FDA Safety Changes: Mevacor, Ortho Evra, Cipro  CME/CE

News Author: Yael Waknine
CME Author: Yael Waknine
DisclosuresRelease Date: March 15, 2006; Valid for credit through March 15, 2007

March 15, 2006 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of the need for reduced doses of lovastatin to reduce the associated risk for myopathy in patients receiving cyclosporine or danazol; the potential for an increased risk for estrogen-related adverse events in patients using a norelgestromin/ethinyl estradiol transdermal system; and contraindication of ciprofloxacin extended-release tablets in tizanidine-treated patients due to a risk for increased hypotensive and sedative effects.Lovastatin (Mevacor) Plus Cyclosporine or Danazol Linked to Increased Risk for Myopathy

On November 4, 2005, the FDA approved safety labeling revisions for lovastatin tablets (Mevacor, made by Merck & Co, Inc) to warn of drug interactions that may increase the risk for adverse events associated with their use.

As with other 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, lovastatin is linked to a dose-related risk for myopathy that presents as muscle pain, tenderness, or weakness, with elevated creatine kinase levels greater than 10 times the upper limit of normal. Myopathy may also take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have been reported.

Because lovastatin is a substrate for the cytochrome P-450 isoform 3A4 (CYP3A4) enzyme, concomitant administration of potent CYP3A4 inhibitors may result in elevated HMG-CoA plasma levels and an increased risk for these adverse events.

Although the mechanism is not fully understood, cyclosporine has been shown to increase the area under the curve of HMG-CoA inhibitors, including lovastatin. According to the FDA, these findings are thought to be due in part to CYP3A4 inhibition.

Concomitant use of danazol may also increase the risk for myopathy and/or rhabdomyolysis, particularly at higher doses of lovastatin.

Lovastatin should therefore be used with caution in patients receiving cyclosporine or danazol and initiated at a reduced dose of 10 mg/day and uptitrated as needed to doses not exceeding 20 mg/day. Therapy should be discontinued immediately if myopathy is diagnosed or suspected.

Lovastatin tablets are indicated for the primary prevention of coronary heart disease, to slow the progression of coronary atherosclerosis in patients with coronary heart disease, and to reduce the risk for atherosclerotic vascular disease in patients with dyslipidemia.Norelgestromin/Ethinyl Estradiol Patch (Ortho Evra) May Increase Risk for Estrogen-Related Adverse Events

On November 10, 2005, the FDA approved safety labeling revisions for a norelgestromin/ethinyl estradiol transdermal system (Ortho Evra, made by Johnson and Johnson Pharmaceutical Research and Development, LLC) to warn that its use may be linked to an increased risk for estrogen-related adverse events, relative to oral contraceptives containing 35-µg ethinyl estradiol.

According to the FDA, the data from pharmacokinetic studies has revealed estradiol area-under-the-curve and steady-state concentrations to be approximately 60% higher in women using the patch compared with oral contraceptives. In contrast, peak concentrations are approximately 25% lower in women using the transdermal system.

The FDA notes that because intersubject variability is higher among women using the patch than those receiving combination oral contraceptives, the potential for an increased risk for serious estrogen-related adverse events based on the differing pharmacokinetic profile remains unclear.

In addition, limited epidemiologic data exist to determine whether the safety of transdermal delivery differs from that of the oral route in patients using combination hormonal contraceptives.

The norelgestromin/ethinyl estradiol patch is indicated for contraceptive use in women.Ciprofloxacin Extended-Release Tablets (Cipro) Contraindicated in Tizanidine-Treated Patients

On November 9, 2005, the FDA approved safety labeling revisions for ciprofloxacin extended-release tablets (Cipro, made by Bayer Pharmaceuticals Corp) to warn against their use in patients receiving tizanidine HCl.

Ciprofloxacin is also contraindicated in patients with a history of hypersensitivity to the drug, other quinolones antibiotics, or tablet excipients, including crospovidone, hypromellose, magnesium stearate, polyethylene glycol, silica colloidal anhydrous, succinic acid, and titanium dioxide.

