Uniphyl

Generic Name: theophylline (Oral route)

thee-OF-i-lin

Commonly used brand name(s)

In the U.S.

• Elixophyllin


• Norphyl


• Phyllocontin


• Quibron-T


• Quibron-T/SR


• Theo-24


• TheoCap


• Theochron


• Theo-Dur


• Theo-Time


• Truxophyllin


• Uniphyl

Available Dosage Forms:

• Solution


• Tablet, Extended Release, 12 HR


• Tablet


• Capsule, Extended Release, 24 HR


• Capsule, Extended Release


• Tablet, Extended Release


• Capsule, Extended Release, 12 HR


• Syrup


• Capsule


• Tablet, Extended Release, 24 HR


• Elixir


• Tablet, Enteric Coated

Therapeutic Class: Bronchodilator

Chemical Class: Methylxanthine

Uses For Uniphyl

Theophylline is used together with other medicines to treat the symptoms of asthma, bronchitis, emphysema, and other lung diseases.

Theophylline belongs to a group of medicines known as bronchodilators. Bronchodilators are medicines that relax the muscles in the bronchial tubes (air passages) of the lungs. They relieve cough, wheezing, shortness of breath, and troubled breathing by increasing the flow of air through the bronchial tubes.

This medicine is available only with your doctor's prescription.

Before Using Uniphyl

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

Allergies

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

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of theophylline in children. However, children younger than 1 year of age are more likely to have serious side effects, which may require caution and an adjustment in the dose for patients receiving theophylline.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of theophylline in the elderly. However, elderly patients may be more sensitive to the effects of theophylline than younger adults, and are more likely to have kidney, liver, heart, or lung problems, which may require caution and an adjustment in the dose for patients receiving theophylline.

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

Studies in women suggest that this medication poses minimal risk to the infant when used during 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 this medicine, 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 this medicine 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.

• Bupropion


• Cimetidine


• Ciprofloxacin


• Deferasirox


• Desogestrel


• Dienogest


• Drospirenone


• Enoxacin


• Erythromycin


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etintidine


• Etonogestrel


• Fluvoxamine


• Halothane


• Idrocilamide


• Imipenem


• Levofloxacin


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Mexiletine


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Pefloxacin


• Peginterferon Alfa-2a


• Rofecoxib


• Thiabendazole


• Troleandomycin


• Vemurafenib


• Zileuton

Using this medicine 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.

• Adenosine


• Adinazolam


• Alprazolam


• Aminoglutethimide


• Amiodarone


• Azithromycin


• Bromazepam


• Brotizolam


• Cannabis


• Carbamazepine


• Chlordiazepoxide


• Clobazam


• Clonazepam


• Clorazepate


• Diazepam


• Disulfiram


• Estazolam


• Febuxostat


• Flunitrazepam


• Flurazepam


• Fosphenytoin


• Halazepam


• Interferon Alfa-2a


• Ipriflavone


• Isoproterenol


• Ketazolam


• Lorazepam


• Lormetazepam


• Medazepam


• Methotrexate


• Midazolam


• Nilutamide


• Nitrazepam


• Oxazepam


• Pancuronium


• Pentoxifylline


• Phenobarbital


• Phenytoin


• Piperine


• Prazepam


• Propafenone


• Quazepam


• Rifampin


• Rifapentine


• Riluzole


• Ritonavir


• Secobarbital


• St John's Wort


• Tacrine


• Tacrolimus


• Telithromycin


• Temazepam


• Ticlopidine


• Triazolam


• Viloxazine


• Zafirlukast

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 this medicine 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 this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Caffeine


• food

Other Medical Problems

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

• Congestive heart failure or


• Cor pulmonale (heart condition) or


• Fever of 102 degrees F or higher for 24 hours or more or


• Hypothyroidism (underactive thyroid) or


• Infection, severe (e.g., sepsis) or


• Kidney disease in infants younger than 3 months of age or


• Liver disease (e.g., cirrhosis, hepatitis) or


• Pulmonary edema (lung condition) or


• Shock (serious condition with very little blood flow in the body)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Heart rhythm problems (e.g., arrhythmia) or


• Seizures, or history of or


• Stomach ulcer—Use with caution. May make these conditions worse.

Proper Use of theophylline

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

Take this medicine exactly as directed by your doctor. Do not take more of it and do not take it more often than your doctor ordered. This medicine works best if there is a constant amount in the blood. To keep the blood level constant, take this medicine at the same time each day and do not miss any doses.

After you or your child begin taking theophylline, it is very important that your doctor check the level of the medicine in the blood at regular intervals to decide if the dose needs to be changed. Keep all appointments for testing the blood level.

Take the extended-release capsule or tablet every morning at the same time each day. You may take your second dose 10 to 12 hours after the morning dose and before the evening meal, unless your doctor tells you otherwise.

Swallow the extended-release tablet whole. Do not break, crush, or chew it. You may take the extended-release tablet with or without food.

It is best to take the extended-release capsule one hour before a high-fat meal or without food.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Dosing

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

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

• To treat symptoms of asthma, bronchitis, and emphysema:
  
  • For oral dosage form (elixir or tablets):
    
    • Adults, teenagers, and children above 1 year of age weighing more than 45 kilograms (kg)—At first, 300 milligrams (mg) per day, divided and given every 6 to 8 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
    
    
    • Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day, divided and given every 6 to 8 hours.
    
    
    • Children and teenagers 1 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day, divided and given every 4 to 6 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
    
    
    • Infants younger than 1 year of age—Dose is based on body weight and age and must be determined by your doctor.
    
    
  
  
  • For oral dosage form (extended-release capsules):
    
    • Adults, teenagers, and children 12 years of age and older weighing more than 45 kilograms (kg)—At first, 300 to 400 milligrams (mg) as a single dose, usually in the morning, or divided and given two times per day. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
    
    
    • Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day as a single dose, usually in the morning, or divided and given two times per day.
    
    
    • Children and teenagers 12 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day as a single dose, usually in the morning, or divided and given two times per day. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
    
    
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (extended-release tablets):
    
    • Adults, teenagers, and children 6 years of age and older weighing more than 45 kilograms (kg)—At first, 300 milligrams (mg) per day, divided and given every 12 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
    
    
    • Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day, divided and given every 12 hours.
    
    
    • Children and teenagers 6 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day, divided and given every 12 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
    
    
    • Children younger than 6 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, 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 Uniphyl

It is very important that your doctor check the progress of you or your child at regular visits, especially for the first few weeks after you begin using this medicine. Blood tests may be needed to check for unwanted effects.

A change in your usual behavior or physical well-being may affect the way this medicine works in your body. Tell your doctor if you or your child:

• Have had a fever of 102 degrees F or higher for at least 24 hours or more.


• Have started or stopped smoking tobacco or marijuana in the last few weeks.


• Have started or stopped taking another medicine in the last few weeks.


