norfloxacin

nor-FLOX-a-sin

Oral route(Tablet)

Fluoroquinolones, including norfloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. Risk further increases with age over 60 years, concomitant steroid therapy, and kidney, heart, or lung transplants. Fluoroquinolones, including norfloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid in patients with known history of myasthenia gravis .

Commonly used brand name(s)

In the U.S.

• Noroxin

Available Dosage Forms:

• Tablet

Therapeutic Class: Antibiotic

Chemical Class: Fluoroquinolone

Uses For norfloxacin

Norfloxacin is used to treat certain bacterial infections in many different parts of the body. Norfloxacin may mask or delay the symptoms of syphilis. It is not effective against syphilis infections.

Norfloxacin belongs to the class of medicines known as fluoroquinolone antibiotics. It works by killing bacteria or preventing their growth. However, norfloxacin will not work for colds, flu, or other virus infections.

norfloxacin is available only with your doctor's prescription.

Before Using norfloxacin

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 norfloxacin, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to norfloxacin 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

Appropriate studies have not been performed on the relationship of age to the effects of norfloxacin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of norfloxacin in the elderly. However, elderly patients are more likely to have age-related heart or kidney problems, or develop severe tendon problems (including tendon rupture), which may require caution and an adjustment in the dose for patients receiving norfloxacin.

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. When you are taking norfloxacin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using norfloxacin with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Cisapride


• Dronedarone


• Mesoridazine


• Pimozide


• Sparfloxacin


• Thioridazine

Using norfloxacin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acarbose


• Acecainide


• Acetohexamide


• Alfuzosin


• Alosetron


• Amiodarone


• Amitriptyline


• Amoxapine


• Apomorphine


• Arsenic Trioxide


• Asenapine


• Astemizole


• Azimilide


• Azithromycin


• Benfluorex


• Bretylium


• Chloroquine


• Chlorpromazine


• Chlorpropamide


• Ciprofloxacin


• Citalopram


• Clarithromycin


• Clomipramine


• Crizotinib


• Dasatinib


• Desipramine


• Disopyramide


• Dofetilide


• Dolasetron


• Droperidol


• Erythromycin


• Flecainide


• Fluconazole


• Gatifloxacin


• Gemifloxacin


• Gliclazide


• Glimepiride


• Glipizide


• Gliquidone


• Glyburide


• Granisetron


• Guar Gum


• Halofantrine


• Haloperidol


• Ibutilide


• Iloperidone


• Imipramine


• Insulin


• Insulin Aspart, Recombinant


• Insulin Glulisine


• Insulin Lispro, Recombinant


• Lapatinib


• Levofloxacin


• Lopinavir


• Lumefantrine


• Mefloquine


• Metformin


• Methadone


• Miglitol


• Moricizine


• Moxifloxacin


• Mycophenolate Mofetil


• Nilotinib


• Nortriptyline


• Octreotide


• Ofloxacin


• Ondansetron


• Paliperidone


• Pazopanib


• Perflutren Lipid Microsphere


• Posaconazole


• Procainamide


• Prochlorperazine


• Promethazine


• Propafenone


• Protriptyline


• Quetiapine


• Quinidine


• Quinine


• Ranolazine


• Salmeterol


• Saquinavir


• Sematilide


• Sodium Phosphate


• Sodium Phosphate, Dibasic


• Sodium Phosphate, Monobasic


• Solifenacin


• Sorafenib


• Sotalol


• Sunitinib


• Tedisamil


• Telavancin


• Telithromycin


• Terfenadine


• Tetrabenazine


• Tizanidine


• Tolazamide


• Tolbutamide


• Toremifene


• Trazodone


• Trifluoperazine


• Trimipramine


• Troglitazone


• Vandetanib


• Vardenafil


• Vemurafenib


• Voriconazole


• Ziprasidone

Using norfloxacin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aluminum Carbonate, Basic


• Aluminum Hydroxide


• Aluminum Phosphate


• Betamethasone


• Calcium


• Corticotropin


• Cortisone


• Cosyntropin


• Cyclosporine


• Deflazacort


• Dexamethasone


• Didanosine


• Dihydroxyaluminum Aminoacetate


• Dihydroxyaluminum Sodium Carbonate


• Fludrocortisone


• Fluocortolone


• Hydrocortisone


• Iron


• Magaldrate


• Magnesium Carbonate


• Magnesium Hydroxide


• Magnesium Oxide


• Magnesium Trisilicate


• Methylprednisolone


• Paramethasone


• Prednisolone


• Prednisone


• Probenecid


• Sucralfate


• Triamcinolone


• Warfarin

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using norfloxacin with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use norfloxacin, or give you special instructions about the use of food, alcohol, or tobacco.

• Dairy Food

Other Medical Problems

The presence of other medical problems may affect the use of norfloxacin. Make sure you tell your doctor if you have any other medical problems, especially:

• Brain or spinal cord disease, including hardening of the arteries in the brain, or epilepsy or other seizures or


• Diabetes or


• Diarrhea or


• Heart attack, recent or


• Heart rhythm problems (e.g., prolonged QT interval) or history of or


• Hypokalemia (low potassium in the blood), uncorrected or


• Slow heartbeat—Use with caution. May make these conditions worse.

• G6PD deficiency (an enzyme problem)—Anemia may occur while using norfloxacin.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of norfloxacin from the body.

• Myasthenia gravis (severe muscle weakness) or


• Tendinitis (inflammation of the tendon), history of or


• Tendon rupture, history of—Should not be used in patients with these conditions.

• Organ transplant (e.g., heart, kidney, or lung) or


• Tendon disorder (e.g., rheumatoid arthritis), history of—Use with caution. May increase the risk of tendon problems.

Proper Use of norfloxacin

Take norfloxacin only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

norfloxacin comes with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Swallow the tablet with a glass (8 ounces) of water. Drink plenty of fluids while you are being treated with norfloxacin. Drinking extra water will help to prevent some unwanted effects of norfloxacin.

Norfloxacin should be taken at least 1 hour before or 2 hours after a meal, milk, or other dairy products.

If you are taking aluminum or magnesium-containing antacids, iron supplements, multivitamins, Didanosine (Videx®), sucralfate (Carafate®), or zinc, do not take them at the same time that you take norfloxacin. It is best to take these medicines at least 2 hours before or 2 hours after taking norfloxacin. These medicines may keep norfloxacin from working properly.

Avoid caffeine-containing products (e.g., coffee, soda, or chocolate) while you are using norfloxacin. Norfloxacin may cause caffeine to stay in your body longer than usual.

Keep using norfloxacin for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Dosing

The dose of norfloxacin 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 norfloxacin. 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 oral dosage form (tablets):
  
  • For infections:
    
    • Adults—400 milligrams (mg) two times a day, taken every 12 hours. Some infections may require 800 mg once a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of norfloxacin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

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.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using norfloxacin

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

norfloxacin may cause serious allergic reactions including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash; itching; hives; hoarseness; shortness of breath; trouble with breathing; trouble with swallowing; or any swelling of your hands, face, or mouth after you receive norfloxacin.

Serious skin reactions can occur with norfloxacin. Check with your doctor right away if you have blistering, peeling, or loosening of the skin; red skin lesions; severe acne or skin rash; sores or ulcers on the skin; or fever or chills while you are using norfloxacin.

Liver problems can occur while using norfloxacin. Stop using norfloxacin and check with your doctor right away if you have dark urine, clay-colored stools, abdominal or stomach pain, or yellow eyes or skin.

Norfloxacin may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Make sure you know how you react to norfloxacin before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert. If these reactions are especially bothersome, check with your doctor.

Norfloxacin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop using norfloxacin. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.

Tell your doctor right away if you start having numbness, tingling, or burning pain in your hands, arms, legs, or feet. These may be symptoms of a condition called peripheral neuropathy.

Norfloxacin may rarely cause inflammation or even tearing of a tendon (the cord that attaches muscles to bones). The risk of having tendon problems may be increased if you are over 60 years of age, using steroid medicines (e.g., dexamethasone, prednisolone, prednisone, or Medrol®), if you have severe kidney problems, a history of tendon problems (e.g., rheumatoid arthritis), or if you have received an organ (e.g., heart, kidney, or lung) transplant. If you get sudden pain or swelling in a tendon after exercise (e.g., in the ankle, back of the knee or leg, shoulder, elbow, or wrist), stop using norfloxacin and check with your doctor right away. Refrain from exercise until your doctor says otherwise.

