Genteal Mild

Generic Name: hypromellose (Ophthalmic route)

hye-PROE-me-lose

Commonly used brand name(s)

In the U.S.

• Genteal


• Genteal Mild


• Gonak


• Goniosoft


• Goniovisc


• Isopto Tears


• Nature's Tears


• Tearisol


• Tears Again Mc

Available Dosage Forms:

• Solution


• Gel/Jelly

Therapeutic Class: Surgical Aid, Ocular

Uses For Genteal Mild

Hydroxypropyl methylcellulose belongs to the group of medicines known as artificial tears. It is used to relieve dryness and irritation caused by reduced tear flow. It helps prevent damage to the eye in certain eye diseases. Hydroxypropyl methylcellulose may also be used to moisten hard contact lenses and artificial eyes. In addition, it may be used in certain eye examinations.

Some of these preparations are available only with your doctor's prescription.

Before Using Genteal Mild

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of hydroxypropyl methylcellulose in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicine have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of hydroxypropyl methylcellulose in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of hypromellose

This section provides information on the proper use of a number of products that contain hypromellose. It may not be specific to Genteal Mild. Please read with care.

To use:

• First, wash your hands. Then tilt the head back and pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close the eyes. Do not blink. Keep the eyes closed for 1 or 2 minutes to allow the medicine to be absorbed.


• To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). Also, keep the container tightly closed.

For patients wearing hard contact lenses:

• Take care not to float the lens from your eye when applying this medicine. If you have any questions about this, check with your health care professional.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For dry eyes:
  
  • For ophthalmic solution (eye drops) dosage form:
    
    • Adults and children—Use 1 drop three or four times a day.
    
    
  
  

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Genteal Mild

If you experience eye pain, changes in vision, continued redness or irritation of the eye, or if your symptoms continue for more than 3 days or become worse, check with your doctor.

Genteal Mild Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Eye irritation not present before use of this medicine

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common - more common with 1% solution

• Blurred vision


• matting or stickiness of eyelashes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

Gentamicin Sulfate

Dosage Form: injection, solution
Gentamicin Injection, USP

(Pediatric)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection, USP and other antibacterial drugs, Gentamicin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Warnings

Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use.

As with other aminoglycosides, Gentamicin Injection is potentially nephrotoxic.  The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage or prolonged therapy.

Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin, primarily in those with pre-existing renal damage and in patients with normal renal function treated with higher doses and/or for longer periods than recommended.  Aminoglycoside-induced ototoxicity is usually irreversible.  Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

Renal and eighth cranial nerve function should be closely monitored, especially in patients with known or suspected reduced renal function at onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy.  Urine should be examined for decreased specific gravity, increased excretion of protein, and the presence of cells or casts.  Blood urea nitrogen (BUN), serum creatinine, or creatinine clearance should be determined periodically.  When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients.  Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug.  As with the other aminoglycosides, on rare occasions changes in renal and eighth cranial nerve function may not become manifest until soon after completion of therapy.

Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels.  When monitoring gentamicin peak concentrations, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided.

When monitoring gentamicin trough concentrations, dosage should be adjusted so that levels above 2 mcg/mL are avoided.  Excessive peak and/or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity.  In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, especially if renal function is, or becomes, compromised.  The rate of removal of gentamicin is considerably less by peritoneal dialysis than by hemodialysis.

In the newborn infant, exchange transfusions may also be considered.

Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin, should be avoided.  Other factors which may increase patient risk of toxicity are advanced age and dehydration.

The concurrent use of gentamicin with potent diuretics, such as ethacrynic acid or furosemide, should be avoided, since certain diuretics by themselves may cause ototoxicity.  In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue.

Aminoglycosides can cause fetal harm when administered to a pregnant woman (see WARNINGS section).

Gentamicin Sulfate Description

Gentamicin Sulfate, a water-soluble antibiotic of the aminoglycoside group, is derived from Micromonospora purpurea, an actinomycete.

It has the following structural formula:

Gentamicin Injection is a sterile, nonpyrogenic, aqueous solution for parenteral administration and is available both with and without preservatives.

Each mL of the preservative free product contains: Gentamicin Sulfate, equivalent to gentamicin 10 mg; Water for Injection q.s.  Sulfuric acid and/or sodium hydroxide may have been added for pH adjustment (3-5.5).

Gentamicin Sulfate - Clinical Pharmacology

After intramuscular administration of Gentamicin Sulfate, peak serum concentrations usually occur between 30 and 60 minutes and serum levels are measurable for 6 to 8 hours.  In infants, a single dose of 2.5 mg/kg usually provides a peak serum level in the range of 3 to 5 mcg/mL.  When gentamicin is administered by intravenous infusion over a two-hour period, the serum concentrations are similar to those obtained by intramuscular administration.  Age markedly affects the peak concentrations: in one report, a 1 mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 mcg/mL in patients six months to five years old, 5 to 10 years old, and over 10 years old, respectively.

In infants one week to six months of age, the half-life is 3 to 3 ½ hours.  In full-term and large premature infants less than one week old, the approximate serum half-life of gentamicin is 5 ½ hours.  In small premature infants, the half-life is inversely related to birth weight.  In premature infants weighing less than 1500 grams, the half-life is 11 ½ hours; in those weighing 1500 to 2000 grams, the half-life is eight hours; in those weighing over 2000 grams, the half-life is approximately five hours.  While some variation is to be expected due to a number of variables such as age, body temperature, surface area and physiologic differences, the individual patient given the same dose tends to have similar levels in repeated determinations.

Gentamicin, like all aminoglycosides, may accumulate in the serum and tissues of patients treated with higher doses and/or for prolonged periods, particularly in the presence of impaired or immature renal function.  In patients with immature or impaired renal function, gentamicin is cleared from the body more slowly than in patients with normal renal function.  The more severe the impairment, the slower the clearance.  (Dosage must be adjusted.)