• Have changed your diet in the last few weeks.

Stop using this medicine and check with your doctor right away if you or your child have the following symptoms while using this medicine: nausea or vomiting that continues, headaches, trouble with sleeping, seizures, or irregular heartbeats.

Do not stop or change the dose of this medicine without checking first with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you or your child are using this medicine. The results of some tests may be affected by this medicine.

This medicine may add to the central nervous system (CNS) stimulant effects of caffeine-containing foods or beverages such as chocolate, cocoa, tea, coffee, and cola drinks. Avoid eating or drinking large amounts of these foods or beverages while using this medicine. If you have questions about this, 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 for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal (e.g., St. John's wort) or vitamin supplements.

Uniphyl 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:

Incidence not known

• Chest pain or discomfort


• dizziness


• fainting


• fast, slow, or irregular heartbeat


• increase in urine volume


• lightheadedness


• persistent vomiting


• pounding or rapid pulse


• seizures


• shakiness

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Abdominal or stomach pain


• blurred vision


• confusion


• confusion about identity, place, and time


• dark-colored urine


• decrease in frequency of urination


• decreased urine


• diarrhea


• difficulty in passing urine (dribbling)


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


• dry mouth


• fast, pounding, or irregular heartbeat or pulse


• fever


• increased thirst


• irregular heartbeat


• loss of appetite


• mood changes


• muscle cramps or spasms


• muscle pain or stiffness


• nausea or vomiting


• nervousness


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


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


• painful urination


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


• shortness of breath


• sweating


• unusual tiredness or weakness


• vomiting of blood or material that looks like coffee grounds

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:

Incidence not known

• Headache


• irritability


• restlessness


• sleeplessness


• trouble sleeping


• unable to sleep

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.

See also: Uniphyl side effects (in more detail)

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 Uniphyl resources

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

• Uniphyl Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Uniphyl Prescribing Information (FDA)


• Uniphyl Concise Consumer Information (Cerner Multum)


• Theophylline Prescribing Information (FDA)


• Theophylline Professional Patient Advice (Wolters Kluwer)


• Elixophyllin Prescribing Information (FDA)


• Elixophyllin Elixir MedFacts Consumer Leaflet (Wolters Kluwer)


• Quibron-T MedFacts Consumer Leaflet (Wolters Kluwer)


• Quibron-T Prescribing Information (FDA)


• Theo-24 Prescribing Information (FDA)


• TheoCap Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Theolair tablets Prescribing Information (FDA)


• Theophyllines Monograph (AHFS DI)

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Ultravate Cream

Dosage Form: cream
Ultravate®

(halobetasol propionate cream) Cream, 0.05%

For Dermatological Use Only. Not for Ophthalmic Use.

Rx only

Ultravate Cream Description

Ultravate® (halobetasol propionate cream) Cream, 0.05% contains halobetasol propionate, a synthetic corticosteroid for topical dermatological use. The corticosteroids constitute a class of primarily synthetic steroids used topically as an anti-inflammatory and antipruritic agent.

Chemically halobetasol propionate is 21-chloro-6α, 9-difluoro-11β, 17-dihydroxy-16β-methylpregna-1, 4-diene-3-20-dione, 17-propionate, C25H31ClF2O5. It has the following structural formula:

Halobetasol propionate has the molecular weight of 485. It is a white crystalline powder insoluble in water.

Each gram of Ultravate Cream contains 0.5 mg/g of halobetasol propionate in a cream base of cetyl alcohol, glycerin, isopropyl isostearate, isopropyl palmitate, steareth-21, diazolidinyl urea, methylchloroisothiazolinone, (and) methylisothiazolinone and water.

Ultravate Cream - Clinical Pharmacology

Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids, 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 dressings with hydrocortisone for up to 24 hours have 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.

Human and animal studies indicate that less than 6% of the applied dose of halobetasol propionate enters the circulation within 96 hours following topical administration of the cream.

Studies performed with Ultravate Cream indicate that it is in the super-high range of potency as compared with other topical corticosteroids.

Indications and Usage for Ultravate Cream

Ultravate Cream 0.05% is a super-high potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond two 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 children under 12 years of age is not recommended.

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 the diagnosis may be necessary.

Contraindications

Ultravate Cream is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Precautions

General

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

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 suppression.

Ultravate Cream produced HPA axis suppression when used in divided doses at 7 grams per day for one week in patients with psoriasis. These effects were reversible upon discontinuation of treatment.

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 upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring 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 (see PRECAUTIONS: Pediatric Use).

If irritation develops, Ultravate Cream should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing 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 Ultravate Cream should be discontinued until the infection has been adequately controlled.

Ultravate Cream should not be used in the treatment of rosacea or perioral dermatitis, and it should not be used on the face, groin, or in the axillae.

Information for Patients

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

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


2. The 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 to their physician any signs of local adverse reactions.

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, and Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol propionate. Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation assay in vitro.

Studies in the rat following oral administration at dose levels up to 50 µg/kg/day indicated no impairment of fertility or general reproductive performance.

In other genotoxicity testing, halobetasol propionate was not found to be genotoxic in the Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster, in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot test to determine point mutations.

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 in laboratory animals.

Halobetasol propionate has been shown to be teratogenic in SPF rats and chinchilla-type rabbits when given systemically during gestation at doses of 0.04 to 0.1 mg/kg in rats and 0.01 mg/kg in rabbits. These doses are approximately 13, 33 and 3 times, respectively, the human topical dose of Ultravate Cream. Halobetasol propionate was embryotoxic in rabbits but not in rats.

Cleft palate was observed in both rats and rabbits. Omphalocele was seen in rats, but not in rabbits.

There are no adequate and well-controlled studies of the teratogenic potential of halobetasol propionate in pregnant women. Ultravate Cream 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 Ultravate Cream is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Ultravate Cream in pediatric patients have not been established and use in pediatric patients under 12 is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

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

Geriatric Use

Of approximately 400 patients treated with Ultravate Cream in clinical studies, 25% were 61 years and over and 6% were 71 years and over. No overall differences in safety or effectiveness were observed between these patients and younger patients; and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Adverse Reactions

In controlled clinical trials, the most frequent adverse events reported for Ultravate Cream included stinging, burning or itching in 4.4% of the patients. Less frequently reported adverse reactions were dry skin, erythema, skin atrophy, leukoderma, vesicles and rash.

The following additional local adverse reactions are reported infrequently with topical corticosteroids, and they may occur more frequently with high potency corticosteroids, such as Ultravate Cream. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria.

Overdosage

Topically applied Ultravate Cream can be absorbed in sufficient amounts to produce systemic effects (seePRECAUTIONS).

Ultravate Cream Dosage and Administration

Apply a thin layer of Ultravate Cream to the affected skin once or twice daily, as directed by your physician, and rub in gently and completely.

