibits both topoisomerases (II and IV) in Gram-positive organisms, some Gram-positive and anaerobic bacteria that are resistant to other quinolones may become susceptible to moxifloxacin.

Moxifloxacin HCl is indicated for the treatment of the following bacterial infections in adults (≥18 years old): Upper respiratory tract infections: Acute exacerbations of chronic bronchitis; Community-acquired pneumonia; Acute bacterial sinusitis.
Complicated of skin & skin tissue infections: which require parenteral initial treatment; to be followed by oral therapy, in patients who have alternative-agent intolerance (especially penicillin allergy), and when caused by known moxifloxacin-susceptible organisms.
Complicated intra-abdominal infections due to polymicrobial in patients with alternative-agents intolerance which is caused by known moxifloxacin-susceptible organisms.
Mild to moderate pelvic inflammatory disease (upper genital tract infections including salpingitis and endometritis), without tubo-ovarium or pelvic abscess.
Not recommended to be used as monotherapy in mild to moderate pelvic inflammatory disease but should be combined with other suitable antibacterial agents (e.g, cephalosporins) as it can increase Neisseria gonorrhoea resistance to moxifloxacin.
Moxifloxacin HCl is indicated for the treatment of previously mentioned infections if caused by moxifloxacin-sensitive bacteria.

Dosage: Recommended dosage: one 400 mg film-coated caplet of moxifloxacin once daily.
No dosage adjustment is required for elderly patients.
No dosage adjustment is required for patients with renal failure (CrCl ≤30 mL/min/1.73 m²). For the treatment of skin and soft tissue infections, intravenous therapy should be started, followed by 400 mg moxifloxacin caplets orally.
Drug Administration: The film-coated caplet should be swallowed whole with adequate water and may be taken without food.
Duration of Treatment: For the treatment of the following infections, moxifloxacin HCl film-coated caplet should be used for: Acute exacerbation of chronic bronchitis: 5-10 days.
Community-acquired pneumonia: 10 days.
Acute sinusitis: 7 days.
Complicated skin and soft tissue infections: 7-21 days (sequential IV/oral therapy).
Complicated intra-abdominal infections: 5-14 days (sequential IV/oral therapy).
Mild to moderate pelvic inflammatory disease: 14 days.
In clinical trials on patients with complicated skin and soft tissue infections, the intravenous therapy duration was about 6 days, with an average total therapy duration of about 13 days. The dose (400 mg once daily) and duration of therapy should not exceed those recommended.
Missed Dose: If a patient misses one dose, it should be taken as soon as remembered on the same day. If it is close to the time for the next dose, skip the missed dose and take the next dose at the regular time. Do not double the dose to make up for the missed dose.

There is no specific treatment for overdose. No specific measures are recommended after an unintentional overdose. General symptomatic treatment should be initiated. The use of activated charcoal immediately after the oral administration of moxifloxacin may be beneficial in preventing increased systemic exposure to excessive moxifloxacin in cases of overdose.

Patients who are hypersensitive to moxifloxacin, other excipients in the tablet, or other quinolones.
Pregnant and breastfeeding women.
Children and adolescents under the age of 18.
Patients with a history of tendon disease or disorders related to quinolone medication.
Both in preclinical and clinical studies, heart electrophysiological changes have been observed after exposure to moxifloxacin, in the form of QT prolongation. Therefore, this drug is contraindicated in patients with: Congenital or a history of QT prolongation.
Electrolyte disturbances, especially hypokalemia that cannot be corrected.
Clinically relevant bradycardia.
Clinically relevant heart failure, with reduced left ventricular ejection fraction.
History of symptomatic arrhythmias.