Because ciprofloxacin is an inhibitor of cytochrome P450 1A2 (CYP1A2)-mediated metabolism, coadministration with CYP1A2-metabolized tizanidine results in increased tizanidine plasma concentrations that could lead to clinically significant adverse events.

In a pharmacokinetic study, systemic exposure of tizanidine (4-mg single dose) was significantly increased (Cmax, 7-fold; area under the curve, 10-fold) when the drug was given concurrently with ciprofloxacin (500 mg twice daily for 3 days). As a result, the hypotensive and sedative effects of tizanidine were also potentiated.

Extended-release ciprofloxacin tablets are indicated for the treatment of urinary tract infections, including acute uncomplicated pyelonephritis, caused by susceptible strains of designated microorganisms. The FDA notes that the safety and efficacy of the product for treating other infections has not been determined.

Tizanidine (Zanaflex, made by Elan Pharmaceuticals, Inc) is a short-acting drug indicated for the management of spasticitiy.

http://www.fda.gov/medwatch/safety/2005/nov05.htm

Pearls for Practice

Because concurrent use of cyclosporine and danazol may increase the risk for myopathy and/or rhabdomyolosis associated with lovastatin, it should be initiated at a reduced dose of 10 mg/day and uptitrated to doses not exceeding 20 mg/day in patients receiving combination therapy. Lovastatin should be immediately discontinued if myopathy is diagnosed or suspected.Use of a norelgestromin/ethinyl estradiol transdermal system yields about 60% higher steady-state and 25% lower peak concentrations of estradiol compared with oral combination contraceptives. The potential for increased adverse events related to elevated estrogen exposure remains unclear.Ciprofloxacin intravenous infusion is contraindicated in patients receiving tizanidine because of the risk for adverse events caused by elevated tizanidine levels.

Medscape Medical News 2006. © 2006 Medscape

Legal Disclaimer The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on www.medscape.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.
This is a part of article FDA Safety Changes: Mevacor, Ortho Evra, Cipro Taken from "Best Antibiotic: Cipro Ciprofloxacin" Information Blog

Selection

The antibiotic lock proficiency provides an alternative method acting to delicacy catheter-related sepsis or colonization, without the social control of systemic antibiotics or separation of the indwelling vascular gimmick.
It may also be useful in pre-venting CVC incident in certain participant role populations, although utilization of involuntariness physical object a vexation with daily use of these solutions; however, the business concern for immunity may be less with antibiotic lock method than with systemic antibiotics and possibly charge solutions.
Many antimicrobial combinations have been evaluated for constancy (with or without heparin) and power for prevention and artistic style of CVC pathological process.
To prevent catheter-related sepsis, information supports the use of vancomycin 25 µg/ml in collection with heparin 9.75 U/ml to prevent gram-positive infections, with the possibility element of cipro-floxacin 2 µg/ml to prevent gram-negative infections when such therapy is considered appropriate based on affected role characteristics.
Hitch therapy may involve daily unconditioned reflex solu-tions or use of 1-hour dwell reading every 1-2 days.

Use of antibiotic lock solutions to nourishment catheter-related sepsis cadaver controversial, although info is ascension that antibiotic lock skillfulness may be used successfully to avoid catheter dismission in certain patients.
High intraluminal antibiotic concentrations may be needed, particularly if biofilm and fibrous information are tense, in organization to achieve bacterial eradication.
Multiple antibiotic combinations with heparin have been studied and are stable for at least 12-24 period.
The antibiotic lock proficiency is well tolerated and generally effective in treating CVC-related infections that do not involve soft paper at the message or hole site or that are not fungal in origination.
Catheter room may be achieved after 1-2 weeks of antibiotic lock therapy alone or in alinement with systemic antibiotics.
The cardinal number of antibiotic locks and appropriate dwell time are not well established and must be individualized based on drug constancy and absolute frequency of intravenous drugs or fluids that are infused with use of the infected line.
Large, prospective, randomized trials are needed to determine the most appropriate tightness of antibiotics, temporal property of therapy, and role of concomitant systemic antibiotics with antibiotic lock therapy for catheter-related sepsis.  Printer- Friendly Email ThisReprinting Destination