Ultravate (halobetasol propionate cream) Cream is a super-high potency topical corticosteroid; therefore, treatment should be limited to two weeks, and amounts greater than 50 g/wk should not be used. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Ultravate Cream should not be used with occlusive dressings.

How is Ultravate Cream Supplied

Ultravate® (halobetasol propionate cream) Cream, 0.05% is supplied in the following tube sizes:

15 g (NDC 10631-103-15)

50 g (NDC 10631-103-50)

STORAGE

Store between 15°C and 30°C (59°F and 86°F).

RANBAXY

Jacksonville, FL 32257 USA

09-0085 (Flat), 09-0086 (Folded)

Revised May 2010

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

15 gram container label

15 gram carton label

50 gram container label

50 gram carton label

ULTRAVATE  halobetasol propionate  cream

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 10631-103 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HALOBETASOL PROPIONATE (HALOBETASOL) HALOBETASOL PROPIONATE 0.5 mg  in 1 g

Inactive Ingredients Ingredient Name Strength STEARETH-21   DIAZOLIDINYL UREA   METHYLCHLOROISOTHIAZOLINONE   CETYL ALCOHOL   GLYCERIN   ISOPROPYL PALMITATE   METHYLISOTHIAZOLINONE   WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 10631-103-15 15 g In 1 TUBE None 2 10631-103-50 50 g In 1 TUBE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019967	03/16/2009

Labeler - Ranbaxy Laboratories Inc. (169932519)

Registrant - Ranbaxy Laboratories Inc. (169932519)

Establishment
Name	Address	ID/FEI	Operations
Contract Pharmaceuticals Limited		248761249	manufacture

Revised: 05/2011Ranbaxy Laboratories Inc.

More Ultravate Cream resources

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

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• Eczema
• Psoriasis

Unna-Flex Elastic Unna Boot 3 inch

Generic Name: zinc oxide topical (ZINK OX ide)

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

What is Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

Zinc oxide is a mineral.

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

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

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

What is the most important information I should know about Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

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

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

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

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

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

What should I discuss with my health care provider before using Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

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

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

It is not known whether zinc oxide topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether zinc oxide topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without medical advice if you are breast-feeding a baby.

How should I use Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

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

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

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

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

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

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

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

Wash your hands before and after inserting a rectal suppository.

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

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

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

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

What happens if I miss a dose?

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

What happens if I overdose?

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

What should I avoid while using Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

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

Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using zinc oxide rectal suppositories if you have rectal bleeding or continued pain.

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

What other drugs will affect Unna-Flex Elastic Unna Boot 3 inch (zinc oxide topical)?

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

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

More Unna-Flex Elastic Unna Boot 3 inch resources

• Unna-Flex Elastic Unna Boot 3 inch Side Effects (in more detail)
• Unna-Flex Elastic Unna Boot 3 inch Use in Pregnancy & Breastfeeding
• 0 Reviews for Unna-Flex Elastic Unna Boot 3 inch - Add your own review/rating

• Arcalyst Monograph (AHFS DI)


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


• Desitin Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Unna-Flex Elastic Unna Boot 3 inch with other medications

• Anal Itching
• Dermatologic Lesion
• Diaper Rash

Where can I get more information?

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

See also: Unna-Flex Elastic Unna Boot 3 inch side effects (in more detail)

UR N-C Urinary Antiseptic

Dosage Form: tablet
UR N-C Urinary Antiseptic

Each tablet for oral administration contains:
Hyoscyamine sulfate	0.12 mg
Methenamine	81.6 mg
Methylene blue	10.8 mg
Phenyl salicylate	36.2 mg
Sodium phosphate, monobasic	40.8 mg

Inactive ingredients: calcium sulfate, carbopol 934P, D &C #27, FD &C Blue #2, FD& C Red #40, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, purified water, starch 1500, talc and titanium dioxide.

Hyoscyamine sulfate. [620-61-1] [3(S)-endo]-α-(Hydroxymethyl)-benzeneacetic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester sulfate(2:1)(salt); 1αH,5α H-tropan-3α-ol(-)-tropate (ester) sulfate(2:1)(salt); 3α-tropanyl S-(-)-tropate; I-tropic acid ester with tropine; I-tropine tropate. C34H48N2O10S. Hyoscyamine sulfate is an alkaloid of belladonna. Exists as a white crystalline powder. Its solutions are alkaline to litmus. Affected by light, it is slightly soluble in water; freely soluble in alcohol; sparingly soluble in ether.

Methenamine. [100-97-0] 1,3,5,7- Tetraazatricyclo [3.3.1.13•7] decane; hexamethylenetetramine; HMT; HMTA; hexamine; 1,3,5,7- tetraazaadamantane hexamethylenemine; Uritone; Urotropin. C6H12N4; mol wt 140.19; C 51.40%, H 8.63%, N 39.96%. Methenamine (hexamethylenetetramine)exists as colorless, lustrous crystals or white crystalline powder. Its solutions are alkaline to litmus. Freely soluble in water, soluble in alcohol and in chloroform.

Phenyl salicylate. [118-55-8] 2-Hydroxybenzoic acid phenyl ester; Salol. C13H10O3 ; mol wt 214.22, C 72.89%, H 4.71%, O 22.41%. Made by the action of phosphorus oxy-chloride on a mixture of phenol and salicylic acid. Phenyl salicylate exists as white crystals with a melting point of 41°-43° C. It is very slightly soluble in water and freely soluble in alcohol.

Sodium phosphate, monobasic. [7558-80-7] Phosphoric acid sodium salt (1:1); Sodium biphosphate; sodium dihydrogen phosphate; acid sodium phosphate; monosodium orthophosphate; primary sodium phosphate; [H2NaO4P:] mol wt 119.98, H 1.68%, Na 19.16%, O 53.34%, P 25.82%. Monohydrate, white, odorless slightly deliquesce crystals or granules. At 100°C loses all its water; when ignited it converts to metaphosphate. It is freely soluble in water and practically insoluble in alcohol. The aqueous solution is acid. pH of 0.1 molar aqueous solution at 25°C: 4.5.

Methylene blue. [61-73-4] 3,7-Bis(dimethylamino) phenothiazin-5-ium chloride; C.I. Basic Blue 9; methylthioninium chloride; tetramethylthionine chloride; 3,7-bis(dimethylamino) phenazathionium chloride. C16H18CIN3S; mol wt 319.85, C 60.08%, H 5.67%, Cl 11.08%, N 13.14%, S 10.03%. Methylene blue (Methylthionine chloride) exists as dark green crystals. It is soluble in water and in chloroform; sparingly soluble in alcohol.

INDICATIONS AND USAGE:

UR N-C is indicated for the treatment of symptoms of irritative voiding. Indicated for the relief of local symptoms, such as inflammation, hypermotility, and pain, which accompany lower urinary tract infections. Indicated for the relief of urinary tract symptoms caused by diagnostic procedures.

