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Monday, June 25, 2012

Address

Bristol-Myers Squibb Company ,
345 Park Avenue

New York, New York, USA 10154-0037

Contact Details

Phone: (212) 546-4000
Website: http://www.bms.com/pages/default.aspx
Careers: http://www.bms.com/careers/Pages...

Sunday, June 24, 2012

Pancof-PD

Generic Name: chlorpheniramine, dihydrocodeine, and phenylephrine (klor feh NEER ah meen, dye hye droe KOE deen, feh nill EH frin)

Brand Names: Pancof-PD

What is Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Chlorpheniramine is an antihistamine. It blocks the effects of the naturally occurring chemical histamine in the body and reduces congestion.

Dihydrocodeine is a narcotic. It is a pain reliever and a cough suppressant.

Phenylephrine is a decongestant. It works by constricting (shrinking) blood vessels (veins and arteries) in the body. Constriction of blood vessels in the sinuses and nose decreases congestion.

Chlorpheniramine, dihydrocodeine, and phenylephrine is used to treat cough and nasal congestion associated with upper respiratory tract infections and allergies.

Chlorpheniramine, dihydrocodeine, and phenylephrine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Chlorpheniramine, dihydrocodeine, and phenylephrine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking chlorpheniramine, dihydrocodeine, and phenylephrine.

Chlorpheniramine, dihydrocodeine, and phenylephrine may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any other medicine without first talking to your doctor.

Dihydrocodeine is habit forming. It is possible become physically and/or psychologically dependent on the medication. Do not take more than the prescribed amount of medication or take it for longer than is directed by your doctor. Withdrawal effects may occur if chlorpheniramine, dihydrocodeine, and phenylephrine is stopped suddenly after several weeks of continuous use. Your doctor may recommend a gradual reduction in dose.

What should I discuss with my healthcare provider before taking Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Do not take chlorpheniramine, dihydrocodeine, and phenylephrine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Before taking chlorpheniramine, dihydrocodeine, and phenylephrine, tell your doctor if you have

epilepsy or another seizure disorder;

been diagnosed with sleep apnea (periods of not breathing during sleep);

thyroid problems;

asthma;

gallbladder disease;

a head injury;

Addison's disease;

diabetes;

glaucoma;

an ulcer or an obstruction in the stomach;

bladder problems or difficulty urinating;

an enlarged prostate;

high blood pressure, irregular heartbeats, or any type of heart disease;

kidney problems; or

liver problems.

You may not be able to take chlorpheniramine, dihydrocodeine, and phenylephrine, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Chlorpheniramine, dihydrocodeine, and phenylephrine is in the FDA pregnancy category C. This means that it is not known whether chlorpheniramine, dihydrocodeine, and phenylephrine will be harmful to an unborn baby. Do not take chlorpheniramine, dihydrocodeine, and phenylephrine without first talking to your doctor if you are pregnant or could become pregnant during treatment. It is not known whether chlorpheniramine, dihydrocodeine, and phenylephrine passes into breast milk. Do not take chlorpheniramine, dihydrocodeine, and phenylephrine without first talking to your doctor if you are breast-feeding a baby. If you are over 60 years of age, you may be more likely to experience side effects from chlorpheniramine, dihydrocodeine, and phenylephrine. Your doctor may prescribe a lower dose of this medication. The safety of chlorpheniramine, dihydrocodeine, and phenylephrine for children younger than 2 years of age has not been established.

How should I take Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Take chlorpheniramine, dihydrocodeine, and phenylephrine exactly as directed by your doctor. If you do not understand the directions on your prescription bottle, ask your pharmacist, nurse, or doctor to explain the instructions to you.

Chlorpheniramine, dihydrocodeine, and phenylephrine can be taken with or without food.

To ensure that you get a correct dose, measure the liquid form of chlorpheniramine, dihydrocodeine, and phenylephrine with a special dose-measuring spoon or cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Store chlorpheniramine, dihydrocodeine, and phenylephrine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose?

Seek emergency medical attention if an overdose is suspected.

Symptoms of a chlorpheniramine, dihydrocodeine, and phenylephrine overdose include severe drowsiness, dizziness, headache, seizures, dry mouth, cold and clammy skin, flushing, nausea, vomiting, difficulty or decreased breathing, and unconsciousness.

What should I avoid while taking Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine) side effects

If you experience any of the following serious side effects, stop taking chlorpheniramine, dihydrocodeine, and phenylephrine and seek emergency medical attention or contact your doctor immediately:

an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); or

confusion, hallucinations, or unusual behavior.

Other, less serious side effects may be more likely to occur. Continue to take chlorpheniramine, dihydrocodeine, and phenylephrine and talk to your doctor if you experience

dizziness, drowsiness, or sleepiness;

restlessness or irritability;

blurred vision;

constipation;

dry mouth, nausea, vomiting, or decreased appetite;

muscle twitches;

sweating;

itching;

decreased urination;

increased sensitivity to sunlight.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Pancof-PD (chlorpheniramine, dihydrocodeine, and phenylephrine)?

Chlorpheniramine, dihydrocodeine, and phenylephrine may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, sedatives (used to treat insomnia), pain relievers, anxiety medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any medicine unless your doctor approves.

Drugs other than those listed here may also interact with chlorpheniramine, dihydrocodeine, and phenylephrine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

More Pancof-PD resources

Pancof-PD Side Effects (in more detail)
Pancof-PD Use in Pregnancy & Breastfeeding
Pancof-PD Drug Interactions
Pancof-PD Support Group
0 Reviews for Pancof-PD - Add your own review/rating

Chlorpheniramine/Dihydrocodeine/Phenylephrine Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Duohist DH Prescribing Information (FDA)

Novahistine DH Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Tusscough DHC Prescribing Information (FDA)

Compare Pancof-PD with other medications

Cough and Nasal Congestion

Where can I get more information?