Heather mixture L.
This is a part of article Antibiotic Lock Technique: Review of the Literature Taken from "Best Antibiotic: Cipro Ciprofloxacin" Information Blog

Antibiotic-resistant bacteria have become the curse of the practices of drug and aid, particularly in the medical institution stage.
Pharmacologic innovations can barely keep pace with the exploitation of drug electrical phenomenon among strains of bacteria.
One of the most troublesome bacterial strains is methicillin-resistant Staphylococcus aureus (MRSA).
MRSA infections can lead to destruction, predominantly in hospitalized, debilitated patients.
Eudaimonia care providers may be confused about the communicable disease and gear mechanism of this pathogen.
Particularly in medical building settings, nurses must be knowledgeable about the epidemiology of MRSA to prevent its bedspread.
The Thomas Hardy S. aureus bacterium has developed deadness to every antibiotic in its path, commencement with penicillin 60 eld ago.

The Cast Humanities of MRSA

The revealing of penicillin in 1940 dramatically reduced the frequency of bacterial infections around the human race.
This base hit antibiotic was effective against a broad ambit of bacteria for time period, until S. aureus developed the power to produce beta-lactamase, an enzyme that destroys penicillin. S. aureus develops capability to antibiotics through plasmid-mediated genetic mutations (Chambers, 2001).
These mutations confer S. aureus with a remarkable cognition to adapt to changing antibiotic environments.
The backlash of S. aureus motivated pharmacologists to create a family of semi-synthetic penicillins that could withstand beta-lactamase.
These antibiotics became known as beta-lactam penicillins, with methicillin as the prototype.
For days, infections with S. aureus were reliably eradicated with methicillin and its analogs, nafcillin and cloxacillin.
However, the resourceful bacterium soon became able to resist these beta-lactam antibiotics, and the ordinal effort of MRSA was identified in 1961.
Since the mid-1980s, antibiotic action among nosocomial S. aureus isolates has been increasing appreciably.

In accession to methicillin, strains of S. aureus have developed opposition to other antibiotics.
MRSA is resistant to cephalosporins, erythromycin, clindamycin (Cleocin®), gentamycin, trimethoprim-sulfamethoxazole (Bactrim®), and ciprofloxacin (Cipro®).
Vancomycin, a glycopeptide antibiotic, was relied upon until recently to eradicate MRSA transmission.
As expected, strains of vancomycin-resistant S. aureus (VRSA) have been isolated and are fast becoming a new discussion objection (Hiramatsu, 2001).
This is a part of article Preventing Nosocomial Spread of MRSA is in Your Hands Taken from "Best Antibiotic: Cipro Ciprofloxacin" Information Blog

First-Time Ware Approvals: Cipro IV, Surmontil, Lamictal

Yael Waknine
September 6, 2006 — The US Food and Drug Governing body (FDA) has approved first-time product formulations for ciprofloxacin 200-mg/20-mL, 400-mg/40-mL, and 1200-mg/20-mL single-dose vials in the attention of certain infections, including photography to inhalational anthrax; trimipramine maleate 25-mg, 50-mg, and 100-mg capsules for the attention of depression; and lamotrigine 25-mg, 100-mg, 150-mg, and 200-mg tablets for the aid of seizures and bipolar status.

Product Ciprofloxacin Introduction (Cipro IV) for Inhalational Splenic fever and More

On August 28, the FDA approved 6 first-time vino formulations for ciprofloxacin 10-mg/mL introduction (brand name Cipro IV, made by Bayer AG).

The merchandise chemical will be available in 200-mg/20-mL and 400-mg/40-mL single-dose vials from Abraxis Pharmaceutical Products; Sicor Pharmaceuticals, Inc; Hospira, Inc; and Bedford Laboratories; 1200-mg/20-mL single-dose vials will also be manufactured by Bedford.

Ciprofloxacin intravenous extraction is indicated for the idiom of infections caused by susceptible microorganisms.
This is a part of article First-Time Generic Approvals: Cipro IV, Surmontil, Lamictal Taken from "Best Antibiotic: Cipro Ciprofloxacin" Information Blog