DOSAGE AND ADMINISTRATION:

FOR ORAL USE ONLY

Adults: One tablet 4 times per day by mouth, followed by liberal fluid intake. Older Children: Dosage must be individualized by physician. Not recommended for use in children younger than six years.

CONTRAINDICATIONS:

UR N-C is contraindicated in patients hypersensitive to any of its ingredients. Risk benefits should be carefully considered when the following medical problems exist: achalasia of esophagus, atony of colon, diseases of cardiovascular system, gastrointestinal hemorrhage; glaucoma; hemolytic anemia from pyruvate kinase and G6PD deficiencies, infected urolithiasis, myasthenia gravis, paralytic ileus, severe ulcerative colitis, toxic megacolon; acute urinary retention may be precipitated in obstructive uropathy (such as bladder neck obstruction due to prostatic hypertrophy).

WARNINGS AND PRECAUTIONS:

Do not exceed recommended dosage. This drug may make you dizzy or drowsy or cause blurred vision; use caution while driving, using machinery, or doing any activity that requires alertness or clear vision. Limit alcohol consumption. Cross sensitivity and/or related problems – patients intolerant of belladonna alkaloids or salicylates may be intolerant of this medication also. Delay in gastric emptying could complicate the management of gastric ulcers. There have been no studies to establish the safety of prolonged use of this product in humans. No known long-term animal studies have been performed to evaluate carcinogenic potential.

Pregnancy: Teratogenic Effects. Pregnancy Category C:

Hyoscyamine sulfate and methenamine cross the placenta. Studies have not been done in animals or humans. It is not known whether UR N-C tablets cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. UR N-C tablets should be given to a pregnant woman only if clearly needed.

Nursing Mothers:

Problems in humans have not been documented; however, methenamine and traces of hyoscyamine sulfate are excreted in breast milk. Accordingly, UR N-C tablets should be given to a lactating woman only if clearly needed. Discuss the risks and benefits with your doctor.

Pediatric Use:

Infants and young children are especially susceptible to the toxic effect of the belladonna alkaloids (hyoscyamine sulfate). This product contains salicylate, which is related to aspirin. Children and teenagers should not take aspirin, aspirin-containing or aspirin-related medications if they have chickenpox, influenza, or any undiagnosed illness without first consulting a doctor. A rare but serious illness known as Reye’s syndrome may occur. This medication is not recommended for children younger than 6 years.

Geriatric Use:

Kidney function becomes impaired with age. This medication is removed by the kidneys. Therefore, use with caution in elderly patients as they may respond to usual doses of hyoscyamine sulfate with excitement, agitation, drowsiness or confusion.

ADVERSE REACTIONS:

Cardiovascular: rapid heartbeat, flushing Central Nervous System: blurred vision, dizziness, drowsiness Genitourinary: difficulty micturition, acute urinary retention Gastrointestinal: dry mouth, nausea and vomiting Respiratory: shortness of breath or trouble breathing

Serious allergic reactions to this drug are rare. Seek immediate medical attention if you notice symptoms of a serious allergic reaction, including itching, rash, severe dizziness, swelling or trouble breathing.

This medication can cause urine and sometimes stools to turn blue-green. This effect is harmless and will subside after medication is stopped.

Call your doctor or physician for medical advice about side effects. The following number does not provide medical advice, but in the U.S. you may report suspected side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

This drug should not be used with the following medications because very serious interactions may occur: live influenza virus vaccine, pramlintide. Because of this product’s effect on gastrointestinal motility and gastric emptying, it may decrease the absorption of other oral medications during concurrent use such as: urinary alkalizers; thiazide diuretics (may cause the urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde); antimuscarinics (concurrent use may intensify antimuscarinic effects of hyoscyamine sulfate because of secondary antimuscarinic activities of these medications); antacids/antidiarrheals (may reduce absorption of hyoscyamine sulfate, concurrent use with antacids may cause urine to become alkaline, reducing effectiveness of methenamine by inhibiting its conversion to formaldehyde). Doses of these medications should be spaced 1 hour apart from doses of hyoscyamine sulfate; antimyasthenics (concurrent use with hyoscyamine sulfate may further reduce intestinal motility); ketoconazole (patients should be advised to take this combination at least 2 hours after ketoconazole); monoamine oxidase (MAO) inhibitors (concurrent use may intensify antimuscarinic side effects), opioid (narcotic analgesics may result in increased risk of severe constipation); sulfonamides (these drugs may precipitate with formaldehyde in the urine, increasing the danger of crystalluria). This is not a complete list of all drug interactions. Tell your doctor or pharmacist of all prescription medications prior to use.

DRUG ABUSE AND DEPENDENCE:

A dependence on the use of UR N-C has not been reported nor expected based on the pharmacology of the ingredients contained in UR N-C.

OVERDOSAGE:

By exceeding the recommended dosage of UR N-C, symptomology related to the overdose of its individual active ingredients may be expected as follows:

Hyoscyamine sulfate: Symptoms associated with overdosage of UR N-C will most probably be manifested in the symptoms related to overdosage of alkaloid hyoscyamine sulfate. Such symptoms as dryness of mucous membranes; dilation of pupils, hot, dry, flushed skin; hyperpyrexia; tachycardia; palpitations; elevated blood pressure; coma; circulatory collapse and death from respiratory failure can occur due to overdosage of these alkaloids.

Methenamine: If large amounts of the drug (2-8 g daily) are used over extended periods (3-4 weeks), bladder and gastrointestinal irritation, painful and frequent micturition, albuminuria and gross hematuria may be expected.

Phenyl salicylate: Symptoms of phenyl salicylate overdosage include burning pain in throat and mouth, white necrotic lesions in the mouth, abdominal pain, vomiting, bloody diarrhea, pallor, sweating, weakness, headache, dizziness and tinnitus. The symptoms, however, are not expected to be discernible from those associated with the other active ingredients in UR N-C.

Sodium phosphate, monobasic: Symptoms of sodium biphosphate overdosage may include diarrhea, dehydration, and electrolyte imbalances.

Methylene blue: Symptoms of methylene blue overdosage associated with the overdosage of UR N-C are not expected to be discernible from those associated with other active ingredients in UR N-C.

Treatment: Emesis or gastric lavage. Slow intravenous administration of physostigmine in doses of 1 to 4 mg (0.5 to 1 mg in children), repeated as needed in one to two hours to reverse severe antimuscarinic symptoms. Administration of small doses of diazepam or baclofen to control excitement and seizures. Artificial respiration with oxygen if needed for respiratory depression. Adequate re-hydration is required. Symptomatic treatment as determined by a doctor.

If overdose is suspected, contact your local poison center or emergency room immediately. US residents can contact the US National Poison Hotline at 1-800-222-1222.