Since gentamicin is distributed in extracellular fluid, peak serum concentrations may be lower than usual in patients who have a large volume of this fluid.  Serum concentrations of gentamicin in febrile patients may be lower than those in afebrile patients given the same dose.  When body temperature returns to normal, serum concentrations of the drug may rise.  Febrile and anemic states may be associated with a shorter than usual serum half-life.  (Dosage adjustment is usually not necessary.)  In severely burned patients, the half-life may be significantly decreased and resulting serum concentrations may be lower than anticipated from the mg/kg dose.

Protein-binding studies have indicated that the degree of gentamicin binding is low, depending upon the methods used for testing, this may be between 0 and 30%.

In neonates less than three days old, approximately 10% of the administered dose is excreted in 12 hours; in infants 5 to 40 days old, approximately 40% is excreted over the same period.  Excretion of gentamicin correlates with postnatal age and creatinine clearance.  Thus, with increasing postnatal age and concomitant increase in renal maturity, gentamicin is excreted more rapidly.  Little, if any, metabolic transformation occurs; the drug is excreted principally by glomerular filtration.  After several days of treatment, the amount of gentamicin excreted in the urine approaches, but does not equal, the daily dose administered.  As with other aminoglycosides, a small amount of the gentamicin dose may be retained in the tissues, especially in the kidneys.  Minute quantities of aminoglycosides have been detected in the urine of some patients weeks after drug administration was discontinued.  Renal clearance of gentamicin is similar to that of endogenous creatinine.

In patients with marked impairment of renal function, there is a decrease in the concentration of aminoglycosides in urine and in their penetration into defective renal parenchyma.  This decreased drug excretion, together with the potential nephrotoxicity of aminoglycosides, should be considered when treating such patients who have urinary tract infections.

Probenecid does not affect renal tubular transport of gentamicin.

The endogenous creatinine clearance rate and the serum creatinine level have a high correlation with the half-life of gentamicin in serum.  Results of these tests may serve as guides for adjusting dosage in patients with renal impairment (see DOSAGE AND ADMINISTRATION).

Following parenteral administration, gentamicin can be detected in serum, lymph, tissues, sputum, and in pleural, synovial, and peritoneal fluids.  Concentrations in renal cortex sometimes may be eight times higher than the usual serum levels.  Concentrations in bile, in general, have been low and have suggested minimal biliary excretion.  Gentamicin crosses the peritoneal as well as the placental membranes.  Since aminoglycosides diffuse poorly into the subarachnoid space after parenteral administration, concentrations of gentamicin in cerebrospinal fluid are often low and dependent upon dose, rate of penetration, and degree of meningeal inflammation.  There is minimal penetration of gentamicin into ocular tissues following intramuscular or intravenous administration.

Microbiology

In vitro tests have demonstrated that gentamicin is a bactericidal antibiotic which acts by inhibiting normal protein synthesis in susceptible microorganisms.  It is active against a wide variety of pathogenic bacteria including Escherichia coli, Proteus species, (indole-positive and indolenegative), Pseudomonas aeruginosa, species of the Klebsiella-Enterobacter-Serratia group, Citrobacter species and Staphylococcus species (including penicillin-and methicillin-resistant strains).  Gentamicin is also active in vitro against species of Salmonella and Shigella.  The following bacteria are usually resistant to aminoglycosides: Streptococcus pneumoniae, most species of streptococci, particularly group D and anaerobic organisms, such as Bacteroides species or Clostridium species.

In vitro studies have shown that an aminoglycoside combined with an antibiotic that interferes with cell wall synthesis may act synergistically against some group D streptococcal strains.  The combination of gentamicin and penicillin G has a synergistic bactericidal effect against virtually all strains of Streptococcus faecalis and its varieties (S. faecalis var. liquifaciens, S. faecalis var. zymogenes), S. faecium and S. durans.  An enhanced killing effect against many of these strains has also been shown in vitro with combinations of gentamicin and ampicillin, carbenicillin, nafcillin, or oxacillin.

The combined effect of gentamicin and carbenicillin is synergistic for many strains of Pseudomonas aeruginosa.  In vitro synergism against other gram-negative organisms has been shown with combinations of gentamicin and cephalosporins.  Gentamicin may be active against clinical isolates of bacteria resistant to other aminoglycosides.  Bacteria resistant to one aminoglycoside may be resistant to one or more other aminoglycosides.  Bacterial resistance to gentamicin is generally developed slowly.

Susceptibility Testing

If the disc method of susceptibility testing used is that described by Bauer et al. (Am J Clin Path 45:493,1966; Federal Register 37:20525-20529,1972), a disc containing 10 mcg of gentamicin should give a zone of inhibition of 15 mm or more to indicate susceptibility of the infecting organism.  Zones of 12 mm or less indicate that the infecting organism is likely to be resistant.  Zones of greater than 12 mm and less than 15 mm indicate intermediate susceptibility.  In certain conditions it may be desirable to do additional susceptibility testing by the tube or agar dilution method; gentamicin substance is available for this purpose.

Indications and Usage for Gentamicin Sulfate

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection, USP and other antibacterial drugs, Gentamicin Injection, USP 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.

Gentamicin Injection is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative).

Clinical studies have shown Gentamicin Injection to be effective in bacterial neonatal sepsis; bacterial septicemia; and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns).  Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity.

Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin.

Gentamicin may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing.  The decision to continue therapy with this drug should be based on the results of susceptibility tests, the severity of the infection, and the important additional concepts contained in the WARNINGS box above.  If the causative organisms are resistant to gentamicin, other appropriate therapy should be instituted.

In serious infections when the causative organisms are unknown, gentamicin may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin type drug before obtaining results of susceptibility testing.  If anaerobic organisms are suspected as etiologic agents, consideration should be given to using other suitable antimicrobial therapy in conjunction with gentamicin.  Following identification of the organism and its susceptibility, appropriate antibiotic therapy should then be continued.

Gentamicin has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa.  It has also been found effective when used in conjunction with a penicillin-type drug for the treatment of endocarditis caused by group D streptococci.

Gentamicin Injection has also been shown to be effective in the treatment of serious staphylococcal infections.  While not the antibiotic of first choice, gentamicin may be considered when penicillins or other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgment indicate its use.  It may also be considered in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.