Some people who take norfloxacin may become more sensitive to sunlight than they are normally. Exposure to sunlight, even for brief periods of time, may cause severe sunburn, or skin rash, redness, itching, or discoloration. When you begin using norfloxacin:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.


• Wear protective clothing, including a hat and sunglasses.


• Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some people may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your doctor.


• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

norfloxacin 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 immediately if any of the following side effects occur:

Rare

• Chest pain or discomfort


• chills


• diarrhea


• discouragement


• fast, irregular, pounding, or racing heartbeat or pulse


• feeling sad or empty


• fever


• flushing or redness of the skin


• hives or welts


• increased sweating


• irritability


• irritation or soreness of the mouth


• itching of the rectal area


• itching skin


• lack of appetite


• loss of interest or pleasure


• nausea


• pain and inflammation at the joints


• pain or discomfort in the arms, jaw, back, or neck


• redness of the skin


• shortness of breath


• skin rash


• sweating


• swelling of the foot or hand


• swelling of the stomach


• tingling of the fingers


• tiredness


• trouble with concentrating


• trouble with sleeping


• unusually warm skin


• vomiting

Incidence not known

• Abdominal or stomach cramps


• abdominal or stomach tenderness


• anxiety


• back, leg, or stomach pains


• black, tarry stools


• bleeding gums


• blistering, peeling, or loosening of the skin


• bloating


• blood in the urine or stools


• blurred vision


• bone pain


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• clay-colored stools


• cold sweats


• constipation


• cool, pale skin


• cough or hoarseness


• cracks in the skin


• dark-colored urine


• decreased frequency or amount of urine


• diarrhea, watery and severe, which may also be bloody


• difficulty with breathing, chewing, swallowing, or talking


• difficulty with moving


• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position


• double vision


• drooping eyelids


• dry mouth


• dry skin


• false sense of well-being


• fever with or without chills


• fruit-like breath odor


• general body swelling


• general feeling of tiredness or weakness


• greatly decreased frequency of urination or amount of urine


• headache


• inability to move the arms and legs


• increased blood pressure


• increased hunger


• increased sensitivity of the skin to sunlight


• increased thirst


• increased urination


• indigestion


• irregular or slow heart rate


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• light-colored stools


• loss of heat from the body


• lower back or side pain


• mood or mental changes


• mood swings


• muscle aching or cramping


• muscle pain or stiffness


• muscle weakness


• nervousness


• nightmares


• nosebleeds


• numbness or tingling in the hands, feet, or lips


• pain or burning while urinating


• pain, inflammation, or swelling in the calves, shoulders, or hands


• pain, swelling, or redness in the joints


• painful or difficult urination


• pains in the stomach, side, or abdomen, possibly radiating to the back


• personality changes


• pinpoint red spots on the skin


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• red skin lesions, often with a purple center


• red, irritated eyes


• red, swollen skin


• scaly skin


• seizures


• severe sunburn


• severe tiredness


• shakiness and unsteady walk


• skin rash


• slurred speech


• sore throat


• sores, ulcers, or white spots on the lips or in the mouth


• sores, welting, or blisters


• stomach pain, continuing


• sudden decrease in the amount of urine


• sudden numbness and weakness in the arms and legs


• swelling of the face, fingers, or lower legs


• swelling or inflammation of the mouth


• swollen glands


• tightness in the chest


• unexplained weight loss


• unpleasant breath odor


• unsteadiness, awkwardness, trembling, or other problems with muscle control or coordination


• unusual behavior, such as disorientation to time or place, failure to recognize people, hyperactivity, or restlessness


• unusual bleeding or bruising


• unusual tiredness or weakness


• unusual weight loss


• vomiting of blood


• weakness in the arms, hands, legs, or feet


• weight gain


• wheezing


• yellowing of the eyes or skin

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

• Lack or loss of strength

Rare

• Acid or sour stomach


• belching


• bitter taste


• cramps


• excess air or gas in the stomach or intestines


• full feeling


• heartburn


• heavy bleeding


• pain


• passing gas


• sleepiness or unusual drowsiness


• sleeplessness


• stomach discomfort, upset, or pain


• unable to sleep


• weight loss

Incidence not known

• Change in taste


• continuing ringing or buzzing or other unexplained noise in the ears


• hearing loss


• itching of the vagina or outside genitals


• loss of taste


• pain during sexual intercourse


• seeing double


• thick, white curd-like vaginal discharge without odor or with mild odor


• uncontrolled eye movements

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.

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More norfloxacin resources

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

• norfloxacin Concise Consumer Information (Cerner Multum)


• Norfloxacin Professional Patient Advice (Wolters Kluwer)


• Norfloxacin MedFacts Consumer Leaflet (Wolters Kluwer)


• Norfloxacin Monograph (AHFS DI)


• Noroxin Prescribing Information (FDA)

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Muckle Wells Syndrome Medications

Drugs associated with Muckle Wells Syndrome

The following drugs and medications are in some way related to, or used in the treatment of Muckle Wells Syndrome. 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:

Arcalyst

Ilaris

Clobetasol Gel

Dosage Form: gel
Clobetasol Propionate Gel, 0.05%

FOR TOPICAL DERMATOLOGIC USE ONLY –

NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE

Rx Only

Clobetasol Gel Description

Clobetasol Propionate Gel, 0.05% contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity.

Chemically, clobetasol propionate is (11ß,16ß) - 21 - chloro - 9 - fluoro - 11 - hydroxy - 16 - methyl - 17 - (1 - oxopropoxy) - pregna - 1,4 - diene - 3,20 - dione, and it has the following structural formula:

Clobetasol propionate has the empirical formula C25H32ClFO5 and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water.

Clobetasol Propionate Gel, 0.05% contains clobetasol propionate 0.5 mg/g in a base of carbomer homopolymer type B, propylene glycol, purified water, and sodium hydroxide.

Clobetasol Gel - Clinical Pharmacology

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacokinetics -

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption. Greater absorption was observed for the clobetasol propionate gel formulation as compared to the cream formulation in in vitro human skin penetration studies.

Studies performed with clobetasol propionate gel, 0.05% indicate that it is in the super-high range of potency as compared with other topical corticosteroids.

Indications and Usage for Clobetasol Gel

Clobetasol Propionate Gel, 0.05% is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use in pediatric patients under 12 years of age is not recommended.

Contraindications

Clobetasol Propionate Gel, 0.05% is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Precautions

General -

Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g/day.

Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.

Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA axis suppression.

If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur that require supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (seePRECAUTIONS: Pediatric Use).

If irritation develops, Clobetasol Propionate Gel, 0.05% should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Clobetasol Propionate Gel, 0.05% should be discontinued until the infection has been adequately controlled.

Clobetasol Propionate Gel, 0.05% should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Information for Patients -

Patients using topical corticosteroids should receive the following information and instructions:

1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

2. This medication should not be used for any disorder other than that for which it was prescribed.

3. The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.

4. Patients should report any signs of local adverse reactions to the physician.

5. Patients should inform their physicians that they are using Clobetasol Propionate Gel, 0.05% if surgery is contemplated.

Laboratory Tests -

The following tests may be helpful in evaluating patients for HPA axis suppression:

 

ACTH stimulation test

 

A.M. plasma cortisol test

 

Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment of Fertility -

Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Studies in the rat following subcutaneous administration at dosage levels up to 50 mcg/kg/day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

Clobetasol propionate was nonmutagenic in 3 different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test.

Pregnancy:

Teratogenic Effects:

Pregnancy Category C -

Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

Clobetasol propionate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.

Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate gel. Abnormalities seen included cleft palate and skeletal abnormalities.

In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate gel. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol Propionate Gel, 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers -

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clobetasol Propionate Gel, 0.05% is administered to a nursing woman.