Your pharmacist has more information about chlorpheniramine, dihydrocodeine, and phenylephrine written for health professionals that you may read.

See also: Pancof-PD side effects (in more detail)

Saturday, June 23, 2012

Apexicon Cream

Pronunciation: dye-FLOR-a-sone die-ASS-eh-tate
Generic Name: Diflorasone Diacetate
Brand Name: Examples include Apexicon and Maxiflor

Apexicon Cream is used for:

Treating inflammation and itching due to certain skin conditions.

Apexicon Cream is a topical corticosteroid. It works by reducing skin inflammation (redness, swelling, itching, and irritation).

Do NOT use Apexicon Cream if:

you are allergic to any ingredient in Apexicon Cream

Contact your doctor or health care provider right away if any of these apply to you.

Before using Apexicon Cream:

Some medical conditions may interact with Apexicon Cream. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have an acne-like rash, measles, inflammation of the skin around the mouth, thinning skin, skin infection, or chickenpox

if you have tuberculosis or have had a positive tuberculin skin test, or if you have recently had a vaccination

Some MEDICINES MAY INTERACT with Apexicon Cream. Because little, if any, of Apexicon Cream is absorbed into the blood, the risk of it interacting with another medicine is low.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Apexicon Cream may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Apexicon Cream:

Use Apexicon Cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Apply a small amount of medicine to the affected area. Gently rub the medicine in until it is evenly distributed.

Wash your hands after applying Apexicon Cream unless your hands are part of the treated area.

Do not bandage or wrap the affected area unless directed otherwise by your doctor.

If you miss a dose of Apexicon Cream, apply it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Ask your health care provider any questions you may have about how to use Apexicon Cream.

Important safety information:

Apexicon Cream is for external use only. Avoid contact with the eyes.

Contact your health care provider if any side effects occur, especially under an occlusive dressing.

Do not use Apexicon Cream for longer than the time prescribed. Overuse of topical products may worsen your condition or increase your risk for side effects.

Do not use Apexicon Cream for other skin conditions at a later time.

If Apexicon Cream is prescribed to treat the diaper area, avoid using tight-fitting diapers or plastic pants.

Check with your doctor before having vaccinations while using Apexicon Cream.

Use Apexicon Cream with extreme caution in CHILDREN. Safety and effectiveness have not been confirmed.

In some instances, corticosteroid medicines may affect the growth rate in CHILDREN and adolescents. Your child's growth may need to be checked regularly while he or she is using Apexicon Cream.

PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, discuss with your doctor the benefits and risks of using Apexicon Cream during pregnancy. It is unknown if Apexicon Cream is excreted in breast milk. If you are or will be breast-feeding while you are using Apexicon Cream, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Apexicon Cream:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dryness; itching.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); acne-like rash; burning, cracking, irritation, itching, or peeling not present before you began using Apexicon Cream; excessive hair growth; inflamed hair follicles; inflammation around the mouth; muscle weakness; thinning, softening, or discoloration of the skin; unusual weight gain, especially in the face.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Apexicon side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Apexicon Cream:

Store Apexicon Cream at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Keep Apexicon Cream out of the reach of children and away from pets.

General information:

If you have any questions about Apexicon Cream, please talk with your doctor, pharmacist, or other health care provider.

Apexicon Cream is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Apexicon Cream. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Apexicon resources

Apexicon Side Effects (in more detail)
Apexicon Use in Pregnancy & Breastfeeding
Apexicon Drug Interactions
Apexicon Support Group
0 Reviews for Apexicon - Add your own review/rating

Compare Apexicon with other medications

Atopic Dermatitis
Eczema
Psoriasis
Skin Rash
Urticaria

Thursday, June 21, 2012

Uloric

Generic Name: febuxostat (fe BUX oh stat)

Brand Names: Uloric

What is febuxostat?

Febuxostat reduces the production of uric acid in your body. Uric acid buildup can lead to gout or kidney stones.

Febuxostat is used to treat gout.

Febuxostat may also be used for purposes not listed in this medication guide.

What is the most important information I should know about febuxostat?

You should not use this medication if you are allergic to febuxostat, or if you are also being treated with azathioprine (Azasan, Imuran), mercaptopurine (Purinethol), or theophylline (Elixophyllin, TheoCap, Theochron, Uniphyl).

Before taking febuxostat, tell your doctor if you have kidney disease, liver disease, heart disease, cancer, Lesch-Nyhan syndrome, a history of heart attack or stroke, or if you have ever received an organ transplant.

You may have an increase in gout symptom flares when you first start taking febuxostat. For best results, keep taking the medication as directed. Your doctor may prescribe other gout medications for you to use during the first 6 months of treatment with febuxostat.

To be sure this medication is helping your condition, your blood may need to be tested often. Visit your doctor regularly.

What should I discuss with my healthcare provider before taking febuxostat?

You should not use this medication if you are allergic to febuxostat, or if you are being treated with any of the following medications:

azathioprine (Azasan, Imuran); or

mercaptopurine (Purinethol).

To make sure you can safely take febuxostat, tell your doctor if you have any of these other conditions:

kidney disease;

liver disease;

heart disease;

a history of heart attack or stroke;

cancer;

Lesch-Nyhan syndrome; or

if you have ever received an organ transplant (kidney, liver, lung, heart).

FDA pregnancy category C. It is not known whether febuxostat will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether febuxostat passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take febuxostat?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

To be sure this medication is helping your condition, your blood may need to be tested often. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

See also: Uloric dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking febuxostat?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Febuxostat side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

sudden numbness or weakness, especially on one side of the body;

sudden headache, confusion, problems with vision, speech, or balance; or

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

nausea;

joint pain, swelling, or stiffness;

mild skin rash; or

dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect febuxostat?