In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

Contraindications

Hypersensitivity to gentamicin is a contraindication to its use.  A history of hypersensitivity or serious toxic reactions to other aminoglycosides may contraindicate use of gentamicin because of the known cross-sensitivity of patients to drugs in this class.

Warnings

(See boxed WARNINGS.)  Aminoglycosides can cause fetal harm when administered to a pregnant woman.  Aminoglycoside antibiotics cross the placenta, and there have been several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy.  Serious side effects to mother, fetus, or newborn have not been reported in the treatment of pregnant women with other aminoglycosides.  Animal reproduction studies conducted on rats and rabbits did not reveal evidence of impaired fertility or harm to the fetus due to Gentamicin Sulfate.        

It is not known whether Gentamicin Sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.  If gentamicin is used during pregnancy or if the patient becomes pregnant while taking gentamicin, she should be apprised of the potential hazard to the fetus.

Preserved Gentamicin Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.  The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.  Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Precautions

General

Prescribing Gentamicin Injection 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.

Neurotoxic and nephrotoxic antibiotics may be almost completely absorbed from body surfaces (except the urinary bladder) after local irrigation and after topical application during surgical procedures.  The potential toxic effects of antibiotics administered in this fashion (neuromuscular blockade, respiratory paralysis, oto- and nephrotoxicity) should be considered (see WARNINGS box).

Increased nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporins.

Neuromuscular blockade and respiratory paralysis have been reported in the cat receiving high doses (40 mg/kg) of gentamicin.  The possibility of these phenomena occurring in man should be considered if aminoglycosides are administered by any route to patients receiving anesthetics, or to patients receiving neuromuscular blocking agents, such as succinylcholine, tubocurarine or decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood.  If neuromuscular blockade occurs, calcium salts may reverse it.

Aminoglycosides should be used with caution in patients with neuromuscular disorders, such as myasthenia gravis, since these drugs may aggravate muscle weakness because of their potential curare-like effects on the neuromuscular junction.  During or following gentamicin therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia.  When this has occurred in infants, tetany and muscle weakness have been described.  Both adults and infants required appropriate corrective electrolyte therapy.

A Fanconi-like syndrome, with amino-aciduria and metabolic acidosis, has been reported in some adults and infants being given gentamicin injections.

Cross-allergenicity among aminoglycosides has been demonstrated.

Patients should be well hydrated during treatment.

Although the in vitro mixing of gentamicin and carbenicillin results in a rapid and significant inactivation of gentamicin, this interaction has not been demonstrated in patients with normal renal function who received both drugs by different routes of administration.  A reduction in gentamicin serum half-life has been reported in patients with severe renal impairment receiving carbenicillin concomitantly with gentamicin.

Treatment with gentamicin may result in overgrowth of nonsusceptible organisms.  If this occurs, appropriate therapy is indicated.

Do not administer unless solution is clear and package undamaged.

See WARNINGS box regarding concurrent use of potent diuretics and regarding concurrent and/or sequential use of other neurotoxic and/or nephrotoxic antibiotics and for other essential information.

Information for Patients

Patients should be counseled that antibacterial drugs including Gentamicin Injection should only be used to treat bacterial infections.  They do not treat viral infections (e.g., the common cold).  When Gentamicin Injection 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 Gentamicin Injection or other antibacterial drugs in the future.

Pregnancy Category D

See WARNINGS section.

Adverse Reactions

Nephrotoxicity

Adverse renal effects, as demonstrated by the presence of casts, cells, or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported.  They occur more frequently in patients treated for longer periods or with larger dosages than recommended.

Neurotoxicity

Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if dialysis is required), and in patients on high doses and/or prolonged therapy.  Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss, which, as with other aminoglycosides, may be irreversible.  Hearing loss is usually manifested initially by diminution of high-tone acuity.  Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs.

Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gravis-like syndrome, have been reported.

Note: The risk of toxic reactions is low in neonates, infants and children with normal renal function who do not receive Gentamicin Injection at higher doses or for longer periods of time than recommended.

Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss, hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly.

Laboratory abnormalities possibly related to gentamicin include: increased levels of serum transaminase (SGOT, SGPT), serum LDH and bilirubin, decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia, increased and decreased reticulocyte counts and thrombocytopenia.  While clinical laboratory test abnormalities may be isolated findings, they may also be associated with clinically related signs and symptoms.  For example, tetany and muscle weakness may be associated with hypomagnesemia, hypocalcemia, and hypokalemia.

While local tolerance of Gentamicin Injection is generally excellent, there has been an occasional report of pain at the injection site.  Subcutaneous atrophy or fat necrosis suggesting local irritation has been reported rarely.

Overdosage

In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, and is especially important if renal function is, or becomes, compromised.  The rate of removal of gentamicin is considerably less by peritoneal dialysis than it is by hemodialysis.  In the newborn infant, exchange transfusions may also be considered.

Gentamicin Sulfate Dosage and Administration

Gentamicin Injection may be given intramuscularly or intravenously.  The patient’s pretreatment body weight should be obtained for calculation of correct dosage.  The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass.  It is desirable to limit the duration of treatment with aminoglycosides to short term.

DOSAGE FOR PATIENTS

WITH NORMAL RENAL FUNCTION

Children: 6 to 7.5 mg/kg/day. (2 to 2.5 mg/kg administered every 8 hours.)

Infants and Neonates: 7.5 mg/kg/day. (2.5 mg/kg administered every 8 hours.)

Premature or Full-term Neonates One Week of Age or Less: 5 mg/kg/day. (2.5 mg/kg administered every 12 hours.)

It is desirable to measure periodically both peak and trough serum concentrations of gentamicin when feasible during therapy to assure adequate but not excessive drug levels.  For example, the peak concentration (at 30 to 60 minutes after intramuscular injection) is expected to be in the range of 3 to 5 mcg/mL.  When monitoring peak concentrations after intramuscular or intravenous administration, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided.  When monitoring trough concentrations (just prior to the next dose), dosage should be adjusted so that levels above 2 mcg/mL are avoided. Determination of the adequacy of a serum level for a particular patient must take into consideration the susceptibility of the causative organism, the severity of the infection, and the status of the patient’s host-defense mechanisms.