Pediatric Use -

Safety and effectiveness of Clobetasol Propionate Gel, 0.05% in children and infants have not been established; therefore, use in children under 12 years of age is not recommended. Because of a higher ratio of skin surface area to body mass, children are at a greater risk than adults of HPA axis suppression when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children (see PRECAUTIONS).

HPA axis suppression, Cushing’s syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric Use -

Clinical studies of clobetasol propionate gel, 0.05% in US clinical trials did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious.

Adverse Reactions

In a controlled trial with clobetasol propionate gel, 0.05%, the only reported adverse reaction that was considered to be drug related was a report of burning sensation (1.8% of treated patients).

In larger controlled clinical trials with other clobetasol propionate formulations, the most frequently reported adverse reactions have included burning, stinging, irritation, pruritus, erythema, folliculitis, cracking and fissuring of the skin, numbness of fingers, skin atrophy, and telangiectasia (all less than 2%).

Cushing’s syndrome has been reported in infants and adults as a result of prolonged use of topical clobetasol propionate formulations.

The following additional local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with super-high potency corticosteroids such as Clobetasol Propionate Gel, 0.05%. These reactions are listed in approximate decreasing order of occurrence: dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, irritation, striae, and miliaria.

Overdosage

Topically applied Clobetasol Propionate Gel, 0.05% can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).

Clobetasol Gel Dosage and Administration

Apply a thin layer of Clobetasol Propionate Gel, 0.05% to the affected skin areas twice daily and rub in gently and completely (see INDICATIONS AND USAGE).

Clobetasol Propionate Gel, 0.05% is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks and amounts greater than 50 g/week should not be used.

As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Clobetasol Propionate Gel, 0.05% should not be used with occlusive dressings.

How is Clobetasol Gel Supplied

Clobetasol Propionate Gel, 0.05% is available as follows:

15 g tube (NDC 45802-925-14)

30 g tube (NDC 45802-925-94)

60 g tube (NDC 45802-925-96)

STORAGE

Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature].  Clobetasol Propionate Gel, 0.05% should not be refrigerated.

Manufactured by Perrigo

Yeruham 80500, Israel

Made in Israel

Distributed By

Perrigo

Allegan, MI 49010 • www.perrigo.com

Rev. 02/11

2P100 RC J3

PRINCIPAL DISPLAY PANEL - Carton

Rx Only

Clobetasol Propionate Gel, 0.05%

For Dermatologic Use Only - Not for Ophthalmic Use

Clobetasol Propionate Gel, 0.05% Carton Image 1

Clobetasol Propionate Gel, 0.05% Carton Image 2

PRINCIPAL DISPLAY PANEL - Tube

Rx Only

Clobetasol Propionate Gel, 0.05%

For Dermatologic Use Only - Not for Ophthalmic Use

Clobetasol Propionate Gel, 0.05% Tube

CLOBETASOL PROPIONATE  clobetasol propionate  gel

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 45802-925 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CLOBETASOL PROPIONATE (CLOBETASOL) CLOBETASOL PROPIONATE 0.05 mg  in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE B   PROPYLENE GLYCOL   WATER   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 45802-925-14 1 TUBE In 1 CARTON contains a TUBE 1 15 g In 1 TUBE This package is contained within the CARTON (45802-925-14) 2 45802-925-94 1 TUBE In 1 CARTON contains a TUBE 2 30 g In 1 TUBE This package is contained within the CARTON (45802-925-94) 3 45802-925-96 1 TUBE In 1 CARTON contains a TUBE 3 60 g In 1 TUBE This package is contained within the CARTON (45802-925-96)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075027	07/30/2008

Labeler - Perrigo New York Inc (078846912)

Registrant - L Perrigo Company (006013346)

Establishment
Name	Address	ID/FEI	Operations
Perrigo Israel Pharmaceuticals LTD		600093611	MANUFACTURE

Revised: 11/2011Perrigo New York Inc

More Clobetasol Gel resources

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

Compare Clobetasol Gel with other medications

• Anal Itching
• Atopic Dermatitis
• Cutaneous T-cell Lymphoma
• Dermatitis
• Lichen Planus
• Lichen Sclerosus
• Necrobiosis Lipoidica Diabeticorum
• Psoriasis
• Seborrheic Dermatitis

calamine Topical

KAL-a-mine

Commonly used brand name(s)

In Canada

• Calamine Lotion

Available Dosage Forms:

• Ointment


• Lotion


• Cream

Therapeutic Class: Antipruritic

Uses For calamine

Calamine is used to relieve the itching, pain, and discomfort of minor skin irritations, such as those caused by poison ivy, poison oak, and poison sumac. calamine also dries oozing and weeping caused by poison ivy, poison oak, and poison sumac.

Calamine is available without prescription.

Before Using calamine

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 calamine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to calamine 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 calamine in children with use in other age groups, calamine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines 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 calamine in the elderly with use in other age groups, calamine is not expected to cause different side effects or problems in older people than it does in younger adults.

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 calamine

Calamine is for external use only. Do not swallow it and do not use it on the eyes or mucous membranes such as the inside of the mouth, nose, genital (sex organs), or anal areas.

To use calamine lotion:

• Shake the lotion well before using.


• Moisten a pledget of cotton with the lotion.


• Use the moistened pledget to apply the lotion to the affected skin area(s).


• Allow the medicine to dry on the skin.

To use calamine ointment:

• Apply enough medicine to cover affected skin area(s) and rub in gently.

Dosing

The dose of calamine 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 calamine. 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 minor skin irritations:
  
  • For topical dosage forms (lotion, ointment):
    
    • Adults and children—Apply to the affected area(s) of skin as often as needed.
    
    
  
  

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 calamine

If your condition gets worse or if it does not improve within 7 days, or if rash or irritation develops, stop using calamine and check with your doctor.

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.

More calamine Topical resources

• Calamine Topical Side Effects (in more detail)
• Calamine Topical Use in Pregnancy & Breastfeeding
• Calamine Topical Support Group
• 1 Review for Calamine Topical - Add your own review/rating

• Calamine Plain topical Concise Consumer Information (Cerner Multum)

Compare calamine Topical with other medications

• Pruritus

Serpazide

Generic Name: hydralazine/hydrochlorothiazide/reserpine (hye DRAL a zeen/hye droe klor oh THYE a zide/re SER peen)

Brand Names: Diuretic Ap-Es, Hydrap-ES, Ser-Ap-Es, Serpazide, Tri-Hydroserpine, Uni Serp

What is Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Hydralazine is a vasodilator. It lowers blood pressure by relaxing (widening) blood vessels (veins and arteries) and making it easier for your heart to pump.

Hydrochlorothiazide is a thiazide diuretic (water pill). It helps to lower your blood pressure and decrease edema (swelling or water retention) by increasing the amount of salt and water you lose in your urine.

Reserpine lowers blood pressure by decreasing the levels of certain chemicals in your blood. This allows your blood vessels (veins and arteries) to relax and your heart to beat more slowly and easily.

The combination, hydralazine/hydrochlorothiazide/reserpine, is used to lower high blood pressure.

Hydralazine/hydrochlorothiazide/reserpine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Stand up slowly from a sitting or lying position. Hydralazine/hydrochlorothiazide/reserpine may make you feel dizzy. Do not stop taking hydralazine/hydrochlorothiazide/reserpine suddenly. Even if you feel better, you need this medication to control your condition. Stopping suddenly could cause severely high blood pressure, anxiety, and other dangerous side effects. Use caution when driving, operating machinery, or performing other hazardous activities. Hydralazine/hydrochlorothiazide/reserpine may cause dizziness. If you experience dizziness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking this medication.

What should I discuss with my healthcare provider before taking Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Do not take hydralazine/hydrochlorothiazide/reserpine without first talking to your doctor if you

• 
  

  have an allergy to sulfa-based drugs such as sulfa antibiotics;

  
  


• 
  

  have coronary heart disease or mitral valvular rheumatic heart disease;

  
  


• 
  

  have peptic ulcer disease (stomach ulcers);

  
  


• 
  

  have ulcerative colitis;

  
  


• 
  

  are suffering from depression (especially if you have suicidal thoughts);

  
  


• 
  

  are receiving electroconvulsive shock therapy; or

  
  


• 
  

  have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

  
  

You may not be able to take hydralazine/hydrochlorothiazide/reserpine if you have any of the conditions listed above.

