Levofloxacin
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Levofloxacin
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| Systematic (IUPAC) name | |
| (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de]-1,4-benzoxazine-6-carboxylic acid |
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| Identifiers | |
| CAS number | |
| ATC code | J01 S01AX19 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C18H20FN3O4 |
| Mol. mass | 361.368 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | 99% |
| Protein binding | 24 to 38% |
| Metabolism | Renal |
| Half life | 6 to 8 hours |
| Excretion | Urinary |
| Therapeutic considerations | |
| Pregnancy cat. |
C (United States) |
| Legal status | |
| Routes | Oral, IV, Ophthalmic |
Levofloxacin is a 3rd generation fluoroquinolone antibiotic, marketed by Ortho-McNeil under the trade name Levaquin in the United States. In Europe, it is marketed by Sanofi-Aventis under the trade name Tavanic, in Chile as Gatigol by Alpes Selection, in India under the trade name Lebact marketed by Nicolas Piramal and in Asia it is marketed by Daiichi under the trade names Cravit and Levox. Levofloxacin was launched in the Japanese market in 1993, and thus has had more than 13 years of testing in efficacy and safety globally. Chemically, levofloxacin is the S-enantiomer (L-isomer) of ofloxacin, and has approximately twice the potency of ofloxacin, because the R+enantiomer (D-isomer) of ofloxacin is essentially inactive. In addition, the S-enantiomer (L-isomer) of ofloxacin, has substantially less toxicity. Like other fluoroquinolines, it works by inhibiting DNA gyrase, an enzyme that negatively supercoils DNA.
Levofloxacin is effective against a number of gram-positive and gram-negative bacteria. Because of its broad spectrum of action, levofloxacin is frequently prescribed empirically for a wide range of infections (e.g. pneumonia, urinary tract infection) before the specific causal organism is known. If the causal organism is identified, levofloxacin may be discontinued and the patient may be switched to an antibiotic with a narrower spectrum of activity. Levofloxacin is currently the only respiratory fluoroquinolone approved by the U.S. FDA for the treatment of nosocomial pneumonia.
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[edit] Susceptible organisms
[edit] Gram-positive bacteria
- Enterococcus faecalis (many strains are only moderately susceptible)
- Staphylococcus aureus (methicillin-susceptible strains)
- Staphylococcus epidermidis (methicillin-susceptible strains)
- Staphylococcus saprophyticus
- Streptococcus pneumoniae (including Multidrug-resistant strains, MDRSP)
- Streptococcus pyogenes
[edit] Gram-negative bacteria
- Enterobacter cloacae
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
- Escherichia coli
- Legionella pneumophila
- Serratia marcescens
- Haemophilus influenzae
- Moraxella catarrhalis
- Haemophilus parainfluenzae
- Proteus mirabilis
- Campylobacter
[edit] Side Effects
This drug has similar side effects to all the other fluoroquinolone antibiotics.
As with all fluoroquinolones there are numerous documented cases of spontaneous tendon rupture (Maurin, 2008; Mehlhorn & Brown, 2007; Ng & Naughton, 2007; Salvi, 2007). Such ruptures may occur both during as well as long after therapy had been discontinued. There are documented cases where such ruptures have occurred over a year later. It is impossible to calculate the risk of such ruptures as the medical community for the most part fails to associate tendon ruptures with the use of the drugs found within this class. Currently there are two petitions pending with the FDA seeking "Black Box Warnings" as well as "Dear Doctor Letters" regarding this particular adverse reaction.
The medical journals have clearly associated such a risk with the fluoroquinolone class since their introduction back in 1982. The FDA has failed to respond to these petitions as required by law and Public Citizen has filed a lawsuit in Federal Court (January 2008) seeking a court order requiring compliance by the FDA. There are other cases of severe pain, and swelling in as little as two days. This is known as "quinolone-induced tendonopathy" and such injury appears to be a life long disability.
Within the recent label changes (2007)it is noted that:
"Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly...Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Tendon rupture can occur during or after therapy with quinolones. "
There are other serious adverse reactions associated with this class including Irreversible Peripheral Neuropathy, (permanent nerve damage), increased QT prolongation, Torsades de Pointes, central nervous system (CNS) events including severe nervousness, agitation, chronic insomnia, anxiety attacks, nightmares, and paranoia. Toxic Pyschosis has also been reported.
Life threatening disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, are also associated with the use of Levaquin.