CLINICAL PHARMACOLOGY:

Hyoscyamine sulfate: Hyoscyamine sulfate is a parasympatholytic which relaxes smooth muscles and thus produces an antispasmodic effect. It is well absorbed from the gastrointestinal tract and is rapidly distributed throughout the body tissues. Following oral administration, the drug has an onset of action of 20 to 30 minutes. The half-life is 3.5 hours. Hyoscyamine is distributed throughout the body, crosses the blood-brain barrier, and is approximately 50% bound to plasma proteins. It is metabolized in the liver to tropic acid, tropine, and hyoscyamine glucuronide. Hyoscyamine is excreted primarily unchanged in the urine within 12 hours. Its biotransformation is hepatic.

Methenamine: Methenamine, after oral administration, undergoes hydrolysis and generates formaldehyde, which provides bactericidal or bacteriostatic action. Methenamine is rapidly absorbed from the intestinal tract and is excreted, for the most part, unchanged in the urine at which point it is hydrolyzed if the urine is acidic. It is almost completely excreted (90%) in the urine within 24 hours; of this at a pH of 5, approximately 10-30% is converted to formaldehyde in the stomach.

Phenyl salicylate: Phenyl salicylate, a form of salicylic acid, is a mild analgesic for pain relief.

Sodium phosphate, monobasic: Sodium phosphate, monobasic increases urinary acidity helping to maintain an acid pH necessary for the degradation of methenamine.

Methylene blue: Methylene blue is a monoamine oxidase inhibitor with weak antiseptic properties. It is well absorbed by the intestinal tract and rapidly reduced to leukomethylene blue, which is stabilized in the urine. Approximately 70-80% is excreted unchanged in the urine.

HOW SUPPLIED:

UR N-C is available as a purple tablet, imprinted “293”: bottles of 100 tablets, NDC 51862-175-01. Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant closure. Store at controlled room temperature 15°-30°C (59°- 86°F). Keep in a cool, dry place.

WARNING: Keep this and all drugs out of reach of children. Caution: Rx Only

Manufactured for:

Libertas Pharma, Inc.

Lawrenceville, GA 30043

Iss. 04/11 175-01

1000412

Container Label

NDC 51862-175-01

UR N-C

Urinary Antiseptic

Each tablet for oral administration contains:

Hyoscyamine sulfate……...12 mg

Methenamine.....81.6 mg

Methylene blue.....10.8 mg

Phenyl salicylate.....36.2 mg

Sodium phosphate monobasic…..40.8 mg

Rx Only

100 TABLETS

Libertas

Pharma, Inc.

UR N-C Urinary Antiseptic  hyoscyamine sulfate, methenamine, phenyl salicylate, sodium phosphate monobasic, methylene blue   tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 51862-175 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYOSCYAMINE SULFATE (HYOSCYAMINE) HYOSCYAMINE SULFATE 0.12 mg SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE (PHOSPHORIC ACID) SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE 40.8 mg PHENYL SALICYLATE (PHENYL SALICYLATE) PHENYL SALICYLATE 36.2 mg METHENAMINE (METHENAMINE) METHENAMINE 81.6 mg METHYLENE BLUE (METHYLENE BLUE) METHYLENE BLUE 10.8 mg

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE   CARBOMER HOMOPOLYMER TYPE B   D&C RED NO. 27   FD&C BLUE NO. 2   FD&C RED NO. 40   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   POLYETHYLENE GLYCOL   POLYVINYL ALCOHOL   WATER   STARCH, CORN   TALC   TITANIUM DIOXIDE

Product Characteristics Color PURPLE Score no score Shape ROUND Size 10mm Flavor Imprint Code 293 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51862-175-01 100 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		05/21/2011

Labeler - Libertas Pharma, Inc. (962128943)

Revised: 05/2011Libertas Pharma, Inc.

More UR N-C Urinary Antiseptic resources

• UR N-C Urinary Antiseptic Use in Pregnancy & Breastfeeding
• UR N-C Urinary Antiseptic Drug Interactions
• UR N-C Urinary Antiseptic Support Group
• 16 Reviews for UR N-C Urinary Antiseptic - Add your own review/rating

Compare UR N-C Urinary Antiseptic with other medications

• Urinary Tract Infection

Urea in Zinc/Lactic Acid Nail Stick

Pronunciation: ue-REE-a/zink/LAK-tik AS-id
Generic Name: Urea in Zinc/Lactic Acid
Brand Name: Urea Nail

Urea in Zinc/Lactic Acid Nail Stick is used for:

Aiding in the healing of certain skin and nail conditions (eg, calluses; corns; dry, rough skin; eczema; psoriasis; ingrown nails). It may also be used for other conditions as determined by your doctor.

Urea in Zinc/Lactic Acid Nail Stick is a debriding agent. It works by helping to loosen, soften, and shed nails or hard and scaly skin.

Do NOT use Urea in Zinc/Lactic Acid Nail Stick if:

• you are allergic to any ingredient in Urea in Zinc/Lactic Acid Nail Stick

Contact your doctor or health care provider right away if this applies to you.

Before using Urea in Zinc/Lactic Acid Nail Stick:

Some medical conditions may interact with Urea in Zinc/Lactic Acid Nail Stick. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

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


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


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


• if you have a history of blood circulation problems or diabetes

Some MEDICINES MAY INTERACT with Urea in Zinc/Lactic Acid Nail Stick. Because little, if any, of Urea in Zinc/Lactic Acid Nail Stick is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Urea in Zinc/Lactic Acid Nail Stick may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Urea in Zinc/Lactic Acid Nail Stick:

Use Urea in Zinc/Lactic Acid Nail Stick as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Shake well before each use.


• Apply Urea in Zinc/Lactic Acid Nail Stick to the affected area as directed by your doctor. Gently rub it in until it is evenly distributed.


• Wash your hands immediately after using Urea in Zinc/Lactic Acid Nail Stick, unless your hands are part of the treated area.


• As Urea in Zinc/Lactic Acid Nail Stick dries, it may turn white in color. This is normal and not a cause for concern.


• Use Urea in Zinc/Lactic Acid Nail Stick on a regular schedule to get the most benefit from it.


• If you miss a dose of Urea in Zinc/Lactic Acid Nail Stick, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Urea in Zinc/Lactic Acid Nail Stick.

Important safety information:

• Urea in Zinc/Lactic Acid Nail Stick is for external use only. Do not use near the vaginal/groin area. Do not get it on your lips or in your eyes, nose, or mouth. If you get it in any of these areas, rinse right away with cool tap water.


• Tell your doctor if your condition persists or worsens while using Urea in Zinc/Lactic Acid Nail Stick.


• Do not use more than the recommended dose or use for longer than prescribed without checking with your doctor.