Hypersensitivity: In some cases, hypersensitivity and allergic reactions can occur after the first dose of fluoroquinolones, including moxifloxacin, and should be immediately reported to a doctor.
Anaphylactic reactions, though very rare, can develop into life-threatening shock, even after the first dose. In this case, moxifloxacin therapy should be discontinued, and appropriate treatment (such as shock therapy) should be initiated.
Cases of bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin. Patients should immediately consult a doctor about the continuation of treatment if skin and/or mucosal reactions occur.
Cardiac Disorders: Women tend to have a longer baseline QTc interval compared to men, making them potentially more sensitive to drugs that can prolong the QTc interval.
Elderly patients may also be more susceptible to drugs affecting the QT interval.
Moxifloxacin, like other fluoroquinolones and macrolides, has been shown to prolong the QTc interval. ECG analysis in clinical trials indicates that the QTc prolongation with moxifloxacin is small (6 msec, ±26 msec, 1.4% compared to baseline). The incidence of potential QTc prolongation was not significantly different between the moxifloxacin group and the control group, including placebo. Because data regarding patients who may be prone to arrhythmias related to QTc prolongation is still limited, moxifloxacin should be used cautiously in patients using other medications that may lower potassium and magnesium levels.
If signs of cardiac arrhythmia occur during moxifloxacin treatment, the medication should be stopped, and an ECG should be performed.
QT prolongation can increase the risk of ventricular arrhythmias, including torsades de pointes. No cardiovascular morbidity or mortality due to QTc prolongation was observed with moxifloxacin treatment in clinical studies, although some predisposing conditions may increase the risk of ventricular arrhythmias.
Women and elderly patients may be more vulnerable to medications that prolong the QTc interval.
Hepatobiliary System: Cases of fulminant hepatitis leading to liver damage (including fatal cases) have been reported with moxifloxacin. Patients should contact their doctor before continuing treatment if signs and symptoms of liver damage appear.
Liver function tests should be performed if liver dysfunction occurs.
Due to limited clinical data, moxifloxacin is not recommended for patients with severe liver impairment (Child-Pugh C).
Renal Disorders: Elderly patients with renal impairment should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, as dehydration may increase the risk of kidney failure.
Seizures: Quinolones are known to trigger seizures. Caution should be used in patients with central nervous system (CNS) disorders (e.g., lowered seizure threshold, a history of seizures, reduced cerebral blood flow, structural brain changes, or stroke), as these conditions may affect seizures or lower the seizure threshold.
Digestive System: Pseudomembranous colitis has been reported in association with broad-spectrum antibiotic use. Therefore, it is important to consider the diagnosis in patients experiencing severe diarrhea during or after moxifloxacin use.
Peristalsis inhibitors are contraindicated in patients with severe diarrhea.
Myasthenia Gravis: Moxifloxacin should be used cautiously in patients with myasthenia gravis as their symptoms may worsen.
Tendinitis and Tendon Rupture: Tendinitis and tendon rupture (primarily Achilles tendon), sometimes bilateral, can occur with quinolone treatments, including moxifloxacin, even within the first 48 hours of therapy. Cases have been reported up to several months after therapy ends. The risk of tendinopathy may be increased in elderly patients, during heavy physical activity, in patients treated with corticosteroids, in those with renal disorders, and in organ transplant patients.
At the first sign of tendinitis (e.g., swelling accompanied by pain or inflammation), the affected extremity should be rested, physical activity should be avoided, and the patient should immediately consult a doctor and discontinue antibiotic therapy.