In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides.  In such patients treated with gentamicin, measurement of serum concentrations is recommended as a basis for dosage adjustment.

The usual duration of treatment is 7 to 10 days.  In difficult and complicated infections, a longer course of therapy may be necessary.  In such cases monitoring of renal, auditory, and vestibular functions is recommended, since toxicity is more apt to occur with treatment extended for more than 10 days.  Dosage should be reduced if clinically indicated.

For Intravenous Administration

The intravenous administration of gentamicin may be particularly useful for treating patients with bacterial septicemia or those in shock.  It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe burns, or those with reduced muscle mass.

For intermittent intravenous administration, a single dose of Gentamicin Injection may be diluted in 0.9% Sodium Chloride Injection or in 5% Dextrose Injection.  The solution may be infused over a period of one-half to two hours.

The recommended dosage for intravenous and intramuscular administration is identical.

Gentamicin Injection should not be physically premixed with other drugs, but should be administered separately in accordance with the recommended route of administration and dosage schedule.

DOSAGE FOR PATIENTS

WITH IMPAIRED RENAL FUNCTION

Dosage must be adjusted in patients with impaired renal function to assure therapeutically adequate but not excessive, blood levels.  Whenever possible, serum concentrations of gentamicin should be monitored.  One method of dosage adjustment is to increase the interval between administration of the usual doses.  Since the serum creatinine concentration has a high correlation with the serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses.  In adults, the interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 mL) by 8.  For example, a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 60 mg (1 mg/kg) every 16 hours (2 x 8).  These guidelines may be considered when treating infants and children with serious renal impairment.

In patients with serious systemic infections and renal impairment, it may be desirable to administer the antibiotic more frequently but in reduced dosage.  In such patients, serum concentrations of gentamicin should be measured so that adequate but not excessive levels result.

A peak and trough concentration measured intermittently during therapy will provide optimal guidance for adjusting dosage.  After the usual initial dose, a rough guide for determining reduced dosage at eight-hour intervals is to divide the normally recommended dose by the serum creatinine level (Table 1).  For example, after an initial dose of 20 mg (2 mg/kg), a child weighing 10 kg with a serum creatinine level of 2 mg/100 mL could be given 10 mg every eight hours (20 ÷ 2).  It should be noted that the status of renal function may be changing over the course of the infectious process.  It is important to recognize that deteriorating renal function may require a greater reduction in dosage than that specified in the above guidelines for patients with stable renal impairment.

TABLE 1 DOSAGE ADJUSTMENT GUIDE FOR PATIENTS WITH RENAL IMPAIRMENT (Dosage at Eight-Hour Intervals After the Usual Initial Dose)
Serum Creatinine (mg %)	Approximate Creatinine Clearance Rate (mL/min/1.73m2)	Percent of Usual Doses Shown Above
≤1	>100	100
1.1-1.3	70-100	80
1.4-1.6	55-70	65
1.7-1.9	45-55	55
2   -2.2	40-45	50
2.3-2.5	35-40	40
2.6-3	30-35	35
3.1-3.5	25-30	30
3.6-4	20-25	25
4.1-5.1	15-20	20
5.2-6.6	10-15	15
6.7-8	<10	10

In patients with renal failure undergoing hemodialysis, the amount of gentamicin removed from the blood may vary depending upon several factors including the dialysis method used.  An eight-hour hemodialysis may reduce serum concentrations of gentamicin by approximately 50%.  In children, the recommended dose at the end of each dialysis period is 2 to 2.5 mg/kg depending upon the severity of the infection.

The above dosage schedules are not intended as rigid recommendations but are provided as guides to dosage when the measurement of gentamicin serum levels is not feasible.

A variety of methods are available to measure gentamicin concentrations in body fluids; these include microbiologic, enzymatic and radioimmunoassay techniques.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

How is Gentamicin Sulfate Supplied

Gentamicin Injection, USP (Preservative Free) is supplied as:

Product No.	NDC No.	Strength
17302	63323-173-02	20 mg/2 mL (10 mg/mL)	2 mL fill in a 2 mL single dose vial, packaged in 25.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

45814I

Revised: August 2011

PACKAGE LABEL - PRINCIPAL DISPLAY - Gentamicin 2 mL Single Dose Vial Label

NDC 63323-173-02

17302

GENTAMICIN INJECTION, USP

(Pediatric)

equivalent to 10 mg/mL Gentamicin 

20 mg/2 mL

For IM or IV Use.

Must be diluted for IV use.

2 mL Single Dose Vial

Preservative Free

Rx only

PACKAGE LABEL - PRINCIPAL DISPLAY - Gentamicin 2 mL Single Dose Vial Tray Label

NDC 63323-173-02

17302

GENTAMICIN INJECTION, USP

(Pediatric)

equivalent to 10 mg/mL Gentamicin

20 mg/2 mL

For IM or IV Use.

Must be diluted for IV use.

2 mL Single Dose Vial

Rx only

GENTAMICIN  gentamicin  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 63323-173 Route of Administration INTRAMUSCULAR, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Gentamicin Sulfate (GENTAMICIN) GENTAMICIN 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM HYDROXIDE   SULFURIC ACID

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 63323-173-02 25 VIAL In 1 TRAY contains a VIAL 1 2 mL In 1 VIAL This package is contained within the TRAY (63323-173-02)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA062366	11/29/2004

Labeler - APP Pharmaceuticals, LLC (608775388)

Establishment
Name	Address	ID/FEI	Operations
APP Pharmaceuticals, LLC		023648251	MANUFACTURE

Revised: 10/2011APP Pharmaceuticals, LLC

More Gentamicin Sulfate resources

• Gentamicin Sulfate Use in Pregnancy & Breastfeeding
• Gentamicin Sulfate Drug Interactions
• Gentamicin Sulfate Support Group
• 0 Reviews for Gentamicin Sulfate - Add your own review/rating

Compare Gentamicin Sulfate with other medications

• Bacteremia
• Bacterial Endocarditis Prevention
• Bacterial Infection
• Bone infection
• Brucellosis
• Burns, External
• Cystic Fibrosis
• Endocarditis
• Endometritis
• Febrile Neutropenia
• Intraabdominal Infection
• Kidney Infections
• Meningitis
• Pelvic Inflammatory Disease
• Peritonitis
• Plague
• Pneumonia
• Rabbit Fever
• Skin Infection
• Surgical Prophylaxis

Gentlax S

Generic Name: docusate and senna (DOK yoo sate and SEN a)

Brand Names: Doc-Q-Lax, Doculax, Dok Plus, Gentlax S, Peri-Colace, Senna Plus, Senna S, Sennalax-S, Senokot S, SenoSol-SS

What is Gentlax S (docusate and senna)?