• Do not use Urea in Zinc/Lactic Acid Nail Stick for other skin conditions without checking with your doctor.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Urea in Zinc/Lactic Acid Nail Stick while you are pregnant. It is not known if Urea in Zinc/Lactic Acid Nail Stick is found in breast milk after topical use. If you are or will be breast-feeding while you use Urea in Zinc/Lactic Acid Nail Stick, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Urea in Zinc/Lactic Acid Nail Stick:

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

Mild, temporary burning, stinging, or itching of the skin.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); severe or persistent skin burning, stinging, or itching; skin redness or irritation.

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

If OVERDOSE is suspected:

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

Proper storage of Urea in Zinc/Lactic Acid Nail Stick:

Store Urea in Zinc/Lactic Acid Nail Stick at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Protect from freezing. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Urea in Zinc/Lactic Acid Nail Stick out of the reach of children and away from pets.

General information:

• If you have any questions about Urea in Zinc/Lactic Acid Nail Stick, please talk with your doctor, pharmacist, or other health care provider.


• Urea in Zinc/Lactic Acid Nail Stick is to be used only by the patient for whom it is prescribed. Do not share it with other people.


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


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

This information is a summary only. It does not contain all information about Urea in Zinc/Lactic Acid Nail Stick. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

Ultravist Injection

Dosage Form: injection
FULL PRESCRIBING INFORMATION

WARNING: NOT FOR INTRATHECAL USE

Inadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. [See Contraindications (4).]

Indications and Usage for Ultravist Injection

ULTRAVIST® Injection is an iodinated contrast agent indicated for:

Intra-Arterial Procedures*

• 150 mg I/mL for intra-arterial digital subtraction angiography (IA-DSA)


• 300 mg I/mL for cerebral arteriography and peripheral arteriography


• 370 mg I/mL for coronary arteriography and left ventriculography, visceral angiography, and aortography

Intravenous Procedures*

• 240 mg I/mL for peripheral venography


• 300 mg I/mL for excretory urography


• 300 mg I/mL and 370 mg I/mL for contrast Computed Tomography (CT) of the head and body (intrathoracic, intra-abdominal and retroperitoneal regions) for the evaluation of neoplastic and non-neoplastic lesions. The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated

*For information on the concentrations and doses for the Pediatric Population [see Dosage and Administration (2.3) and Use in Specific Populations (8.4)].

Ultravist Injection Dosage and Administration

• Visually inspect ULTRAVIST for particulate matter and/or discoloration, whenever solution and container permit. Do not administer ULTRAVIST if particulate matter and/or discoloration is observed.


• Determine the volume and concentration of Ultravist Injection to be used taking into account factors such as age, body weight, size of the vessel and the rate of blood flow within the vessel; consider also extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed. Specific dose adjustments for age, gender, weight and renal function have not been studied for Ultravist Injection. As with all iodinated contrast agents, lower doses may have less risk. The efficacy of Ultravist Injection below doses recommended has not been established.


• The maximum recommended total dose of iodine in adults is 86 grams; a maximum recommended total dose of iodine has not been established for pediatric patients.


• Hydrate patients adequately prior to and following the intravascular administration of ULTRAVIST. [See Warnings and Precautions (5.2).]

Intra-Arterial Procedures

The volume and rate of injection of the contrast agent will vary depending on the injection site and the area being examined. Inject contrast at rates approximately equal to the flow rate in the vessel being injected.

• Cerebral Arteriography (300 mg I/mL), Coronary Arteriography and Left Ventriculography (370 mg I/mL), Peripheral Arteriography (300 mg I/mL), Intra-arterial Digital Subtraction Angiography (IA-DSA) (150 mg I/mL): see Table 1.


• Aortography and Visceral Angiography (370 mg I/mL):
  

  Use a volume and rate of contrast injection proportional to the blood flow and related to the vascular and pathological characteristics of the specific vessels being studied. Do not exceed 225 mL as total dose for the procedure.

  
  

Table 1: Suggested Single Injection Doses for Adult Intra-Arterial Procedures

* *IA-DSA = Intra-Arterial Digital Subtraction Angiography
		IA-DSA** (150 mg I/mL)	Cerebral Arteriography (300 mg I/mL)	Peripheral Arteriography (300 mg I/mL)	Coronary Arteriography and Left Ventriculography (370 mg I/mL)
Intra-Arterial Injection Sites	Carotid Arteries Vertebral Arteries Aortic Arch Injection (4 vessel study)	6–10 mL 4–8 mL -	3–12 mL 4–12 mL 20–50 mL	- - -	- - -
	Right Coronary Artery Left Coronary Artery Left Ventricle	- - -	- - -	- - -	3–14 mL 3–14 mL 30–60 mL
	Aorta Major Branches of the Abdominal Aorta	20–50 mL 2–20 mL	- -	- -	- -
	Subclavian or Femoral Artery Aortic Bifurcation (distal runoff)	- -	- -	5–40 mL 25–50 mL	- -
	Maximum Total Dose	250 mL	150 mL	250 mL	225 mL

 2.2 Intravenous Procedures

• Peripheral Venography (240 mg I/mL):


• Inject the minimum volume necessary to visualize satisfactorily the structures under examination. Do not exceed 250 mL as total dose for the procedure.


• Contrast Computed Tomography (CT) (300 mg I/mL and 370 mg I/mL) and Excretory Urography (300 mg I/mL): see Table 2.

Table 2: Suggested Ultravist Injection Dosing for Adult Intravenous Contrast Administration

	Excretory Urography (300 mg I/mL)	Contrast Computed Tomography (300 mg I/mL)	Contrast Computed Tomography (370 mg I/mL)
Excretory Urography	Approximately 300 mg I/kg body wt. (Adults with normal renal function)	-	-
Head	-	50–200 mL	41–162 mL
Body     Bolus Injection     Rapid Infusion	- -	50–200 mL 100–200 mL	41–162 mL 81–162 mL
Maximum Total Dose	100 mL	200 mL (60 g iodine)	162 mL (60 g iodine)

 

Pediatric Dosing

The recommended dose in children over 2 years of age for the following evaluations is:

• Intra-arterial:

Cardiac chambers and related arteries (370 mg I/mL):

Inject 1 to 2 milliliters per kilogram (mL/kg). Do not exceed 4 mL/kg as total dose.

• Intravenous:

Contrast Computerized Tomography or Excretory Urography (300 mg I/mL):

Inject 1 to 2 mL/kg. Do not exceed 3 mL/kg as total dose.

The safety and efficacy relationships of other doses, concentrations or procedures have not been established [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].

Dosage Forms and Strengths

Ultravist Injection is a nonionic, sterile, clear, colorless to slightly yellow, odorless, pyrogen-free aqueous solution of iopromide, containing 2.42 mg/mL tromethamine buffer and 0.1 mg/mL edetate calcium disodium stabilizer.