Skin: Quinolones have been shown to cause photosensitivity. However, studies show that moxifloxacin does not have significant potential to induce photosensitivity. Nevertheless, patients should be advised to avoid excessive UV radiation or sun exposure during treatment with moxifloxacin.
Complex Pelvic Inflammatory Disease: For patients with complex pelvic inflammatory disease (e.g., tubo-ovarian abscess or pelvic abscess), where intravenous treatment is required, oral moxifloxacin is not recommended.
Pelvic Inflammatory Disease: Pelvic inflammatory disease may be caused by Neisseria gonorrhoeae, which is resistant to fluoroquinolones. Therefore, moxifloxacin should be given in combination with another appropriate antibiotic (e.g., cephalosporins), unless Neisseria gonorrhoeae resistant to moxifloxacin can be excluded. If clinical improvement is not achieved after 3 days of treatment, continued therapy should be reconsidered.
MRSA Infections: Moxifloxacin is not recommended for the treatment of MRSA infections. In cases of confirmed or suspected MRSA infection, treatment with the appropriate antibacterial agents should be initiated.
Peripheral Neuropathy: Cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoaesthesia, dysaesthesia, or weakness have been reported in patients receiving quinolones, including moxifloxacin. Patients treated with moxifloxacin should inform their doctor before continuing treatment if neuropathy symptoms such as pain, burning, tingling, numbness, or weakness occur.
Psychiatric Reactions: Psychiatric reactions can occur even after the first dose of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions may progress to suicidal thoughts and self-harming behaviors such as suicide attempts. If these reactions occur, moxifloxacin should be stopped, and appropriate measures should be taken.
Moxifloxacin should be used cautiously in patients with psychotic disorders or a history of mental illness.
Genital Tract Infections: Due to the widespread and increasing prevalence of Neisseria gonorrhoeae infections resistant to fluoroquinolones, monotherapy with moxifloxacin should be avoided in patients with pelvic inflammatory disease, unless Neisseria gonorrhoeae resistant to moxifloxacin can be excluded. If resistant N. gonorrhoeae can be excluded, adding an appropriate antibiotic that is usually active against N. gonorrhoeae (e.g., cephalosporins) to moxifloxacin therapy should be considered.
Dysglycemia: Like other fluoroquinolones, moxifloxacin has been reported to cause blood glucose disorders, including hypoglycemia and hyperglycemia. Dysglycemia is particularly common in elderly diabetic patients receiving concurrent oral hypoglycemic agents (e.g., sulfonylureas) or insulin. Blood glucose levels should be closely monitored in diabetic patients.
Glucose-6-Phosphate Dehydrogenase Deficiency: Patients with or a history of glucose-6-phosphate dehydrogenase deficiency are susceptible to hemolytic reactions when treated with fluoroquinolones. Therefore, moxifloxacin should be used cautiously in these patients.
Galactose Intolerance, Lapp Lactase Deficiency, or Glucose-Galactose Malabsorption: Patients with rare inherited disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not use this medication.
Visual Disorders: If visual disturbances or other eye-related effects occur, consult an ophthalmologist immediately.
Excipients Information: For patients with sodium intake concerns (e.g., patients with congestive heart failure, kidney failure, nephrotic syndrome, etc.), the additional sodium load from the infusion solution should be considered.
Effects on Driving and Operating Machinery: Fluoroquinolones may affect a patient's ability to drive or operate machinery due to reactions in the central nervous system (CNS) (e.g., dizziness) and temporary or acute vision loss, as well as temporary loss of consciousness (syncope). Patients are advised to see how they react to moxifloxacin before driving or operating machinery.
Use in Children: Due to effects on animal cartilage, moxifloxacin is contraindicated in children and adolescents under 18 years of age.