Docusate is a stool softener. It makes bowel movements softer and easier to pass.

Senna is a laxative. It stimulates muscle movement in the intestines.

The combination of docusate and senna is used to treat occasional constipation.

Docusate and senna may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Gentlax S (docusate and senna)?

Use this medication as directed on the label, or as your doctor has prescribed. Do not use the medication in larger amounts or for longer than recommended.

You should not use this medication if you are allergic to docusate and senna, or if you are also taking mineral oil.

Ask a doctor or pharmacist before using docusate and senna if you have nausea, vomiting, stomach pain, a sudden change in bowel habits, or an intestinal disorder (such as Crohn's disease or ulcerative colitis).

Do not use this medication without your doctor's advice if you are pregnant or breast-feeding. Do not take this medication for longer than 7 days in a row. Call your doctor if your constipation does not improve or if it gets worse. Stop taking this docusate and senna and call your doctor at once if you have rectal bleeding, severe stomach pain, nausea and vomiting, or if you do not have a bowel movement. Do not use any other over-the-counter laxatives or other stool softener without first asking your doctor or pharmacist.

What should I discuss with my healthcare provider before using Gentlax S (docusate and senna)?

You should not use this medication if you are allergic to docusate and senna, or if you are also taking mineral oil.

Ask a doctor or pharmacist about using docusate and senna if you have:

• 
  

  nausea or vomiting;

  
  


• 
  

  stomach pain;

  
  


• 
  

  a sudden change in bowel habits that lasts for 2 weeks or longer; or

  
  


• 
  

  if you have an intestinal disorder such as Crohn's disease or ulcerative colitis.

  
  

Do not use this medication without your doctor's advice if you are pregnant. It is not known whether docusate and senna 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. Ask a doctor before giving this medication to a child younger than 2 years old.

How should I use Gentlax S (docusate and senna)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Take this medication with a full glass of water.

It may be best to take this medication at night or at bedtime. Docusate and senna should cause you to have a bowel movement within 6 to 12 hours.

Do not take this medication for longer than 7 days in a row, unless your doctor tells you to. Call your doctor if your constipation does not improve or if it gets worse after taking docusate and senna. Store docusate and senna at room temperature away from moisture and heat.

What happens if I miss a dose?

Since docusate and senna is taken as needed, you are not likely to be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, vomiting, stomach pain, or diarrhea.

What should I avoid while using Gentlax S (docusate and senna)?

Do not use any other over-the-counter laxatives or other stool softener without first asking your doctor or pharmacist. Docusate or senna may be contained in other medicines available over the counter. If you take certain products together you may accidentally take too much of a certain medicine. Read the label of any other medicine you are using to see if it contains docusate or senna.

Gentlax S (docusate and senna) 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. Stop using docusate and senna and call your doctor at once if you have a serious side effect such as:

• 
  

  rectal bleeding;

  
  


• 
  

  severe stomach pain, nausea, vomiting; or

  
  


• 
  

  no bowel movement.

  
  

Less serious side effects may include:

• 
  

  gas, bloating;

  
  


• 
  

  diarrhea; or

  
  


• 
  

  mild nausea.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Gentlax S (docusate and senna)?

There may be other drugs that can interact with docusate and senna. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Gentlax S resources

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

• Senna Plus MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Gentlax S with other medications

• Constipation, Acute

Where can I get more information?

• Your pharmacist can provide more information about docusate and senna.

See also: Gentlax S side effects (in more detail)

Geri-Protect

Generic Name: zinc oxide topical (ZINK OX ide)

Brand Names: ARC, Balmex, Boudreaux Butt Paste, Caldesene, Calmol-4 Suppository, Critic-Aid Skin Paste, Delazinc, Dermagran BC, Desitin, Desitin Maximum Strength Original, Desitin Rapid Relief Creamy, Diaper Rash Ointment, Diaper Relief, Dr. Smith's Diaper, Flanders Buttocks Ointment, Geri-Protect, Medi-Paste, PeriGuard, Pinxav, Rash Relief, RVPaque, Seniortopix Healix, Soothe & Cool Skin Paste, Sportz Block Dark, Sportz Block Light, Sportz Block Medium, Triple Paste, Tronolane Suppositories, Unna-Flex Elastic Unna Boot 3 inch, Unna-Flex Elastic Unna Boot 4 inch, Znlin

What is Geri-Protect (zinc oxide topical)?

Zinc oxide is a mineral.

Zinc oxide topical (for the skin) is used to treat diaper rash, minor burns, severely chapped skin, or other minor skin irritations.

Zinc oxide rectal suppositories are used to treat itching, burning, irritation, and other rectal discomfort caused by hemorrhoids or painful bowel movements.

Zinc oxide topical may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Geri-Protect (zinc oxide topical)?

You should not use this medication if you are allergic to zinc, dimethicone, lanolin, cod liver oil, petroleum jelly, parabens, mineral oil, or wax.

Zinc oxide topical will not treat a bacterial or fungal infection. Call your doctor if you have any signs of infection such as redness and warmth or oozing skin lesions.

Keep the diaper area clean and dry to prevent worsening of skin rash. Change wet diapers as soon as possible. Allow the skin to dry thoroughly before putting on a fresh diaper.

Stop using this medication and call your doctor if your condition does not improve within 7 days of treatment. Avoid getting this medication in your mouth or eyes. If this does happen, rinse with water right away. Do not use zinc oxide topical on deep skin wounds or severe burns. Get medical attention for more severe skin irritation or injury.

Avoid using other medications on the areas you treat with zinc oxide unless you doctor tells you to.