Tell your doctor about all other medicines you use, especially theophylline (Elixophyllin, TheoCap, Theochron, Uniphyl).

There may be other drugs that can interact with febuxostat. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Uloric resources

Uloric Side Effects (in more detail)
Uloric Dosage
Uloric Use in Pregnancy & Breastfeeding
Uloric Drug Interactions
Uloric Support Group
6 Reviews for Uloric - Add your own review/rating

Uloric Prescribing Information (FDA)

Uloric Monograph (AHFS DI)

Uloric Advanced Consumer (Micromedex) - Includes Dosage Information

Uloric Consumer Overview

Uloric MedFacts Consumer Leaflet (Wolters Kluwer)

Febuxostat Professional Patient Advice (Wolters Kluwer)

Compare Uloric with other medications

Gout

Where can I get more information?

Your pharmacist can provide more information about febuxostat.

See also: Uloric side effects (in more detail)

Wednesday, June 20, 2012

Maxaquin

lomefloxacin hydrochloride

Dosage Form: Tablets

Maxaquin Description

Maxaquin (lomefloxacin HCl) is a synthetic broad-spectrum antimicrobial agent for oral administration. Lomefloxacin HCl, a difluoroquinolone, is the monohydrochloride salt of (±)-1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid. Its empirical formula is C17H19F2N3O3•HCl, and its structural formula is:

Lomefloxacin HCl is a white to pale yellow powder with a molecular weight of 387.8. It is slightly soluble in water and practically insoluble in alcohol. Lomefloxacin HCl is stable to heat and moisture but is sensitive to light in dilute aqueous solution.

Maxaquin is available as a film-coated tablet formulation containing 400 mg of lomefloxacin base, present as the hydrochloride salt. The base content of the hydrochloride salt is 90.6%. The inactive ingredients are carboxymethylcellulose calcium, hydroxypropyl cellulose, hypromellose, lactose, magnesium stearate, polyethylene glycol, polyoxyl 40 stearate, and titanium dioxide.

Maxaquin - Clinical Pharmacology

Pharmacokinetics in healthy volunteers

In 6 fasting healthy male volunteers, approximately 95% to 98% of a single oral dose of lomefloxacin was absorbed. Absorption was rapid following single doses of 200 and 400 mg (Tmax 0.8 to 1.4 hours). Mean plasma concentration increased proportionally between 100 and 400 mg as shown below:

Dose (mg)	Mean Peak Plasma Concentration (µg/mL)	Area Under Curve (AUC) (µg∙h/mL)
100	0.8	5.6
200	1.4	10.9
400	3.2	26.1

In 6 healthy male volunteers administered 400 mg of lomefloxacin on an empty stomach qd for 7 days, the following mean pharmacokinetic parameter values were obtained:


Cmax	2.8 µg/mL
Cmin	0.27 µg/mL
AUC0–24 h	25.9 µg∙h/mL
Tmax	1.5 h
t1/2	7.75 h

The elimination half-life in 8 subjects with normal renal function was approximately 8 hours. At 24 hours postdose, subjects with normal renal function receiving single doses of 200 or 400 mg had mean plasma lomefloxacin concentrations of 0.10 and 0.24 µg/mL, respectively. Steady-state concentrations were achieved within 48 hours of initiating therapy with one-a-day dosing. There was no drug accumulation with single-daily dosing in patients with normal renal function.

Approximately 65% of an orally administered dose was excreted in the urine as unchanged drug in patients with normal renal function. Following a 400-mg dose of lomefloxacin administered qd for 7 days, the mean urine concentration 4 hours postdose was in excess of 300 µg/mL. The mean urine concentration exceeded 35 µg/mL for at least 24 hours after dosing.

Following a single 400-mg dose, the solubility of lomefloxacin in urine usually exceeded its peak urinary concentration 2- to 6-fold. In this study, urine pH affected the solubility of lomefloxacin with solubilities ranging from 7.8 mg/mL at pH 5.2, to 2.4 mg/mL at pH 6.5, and 3.03 mg/mL at pH 8.12.

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. The mean renal clearance was 145 mL/min in subjects with normal renal function (GFR = 120 mL/min). This may indicate tubular secretion.

Food effect

When lomefloxacin and food were administered concomitantly, the rate of drug absorption was delayed (Tmax increased to 2 hours [delayed by 41%], Cmax decreased by 18%), and the extent of absorption (AUC) was decreased by 12%.

Pharmacokinetics in the geriatric population

In 16 healthy elderly volunteers (61 to 76 years of age) with normal renal function for their age, the half-life of lomefloxacin (mean of 8 hours) and its peak plasma concentration (mean of 4.2 µg/mL) following a single 400-mg dose were similar to those in 8 younger subjects dosed with a single 400-mg dose. Thus, drug absorption appears unaffected in the elderly. Plasma clearance was, however, reduced in this elderly population by approximately 25%, and the AUC was increased by approximately 33%. This slower elimination most likely reflects the decreased renal function normally observed in the geriatric population.

Pharmacokinetics in renally impaired patients

In 8 patients with creatinine clearance (ClCr) between 10 and 40 mL/min/1.73 m2, the mean AUC after a single 400-mg dose of lomefloxacin increased 335% over the AUC demonstrated in patients with a ClCr> 80 mL/min/1.73 m2. Also, in these patients, the mean t1/2 increased to 21 hours. In 8 patients with ClCr< 10 mL/min/1.73 m2, the mean AUC after a single 400-mg dose of lomefloxacin increased 700% over the AUC demonstrated in patients with a ClCr> 80 mL/min/1.73 m2. In these patients with ClCr< 10 mL/min/1.73 m2, the mean t1/2 increased to 45 hours. The plasma clearance of lomefloxacin was closely correlated with creatinine clearance, ranging from 31 mL/min/1.73 m2 when creatinine clearance was zero to 271 mL/min/1.73 m2 at a normal creatinine clearance of 110 mL/min/1.73 m2. Peak lomefloxacin concentrations were not affected by the degree of renal function when single doses of lomefloxacin were administered. Adjustment of dosage schedules for patients with such decreases in renal function is warranted. (See Dosage and Administration.)