Before taking this medication, tell your doctor if you

• 
  

  have gallstones,

  
  


• have kidney or liver disease,


• 
  

  have diabetes,

  
  


• 
  

  have gout,

  
  


• 
  

  have a collagen vascular disease such as systemic lupus erythematosus,

  
  


• 
  

  have pancreatitis,

  
  


• 
  

  have asthma,

  
  


• 
  

  have any type of heart disease,

  
  


• 
  

  have had a stroke or a transient ischemic attack (mini-stroke),

  
  


• 
  

  have high cholesterol or high levels of fat in your blood, or

  
  


• 
  

  have pulmonary hypertension (a type of lung disease).

  
  

You may require a dosage adjustment or special monitoring during therapy with hydralazine/hydrochlorothiazide/reserpine if you have any of the conditions listed above.

Hydralazine/hydrochlorothiazide/reserpine is in the FDA pregnancy category C. This means that it is not known whether hydralazine/hydrochlorothiazide/reserpine will harm an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant. Hydralazine/hydrochlorothiazide/reserpine passes into breast milk and may harm a nursing infant. Do not take this medication 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 hydralazine/hydrochlorothiazide/reserpine therapy. You may require a lower dose of this medication.

How should I take Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Take the medication exactly as directed. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Take the medication with food or milk if it upsets your stomach.

Do not suddenly stop taking hydralazine/hydrochlorothiazide/reserpine. Stopping suddenly could make your condition much worse or cause very serious side effects. Talk to your doctor before you stop taking this medication.

Store this medication 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 your next dose, skip the dose you missed and take only your next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of an overdose include low blood pressure (fainting, dizziness, weakness), slow pulse or an irregular heartbeat, low body temperature, diarrhea, increased urination, vomiting, headache, flushing of the skin, and slow breathing.

What should I avoid while taking Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Use caution when driving, operating machinery, or performing other hazardous activities. This medicine may cause dizziness. If you experience dizziness, avoid these activities. Avoid alcohol while taking hydralazine/hydrochlorothiazide/reserpine. Alcohol may increase the drowsiness caused by this medication and may increase dizziness. Use caution even with small amounts of alcohol. Use caution when rising from a sitting or lying position, especially first thing in the morning. You may become dizzy while taking hydralazine/hydrochlorothiazide/reserpine, and you may fall and injure yourself.

Do not let yourself become overheated in hot weather or during exercise, and use caution if you have a fever. Dehydration may increase the effects of hydralazine/hydrochlorothiazide/reserpine, and you may become very dizzy.

Avoid prolonged exposure to sunlight. Hydrochlorothiazide may increase the sensitivity of your skin to sunlight. Use a sunscreen and wear protective clothing when exposure to the sun is unavoidable.

Serpazide (hydralazine/hydrochlorothiazide/reserpine) side effects

If you experience any of the following serious side effects, stop taking hydralazine/hydrochlorothiazide/reserpine and seek emergency medical attention:

• 
  

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

  
  


• 
  

  irregular or fast heartbeats or a fluttering feeling in your chest;

  
  


• 
  

  new or worsening chest pain;

  
  


• 
  

  heart failure (shortness of breath, swelling of ankles or legs, sudden weight gain of 2 pounds in one day or 5 pounds in one week);

  
  


• 
  

  unusual fatigue or confusion;

  
  


• 
  

  abnormal bleeding or bruising;

  
  


• 
  

  yellow skin or eyes;

  
  


• 
  

  blood in your urine or stools;

  
  


• 
  

  little or no urine;

  
  


• 
  

  numbness, tingling, pain, or weakness of your arms or legs; or

  
  


• 
  

  fainting.

  
  

Other, less serious side effects are more likely to occur. Continue to take hydralazine/hydrochlorothiazide/reserpine and talk to your doctor if you experience

• 
  

  mild fatigue, drowsiness, or dizziness;

  
  


• 
  

  headache;

  
  


• 
  

  water retention (swelling of the hands, feet, or ankles);

  
  


• 
  

  anxiety, depression, or nightmares;

  
  


• 
  

  diarrhea, nausea, vomiting , abdominal pain;

  
  


• 
  

  stuffy nose or a dry mouth;

  
  


• 
  

  muscle weakness or cramps;

  
  


• 
  

  increased hunger, thirst, or urination;

  
  


• 
  

  a rash;

  
  


• 
  

  sensitivity to sunlight; or

  
  


• impotence or difficulty ejaculating.

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.

What other drugs will affect Serpazide (hydralazine/hydrochlorothiazide/reserpine)?

Do not take this medication if you have taken a monoamine oxidase inhibitor (MAOI), such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate), in the last 14 days.

Before taking this medication, tell your doctor if you are taking any of the following drugs:

• 
  

  digoxin (Lanoxin, Lanoxicaps);

  
  


• 
  

  quinidine (Cardioquin, others);

  
  


• 
  

  lithium (Lithobid, Eskalith, others);

  
  


• a tricyclic antidepressant such as amitriptyline (Elavil, Endep), imipramine (Tofranil), nortriptyline (Pamelor), doxepin (Sinequan), and others;


• a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil), ketoprofen (Orudis, Orudis KT, Oruvail), naproxen (Naprosyn, Anaprox, Aleve), and others;


• 
  

  an antidiabetic medicine such as glipizide (Glucotrol), glyburide (Micronase, Glynase, Diabeta), and others; or

  
  


• 
  

  a steroid medicine such as prednisone (Orasone, Deltasone), prednisolone (Delta Cortef, Prelone), methylprednisolone (Medrol), and others.

  
  

You may not be able to take hydralazine/hydrochlorothiazide/reserpine, or you may require a dosage adjustment or special monitoring during your treatment if you are taking any of the medicines listed above.

Also, before taking hydralazine/hydrochlorothiazide/reserpine, tell your doctor if you are taking any medicine to treat high blood pressure, water retention, heart problems, prostate problems, or another condition. Some medicines used to treat these conditions may interact with hydralazine/hydrochlorothiazide/reserpine, and the interaction may increase the effects on your heart.

Hydralazine/hydrochlorothiazide/reserpine may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, 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 hydralazine/hydrochlorothiazide/reserpine or affect your condition. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Serpazide resources

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

• Ser-Ap-Es Prescribing Information (FDA)

Compare Serpazide with other medications

• High Blood Pressure

Where can I get more information?

• Your pharmacist has additional information about hydralazine/hydrochlorothiazide/reserpine written for health professionals that you may read.

What does my medication look like?

Hydralazine/hydrochlorothiazide/reserpine is available with a prescription under the brand name Ser-Ap-Es. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

Hydralazine/hydrochlorothiazide/reserpine strengths are as follows:

• 
  

  Ser-Ap-Es (25 mg/15 mg/0.1mg)--round, salmon-pink, dry-coated tablets

  
  

See also: Serpazide side effects (in more detail)

silver sulfadiazine topical

Generic Name: silver sulfadiazine topical (SIL ver SUL fa DYE a zeen TOP ik al)

Brand Names: Silvadene, SSD, SSD AF, Thermazene

What is silver sulfadiazine topical?

Silver sulfadiazine is an antibiotic. It fights bacteria and fungus on the skin.

Silver sulfadiazine topical (for the skin) is used to treat or prevent infections on areas of burned skin.

Silver sulfadiazine topical may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about silver sulfadiazine topical?

You should not use this medication if you are allergic to silver sulfadiazine or another sulfa medication.

Before using this medication, tell your doctor if you have liver disease, kidney disease, or an enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency (G6PD).

The person applying this medication to burn wounds should wear sterile disposable gloves. Take care to keep the treatment area as clean as possible to prevent further infection.

Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.

Avoid exposing treated skin areas to sunlight, sunlamps, or tanning beds. Silver sulfadiazine can make your skin more sensitive to sunlight, and a sunburn may result. Wear protective clothing when you are outdoors. Call your doctor at once if you have a serious side effect such as fever, chills, flu symptoms, easy bruising or bleeding, unusual weakness, pale or yellowed skin, dark colored urine, ulcers on treated skin areas, swelling or weight gain, urinating less than usual, or a severe blistering or peeling red skin rash.