What should I discuss with my health care provider before using Geri-Protect (zinc oxide topical)?

You should not use this medication if you are allergic to zinc, dimethicone, lanolin, cod liver oil, petroleum jelly, parabens, mineral oil, or wax.

Zinc oxide topical will not treat a bacterial or fungal infection. Call your doctor if you have any signs of infection such as redness and warmth or oozing skin lesions.

It is not known whether zinc oxide topical 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 zinc oxide topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without medical advice if you are breast-feeding a baby.

How should I use Geri-Protect (zinc oxide topical)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Apply enough of this medication to cover the entire area to be treated. Zinc oxide often leaves a thin white residue that may not be entirely rubbed in.

To treat chapped skin, minor burn wounds, or other skin irritations, use the medication as often as needed. Apply a thin layer to the affected area and rub in gently.

To treat diaper rash, use this medication each time the diaper is changed. It is especially important to apply the medication at bedtime or whenever there will be a long period of time between diaper changes.

Keep the diaper area clean and dry to prevent worsening of skin rash. Change wet diapers as soon as possible. Allow the skin to dry thoroughly before putting on a fresh diaper.

When using the powder form of this medicine, pour the powder slowly to avoid a large puff into the air. Do not allow a baby to handle a powder bottle during use. Always close the lid after using the powder.

Zinc oxide rectal suppositories come with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Wash your hands before and after inserting a rectal suppository.

Try to empty your bowel and bladder just before using the suppository. Cleanse and dry your rectal area thoroughly.

Remove the outer wrapper from the suppository before inserting it. Avoid handling the suppository too long or it will melt in your hands.

For best results, stay lying down after inserting the suppository and hold it in your rectum for a few minutes. The suppository will melt quickly once inserted and you should feel little or no discomfort while holding it in.

Stop using this medication and call your doctor if your condition does not improve within 7 days of treatment. Store at room temperature away from moisture and heat. Keep the tube cap tightly closed when not in use. You may store zinc oxide rectal suppositories in a refrigerator to prevent melting.

What happens if I miss a dose?

Since zinc oxide is used on an as needed basis, you are not likely to miss a dose. Using extra zinc oxide to make up a missed dose will not make the medication more effective.

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 using Geri-Protect (zinc oxide topical)?

Avoid getting this medication in your mouth or eyes. If this does happen, rinse with water right away. Do not use zinc oxide topical on deep skin wounds or severe burns. Get medical attention for more severe skin irritation or injury.

Geri-Protect (zinc oxide topical) 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. Stop using zinc oxide rectal suppositories if you have rectal bleeding or continued pain.

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 Geri-Protect (zinc oxide topical)?

Avoid applying other skin medications on the same treatment area with zinc oxide, unless your doctor has told you to.

There may be other drugs that can interact with zinc oxide topical or rectal suppositories. 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 Geri-Protect resources

• Geri-Protect Side Effects (in more detail)
• Geri-Protect Use in Pregnancy & Breastfeeding
• Geri-Protect Support Group
• 0 Reviews for Geri-Protect - Add your own review/rating

• Arcalyst Monograph (AHFS DI)


• Caldesene Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Desitin Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Geri-Protect with other medications

• Anal Itching
• Dermatologic Lesion
• Diaper Rash

Where can I get more information?

• Your pharmacist can provide more information about zinc oxide topical.

See also: Geri-Protect side effects (in more detail)

Geodon

Generic Name: Ziprasidone
Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one monohydrochloride monohydrate
Molecular Formula: C₂₁H₂₁ClN₄OS•HCl•H₂OC₂₁H₂₁ClN₄OS•CH₄O₃S•3H₂O
CAS Number: 138982-67-9

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

• Increased Mortality in Geriatric Patients


• 
  

  Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) compared with those receiving placebo (2.6%).^{1 68}

  
  


• 
  

  Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{1 68}

  
  


• 
  

  Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68} (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

  
  

Introduction

Atypical or second-generation antipsychotic agent.^{1 4 10 11 29}

Uses for Geodon

Schizophrenia

Symptomatic management of schizophrenia.¹

Should be reserved for patients whose disease fails to respond adequately to appropriate courses of other antipsychotic agents because of a greater capacity to prolong the QT/QT_c-interval compared with that of several other antipsychotic agents.¹ (See Prolongation of QT Interval under Cautions)

IM injection used for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior).¹

Bipolar Disorder

Treatment of acute manic and mixed epsiodes (with or without psychotic features) associated with bipolar 1 disorder.^{1 73 74}

Geodon Dosage and Administration

Administration

Administer orally or by IM injection.¹

Concomitant use of oral and IM ziprasidone not recommended by manufacturer.¹

Oral Administration

Administer orally twice daily with food.¹

IM Administration

Vials are for single use only.¹

Reconstitution

Reconstitute vial containing 20 mg with 1.2 mL of sterile water for injection to provide a solution containing 20 mg/mL.¹ Do not use other solutions to reconstitute the injection, and do not admix with other drugs.¹ Shake vigorously to ensure complete dissolution.¹

Observe strict aseptic technique since the drug contains no preservative.¹ Discard unused portions.¹

Dosage

Available as ziprasidone hydrochloride or ziprasidone mesylate; oral dosage expressed in terms of hydrochloride monohydrate and IM dosage expressed in terms of ziprasidone.^{1 12}

Adults

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Schizophrenia

Oral

Initially, 20 mg twice daily.¹

Dosage may be increased after a minimum of 2 days.^{1 12} Observe patients for several weeks prior to upward titrations of dosage to ensure use of the lowest effective dosage.¹

In patients responding to ziprasidone therapy, continue the drug as long as clinically necessary and tolerated, but at lowest possible effective dosage;¹² periodically reassess need for continued therapy.¹ Efficacy maintained for up to 52 weeks in clinical trials, but optimum duration of therapy currently is not known.¹

Acute Agitation in Schizophrenia

IM

Initially, 10–20 mg given as a single dose.¹

Repeat doses of 10 mg every 2 hours or 20 mg every 4 hours, up to a maximum cumulative dosage of 40 mg daily.¹

Oral therapy should replace IM therapy as soon as possible; safety and efficacy of administering ziprasidone IM injection for longer than 3 consecutive days not evaluated.¹

Bipolar Disorder

Oral

Initially, 40 mg twice daily on day 1.¹ Increase dosage to 60 or 80 mg twice daily on the second day.¹

Subsequent dosage adjustments based on efficacy and tolerability may be made within a dosage range of 40–80 mg twice daily.¹

Efficacy for long-term use (i.e., >3 weeks) or for prophylactic use in patients with bipolar disorder not systematically evaluated.¹ If used for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.¹

Prescribing Limits

Adults

Schizophrenia

Oral

Maximum 80 mg twice daily.^{1 12}

Acute Agitation

IM

Maximum cumulative dosage of 40 mg daily.