Pharmacokinetics in patients with cirrhosis

In 12 patients with histologically confirmed cirrhosis, no significant changes in rate or extent of lomefloxacin exposure (Cmax, Tmax, t1/2, or AUC) were observed when they were administered 400 mg of lomefloxacin as a single dose. No data are available in cirrhotic patients treated with multiple doses of lomefloxacin. Cirrhosis does not appear to reduce the nonrenal clearance of lomefloxacin. There does not appear to be a need for a dosage reduction in cirrhotic patients, provided adequate renal function is present.

Metabolism and pharmacodynamics of lomefloxacin

Lomefloxacin is minimally metabolized although 5 metabolites have been identified in human urine. The glucuronide metabolite is found in the highest concentration and accounts for approximately 9% of the administered dose. The other 4 metabolites together account for < 0.5% of the dose.

Approximately 10% of an oral dose was recovered as unchanged drug in the feces.

Serum protein binding of lomefloxacin is approximately 10%.

The following are mean tissue- or fluid-to-plasma ratios of lomefloxacin following oral administration. Studies have not been conducted to assess the penetration of lomefloxacin into human cerebrospinal fluid.

Tissue or Body Fluid	Mean Tissue- or Fluid-to-Plasma Ratio
Bronchial mucosa	2.1
Bronchial secretions	0.6
Prostatic tissue	2.0
Sputum	1.3
Urine	140.0

In two studies including 74 healthy volunteers, the minimal dose of UVA light needed to cause erythema (MED-UVA) was inversely proportional to plasma lomefloxacin concentration. The MED-UVA values (16 hours and 12 hours postdose) were significantly higher than the MED-UVA values 2 hours postdose at steady state. Increasing the interval between lomefloxacin dosing and exposure to UVA light increased the amount of light energy needed for photoreaction. In a study of 27 healthy volunteers, the steady state AUC values and Cmin values were equivalent whether the drug was administered in the morning or in the evening.

Microbiology

Lomefloxacin is a bactericidal agent with in vitro 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 enzyme DNA gyrase, which is needed for the transcription and replication of bacterial DNA. The minimum bactericidal concentration (MBC) generally does not exceed the minimum inhibitory concentration (MIC) by more than a factor of 2, except for staphylococci, which usually have MBCs 2 to 4 times the MIC.

Lomefloxacin has been shown to be active against most strains of the following organisms both in vitro and in clinical infections: (See Indications and Usage.)

Gram-positive aerobes

: Staphylococcus saprophyticus

Gram-negative aerobes

: Citrobacter diversus
: Enterobacter cloacae
: Escherichia coli
: Haemophilus influenzae
: Klebsiella pneumoniae
: Moraxella catarrhalis
: Proteus mirabilis
: Pseudomonas aeruginosa (urinary tract only—See Indications and Usage and Warnings)

The following in vitro data are available; however, their clinical significance is unknown.

Lomefloxacin exhibits in vitro MICs of 2 µg/mL or less against most strains of the following organisms; however, the safety and effectiveness of lomefloxacin in treating clinical infections due to these organisms have not been established in adequate and well-controlled trials:

Gram-positive aerobes

: Staphylococcus aureus (including methicillin-resistant strains)
: Staphylococcus epidermidis (including methicillin-resistant strains)

Gram-negative aerobes

: Aeromonas hydrophila
: Citrobacter freundii
: Enterobacter aerogenes
: Enterobacter agglomerans
: Haemophilus parainfluenzae
: Hafnia alvei
: Klebsiella oxytoca
: Klebsiella ozaenae
: Morganella morganii
: Proteus vulgaris
: Providencia alcalifaciens
: Providencia rettgeri
: Serratia liquefaciens
: Serratia marcescens

Other organisms

: Legionella pneumophila

Beta-lactamase production should have no effect on the in vitro activity of lomefloxacin.

Most group A, B, D, and G streptococci, Streptococcus pneumoniae, Pseudomonas cepacia, Ureaplasma urealyticum, Mycoplasma hominis, and anaerobic bacteria are resistant to lomefloxacin.

Lomefloxacin appears slightly less active in vitro when tested at acidic pH. An increase in inoculum size has little effect on the in vitro activity of lomefloxacin. In vitro resistance to lomefloxacin develops slowly (multiple-step mutation). Rapid one-step development of resistance occurs only rarely (< 10–9) in vitro.

Cross-resistance between lomefloxacin and other quinolone-class antimicrobial agents has been reported; however, cross-resistance between lomefloxacin and members of other classes of antimicrobial agents, such as aminoglycosides, penicillins, tetracyclines, cephalosporins, or sulfonamides has not yet been reported. Lomefloxacin is active in vitro against some strains of cephalosporin- and aminoglycoside-resistant gram-negative bacteria.

Susceptibility tests

Diffusion techniques

Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents. One such standardized procedure1 that has been recommended for use with disks to test the susceptibility of organisms to lomefloxacin uses the 10-µg lomefloxacin disk. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for lomefloxacin.