What should I discuss with my healthcare provider before using silver sulfadiazine topical?

You should not use this medication if you are allergic to silver sulfadiazine or another sulfa medication.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:

• liver disease;


• kidney disease; or


• 
  

  an enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency (G6PD).

  
  

FDA pregnancy category B. Silver sulfadiazine is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether silver sulfadiazine 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 use silver sulfadiazine topical?

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

Wash your hands before and after applying silver sulfadiazine cream. The person applying this medication to burn wounds should wear sterile disposable gloves. Take care to keep the treatment area as clean as possible to prevent further infection.

Clean the area to be treated as directed by your doctor. Apply enough of the medication to cover the affected area evenly. Silver sulfadiazine cream should be applied in a layer about one 16th of an inch thick (1.5 millimeter).

Silver sulfadiazine cream is usually applied 1 or 2 times daily. Burn wounds must be kept covered with this medication at all times. Treated skin areas can be left uncovered, or you may use a gauze bandage if directed by your doctor.

If needed, apply more cream to replace any medication that has come off on bandages, clothing, or bed linens. Reapply the cream after bathing or water therapy.

To be sure this medication is not causing harmful effects, your blood may need to be tested on a regular basis. Your kidney function may also need to be tested. Do not miss any follow-up visits to your doctor.

Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.

Store silver sulfadiazine topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. Your burn wounds should be kept covered with silver sulfadiazine cream at all times.

What happens if I overdose?

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

An overdose of silver sulfadiazine is not likely to cause life-threatening symptoms.

What should I avoid while using silver sulfadiazine topical?

Avoid exposing treated skin areas to sunlight, sunlamps, or tanning beds. Silver sulfadiazine can make your skin more sensitive to sunlight, and a sunburn may result. Wear protective clothing when you are outdoors. Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water. Do not use silver sulfadiazine topical on sunburned, windburned, dry, chapped, irritated, or broken skin.

Silver sulfadiazine topical side effects

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

• 
  

  fever, chills, body aches, flu symptoms;

  
  


• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  pale or yellowed skin, dark colored urine;

  
  


• 
  

  ulcers on treated skin areas;

  
  


• 
  

  blood in your urine;

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  drowsiness, confusion, mood changes, nausea and vomiting;

  
  


• 
  

  swelling, weight gain; or

  
  


• 
  

  fever, sore throat, and headache with a severe blistering, peeling, and red skin rash.

  
  

Less serious side effects may include:

• 
  

  brown or gray discoloration of treated skin;

  
  


• 
  

  mild itching or burning; or

  
  


• 
  

  upset stomach.

  
  

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.

Silver sulfadiazine topical Dosing Information

Usual Adult Dose for Burns - External:

Wound sepsis - Second and Third degree burns:
Apply to affected areas once or twice daily to a thickness of approximately 1/16 inch.

What other drugs will affect silver sulfadiazine topical?

Tell your doctor about all other medications you use, especially cimetidine (Tagamet).

This list is not complete and there may be other drugs that can interact with silver sulfadiazine. 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 silver sulfadiazine topical resources

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

• Silvadene Prescribing Information (FDA)


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


• Silvadene MedFacts Consumer Leaflet (Wolters Kluwer)


• Thermazene Prescribing Information (FDA)

Compare silver sulfadiazine topical with other medications

• Burns, External

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• Your pharmacist can provide more information about silver sulfadiazine topical.

See also: silver sulfadiazine side effects (in more detail)

tetrahydrozoline nasal

Generic Name: tetrahydrozoline nasal (TE tra hye DROZ oh leen)

Brand Names: Tyzine Nasal

What is tetrahydrozoline nasal?

Tetrahydrozoline is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

Tetrahydrozoline nasal is used to treat nasal and sinus congestion.

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

What is the most important information I should know about tetrahydrozoline nasal?

Do not use tetrahydrozoline nasal if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Before using tetrahydrozoline nasal, tell your doctor if you are allergic to any drugs, or if you have heart disease, coronary artery disease, high blood pressure, diabetes, or a thyroid disorder.

The adult dose of this medication (0.1% nasal spray) should not be used in a child younger than 6 years old. The child's dose (0.05% pediatric drops) should not be used in a child younger than 2 years old.

What should I discuss with my health care provider before taking tetrahydrozoline nasal?

Do not use this medication if you are allergic to tetrahydrozoline. Do not use tetrahydrozoline nasal if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Before using tetrahydrozoline nasal, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  heart disease or coronary artery disease;

  
  


• 
  

  high blood pressure;

  
  


• 
  

  diabetes; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether tetrahydrozoline nasal 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. Do not give this medication to a child without a doctor's advice.

How should I take tetrahydrozoline nasal?

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.

The adult dose of this medication (0.1% nasal spray) should not be used in a child younger than 6 years old. The child's dose (0.05% pediatric drops) should not be used in a child younger than 2 years old.

Use the nasal spray while standing or sitting, with your head upright. Tilt your head forward slightly, keep the bottle upright, and carefully insert the nasal applicator into your nostril. Squeeze the bottle quickly and sniff deeply at the same time.

If a second spray is required in that nostril, repeat the above steps.

To use the nasal drops, it is best to be lying down.

Store tetrahydrozoline nasal at room temperature away from moisture and heat.

See also: Tetrahydrozoline nasal dosage (in more detail)

What happens if I miss a dose?

Since tetrahydrozoline is often used as needed, you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use 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 extreme drowsiness, blurred vision, severe sweating, slow heart rate, trouble breathing, and feeling light-headed or fainting.

What should I avoid while taking tetrahydrozoline nasal?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using tetrahydrozoline nasal.

Tetrahydrozoline nasal 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 tetrahydrozoline and call your doctor at once if you have any of these serious side effects:

• 
  

  severe burning, stinging, redness, or swelling of your nose;

  
  


• 
  

  fast or pounding heartbeats; or

  
  


• 
  

  tremors, uncontrolled shaking.

  
  

Less serious side effects may include:

• 
  

  runny or stuffy nose;

  
  


• 
  

  sneezing;

  
  


• 
  

  headache;

  
  


• 
  

  drowsiness;

  
  


• 
  

  sleep problems (insomnia); or

  
  


• 
  

  headache.

  
  

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.

Tetrahydrozoline nasal Dosing Information

Usual Adult Dose for Nasal Congestion:

2 to 4 drops of 0.1% solution in each nostril every 4 to 8 hours as needed

or

3 to 4 squirts of 0.1% spray in each nostril every 4 to 8 hours as needed.

Usual Pediatric Dose for Nasal Congestion:

>=2 years to
2 to 3 drops of 0.05% solution in each nostril every 4 to 6 hours as needed.

>= 6 years to
2 to 4 drops of 0.1% solution in each nostril every 4 to 8 hours as needed

or

3 to 4 squirts of 0.1% spray in each nostril every 4 to 8 hours as needed.

What other drugs will affect tetrahydrozoline nasal?

There may be other drugs that can interact with tetrahydrozoline nasal. 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 tetrahydrozoline nasal resources

• Tetrahydrozoline nasal Dosage
• Tetrahydrozoline nasal Use in Pregnancy & Breastfeeding
• Tetrahydrozoline nasal Drug Interactions
• Tetrahydrozoline nasal Support Group
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Thymoglobulin

lapine t-lymphocyte immune globulin

Dosage Form: injection, powder, lyophilized, for solution
Sterile Lyophilized Powder

For Intravenous Use Only

Rx only

Warning

Thymoglobulin® should only be used by physicians experienced in immunosuppressive therapy for the management of renal transplant patients.

Thymoglobulin Description

Thymoglobulin® [Anti-thymocyte Globulin (Rabbit)] is a purified, pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes.

Thymoglobulin is a sterile, freeze-dried product for intravenous administration after reconstitution with Sterile Water for Injection, USP (SWFI).

Each 10 mL vial contains 25 mg anti-thymocyte globulin (rabbit) as well as 50 mg glycine, 50 mg mannitol, and 10 mg sodium chloride.

