Letanex®
Levofloxacin F.C tablet
Category:
Antibacterial (Systemic ) (USP DI)
Chemistry:
Levofloxacine 250, 500 and 750 mg Film-Coated tablets.
(-)-(S)-9-fluoro 2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4benzoxazine-6-carboxylic acid .
C18H20FN3O4 =361.4
(Martindale)
Mechanism of action:
Levofloxacin acts by inhibiting DNA gyrase (bacterial topoisomerase II), an enzyme required for DNA replication,transcription,repair and recombination.
(USP DI )
Pharmacokinetics:
Absorption, bioavailability and protein binding of Levofloxacin are rapid and complete, approximately 99% and moderate (24-38%), respectively. This medicine is widely distributed and penetrates well into blister fluid and lung tissues. Its half-life is 6-8 hours and time to peak concentration and peak serum concentration are approximately 1-2 hours and approximately 5.7 mcg / ml, respectively. Levofloxacin has approximately 87% renal and approximately 4% fecal elimination and is not efficiently removed by hemodialysis or peritoneal dialysis.
(USP DI)
Indications
All this indications are for treatment (not prophylaxis)
Anthrax, inhalational - Bronchitis , bacterial exacerbations - Pneumonia ,community-acquired - Pneumonia ,nosocomial - Prostatitis, bacterial – Pyelonephritis - Sinusitis - Skin and soft tissue infections , complicated - Skin and soft tissue infections , Uncomplicated - Urinary tract infections, bacterial , complicated - Urinary tract infections, bacterial , uncomplicated.
(USP DI)
Contraindications:
1- Levofloxacin is contraindicated for patients known to have hypersensitivity to the drug or any of the ingredients.
2- Discontinuing Levofloxacin at the first sign of skin rash or other allergic reaction.
3- Discontinuing Levofloxacin and notifying physician if pain, inflammation or rupture of a tendon is experienced. Resting and refraining from exercise until the diagnosis of tendinitis or tendon rupture has been excluded.
4- Discontinuing Levofloxacin and contacting physician if patient is a diabetic being treated with insulin or an oral hypoglycemic agent and a hypoglycemic episode occurs.
5- Discontinuing Levofloxacin and contacting physician if patient is hypokalemic or bradycardic and develops a fast, slow or irregular heartbeat.
6- In patients with epilepsy
7- In breast – feeding women and During pregnancy
8- In children or growing adolescents
(USP DI &www.medicines.org.uk) Warnings & Precautions:
1- Patients allergic to one fluoroquinolone or other chemically related quinolone derivatives (e.g.,cinoxacin ,nalidixic acid) may be allergic to other fluoroquinolones also.
2- Fluoroquinolones, are associated with an increased risk of tendinitis and tendon rupture in all ages. The risk is further increased in older patients ( older than 60 years of age ) , in patients taking corticosteroid drugs, and in patients with kidney , heart,or lung transplants.
3- CNS stimulation may occur ( e.g.tremor,restlessness,confusion); use with caution in patients predisposed to seizures or with other CNS disorders.
4- Convulsions have been reported in patients taking quinolones. Notify physician before taking quinolones if there is a history of this condition.
5- Inform physician if development of symptoms suggestive of pancreatitis including abdominal pain or nausea and vomiting occurs.
6- Avoiding excessive sunlight / artificial UV. light. Reactions may occur following the first dose. Discontiuing drug if phototoxicity reactions occur.
7- Caution when driving or doing anything else requiring alertness because of possible dizziness, drowsiness, or lightheadedness.
8- Patients should notify their physician if they are taking warfarin or treated with Vitamin K antagonists . Concurrent administration of warfarin and Levofloxacin has been associated with increase of the International Normalized Ratio (INR) or prothrombin time and clinical episodes of bleeding.
9- Inform physician of any other medications when taken concurrently with fluoroquinolones, including OTC medications.
10- Levofloxacin is renally excreted; is recommended that patients with a creatinine clearance of less than 50 ml per minute receive a reduced dosage of Levofloxacin.
11- Pseudomembranous colitis has been reported with nearly all antibiotic agents, and ranges in severity from mild to life-threatening; it is important to consider the diagnosis in patients who present with diarrhea subsequent to the administration of any antibacterial agent; once diagnosed therapeutic measures should be instituted.
12- Patients with glucose- 6-phosphate dehydrogenase deficiency, QT interval prolongation, psychotic reaction, sever bullous reaction, dysglycemia.