Reports from the laboratory giving results of the standard single-disk susceptibility test with a 10-µg lomefloxacin disk should be interpreted according to the following criteria:

Zone Diameter (mm)	Interpretation
≥ 22	Susceptible (S)
19–21	Intermediate (I)
≤ 18	Resistant (R)

A report of "susceptible" indicates that the pathogen is likely to be inhibited by generally achievable drug concentrations. A report of "intermediate" indicates that the result should be considered equivocal, and, if the organism is not fully susceptible to alternative clinically feasible drugs, the test should be repeated. This category provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that achievable drug concentrations are unlikely to be inhibitory, and other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control organisms. The 10-µg lomefloxacin disk should give the following zone diameters:

Organism	Zone Diameter (mm)
S aureus (ATCC 25923)	23–29
E coli (ATCC 25922)	27–33
P aeruginosa (ATCC 27853)	22–28

Dilution techniques

Use a standardized dilution method2 (broth, agar, or microdilution) or equivalent with lomefloxacin powder. The MIC values obtained should be interpreted according to the following criteria:

MIC (µg/mL)	Interpretation
≤ 2	Susceptible (S)
4	Intermediate (I)
≥ 8	Resistant (R)

As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard lomefloxacin powder should provide the following MIC values:

Organism	MIC (µg/mL)
S aureus (ATCC 29213)	0.25–2.0
E coli (ATCC 25922)	0.03–0.12
P aeruginosa (ATCC 27853)	1.0–4.0

Indications and Usage for Maxaquin

Treatment

Maxaquin (lomefloxacin HCl) film-coated tablets are indicated for the treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below: (See Dosage and Administration for specific dosing recommendations.)

LOWER RESPIRATORY TRACT

Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae or Moraxella catarrhalis.1

NOTE: Maxaquin IS NOT INDICATED FOR THE EMPIRIC TREATMENT OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS WHEN IT IS PROBABLE THAT S PNEUMONIAE IS A CAUSATIVE PATHOGEN. S PNEUMONIAE EXHIBITS IN VITRO RESISTANCE TO LOMEFLOXACIN, AND THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN THE TREATMENT OF PATIENTS WITH ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS CAUSED BY S PNEUMONIAE HAVE NOT BEEN DEMONSTRATED. IF LOMEFLOXACIN IS TO BE PRESCRIBED FOR GRAM–STAIN–GUIDED EMPIRIC THERAPY OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS, IT SHOULD BE USED ONLY IF SPUTUM GRAM STAIN DEMONSTRATES AN ADEQUATE QUALITY OF SPECIMEN (> 25 PMNs/LPF) AND THERE IS BOTH A PREDOMINANCE OF GRAM-NEGATIVE MICROORGANISMS AND NOT A PREDOMINANCE OF GRAM-POSITIVE MICROORGANISMS.

1: Although treatment of infections due to this microorganism in this organ system demonstrated a clinically acceptable overall outcome, efficacy was studied in fewer than 10 infections.

URINARY TRACT

Uncomplicated Urinary Tract Infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES—UNCOMPLICATED CYSTITIS.)

Complicated Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus,1 or Enterobacter cloacae.1

NOTE: In clinical trials with patients experiencing complicated urinary tract infections (UTIs) due to P aeruginosa, 12 of 16 patients had the microorganism eradicated from the urine after therapy with lomefloxacin. None of the patients had concomitant bacteremia. Serum levels of lomefloxacin do not reliably exceed the MIC of Pseudomonas isolates. THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN TREATING PATIENTS WITH PSEUDOMONAS BACTEREMIA HAVE NOT BEEN ESTABLISHED.

Appropriate culture and susceptibility tests should be performed before antimicrobial treatment in order to isolate and identify microorganisms causing infection and to determine their susceptibility to lomefloxacin. In patients with UTIs, therapy with Maxaquin film-coated tablets may be initiated before results of these tests are known; once these results become available, appropriate therapy should be continued. In patients with an acute bacterial exacerbation of chronic bronchitis, therapy should not be started empirically with lomefloxacin when there is a probability the causative pathogen is S pneumoniae.

Beta-lactamase production should have no effect on lomefloxacin activity.

Prevention / prophylaxis

Maxaquin is indicated preoperatively for the prevention of infection in the following situations:

Transrectal prostate biopsy: to reduce the incidence of urinary tract infection, in the early and late postoperative periods (3–5 days and 3–4 weeks postsurgery).

Transurethral surgical procedures: to reduce the incidence of urinary tract infection in the early postoperative period (3–5 days postsurgery).

Efficacy in decreasing the incidence of infections other than urinary tract infection has not been established. Maxaquin, like all drugs for prophylaxis of transurethral surgical procedures, usually should not be used in minor urologic procedures for which prophylaxis is not indicated (eg, simple cystoscopy or retrograde pyelography). (See Dosage and Administration.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Maxaquin and other antibacterial drugs, Maxaquin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Contraindications

Maxaquin (lomefloxacin HCl) is contraindicated in persons with a history of hypersensitivity to lomefloxacin or any member of the quinolone group of antimicrobial agents.

Warnings

MODERATE TO SEVERE PHOTOTOXIC REACTIONS HAVE OCCURRED IN PATIENTS EXPOSED TO DIRECT OR INDIRECT SUNLIGHT OR TO ARTIFICIAL ULTRAVIOLET LIGHT (eg, sunlamps) DURING OR FOLLOWING TREATMENT WITH LOMEFLOXACIN. THESE REACTIONS HAVE ALSO OCCURRED IN PATIENTS EXPOSED TO SHADED OR DIFFUSE LIGHT, INCLUDING EXPOSURE THROUGH GLASS. PATIENTS SHOULD BE ADVISED TO DISCONTINUE LOMEFLOXACIN THERAPY AT THE FIRST SIGNS OR SYMPTOMS OF A PHOTOTOXICITY REACTION SUCH AS A SENSATION OF SKIN BURNING, REDNESS, SWELLING, BLISTERS, RASH, ITCHING, OR DERMATITIS.