After reconstitution with 5 mL SWFI, each vial of reconstituted product contains approximately 5 mg/mL of Thymoglobulin, of which >90% is rabbit gamma immune globulin (IgG). The reconstituted solution has a pH of 6.5 - 7.2. Human red blood cells are used in the manufacturing process to deplete cross-reactive antibodies to non-T-cell antigens. The manufacturing process is validated to remove or inactivate potential exogenous viruses. All human red blood cells are from US registered or FDA licensed blood banks. A viral inactivation step (pasteurization, i.e., heat treatment of active ingredient at 60°C/10 hr) is performed for each lot. Each Thymoglobulin lot is released following potency testing (lymphocytotoxicity and E-rosette inhibition assays), and cross-reactive antibody testing (hemagglutination, platelet agglutination, anti-human serum protein antibody, antiglomerular basement membrane antibody, and fibroblast toxicity assays on every fifth lot).

PHARMACOLOGY

Mechanism of Action

The mechanism of action by which polyclonal antilymphocyte preparations suppress immune responses is not fully understood. Possible mechanisms by which Thymoglobulin may induce immunosuppression in vivo include: T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Thymoglobulin includes antibodies against T-cell markers such as CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, HLA-DR, HLA Class I heavy chains, and ß2 micro-globulin. In vitro, Thymoglobulin (concentrations >0.1 mg/mL) mediates T-cell suppressive effects via inhibition of proliferative responses to several mitogens. In patients, T-cell depletion is usually observed within a day from initiating Thymoglobulin therapy. Thymoglobulin has not been shown to be effective for treating antibody (humoral) mediated rejections.

Pharmacokinetics and Immunogenicity

After an intravenous dose of 1.25 to 1.5 mg/kg/day (over 4 hours for 7-11 days) 4-8 hours post-infusion, Thymoglobulin levels were on average 21.5 mcg/mL (10-40 mcg/mL) with a half-life of 2-3 days after the first dose, and 87 mcg/mL (23-170 mcg/mL) after the last dose. During the Thymoglobulin1 Phase 3 randomized trial, of the 108 of 163 patients evaluated, anti-rabbit antibodies developed in 68% of the Thymoglobulin-treated patients, and anti-horse antibodies developed in 78% of the Atgam2-treated patients (p=n.s.). No controlled studies have been conducted to study the effect of anti-rabbit antibodies on repeat use of Thymoglobulin. However, monitoring the lymphocyte count to ensure that T-cell depletion is achieved upon retreatment with Thymoglobulin is recommended. Based on data collected from a limited number of patients (Clinical study Phase 3, n=12), T-cell counts are presented in the chart below. These data were collected using flow cytometry (FACSCAN, Becton-Dickinson).

1

Thymoglobulin is a registered trademark of Genzyme Corporation, Cambridge, MA 02142

2

Atgam is a registered trademark of Pfizer Inc, New York, NY 10017

Clinical Trials

US Phase 3 Study

A controlled, double-blind, multicenter, randomized clinical trial comparing Thymoglobulin and Atgam was conducted at 28 US transplant centers in renal transplant patients (n=163) with biopsy-proven Banff Grade II (moderate), Grade III (severe), or steroid-resistant Grade I (mild) acute graft rejection. This clinical trial rejected the null hypothesis that Thymoglobulin was more than 20% less effective in reversing acute rejection than Atgam. The overall weighted estimate of the treatment difference (Thymoglobulin – Atgam success rate) was 11.1% with a lower 95% confidence bound of 0.07%. Therefore, Thymoglobulin was at least as effective as Atgam in reversing acute rejection episodes.

In the study, patients were randomized to receive 7 to 14 days of Thymoglobulin (1.5 mg/kg/day) or Atgam (15 mg/kg/day). For the entire study, the two treatment groups were comparable with respect to donor and recipient characteristics. During the trial, the FDA approved new maintenance immunosuppressive agents (tacrolimus and mycophenolate). Off-protocol use of these agents occurred during the second half of the study in some patients without affecting the overall conclusions (Thymoglobulin 22/43, Atgam 20/37; p=0.826). The results, however, are presented for the first and second halves of the study (Table 1). In Table 1, successful treatment is presented as those patients whose serum creatinine levels (14 days from the diagnosis of rejection) returned to baseline and whose graft was functioning on day 30 after the end of therapy.

Table 1: Response to Study Treatment by Rejection Severity and Study Half

Sucess/n	Total		First Half		Second Half
	Thymoglobulin	Atgam	Thymoglobulin	Atgam	Thymglobulin	Atgam
* across rejection severity and study half † under null hypothesis of equivalence (Cochran-Mantel-Haenszel test) ‡ one-sided stratified on rejection severity and study half § one-sided stratified on rejection severity
Risk Factor:
Baseline
Rejection Severity:
Mild	9/10 (90.0%)	5/8 (62.5%)	5/5 (100%)	1/3 (33.3%)	4/5 (80.0%)	4/5 (80%)
Moderate	44/58 (75.5%)	41/58 (70.7%)	22/26 (84.6%)	22/32 (68.8%)	22/32 (68.8%)	19/26 (73.1%)
Severe	11/14 (71.6%)	8/14 (57.1%)	6/8 (75.0%)	3/8 (37.5%)	5/6 (83.3%)	5/6 (83.3%)
Overall	64/82 (78.0%)	54/80 (67.5%)	33/39 (84.6%)	26/43 (60.5%)	31/43 (72.1%)	28/37 (75.7%)
Weighted estimate of difference (Thymoglobulin – Atgam)		11.1%*		19.3%		-3.2%
Lower one-sided 95% confidence bound		0.07%		4.6%		-19.7%
p Value†		0.061‡		0.008§		0.625§

There were no significant differences between the two treatments with respect to (i) day 30 serum creatinine levels relative to baseline, (ii) improvement rate in post-treatment histology, (iii) one-year post-rejection Kaplan-Meier patient survival (Thymoglobulin 93%, n=82 and Atgam 96%, n=80), (iv) day 30 and (v) one-year post-rejection graft survival (Thymoglobulin 83%, n=82; Atgam 75%, n=80).

Indications and Usage for Thymoglobulin

Thymoglobulin is indicated for the treatment of renal transplant acute rejection in conjunction with concomitant immunosuppression.

Contraindications

Thymoglobulin is contraindicated in patients with history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression.

Warnings

Thymoglobulin should only be used by physicians experienced in immunosuppressive therapy for the treatment of renal transplant patients. Medical surveillance is required during Thymoglobulin infusion.

Immune-mediated reactions

Serious immune-mediated reactions have been reported with the use of Thymoglobulin and consist of anaphylaxis or severe cytokine release syndrome (CRS).

Fatal anaphylaxis has been reported. If an anaphylactic reaction occurs, the infusion should be terminated immediately. Medical personnel should be available to treat patients who experience anaphylaxis. Emergency treatment such as 0.3 mL to 0.5 mL aqueous epinephrine (1:1000 dilution) subcutaneously and other resuscitative measures including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated, should be provided. Any further administration of Thymoglobulin to a patient who has a history of anaphylaxis to Thymoglobulin is not recommended.

Severe, acute infusion-associated reactions (IARs) are consistent with CRS which is attributed to the release of cytokines by activated monocytes and lymphocytes. Severe acute CRS can cause serious cardiorespiratory events and/or death (See PRECAUTIONS and ADVERSE REACTIONS: Post-Marketing Experience).

Infection

Thymoglobulin is routinely used in combination with other immunosuppressive agents. Infections (bacterial, fungal, viral and protozoal), reactivation of infection (particularly cytomegalovirus [CMV]) and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. Severe acute reactions can be fatal.

Precautions

General

Appropriate dosing for Thymoglobulin is different from dosing for other anti-thymocyte globulin (ATG) products, as protein composition and concentrations vary depending on the source of ATG used. Physicians should therefore exercise care to ensure that the dose prescribed is appropriate for the ATG product being administered.