Ultravist Injection is available in four strengths:

150 mg I/mL provides 311.7 mg/mL iopromide,

240 mg I/mL provides 498.72 mg/mL iopromide,

300 mg I/mL provides 623.4 mg/mL iopromide,

370 mg I/mL provides 768.86 mg/mL iopromide.

Contraindications

• Do not administer Ultravist Injection intrathecally. Inadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.


• Preparatory dehydration (for example, prolonged fasting and the administration of a laxative) before Ultravist Injection is contraindicated in pediatric patients because of risk of acute renal failure.

Warnings and Precautions

Anaphylactoid Reactions

Life-threatening or fatal, anaphylactoid reactions, may occur during or after ULTRAVIST administration. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock. Increased risk is associated with a history of previous reaction to a contrast agent (3-fold), a known sensitivity to iodine and known allergic disorders (that is, bronchial asthma, hay fever and food allergies) or other hypersensitivities (2-fold) [see Drug Interactions (7.1)]. Exercise extreme caution when considering the use of iodinated contrast agents in patients with these histories or disorders.

Emergency facilities and personnel trained in the treatment of anaphylactoid reactions should be available for at least 30 to 60 minutes after ULTRAVIST administration.

Acute Renal Failure

Acute renal insufficiency or failure may occur following ULTRAVIST administration, particularly in patients with advanced vascular disease, congestive heart disease, diabetes, multiple myeloma or other paraproteinacious diseases, patients on medications which alter renal function and the elderly with age-related renal impairment. ULTRAVIST is cleared by glomerular filtration; patients with renal insufficiency have increased systemic exposure to ULTRAVIST as compared to patients with normal renal function [see Use in Specific Populations (8.6)].

Exercise caution and use the lowest necessary dose of ULTRAVIST in patients with renal insufficiency. Adequately hydrate patients prior to and following ULTRAVIST administration. Patients with congestive heart failure receiving concurrent diuretic therapy may have relative intravascular volume depletion, which may affect the renal response to the contrast agent osmotic load. Observe such patients for several hours following the procedure to detect delayed hemodynamic renal function disturbances.

Cardiovascular Reactions

The increase in the circulatory osmotic load may induce acute or delayed hemodynamic disturbances in patients with congestive heart failure, severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, particularly when repetitive and/or large doses are administered [see Drug Interactions (7)].

Among patients who have had cardiovascular reactions, most deaths occurred from the start of injection to 10 minutes later; the main feature was cardiac arrest with cardiovascular disease as the main underlying factor. Isolated reports of hypotensive collapse and shock have been published. Based upon published reports, deaths from the administration of iodinated contrast agents range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients (0.01 percent). Observe patients with preexisting cardiovascular disease for several hours following ULTRAVIST administration.

Thromboembolic Complications

• Angiography may be associated with local and distal organ damage, ischemia, thromboembolism and organ failure including stroke, brachial plexus palsy, chest pain, myocardial infarction, sinus arrest, hepato-renal function abnormalities. For these reasons, meticulous angiographic techniques are recommended, including close attention to guide wire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions and minimizing the length of the procedure.  In angiographic procedures, consider the possibility of dislodging plaques or damaging or perforating the vessel wall with resultant pseudoaneurysms, hemorrhage at puncture site, dissection of coronary artery during catheter manipulations and contrast agent injection. The physicochemical properties of the contrast agent, the dose and the speed of injection can influence the reactions. Test injections to ensure proper catheter placement are suggested. Increased thrombosis and activation of the complement system has also occurred. Specialized personnel, and adequate equipment and facilities for immediate resuscitation and cardioversion are necessary. Monitor electrocardiograms and vital signs throughout the procedure.


• Exercise care when performing venography in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection, venous thrombosis or a totally obstructed venous system.


• Clotting may occur when blood remains in contact with syringes containing iodinated contrast agents.


• Avoid angiography whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism [see Clinical Pharmacology (12.2)].

Reactions in Patients with Hyperthyroidism, Pheochromocytoma, or Sickle Cell Disease

Thyroid storm in patients with hyperthyroidism. Thyroid storm has occurred after the intravascular use of iodinated contrast agents in patients with hyperthyroidism, or with an autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of any iodinated contrast agent.

Hypertensive crises in patients with pheochromocytoma. Administer iodinated contrast agents with extreme caution in patients with known or suspected of having pheochromocytoma. Inject the minimum amount of contrast necessary. Assess the blood pressure throughout the procedure, and have measures for treatment of a hypertensive crisis readily available.

Sickle cell disease. Contrast agents may promote sickling in individuals who are homozygous for sickle cell disease when administered intravascularly.

Extravasation

Extravasation of Ultravist Injection may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease.

Increased Radiation Exposure

The decision to use contrast enhancement is associated with risk and increased radiation exposure. Use contrast after a careful evaluation of clinical, other radiologic data, and the results of non-contrast CT findings, taking into account the increased radiation dose and other risks.

Interference with Image Interpretation

As with other iodinated contrast agents, the use of Ultravist Injection may obscure some lesions which were seen on non-contrast CT scans.

Calcified lesions are less likely to enhance. The enhancement of tumors after therapy may decrease. The opacification of the inferior vermis following contrast agent administration has resulted in false-positive diagnosis. Cerebral infarctions of recent onset may be better visualized with contrast enhancement. However, older infarctions may be obscured by the contrast agent.

In patients with normal blood-brain barriers and renal failure, iodinated contrast agents have been associated with blood-brain barrier disruption and accumulation of contrast in the brain. Accumulation of contrast in the brain also occurs in patients where the blood-brain barrier is known or suspected to be disrupted.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.

The following table of incidence of reactions is based upon controlled clinical trials in which Ultravist Injection was administered to 1142 patients. This listing includes all reported adverse reactions regardless of attribution.

Adverse reactions are listed by System Organ Class and in decreasing order of occurrence for rates greater than 1% in the ULTRAVIST group.

Table 3: ADVERSE REACTIONS REPORTED IN > 1% OF PATIENTS WHO RECEIVED Ultravist Injection IN CLINICAL TRIALS
System Organ Class	Adverse Reaction	Ultravist Injection
		N=1142 (%)
Nervous system disorders	Headache	46 (4)
	Dysgeusia	15 (1.3)
Eye disorders	Abnormal Vision	12 (1.1)
Cardiac disorders	Chest pain	18 (1.6)
Vascular disorders	Vasodilatation	30 (2.6)
Gastrointestinal disorders	Nausea	42 (3.7)
	Vomiting	22 (1.9)
Musculoskeletal and connective tissue disorders	Back pain	22 (1.9)
Renal and urinary disorders	Urinary urgency	21 (1.8)
General disorders and administration site conditions	Injection site and infusion site reactions (hemorrhage, hematoma, pain, edema, erythema, rash)	41 (3.7)
	Pain	13 (1.4)

 

One or more adverse reactions were recorded in 273 of 1142 (24%) patients during the clinical trials, coincident with the administration of Ultravist Injection or within the defined duration of the study follow-up period (24–72 hours). Ultravist Injection is often associated with sensations of warmth and/or pain.