These phototoxic reactions have occurred with and without the use of sunscreens or sunblocks. Single doses of lomefloxacin have been associated with these types of reactions. In a few cases, recovery was prolonged for several weeks. As with some other types of phototoxicity, there is the potential for exacerbation of the reaction on re-exposure to sunlight or artificial ultraviolet light prior to complete recovery from the reaction. In rare cases, reactions have recurred up to several weeks after stopping lomefloxacin therapy.

EXPOSURE TO DIRECT OR INDIRECT SUNLIGHT (EVEN WHEN USING SUNSCREENS OR SUNBLOCKS) SHOULD BE AVOIDED WHILE TAKING LOMEFLOXACIN AND FOR SEVERAL DAYS FOLLOWING THERAPY. LOMEFLOXACIN THERAPY SHOULD BE DISCONTINUED IMMEDIATELY AT THE FIRST SIGNS OR SYMPTOMS OF PHOTOTOXICITY. RISK OF PHOTOTOXICITY MAY BE REDUCED BY TAKING LOMEFLOXACIN IN THE EVENING (See Dosage and Administration.)

THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN PEDIATRIC PATIENTS AND ADOLESCENTS (UNDER THE AGE OF 18 YEARS), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. (See PRECAUTIONS—Pediatric Use, Pregnancy and Nursing Mothers subsections.) The oral administration of multiple doses of lomefloxacin to juvenile dogs at 0.3 times and to rats at 5.4 times the recommended adult human dose based on mg/m2 (0.6 and 34 times the recommended adult human dose based on mg/kg, respectively) caused arthropathy and lameness. Histopathologic examination of the weight-bearing joints of these animals revealed permanent lesions of the cartilage. Other quinolones also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in juvenile animals of various species. (See Animal Pharmacology.)

Convulsions have been reported in patients receiving lomefloxacin. Whether the convulsions were directly related to lomefloxacin administration has not yet been established. However, convulsions, increased intracranial pressure, and toxic psychoses have been reported in patients receiving other quinolones. Nevertheless, lomefloxacin has been associated with a possible increased risk of seizures compared to other quinolones. Some of these may occur with a relative absence of predisposing factors. Quinolones may also cause central nervous system (CNS) stimulation, which may lead to tremors, restlessness, lightheadedness, confusion, and hallucinations. If any of these reactions occurs in patients receiving lomefloxacin, the drug should be discontinued and appropriate measures instituted. However, until more information becomes available, lomefloxacin, like all other quinolones, should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, or other factors that predispose to seizures. (See Adverse Reactions.) Psychiatric disturbances, agitation, anxiety, and sleep disorders may be more common with lomefloxacin than other products in the quinolone class.

The safety and efficacy of lomefloxacin in the treatment of acute bacterial exacerbation of chronic bronchitis due to S pneumoniae have not been demonstrated. This product should not be used empirically in the treatment of acute bacterial exacerbation of chronic bronchitis when it is probable that S pneumoniae is a causative pathogen.

In clinical trials of complicated UTIs due to P aeruginosa, 12 of 16 patients had the microorganism eradicated from the urine after therapy with lomefloxacin. No patients had concomitant bacteremia. Serum levels of lomefloxacin do not reliably exceed the MIC of Pseudomonas isolates. THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN TREATING PATIENTS WITH PSEUDOMONAS BACTEREMIA HAVE NOT BEEN ESTABLISHED.

Serious and occasionally fatal hypersensitivity (anaphylactoid or anaphylactic) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, or itching. Only a few of these patients had a history of previous hypersensitivity reactions. Serious hypersensitivity reactions have also been reported following treatment with lomefloxacin. If an allergic reaction to lomefloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment with epinephrine. Oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, including intubation, should be administered as indicated.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including lomefloxacin, and may range from mild to life-threatening in severity. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antimicrobial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C difficile colitis.

QT interval prolongation/torsades de pointes

Rare cases of torsades de pointes have been spontaneously reported during post-marketing surveillance in patients receiving quinolones, including lomefloxacin. These rare cases were associated with one or more of the following factors: age over 60, female gender, underlying cardiac disease, and/or use of multiple medications. Lomefloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving class IA (quinidine, procainamide), or class III (amiodarone, sotalol) antiarrhythmic agents.

Peripheral neuropathy

Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including lomefloxacin. Lomefloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

Tendon effects

Ruptures of the shoulder, hand, Achilles tendon or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including lomefloxacin. Postmarketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. Lomefloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been excluded. Tendon rupture can occur during or after therapy with quinolones, including lomefloxacin.

Precautions

General

Alteration of the dosage regimen is recommended for patients with impairment of renal function (ClCr< 40 mL/min/1.73 m2). (See Dosage and Administration.)

Prescribing Maxaquin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for patients

Patients should be advised

to avoid to the maximum extent possible direct or indirect sunlight (including exposure through glass and exposure through sunscreens and sunblocks) and artificial ultraviolet light (eg sunlamps) during treatment with lomefloxacin and for several days after therapy;

that they may reduce the risk of developing phototoxicity from sunlight by taking the daily dose of lomefloxacin at least 12 hours before exposure to the sun (eg in the evening);

to discontinue lomefloxacin therapy at the first signs or symptoms of phototoxicity reaction such as a sensation of skin burning, redness, swelling, blisters, rash, itching, or dermatitis;

that a patient who has experienced a phototoxic reaction should avoid re-exposure to sunlight and artificial ultraviolet light until he has completely recovered from the reaction. In rare cases, reactions have recurred up to several weeks after stopping lomefloxacin therapy.

to drink fluids liberally;

that lomefloxacin can be taken without regard to meals;

that mineral supplements or vitamins with iron or minerals should not be taken within the 2-hour period before or after taking lomefloxacin (see Drug Interactions);

that sucralfate and antacids containing magnesium or aluminum, or Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 4 hours before or 2 hours after taking lomefloxacin. (See PRECAUTIONS — Drug Interactions.)

that lomefloxacin can cause dizziness and lightheadedness and, therefore, patients should know how they react to lomefloxacin before they operate an automobile or machinery or engage in activities requiring mental alertness and coordination;

to discontinue treatment and inform their physician if they experience pain, inflammation, or rupture of a tendon, and to rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been confidently excluded;

that lomefloxacin may be associated with hypersensitivity reactions, even following the first dose, and to discontinue the drug at the first sign of a skin rash or other allergic reaction;

that convulsions have been reported in patients taking quinolones, including lomefloxacin, and to notify their physician before taking this drug if there is a history of this condition.

that antibacterial drugs including Maxaquin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Maxaquin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Maxaquin or other antibacterial drugs in the future.