Thymoglobulin should be used under strict medical supervision in a hospital setting, and patients should be carefully monitored during the infusion. The first dose should be infused over a minimum of 6 hours into a high-flow vein. Close compliance with the recommended dosage and infusion time may reduce the incidence and severity of infusion associated reactions (IARs). Additionally, reducing the infusion rate may minimize many of these IARs. Premedication with corticosteroids, acetaminophen, and/or an antihistamine and/or slowing the infusion rate may reduce reaction incidence and intensity (See DOSAGE AND ADMINISTRATION).

Rapid infusion rates have been reported with case reports consistent with cytokine release syndrome (CRS). Severe acute CRS can be fatal.

Hematologic Effects

Thrombocytopenia and/or leukopenia (including lymphopenia and neutropenia) have been identified and are reversible following dose adjustments (See DOSAGE AND ADMINISTRATION).

Infection

Infections, reactivation of infection, and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. Careful patient monitoring and appropriate anti-infective prophylaxis are recommended.

Malignancy

Use of immunosuppressive agents, including Thymoglobulin, may increase the incidence of malignancies, including lymphoma or post-transplant lymphoproliferative disease (PTLD) (See ADVERSE REACTIONS: Post-Marketing Experience).

Special Considerations for Thymoglobulin Infusion

Reactions at the infusion site can occur and may include pain, swelling, and erythema.

The recommended route of administration for Thymoglobulin is intravenous infusion using a high-flow vein (See DOSAGE AND ADMINISTRATION).

Immunizations

The safety of immunization with attenuated live vaccines following Thymoglobulin therapy has not been studied; therefore, immunization with attenuated live vaccines is not recommended for patients who have recently received Thymoglobulin.

Laboratory Tests

During Thymoglobulin therapy, monitoring the lymphocyte count (i.e., total lymphocyte and/or T-cell subset) may help assess the degree of T-cell depletion (See Pharmacokinetics and Immunogenicity). For safety, WBC and platelet counts should also be monitored (See DOSAGE AND ADMINISTRATION).

Drug Interactions

• No drug interaction studies have been performed.


• Because Thymoglobulin is administered to patients receiving a standard immunosuppressive regimen, this may predispose patients to overimmunosuppression. Many transplant centers decrease maintenance immunosuppression therapy during the period of antibody therapy.


• Thymoglobulin can stimulate the production of antibodies which crossreact with rabbit immune globulins (See Pharmacokinetics and Immunogenicity).

Drug/Laboratory Test Interactions

Thymoglobulin has not been shown to interfere with any routine clinical laboratory tests which do not use immunoglobulins. Thymoglobulin may interfere with rabbit antibody-based immunoassays and with cross-match or panel-reactive antibody cytotoxicity assays.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic and mutagenic potential of Thymoglobulin and its potential to impair fertility have not been studied.

Pregnancy: Pregnancy Category C

Animal reproduction studies have not been conducted with Thymoglobulin. It is also not known whether Thymoglobulin can cause fetal harm or can affect reproduction capacity. Thymoglobulin should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Thymoglobulin has not been studied in nursing women. It is not known whether this drug is excreted in human milk. Because other immunoglobulins are excreted in human milk, breast-feeding should be discontinued during Thymoglobulin therapy.

Pediatric Use

The safety and effectiveness of Thymoglobulin in pediatric patients has not been established in controlled trials. However, the dose, efficacy, and adverse event profile are not thought to be different from adults based on limited European studies and US compassionate use.

Adverse Reactions

Clinical Trials

US Phase 3 Study

Thymoglobulin adverse events are generally manageable or reversible. In the US Phase 3 controlled clinical trial (n=163) comparing the efficacy and safety of Thymoglobulin and Atgam, there were no significant differences in clinically significant adverse events between the two treatment groups (Table 2). Malignancies were reported in 3 patients who received Thymoglobulin and in 3 patients who received Atgam during the one-year follow-up period. These included two post-transplant lymphoproliferative diseases (PTLDs) in the Thymoglobulin group and two PTLDs in the Atgam group.

Table 2. Frequently Reported and Significant Adverse Events*  

Preferred Term	Thymoglobulin n=82		Atgam n=81		p Value†
	No. of     Patients	(%)	No. of     Patients	(%)
* Treatment Emergent Adverse Events (TEAE) are summarized. Frequently reported adverse events are those reported by more than 25% of patients in a treatment group; significant adverse events are those where the incidence rate differed between treatment groups by a significance level of ≤0.05. † p Value comparing treatment groups using Fisher's exact test. ‡ statistically significant differences in the AEs.
Frequently Reported Events
Fever	52	(63.4)	51	(63.0)	1.0
Chills	47	(57.3)	35	(43.2)	0.086
Leukopenia	47	(57.3)	24	(29.6)	<0.001
Pain	38	(46.3)	35	(43.2)	0.753
Headache	33	(40.2)	28	(34.6)	0.518
Abdominal pain	31	(37.8)	22	(27.2)	0.181
Diarrhea	30	(36.6)	26	(32.1)	0.622
Hypertension	30	(36.6)	23	(28.4)	0.316
Nausea	30	(36.6)	23	(28.4)	0.316
Thrombocytopenia	30	(36.6)	36	(44.4)	0.341
Peripheral edema	28	(34.1)	28	(34.6)	1.0
Dyspnea	23	(28.0)	16	(19.8)	0.271
Asthenia	22	(26.8)	26	(32.1)	0.495
Hyperkalemia	22	(26.8)	15	(18.5)	0.262
Tachycardia	22	(26.8)	19	(23.5)	0.719
Significant Events‡
Leukopenia	47	(57.3)	24	(29.6)	<0.001
Malaise	11	(13.4)	3	(3.7)	0.047
Dizziness	7	(8.5)	20	(24.7)	0.006

Infections occurring in both treatment groups during the 3-month follow-up are summarized in Table 3. No significant differences were seen between the Thymoglobulin and Atgam groups for all types of infections, and the incidence of cytomegalovirus (CMV) infection was equivalent in both groups. (Viral prophylaxis was by the center’s discretion during antibody treatment, but all centers used gancyclovir infusion during treatment.)

Table 3. Infections

BODY SYSTEM Preferred Term	Thymoglobulin n=82			Atgam n=81			p Value*
	No. of      Patients	(%)	Total     Reports	No. of     Patients	(%)	Total     Reports
* p Value comparing treatment groups using Fisher’s exact test.
BODY AS A WHOLE	30	(36.6)	36	22	(27.2)	29	0.240
Infection	25	(30.5)	26	19	(23.5)	21	0.378
Other	14	(17.1)	15	11	(13.6)	12	0.665
CMV	11	(13.4)	11	9	(11.1)	9	0.812
Sepsis	10	(12.2)	10	7	(9.6)	7	0.610
Moniliasis	0	(0.0)	0	1	(1.2)	1	0.497
DIGESTIVE	5	(6.1)	5	3	(3.7)	3	0.720
Gastrointestinal moniliasis	4	(4.9)	4	1	(1.2)	1	0.367
Oral moniliasis	3	(3.7)	0	2	(2.5)	1	0.497
Gastritis	1	(1.2)	1	0	(0.0)	0	1.000
RESPIRATORY	0	(0.0)	0	1	(1.2)	1	0.497
Pneumonia	0	(0.0)	0	1	(1.2)	1	0.497
SKIN	4	(4.9)	4	0	(0.0)	0	0.120
Herpes simplex	4	(4.9)	4	0	(0.0)	0	0.120
UROGENITAL	15	(18.3)	15	22	(29.2)	22	0.195
Urinary tract infection	15	(18.3)	15	21	(25.9)	21	0.262
Vaginitis	0	(0.0)	0	1	(1.2)	1	0.497
NOT SPECIFIED	0	(0.0)	0	2	(2.5)	2	0.245

Post-marketing Experience

The following adverse reactions have been identified during post approval use of Thymoglobulin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infusion-Associated Reactions and Immune System Disorders

IARs may occur following the administration of Thymoglobulin and may occur as soon as the first or second infusion during a single course of Thymoglobulin treatment. Clinical manifestations of infusion-associated reactions IARs have included some of the following signs and symptoms: fever, chills/rigors, dyspnea, nausea/vomiting, diarrhea, hypotension or hypertension, malaise, rash, and/or headache. IARs with Thymoglobulin are generally manageable with a reduction in infusion rates and/or with medications (See PRECAUTIONS). Serious and fatal anaphylactic reactions have been reported (See WARNINGS). The fatalities occurred in patients who did not receive epinephrine during the event.