(DRUG FACTS & USP DI& www.medicines.org.uk)
Pregnancy and Breast - feeding:
FDA Pregnancy Category: C
Because of the potential for serious adverse effects during pregnancy and breast – feeding, a decision should be made base on the potential benefit to the mother outweighs the potential risk to the fetus or infants.
(USP DI) Drug Interactions:
The following drug interactions have been selected on the basis of their potential clinical significance:
Note: Unlike other Fluoroquinolones , Levofloxacin does not alter the pharmacokinetics of cyclosporine, digoxin, theophyline, or warfarin.
- Antacids (aluminium -, calcium - or magnesium - containing), Didanosin, Ferrous sulfate, Sucralfate , zinc. (may reduce absorption of Levofloxacin by chelation ), Anti arrhythmic agents class Ia or class III, Anti diabetic agents, Nonstroidal anti – inflammatory drugs (NSAIDs), Cimetidine or Probenecid, Corticosteroids, warfarin.
(USP DI)
Adverse reactions:
Those indicating need for medical attention:
- Incidence rare: Central nervous system(CNS) stimulation, hypersensitivity reactions, phototoxicity, pseudomembranous colitis, tendonitis or tendon rupture.
- Incidence not determined: Abnormal electroencephalogram, allergic pneumonitis, anaphylactic shock, anaphylactoid reaction, dysphonia, encephalopathy, eosinophilia, erythema multiforme, hemolytic anemia, increased international normalized ratio/prothrombin time, multi-system organ failure, peripheral neuropathy, rhabdomyolysis, Stevens-Johnson Syndrome, torsades de pointes.
Those indicating need for medical attention if they continue or are bothersome :
- Incidence less frequent: CNS effects, gastrointestinal effects, taste perversion, vaginal candidiasis.
- Incidence not determined: Vasodilation
Those indicating possible pseudomembranous colitis and the need for medical attention if they occur after medication is discontinued:
Abdominal or stomach cramps and pain, severe; abdominal tenderness; diarrhea, watery and severe, which may also be bloody; fever. (USP DI)
OVERDOSE:
In the event of an acute overdose, the stomach should be emptied. The patient should be observed and hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.Levofloxacin exhibits a low potential for acute toxicity.
Treatment of overdose:
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Antacids may be used for protection of gastric mucosa. Haemodialysis, including peritoneal dialysis and CAPD, are not effective in removing Levofloxacin from the body. [No specific antidote exists.]
(USP DI & www.medicines.org.uk )
DOSAGE AND ADMINISTRATION:
Usual adult dose:
Type of Infection Every 24 hours (days)
Nosocomial pneumonia 750 mg 7-14
Community-acquired pneumonia 500 mg 7-14
750 mg 5
Adult bacterial sinusities 500 mg 10-14
750 mg 5
Acute bacterial exacerbation of chronic bronchitis 500 mg 7
Complicated Skin and Soft tissue Infections (SSSI) 750 mg 7-14
Uncomplicated SSSI 500 mg 7-10
Chronic bacterial prostatitis 500 mg 28
Uncomplicated Bacterial Urinary Tract Infections 250 mg 3
Inhalational anthrax (Postexposure) 500 mg s 60
UTI (complicated) or acure pyelonephritis 250 mg 10
750 mg 5
(DRUG FACTS & USP DI)
* Safety and efficacy have not been established in pediatric.
Administration:
* Levofloxacin tablets may be taken with or without food.
*Importance of beginning Levofloxacin as soon as possible following suspected or confirmed exposure to anthrax.
*Adequate hydration of patients receiving Levofloxacin should be maintained to prevent the formation of highly concentration urine. Crystaluria and cylindruria have been reported with quinolones.
*Administer Levofloxacin tablets and oral solution at heast 2 hours before or after antacids containing magnesium or aluminum, as well as sucralfate, metal cations (eg, iron), multivitamins with zinc, or didanosine chewable/buffered tablets or the pediatric powder for oral solution.
Missed dose : Taking as soon as possible ;not taking it almost time for next dose ; not doubling doses .
(DRUG FACTS & USP DI)
Storage:
Store between 15 & 30°C in a dry place. (USP DI & DRUG FACTS)
How supplied:
Levofloxacin 500 and 750 mg tablets are manufactured at Tehran Darou pharmaceuticals and are available, blister of 5&7 in a box of 5׳s & 7׳s.
References:
1) Martindale (39) 2017
2) USP DI 2007
3) DRUG FACTS and COMPARISONS 2015
4) www.medicines.org.uk