Drug interactions

Theophylline

In three pharmacokinetic studies including 46 normal, healthy subjects, theophylline clearance and concentration were not significantly altered by the addition of lomefloxacin. In clinical studies where patients were on chronic theophylline therapy, lomefloxacin had no measurable effect on the mean distribution of theophylline concentrations or the mean estimates of theophylline clearance. Though individual theophylline levels fluctuated, there were no clinically significant symptoms of drug interaction.

Antacids and sucralfate

Sucralfate and antacids containing magnesium or aluminum, as well as formulations containing divalent and trivalent cations such as Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution can form chelation complexes with lomefloxacin and interfere with its bioavailability. Sucralfate administered 2 hours before lomefloxacin resulted in a slower absorption (mean Cmax decreased by 30% and mean Tmax increased by 1 hour) and a lesser extent of absorption (mean AUC decreased by approximately 25%). Magnesium- and aluminum-containing antacids, administered concomitantly with lomefloxacin, significantly decreased the bioavailability (48%) of lomefloxacin. Separating the doses of antacid and lomefloxacin minimizes this decrease in bioavailability; therefore, administration of these agents should precede lomefloxacin dosing by 4 hours or follow lomefloxacin dosing by at least 2 hours.

Caffeine

Two hundred mg of caffeine (equivalent to 1 to 3 cups of American coffee) was administered to 16 normal, healthy volunteers who had achieved steady-state blood concentrations of lomefloxacin after being dosed at 400 mg qd. This did not result in any statistically or clinically relevant changes in the pharmacokinetic parameters of either caffeine or its major metabolite, paraxanthine. No data are available on potential interactions in individuals who consume greater than 200 mg of caffeine per day or in those, such as the geriatric population, who are generally believed to be more susceptible to the development of drug-induced CNS-related adverse effects. Other quinolones have demonstrated moderate to marked interference with the metabolism of caffeine, resulting in a reduced clearance, a prolongation of plasma half-life, and an increase in symptoms that accompany high levels of caffeine.

Cimetidine

Cimetidine has been demonstrated to interfere with the elimination of other quinolones. This interference has resulted in significant increases in half-life and AUC. The interaction between lomefloxacin and cimetidine has not been studied.

Cyclosporine

Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with other members of the quinolone class. Interaction between lomefloxacin and cyclosporine has not been studied.

Omeprazole

No clinically significant changes in lomefloxacin pharmacokinetics (AUC, Cmax, or Tmax) were observed when a single dose of lomefloxacin 400 mg was given after multiple doses of omeprazole (20 mg qd) in 13 healthy volunteers. Changes in omeprazole pharmacokinetics were not studied.

Phenytoin

No significant differences were observed in mean phenytoin AUC, Cmax, Cmin or Tmax (although Cmax increased by 11%) when extended phenytoin sodium capsules (100 mg tid) were coadministered with lomefloxacin (400 mg qd) for five days in 15 healthy males. Lomefloxacin is unlikely to have a significant effect on phenytoin metabolism.

Probenecid

Probenecid slows the renal elimination of lomefloxacin. An increase of 63% in the mean AUC and increases of 50% and 4%, respectively, in the mean Tmax and mean Cmax were noted in 1 study of 6 individuals.

Terfenadine

No clinically significant changes occurred in heart rate or corrected QT intervals, or in terfenadine metabolite or lomefloxacin pharmacokinetics, during concurrent administration of lomefloxacin and terfenadine at steady-state in 28 healthy males.

Warfarin

Quinolones may enhance the effects of the oral anticoagulant, warfarin, or its derivatives. When these products are administered concomitantly, prothrombin or other suitable coagulation tests should be monitored closely. However, no clinically or statistically significant differences in prothrombin time ratio or warfarin enantiomer pharmacokinetics were observed in a small study of 7 healthy males who received both warfarin and lomefloxacin under steady-state conditions.

Carcinogenesis, mutagenesis, impairment of fertility

Carcinogenesis

Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours five times every two weeks for up to 52 weeks while concurrently being administered lomefloxacin. The lomefloxacin doses used in this study caused a phototoxic response. In mice treated with both UVA and lomefloxacin concomitantly, the time to development of skin tumors was 16 weeks. In mice treated concomitantly in this model with both UVA and other quinolones, the times to development of skin tumors ranged from 28 to 52 weeks.

Ninety-two percent (92%) of the mice treated concomitantly with both UVA and lomefloxacin developed well-differentiated squamous cell carcinomas of the skin. These squamous cell carcinomas were nonmetastatic and were endophytic in character. Two-thirds of these squamous cell carcinomas contained large central keratinous inclusion masses and were thought to arise from the vestigial hair follicles in these hairless animals.

In this model, mice treated with lomefloxacin alone did not develop skin or systemic tumors.

There are no data from similar models using pigmented mice and/or fully haired mice

The clinical significance of these findings to humans is unknown.