Bipolar Disorder

Oral

Maximum 80 mg twice daily.¹

Cautions for Geodon

Contraindications

• 
  

  Known history of QT interval prolongation (including congenital long QT syndrome), recent AMI, or uncompensated heart failure.¹ (See Prolongation of QT Interval under Cautions.)

  
  


• 
  

  Concomitant therapy with other drugs that prolong the QT interval (e.g., class Ia and III antiarrhythmics, arsenic trioxide, chlorpromazine, dofetilide, dolasetron mesylate, droperidol, gatifloxacin, halofantrine, levomethadyl acetate, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, quinidine, sotalol, sparfloxacin, tacrolimus, thioridazine).¹ Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.¹

  
  


• 
  

  Known hypersensitivity to ziprasidone.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.^{1 68} (See Boxed Warning and see Geriatric Use under Cautions.)

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68}

Prolongation of QT Interval

Greater capacity to prolong the QT/QT_c interval compared with that of several other antipsychotic agents.¹

Experience is too limited to rule out the possibility that ziprasidone may be associated with a greater risk of ventricular arrhythmias (e.g., torsades de pointes) and/or sudden death than other antipsychotic agents.¹

Patients at particular risk of torsades de pointes include those with bradycardia, hypokalemia, or hypomagnesemia, those receiving concomitant therapy with other drugs that prolong the QT_c interval, and those with congenital prolongation of QT_c interval.¹ (See Contraindications under Cautions.) Avoid ziprasidone therapy in patients with history of cardiac arrhythmias.¹

Determine baseline serum potassium and magnesium concentrations in patients at risk for substantial electrolyte disturbances, particularly those receiving concomitant diuretic therapy.¹ Correct hypokalemia or hypomagnesemia prior to initiating ziprasidone.¹

Clinical and ECG monitoring of cardiac function, including appropriate ambulatory ECG monitoring (e.g., Holter monitoring), is recommended during ziprasidone therapy in patients with symptoms that could indicate torsades de pointes (e.g., dizziness, palpitations, syncope).¹

Discontinue ziprasidone if the QT_c interval exceeds 500 msec.¹

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, may occur in patients receiving antipsychotic agents.^{1 12}

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, has been reported.¹ Consider discontinuance of ziprasidone.¹

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.^{1 13 14 15 16 17 18 19 20 21 22 23 24 25 26 40 41 42 43 47} Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control, and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).^{1 13 14 16 17 18 19 20 21 22 23 24 25} If manifestations of hyperglycemia occur, test for diabetes mellitus.^{1 13 14 16 17 18 19 20 21 22 23 24 25}

Sensitivity Reactions

Rash

Rash and/or urticaria, possibly related to dose and/or duration of therapy, reported.¹ Adjunctive treatment with antihistamines or steroids and/or drug discontinuance may be required.¹ Discontinue ziprasidone if alternative etiology of rash cannot be identified.¹

General Precautions

Cardiovascular Effects

Orthostatic hypotension reported, particularly during initial dosage titration period.¹ Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).¹

Nervous System Effects

Possible risk of seizures;¹ use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).¹

Disruption of ability to reduce core body temperature possible; use caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).¹

Somnolence reported.¹ Potential impairment of judgment, thinking, or motor skills.¹

GI Effects

Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer’s dementia).¹ (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Suicide

Attendant risk with psychotic illnesses; closely supervise high-risk patients.¹ Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.¹

Sexual Dysfunction

Priapism possible.¹

Endocrine Effects

Elevated prolactin concentrations possible.⁷

Metabolic Effects

Weight gain possible.^{1 7} May cause less weight gain than clozapine, olanzapine, quetiapine, or risperidone.^{4 10 11 12}

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.¹

Lactation

Not known whether ziprasidone is distributed into milk.¹ Women receiving ziprasidone should not breast-feed.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

No substantial differences in safety of oral ziprasidone relative to younger adults.¹

Lower initial dosages, slower titration, and careful monitoring during the initial dosing period may be advisable in some geriatric patients.¹

IM ziprasidone mesylate not systematically evaluated in geriatric patients.¹

Possible increased risk of death in geriatric patients with dementia-related psychosis.^{1 68} Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{1 68}

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68} (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Renal Impairment

Commercially available ziprasidone mesylate injections contain sulfobutylether β-cyclodextrin sodium, an excipient that is cleared by renal filtration; use with caution.¹

Common Adverse Effects

Oral therapy for schizophrenia: somnolence, respiratory tract infection.¹

Oral therapy for bipolar mania: somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting.^{1 73 74}

IM therapy for acute agitation in schizophrenia: somnolence, headache, nausea.¹

Interactions for Geodon

Ziprasidone is metabolized by the CYP3A4 isoenzyme; CYP1A2 also may contribute but to a much lesser extent.¹ Little inhibitory effect on CYP isoenzymes 1A2, 2C9, 2C19, 2D6, or 3A4; pharmacokinetic interaction unlikely with drugs metabolized by these isoenzymes.¹

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions (altered metabolism) with inhibitors or inducers of CYP3A4.¹

Pharmacokinetic interaction with inhibitors or inducers of CYP1A2, CYP2C9, CYP2C19, or CYP2D6 are unlikely.¹