In 2004 new warning labels were added to all of the Fluoroquinolones regarding Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Problems (prolonged QT Interval / Torsades de pointes), Pseudomembranous colitis, Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
Fluoroquinolones caused fetal harm in animal studies, including decreased body weights and malformed bones as well as an increased risk of death. Because of the potential for serious adverse effects to the fetus, these drugs should not be used by pregnant women.
Fluoroquinolones are excreted in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take these drugs while nursing.
Other adverse events found within the package inserts for Levaquin include the following:
Cardiovascular: Palpitation, atrial flutter, ventricular ectopy, syncope, hypertension, angina pectoris, myocardial infarction, cardiopulmonary arrest, cerebral thromobosis. Cardiovascular collapse, cardiopulmonary arrest, myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina pectoris. Postural hypotension, vasculitis.
Central Nervous System: Dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia. paranoia, toxic psychosis, dysphasia, phobia, unresponsiveness, confusion, anxiety, agitation, delirium, myoclonus, nystagmus.
Gastrointestinal: Painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding. Cholestatic jaundice has been reported. Ileus, jaundice, C. difficle associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis, dyspepsia, epigastric or abdominal pain, vomiting, constipation, oral ulceration, mouth dryness, anorexia, flatulence. Constipation, dyspepsia. (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.)
Hemic/Lymphatic: Agranulocytosis, hemolytic anemia, methemaglobinemia, prolongation of prothrombin time
Metabolic/Nutritional: Elevation of serum triglycerides, cholesterol, blood glucose, serum potassium.
Musculoskeletal: Arthralgia or back pain, joint stiffness, achiness, neck or chest pain, flare up of gout. Arthralgia, jaw, arm or back pain, joint stiffness, neck and chest pain, achiness, flare up of gout Myalgia, possible exacerbation of myasthenia gravis, tendinitis/tendon rupture.
Renal/Urogenital: Interstitial nephritis, nephritis, renal failure, polyuria, urinary retention, urethral bleeding, vaginitis, acidosis. Renal failure, hemorrhagic cystitis, renal calcuti, frequent urination, polyuria, urinary retention, gynecomastia, candiduria. Crystalluria, cylindruria, hematuria, and albuminutia have also been reported. Albuminuria, vaginal candidiasis.
Respiratory: Dyspnea, epistaxis, laryngeal or pulmonary edema, hiccough, hemophysis, bronchospasm, pulmonary embolism. Respiratory arrest, pulmonary edema, respiratory distress, pleural effusion, hemoptysis,
Skin/Hypersensitivity: Pruritus, urticaria, photosensitivity, flushing, fever, chills, angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous candidiasis, hyperpigmentation, erytherna nodosum. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or lower extremities, purpura, fever, chills, flushing, pruritus, urtigaria, cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation, erythema nodosum, photosensitivity. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis.
Special Senses: Blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste. Decreased visual acuity, eye pain, anosmia, hearing loss, tinnitus, nystagmus, a bad taste. Also reported were agranulocytosis, prolongation of prothrombin time, and possible exacerbation of myasthenia gravis. anosmia, taste loss.
Adverse Laboratory Changes include:
Hepatic: Elevations of ALT (SGPT), AST (SGOT), alkaline phosphatase, LDH, serum bilirubin. Hematologic: Eosinophilia, leukopenia, decreased blood platelets, elevated blood platelets, pancytopenia.
Renal: Elevations of serum creatinine, BUN, CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA HAVE BEEN REPORTED.
Other Changes: Elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, leukocytosis.
[edit] Other
- More bacterial coverage is available as per prescribing information for levofloxacin in Japan
[edit] External Link
http://www.bangladesh-drug-medicine.info/wiki/Ovel-500
[edit] References
http://www.jabfm.org/cgi/content/full/16/5/458 http://jac.oxfordjournals.org/cgi/content/full/51/3/747
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails
Maurin N., Fluoroquinolone-induced Achilles tendon rupture, Deutsche medizinische Wochenschrift (1946) (0012-0472) 2008 Feb. Vol.133,Iss.6;p.241-4
Mehlhorn AJ; Brown DA., Safety concerns with fluoroquinolones, The Annals of pharmacotherapy (1060-0280), 2007 Nov. Vol.41,Iss.11;p.1859-66
Ng WF; Naughton M., Fluoroquinolone-associated tendinopathy: a case report. Journal of medical case reports 2007 Jul 23. Vol.1;p.55
Salvi, A. E., Spontaneous bilateral Achilles tendon rupture in a patient treated with oral levofloxacin, Journal of Orthopaedics and Traumatology (1590-9921), 1 Jun 2007. Vol.8, Iss.2;p.86(5),
(Cravit)
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