There have been no studies on the safety of moxifloxacin during pregnancy. Reproductive studies in rats and monkeys did not show any evidence of teratogenicity or fertility disturbances. However, like other quinolones, moxifloxacin has been shown to cause cartilage lesions in the weight-bearing joints of immature animals. Preclinical data suggest that moxifloxacin is excreted into breast milk. The use of moxifloxacin is contraindicated in pregnant and breastfeeding mothers.

Frequency is defined as: common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
Infections and infestations: Common: fungal superinfection.
Disorders of the lymphatic and blood systems: Uncommon: anemia, leukopenia, neutropenia, thrombocytopenia, thrombocytosis, prolonged prothrombin time/increased INR.
Rare: abnormal thromboplastin levels.
Very rare: increased prothrombin levels/decreased INR, abnormal prothrombin/INR levels.
Immune system disorders: Uncommon: allergic reactions, pruritus, rash, urticaria, eosinophilia.
Rare: anaphylactic/anaphylactoid reactions, peripheral edema, allergic edema/angioedema (including laryngeal edema, potentially life-threatening).
Very rare: anaphylactic/anaphylactoid shock (potentially life-threatening).
Metabolism and nutrition disorders: Uncommon: hyperlipidemia.
Rare: hyperglycemia, hyperuricemia.
Very rare: hypoglycemia.
Psychiatric disorders: Uncommon: anxiety reactions, psychomotor hyperactivity/agitation.
Rare: emotional instability, depression (in very rare cases potentially progressing to self-harm behaviors such as suicidal thoughts/attempts), hallucinations.
Very rare: depersonalization, psychotic reactions (potentially progressing to self-harm behaviors, such as suicidal thoughts/attempts).
Nervous system disorders: Common: headache, dizziness.
Uncommon: paresthesia and/or dysesthesia, taste disturbances (including ageusia in very rare cases), confusion and disorientation, sleep disturbances, tremor, vertigo, drowsiness.
Rare: hypoesthesia, olfactory disturbances, abnormal dreams, coordination problems (including gait disturbances, especially due to dizziness or vertigo; in very rare cases causing falls with injuries, especially in the elderly), seizures (including grand mal seizures), attention disorders, speech disorders, amnesia, peripheral neuropathy, and polyneuropathy.
Very rare: hyperesthesia.
Eye disorders: Rare: visual disturbances (mainly related to central nervous system reactions).
Very rare: temporary vision loss (mainly related to central nervous system reactions).
Ear and labyrinth disorders: Uncommon: vertigo.
Rare: tinnitus, hearing disturbances including deafness (usually reversible).
Cardiac disorders: Uncommon: QT prolongation, palpitations, tachycardia, atrial fibrillation, angina pectoris.
Rare: ventricular arrhythmias, syncope.
Very rare: torsades de pointes, heart attack.
Cardiovascular system disorders: Common: QT prolongation in patients with hypokalemia.
Uncommon: QT prolongation, palpitations, tachycardia, vasodilation.
Rare: ventricular arrhythmias, syncope, hypertension, hypotension.
Respiratory, thoracic, and mediastinal disorders: Uncommon: nonspecific arrhythmias, torsades de pointes*, heart attack** (especially in patients with proarrhythmic conditions such as clinically significant bradycardia, acute ischemic myocardium).
Respiratory, thoracic, and mediastinal disorders: Uncommon: shortness of breath (including asthma conditions).
Gastrointestinal disorders: Common: nausea, vomiting, abdominal pain, diarrhea.
Uncommon: loss of appetite and food intake, constipation, dyspepsia, bloating, gastroenteritis (excluding erosive gastroenteritis), increased amylase.
Rare: dysphagia, stomatitis, antibiotic-associated colitis (in very rare cases associated with life-threatening complications).
Liver and Gallbladder Disorders: Common: increased transaminases.
Uncommon: liver disorders (including increased LDH), increased bilirubin, increased gamma-glutamyl transferase, increased alkaline phosphatase.
Rare: jaundice, hepatitis (especially cholestatic).
Very rare: fulminant hepatitis potentially causing life-threatening liver damage (including fatal cases).
Skin and Subcutaneous Tissue Disorders: Very rare: bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).
Musculoskeletal and Bone Disorders: Uncommon: arthralgia, myalgia.
Rare: tendonitis, increased muscle tone and cramps, muscle weakness.
Very rare: tendon rupture, arthritis, gait disturbances (caused by nonspecific muscle or joint symptoms), exacerbation of myasthenia gravis symptoms.
Kidney and Urinary Tract Disorders: Uncommon: dehydration (caused by diarrhea or decreased fluid intake).
Rare: kidney function disorders due to renal failure (caused by dehydration), especially in the elderly with pre-existing kidney disorders.
General Disorders and Site of Administration Conditions: Common: injection and infusion site reactions.
Uncommon: malaise, nonspecific pain, sweating, thrombophlebitis at the infusion site.
Rare: edema.
In some cases, certain serious adverse drug reactions may last for an extended period (>30 days) and be debilitating, such as tendonitis, tendon rupture, musculoskeletal disorders, and other reactions affecting the nervous system, including psychiatric disorders and sensory disturbances.
The following undesirable effects are more frequent in subgroups of patients receiving consecutive IV/oral treatment: Common: increased gamma-glutamyl transferase.
Uncommon: ventricular arrhythmias, hypotension, edema, antibiotic-associated colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including grand mal seizures), hallucinations, kidney disorders (in some cases due to dehydration leading to renal failure, especially in the elderly with pre-existing kidney conditions).