Mutagenesis

One in vitro mutagenicity test (CHO/HGPRT assay) was weakly positive at lomefloxacin concentrations ≥ 226 µg/mL and negative at concentrations < 226 µg/mL. Two other in vitro mutagenicity tests (chromosomal aberrations in Chinese hamster ovary cells, chromosomal aberrations in human lymphocytes) and two in vivo mouse micronucleus mutagenicity tests were all negative.

Impairment of fertility

Lomefloxacin did not affect the fertility of male and female rats at oral doses up to 8 times the recommended human dose based on mg/m2 (34 times the recommended human dose based on mg/kg).

Pregnancy

Teratogenic effects. 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.

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. (See Warnings and Animal Pharmacology.)

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.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See Clinical Pharmacology — Pharmacokinetics in the geriatric population.)

Adverse Reactions

In clinical trials, most of the adverse events reported were mild to moderate in severity and transient in nature. During these clinical investigations, 5,623 patients received Maxaquin. In 2.2% of the patients, lomefloxacin was discontinued because of adverse events, primarily involving the gastrointestinal system (0.7%), skin (0.7%), or CNS (0.5%).

Adverse clinical events

The events with the highest incidence (≥ 1%) in patients, regardless of relationship to drug, were headache (3.6%), nausea (3.5%), photosensitivity (2.3%) [see Warnings], dizziness (2.1%), diarrhea (1.4%), and abdominal pain (1.2%).

Additional clinical events reported in < 1% of patients treated with Maxaquin, regardless of relationship to drug, are listed below:

Autonomic: increased sweating, dry mouth, flushing, syncope.

Body as a whole: fatigue, back pain, malaise, asthenia, chest pain, face edema, hot flashes, influenza-like symptoms, edema, chills, allergic reaction, anaphylactoid reaction, decreased heat tolerance.

Cardiovascular: tachycardia, hypertension, hypotension, myocardial infarction, angina pectoris, cardiac failure, bradycardia, arrhythmia, phlebitis, pulmonary embolism, extrasystoles, cerebrovascular disorder, cyanosis, cardiomyopathy.

Central and peripheral nervous system: tremor, vertigo, paresthesias, twitching, hypertonia, convulsions, hyperkinesia, coma.

Gastrointestinal: dyspepsia, vomiting, flatulence, constipation, gastrointestinal bleeding, dysphagia, stomatitis, tongue discoloration, gastrointestinal inflammation.

Hearing: earache, tinnitus.

Hematologic: purpura, lymphadenopathy, thrombocythemia, anemia, thrombocytopenia, increased fibrinolysis.

Hepatic: abnormal liver function.

Metabolic: thirst, hyperglycemia, hypoglycemia, gout.

Musculoskeletal: arthralgia, myalgia, leg cramps.

Ophthalmologic: abnormal vision, conjunctivitis, photophobia, eye pain, abnormal lacrimation.

Psychiatric: insomnia, nervousness, somnolence, anorexia, depression, confusion, agitation, increased appetite, depersonalization, paranoid reaction, anxiety, paroniria, abnormal thinking, concentration impairment.

Reproductive system: Female: vaginal moniliasis, vaginitis, leukorrhea, menstrual disorder, perineal pain, intermenstrual bleeding. Male: epididymitis, orchitis.

Resistance mechanism: viral infection, moniliasis, fungal infection.

Respiratory: respiratory infection, rhinitis, pharyngitis, dyspnea, cough, epistaxis, bronchospasm, respiratory disorder, increased sputum, stridor, respiratory depression.

Skin/Allergic: pruritus, rash, urticaria, skin exfoliation, bullous eruption, eczema, skin disorder, acne, skin discoloration, skin ulceration, angioedema. (See also Body as a whole.)

Special senses: taste perversion.

Urinary: hematuria, micturition disorder, dysuria, strangury, anuria.

Adverse laboratory events

Changes in laboratory parameters, listed as adverse events, without regard to drug relationship include:

Hematologic: monocytosis (0.2%), eosinophilia (0.1%), leukopenia (0.1%), leukocytosis (0.1%).

Renal: elevated BUN (0.1%), decreased potassium (0.1%), increased creatinine (0.1%).

Hepatic: elevations of ALT (SGPT) (0.4%), AST (SGOT) (0.3%), bilirubin (0.1%), alkaline phosphatase (0.1%).

Additional laboratory changes occurring in < 0.1% in the clinical studies included: elevation of serum gamma glutamyl transferase, decrease in total protein or albumin, prolongation of prothrombin time, anemia, decrease in hemoglobin, thrombocythemia, thrombocytopenia, abnormalities of urine specific gravity or serum electrolytes, increased albumin, elevated ESR, albuminuria, macrocytosis.

Post-Marketing Adverse Events

Post-marketing adverse events

Adverse events reported from worldwide marketing experience with lomefloxacin are: anaphylaxis, cardiopulmonary arrest, laryngeal or pulmonary edema, ataxia, cerebral thrombosis, hallucinations, painful oral mucosa, pseudomembranous colitis, hemolytic anemia, hepatitis, tendinitis, diplopia, photophobia, phobia, exfoliative dermatitis, hyperpigmentation, Stevens-Johnson syndrome, toxic epidermal necrolysis, dysgeusia, interstitial nephritis, polyuria, renal failure, urinary retention, and vasculitis.

Quinolone-class adverse events

Additional quinolone-class adverse events include: peripheral neuropathy, torsades de pointes, erythema nodosum, hepatic necrosis, possible exacerbation of myasthenia gravis, dysphasia, nystagmus, intestinal perforation, manic

Friday, June 15, 2012

Lactation Augmentation Medications

Drugs associated with Lactation Augmentation

The following drugs and medications are in some way related to, or used in the treatment of Lactation Augmentation. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List:

Reglan

Bronchospasm Prophylaxis Medications

Drugs associated with Bronchospasm Prophylaxis

The following drugs and medications are in some way related to, or used in the treatment of Bronchospasm Prophylaxis. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.