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation; concomitant use contraindicated) when used with drugs that prolong the QT_c interval.¹ Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.¹ (See Contraindications and Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Antacids	No effects on ziprasidone pharmacokinetics1
Antiarrhythmics (class Ia and III)	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Arsenic trioxide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Benztropine	Pharmacokinetic interaction unlikely1
Carbamazepine	Increased ziprasidone metabolism1
Chlorpromazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Cimetidine	No change observed in ziprasidone pharmacokinetics1
CNS agents	Additive sedative effects12
Dextromethorphan	No change observed in dextromethorphan metabolism1
Dofetilide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Dolasetron mesylate	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Dopamine agonists	Antagonistic effects1
Droperidol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Gatifloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Halofantrine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Hypotensive agents	Additive hypotensive effects1	Use with caution1
Ketoconazole	Increased plasma ziprasidone concentrations1
Levodopa	Antagonistic effects1
Levomethadyl acetate	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Lithium	No change observed in lithium clearance1
Lorazepam	Pharmacokinetic interaction unlikely1
Mefloquine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Mesoridazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Moxifloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Oral contraceptives	No change observed in estradiol or levonorgestrel pharmacokinetics1
Pentamidine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Pimozide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Probucol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Protein-bound drugs (e.g., propranolol, warfarin)	Pharmacokinetic interaction unlikely1
Quinidine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Sotalol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Sparfloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Tacrolimus	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Thioridazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1

Geodon Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 60% following a 20 mg oral dose under fed conditions.¹

Peak plasma concentrations occur 6–8 hours after oral administration or about 1 hour after IM injection.¹

Food

Food increases the absorption up to twofold.¹

Distribution

Extent

Not known whether the drug is distributed into milk in humans.¹

Plasma Protein Binding

>99% bound to plasma proteins, principally to albumin and α₁-acid glycoprotein.¹

Elimination

Metabolism

Extensively metabolized in the liver principally via reduction by aldehyde oxidase; about one-third of metabolic clearance is mediated by CYP isoenzymes, principally CYP3A4.¹

Elimination Route

Approximately 20% of a dose is excreted in the urine and about 66% in feces, principally as metabolites.¹ Not removed by hemodialysis.¹

Half-life

Mean terminal half-life following oral administration is about 7 hours;¹ following IM administration, the half-life is 2–5 hours.¹

Special Populations

In patients with clinically important (Child-Pugh class A or B) cirrhosis, half-life increased by 2.3 hours compared with that of patients in the control group.¹

Stability

Storage

Oral

Capsules

15–30°C.¹

Parenteral

Powder for Injection

15–30°C.¹

Following reconstitution, store at 15–30°C protected from light for up to 24 hours or at 2–8°C for up to 7 days.¹

ActionsActions

• 
  

  Exact mechanism of antipsychotic action has not been fully elucidated; may involve antagonism of central type 2 serotonergic (5-HT₂) receptors and central dopamine D₂ receptors.^{1 8 9}

  
  


• 
  

  Precise mechanism of antimanic action has not been fully elucidated.¹

  
  


• 
  

  Antagonism of other receptors (e.g., histamine H₁ receptors, α₁-adrenergic receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of taking medication exactly as prescribed by the clinician.¹

  
  


• 
  

  Importance of avoiding driving, operating machinery, or performing hazardous tasks until gain experience with the drug’s effects.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs, dietary supplements, and herbal products, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).¹

  
  


• 
  

  Importance of avoiding alcohol during ziprasidone therapy.¹

  
  


• 
  

  Importance of avoiding overheating or dehydration.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ziprasidone Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	20 mg	Geodon	Pfizer
		40 mg	Geodon	Pfizer
		60 mg	Geodon	Pfizer
		80 mg	Geodon	Pfizer

Ziprasidone Mesylate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use only	20 mg (of ziprasidone) per mL	Geodon (with sulfobutylether β-cyclodextrin sodium 294 mg/mL)	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Geodon 20MG Capsules (PFIZER U.S.): 60/$478.01 or 180/$1402.96

Geodon 40MG Capsules (PFIZER U.S.): 60/$482.99 or 180/$1407.94

Geodon 60MG Capsules (PFIZER U.S.): 60/$574.97 or 180/$1687.92

Geodon 80MG Capsules (PFIZER U.S.): 60/$574.97 or 180/$1687.92

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions March 15, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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37. Barrett EJ. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to Holt, Citrome and Volevka, Isaac and Isaac, and Boehm et al. Diabetes Care. 2004; 27:2089-90.

38. Fuller MA, Shermock KM, Secic M et al. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2002; 23:1037-43.

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40. Koller EA, Weber J, Doraiswamy PM et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004; 65:857-63. [IDIS 518849] [PubMed 15291665]

41. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [IDIS 516345] [PubMed 15163265]

42. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [IDIS 516756] [PubMed 14638601]

43. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [IDIS 516757] [PubMed 14638600]

44. Koro CE, Fedder DO, L’Italien GJ et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002; 325:243. [IDIS 485916] [PubMed 12153919]

45. Citrome LL. Efficacy should drive atypical antipsychotic treatment. BMJ. 2003; 326:283. [IDIS 492968] [PubMed 12561827]

46. Anon. Which atypical antipsychotic for schizophrenia?. Drug Ther Bull. 2004; 42:57-60. [PubMed 15310154]

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48. Sussman N. The implications of weight changes with antipsychotic treatment. J Clin Psychopharmacol. 2003; 23 (Suppl 1):S21-6.

49. Gianfrancesco F, Grogg A, Mahmoud R et al. Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther. 2003; 25:1150-71. [IDIS 497269] [PubMed 12809963]

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51. Cavazzoni P, Mukhopadhyay N, Carlson C et al. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl. 2004; 47:s94-101. [PubMed 15056601]

52. Gianfrancesco FD, Grogg AL, Mahmoud RA et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002; 63:920-30. [IDIS 488480] [PubMed 12416602]

53. Etminan M, Streiner DL, Rochon PA. Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults. Pharmacotherapy. 2003; 23:1411-15. [IDIS 510498] [PubMed 14620387]

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60. Reviewer Comments (personal observations).

61. Bristol-Myers Squibb., Princeton, NJ: Personal communication.

62. AstraZeneca. Wayne, PA: Personal communication.

63. Eli Lilly and Company. Indianapolis, IN: Personal com