IARs consistent with cytokine release syndrome (CRS) have been reported. Severe and potentially life-threatening CRS have also been reported. Post-marketing reports of severe CRS have included cardiorespiratory dysfunction (including hypotension, acute respiratory distress syndrome, pulmonary edema, myocardial infarction, tachycardia, and/or death).

During post-marketing surveillance, reactions such as fever, rash, arthralgia, and/or myalgia, indicating possible serum sickness, have been reported. Serum sickness tends to occur 5 to 15 days after onset of Thymoglobulin therapy. Symptoms are manageable with corticosteroid treatment. 

Adverse Events Due to Immunosuppression

Infections, reactivation of infection, and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents (See WARNINGS and PRECAUTIONS). Malignancies including, but not limited to post-transplant lymphoproliferative disorder (PTLD) and other lymphomas as well as solid tumors have been reported (See PRECAUTIONS). These adverse events were reported with use of a combination of multiple immunosuppressive agents.

Overdosage

Thymoglobulin overdosage may result in leukopenia (including lymphopenia and neutropenia) or thrombocytopenia, which can be managed with dose reduction (See DOSAGE AND ADMINISTRATION).

Thymoglobulin Dosage and Administration

The recommended dosage of Thymoglobulin for treatment of acute renal graft rejection is 1.5 mg/kg of body weight administered daily for 7 to 14 days. The recommended route of administration is intravenous infusion using a high-flow vein. Thymoglobulin should be infused over a minimum of 6 hours for the first infusion and over at least 4 hours on subsequent days of therapy.

Thymoglobulin should be administered through an in-line 0.22 micrometer filter.

Thymoglobulin is supplied as a 10 mL vial containing lyophilized (solid) Thymoglobulin (25 mg).

Please see Preparation for Administration for vial reconstitution and dilution in infusion solution recommendations. Investigations indicate that Thymoglobulin is less likely to produce side effects when administered at the recommended flow rate. Administration of antiviral prophylactic therapy is recommended. Premedication with corticosteroids, acetaminophen, and/or an antihistamine 1 hour prior to the infusion is recommended and may reduce the incidence and intensity of side effects during the infusion (See PRECAUTIONS: General and ADVERSE REACTIONS: Post-Marketing Experience). Medical personnel should monitor patients for adverse events during and after infusion. Monitoring T-cell counts (absolute and/or subsets) to assess the level of T-cell depletion is recommended. Total white blood cell and platelet counts should be monitored.

Overdosage of Thymoglobulin may result in leukopenia (including lymphopenia and neutropenia) and/or thrombocytopenia. The Thymoglobulin dose should be reduced by one-half if the WBC count is between 2,000 and 3,000 cells/mm3 or if the platelet count is between 50,000 and 75,000 cells/mm3. Stopping Thymoglobulin treatment should be considered if the WBC count falls below 2,000 cells/mm3 or platelets below 50,000 cells/mm3.

Preparation for Administration

Reconstitution

After calculating the number of vials needed, using aseptic technique, reconstitute each vial of Thymoglobulin with 5 mL of Sterile Water for Injection, USP (SWFI). Reconstituted Thymoglobulin is physically and chemically stable for up to 24 hours at room temperature; however, room temperature storage is not recommended. As Thymoglobulin contains no preservatives, reconstituted product should be used immediately.

1. Allow Thymoglobulin vials to reach room temperature before reconstituting the lyophilized product.


2. Aseptically remove caps to expose rubber stoppers.


3. Clean stoppers with germicidal or alcohol swab.


4. Aseptically reconstitute each vial of Thymoglobulin lyophilized powder with the 5 mL of SWFI.


5. Rotate vial gently until powder is completely dissolved. Each reconstituted vial contains 25 mg or 5 mg/mL of Thymoglobulin.


6. Inspect solution for particulate matter after reconstitution. Should some particulate matter remain, continue to gently rotate the vial until no particulate matter is visible. If particulate matter persists, discard this vial.

Dilution

1. Transfer the contents of the calculated number of Thymoglobulin vials into the bag of infusion solution (saline or dextrose). Recommended volume: per one vial of Thymoglobulin use 50 mL of infusion solution (total volume usually between 50 to 500 mL).


2. Mix the solution by inverting the bag gently only once or twice.

Infusion

1. Follow the manufacturer’s instructions for the infusion administration set. Infuse through a 0.22 micrometer filter into a high-flow vein.


2. Set the flow rate to deliver the dose over a minimum of 6 hours for the first dose and over at least 4 hours for subsequent doses.

How is Thymoglobulin Supplied

Thymoglobulin is available as sterile, lyophilized powder to be reconstituted with sterile Water for Injection, USP (SWFI). Each package contains a 10 mL vial of freeze-dried Thymoglobulin (25 mg) NDC# 58468-0080-1.

Storage

• Store in refrigerator at 2°C to 8°C (36°F to 46°F).


• Protect from light.


• Do not freeze.


• Do not use after the expiration date indicated on the label.


• Reconstituted Thymoglobulin is physically and chemically stable for up to 24 hours at room temperature; however, room temperature storage is not recommended. As Thymoglobulin contains no preservatives, reconstituted product should be used immediately.


• Infusion solutions of Thymoglobulin must be used immediately.


• Any unused drug remaining after infusion must be discarded.

REFERENCES

1. Bonnefoy-Bérard N, et al. Antibodies against functional leukocyte surface molecules in polyclonal antilymphocyte and antithymocyte globulins. Transplantation (1991)51:669-673.


2. Bonnefoy-Bérard N, et al. Inhibition of CD25 (IL-2Rα) expression and Tcell proliferation by polyclonal anti-thymocyte globulins. Immunology (1992)77:61-67.


3. Bonnefoy-Bérard N, et al. Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines. Blood (1992)79:2164-2170.


4. Bonnefoy-Bérard N, Revillard J-P. Mechanisms of immunosuppression induced by antilymphocyte globulins and OKT3. J Heart Lung Transplant (1996)15:435-442.


5. Bourdage J, et al. Comparative polyclonal antithymocyte globulin and antilymphocyte/antilymphoblast globulin anti-CD antigen analysis by flow cytometry. Transplantation (1995)59:1194-1200.


6. Broyer M, et al. Triple therapy including cyclosporine A versus conventional regimen–a randomized prospective study in pediatric kidney transplantation. Transplant Proc (1987)19:3582-3585.


7. Clark KR, et al. Administration of ATG according to the absolute T lymphocyte count during therapy for steroid-resistant rejection. Transpl Int (1993)6:18-21.


8. Gaber AO, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation (1998)66:29-37.


9. Guttmann RD, et al. Pharmacokinetics, foreign protein immune response, cytokine release, and lymphocyte subsets in patients receiving Thymoglobuline and immunosuppression. Transplant Proc (1997)29(suppl 7A):24S-26S.


10. Ippoliti G, et al. Prophylactic use of rabbit ATG vs horse ALG in hearttransplanted patients under Sandimmun (CyA) therapy: clinical and immunological effects. Clin Transplantation (1989)3:204-208.

Manufactured for:                       By:               

Genzyme Corporation                         Genzyme Polyclonals, S.A.S.    

500 Kendall Street                               Marcy L’Etoile, France

Cambridge, MA 02142 USA              US License No. 1596    

©2007 Genzyme Corporation. All rights reserved.

Package Label - Principal Display Panel – 25 mg Carton

NDC 58468-0080-1

 

Thymoglobulin®

Anti-thymocyte Globulin (Rabbit)

 

25 mg

 

For Intravenous Infusion Only

 

Rx Only

 

genzyme

Thymoglobulin  anti-thymocyte globulin (rabbit)  injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 58468-0080 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN (RABBIT) LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN 5 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength GLYCINE 10 mg  in 1 mL SODIUM CHLORIDE 2 mg  in 1 mL MANNITOL 10 mg  in 1 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 58468-0080-1 5 mL In 1 VIAL, GLASS None

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