Cytochrome P450-Mediated Interactions: In vitro studies with cytochrome P450 isoenzymes (CYP) have shown that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, so it is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes. Cytochrome P450 isoenzymes are also not known to be involved in the metabolism of moxifloxacin. Based on these results, metabolic interactions via cytochrome P450 enzymes are unlikely to occur.
Clinical studies indicate no interactions when moxifloxacin is administered with ranitidine, probenecid, oral contraceptives, calcium supplements, parenterally administered morphine, theophylline, cyclosporine, or itraconazole.
Rifampicin: When given with a double dose of rifampicin, the AUC (Area Under the Curve) of moxifloxacin decreased by approximately 30%. The clinical consequences of this are unknown, and no dose adjustments are recommended when used together.
Rifapentine: When given with a double dose of rifapentine, the AUC of moxifloxacin decreased by 17%. The clinical consequences of this are unknown, and no dose adjustments are recommended when used together.
Drugs that Prolong the QT Interval: The additive effect on QT interval prolongation of moxifloxacin and other drugs that prolong the QT interval cannot be ignored, for example: Class IA antiarrhythmic drugs (e.g., quinidine, hydroquinidine, disopyramide).
Class III antiarrhythmic drugs (e.g., amiodarone, sotalol, dofetilide, ibutilide).
Neuroleptics (e.g., phenothiazine, pimozide, sertindole, haloperidol, sultopride).
Tricyclic antidepressants.
Certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine).
Certain antihistamines (terfenadine, astemizole, mizolastine).
Others (e.g., cisapride, bepridil).
This effect may increase the risk of ventricular arrhythmias, particularly torsades de pointes.
Therefore, moxifloxacin is contraindicated in patients treated with these drugs.
Bivalent and Trivalent Cations: Chelating agents such as iron, aluminum, and magnesium can inhibit the absorption of moxifloxacin. Co-administration or administration of drugs containing these cations with moxifloxacin can reduce its exposure by approximately 25-60%. A minimum separation of 6 hours between the administration of drugs containing bivalent or trivalent cations (e.g., magnesium or aluminum-containing antacids, didanosine, sucralfate, and iron or zinc-containing medications) and moxifloxacin is recommended. Calcium does not affect moxifloxacin exposure, and calcium-containing supplements can be taken with moxifloxacin.
Changes in INR (International Normalized Ratio): A significant number of cases have reported increased oral anticoagulant activity in patients receiving antibiotics, especially fluoroquinolones, macrolides, tetracyclines, cotrimoxazole, and some cephalosporins. It is difficult to evaluate whether infection or antibiotic therapy is the cause of the INR disturbance. INR should be closely monitored in patients receiving warfarin or other anticoagulants.
Food Interactions: Moxifloxacin has no clinically relevant interactions with food, including dairy products.
Warfarin: No interaction was observed with warfarin in terms of prothrombin time and other coagulation parameters when used concomitantly.
Digoxin: The pharmacokinetics of digoxin are not affected by moxifloxacin (and vice versa).
Antidiabetic Medications: No clinical interaction was observed between glibenclamide and moxifloxacin.

Quinolones

J01MA14 - moxifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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