Serious, life-threatening and fatal reactions have been associated with the administration of iodine-containing contrast media, including Ultravist Injection. In clinical trials 7/1142 patients given Ultravist Injection died 5 days or later after drug administration. Also, 10/1142 patients given Ultravist Injection had serious adverse events.

The following adverse reactions were observed in ≤1% of the subjects receiving Ultravist Injection:

Cardiac disorders: atrio ventricular block (complete), bradycardia, ventricular extrasystole;

Gastrointestinal disorders: abdominal discomfort, abdominal pain, abdominal pain upper, constipation, diarrhea, dry mouth, dyspepsia, gastrointestinal disorder, gastrointestinal pain, salivation increased, stomach discomfort, rectal tenesmus;

General disorders and administration site conditions: asthenia, chest discomfort, chills, excessive thirst, extravasation, feeling hot, hyperhydrosis, malaise, edema peripheral, pyrexia;

Immune system disorders: asthma, face edema;

Investigations: blood lactate dehydrogenase increased, blood urea increased, hemoglobin increased, white blood cell count increased;

Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, myasthenia, neck pain, pain in extremity;

Nervous system disorders: agitation, confusion, convulsion, dizziness, hypertonia, hypesthesia, incoordination, neuropathy, somnolence, speech disorder, tremor, paresthesia, visual field defect;

Psychiatric disorders: anxiety;

Renal and urinary disorders: dysuria, renal pain, urinary retention;

Respiratory, thoracic and mediastinal disorders: apnea, cough increased, dyspnea, hypoxia, pharyngeal edema, pharyngitis, pleural effusion, pulmonary hypertension, respiratory disorder, sore throat;

Skin and subcutaneous tissue disorders: erythema, pruritus, rash, urticaria;

Vascular disorders: coronary artery thrombosis, flushing, hypertension, hypotension, peripheral vascular disorder, syncope, vascular anomaly.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Ultravist Injection. 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.

Adverse reactions reported in foreign postmarketing surveillance and other trials with the use of Ultravist Injection include:

Cardiac disorders: cardiac arrest, ventricular fibrillation, atrial fibrillation,  tachycardia, palpitations, congestive heart failure, myocardial infarction, angina pectoris;

Ear and labyrinth disorders: vertigo, tinnitus;

Endocrine disorders: hyperthyroidism, thyrotoxic crisis, hypothyroidism;

Eye disorders: mydriasis, lacrimation disorder;

Gastrointestinal disorders: dysphagia, swelling of salivary glands;

Immune system disorders: anaphylactoid reaction (including fatal cases), respiratory arrest, anaphylactoid shock, angioedema, laryngeal edema, laryngospasm, bronchospasm, hypersensitivity;

Nervous system disorders: cerebral ischemia/infarction, paralysis, paresis, transient cortical blindness, aphasia, coma, unconsciousness, amnesia, hypotonia;

Renal and urinary disorders: renal failure, hematuria;

Respiratory, thoracic and mediastinal disorders: pulmonary edema, acute respiratory distress syndrome, asthma;

Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome, skin discoloration;

Vascular disorders: vasospasm.

Pediatrics

The overall character, quality, and severity of adverse reactions in pediatric patients are generally similar to those reported in adult patients. Additional adverse reactions reported in pediatric patients from foreign marketing surveillance or other information are: epistaxis, angioedema, migraine, joint disorder (effusion), muscle cramps, mucous membrane disorder (mucosal swelling), conjunctivitis, hypoxia, fixed eruptions, vertigo, diabetes insipidus, and brain edema. [See Use in Specific Populations (8.4).]

Drug Interactions

Drug-Drug Interactions

In patients taking biguanides (for example, metformin), acute alterations in renal function after iodinated contrast agents may precipitate lactic acidosis. Stop biguanides 48 hours before the contrast medium examination and withhold until 48 hours after the procedure. (See biguanide package insert.)

Patients on beta-blockers may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. Because of the risk of hypersensitivity reactions, use caution when administering iodinated contrast agents to patients taking beta-blockers.

Interleukins are associated with an increased prevalence of delayed hypersensitivity reactions after iodinated contrast agent administration. These reactions include fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria.

Renal toxicity has been reported in a few patients with liver dysfunction who were given an oral cholecystographic agent followed by intravascular contrast agents. Administration of any intravascular contrast agent should therefore be postponed in patients who have recently received a cholecystographic contrast agent.

Do not mix other drugs with Ultravist Injection [see How Supplied/Storage and Handling (16)].

Drug-Laboratory Test Interactions

Thyroid Function Tests:

The results of protein bound iodine and radioactive iodine uptake studies, which depend on iodine estimation, will not accurately reflect thyroid function for at least 16 days following administration of iodinated contrast agents. However, thyroid function tests which do not depend on iodine estimations, for example, T3 resin uptake and total or free thyroxine (T4) assays are not affected.

Laboratory Assay of Coagulation Parameters, Fibrinolysis and Complement System:

The effect of iopromide on coagulation factors in in vitro assays increased with the administered dose. Coagulation, fibrinolysis and complement activation were evaluated with standard citrated human plasma in the following assays: thrombin time, thrombin coagulase time, calcium thromboplastin time, partial thromboplastin time, plasminogen, thrombin, alpha-2 antiplasmin and factor XIIa activity. Thrombin inhibition was almost complete. Data on reversibility are not available. The thrombin time increased from approximately 20 seconds at an iopromide concentration of 10 mg I/mL, up to 100 seconds at an iopromide concentration of 70 mg I/mL.

The PTT increased from approximately 50 seconds at an iopromide concentration of 10 mg I/mL, up to approximately 100 seconds at an iopromide concentration of 70 mg I/mL. A similar increase was noted in the thrombin coagulase time. Lesser effects were noted in the calcium thromboplastin time. Coagulation time increased from 13.5 to 23 seconds at the highest iopromide concentration of 70 mg I/mL. The Hageman factor split products decreased by about 20% over the range of 10 to 70 mg I/mL of iopromide. Plasminogen was relatively stable. There was no evidence of activation of fibrinolysis. The complement alternate pathway was activated. Factor B conversion increased in a dose dependent manner. The duration of these effects was not studied.

In vitro studies with human blood showed that iopromide had a slight effect on coagulation and fibrinolysis. No Factor XIIa formation could be demonstrated. The complement alternate pathway also can be activated.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects: Pregnancy Category B

Reproduction studies performed with iopromide in rats and rabbits at doses up to 3.7 g I/kg (2.2 times the maximum recommended dose for a 50 kg human, or approximately 0.7 times the human dose following normalization of the data to body surface area estimates) have revealed no evidence of direct harm to the fetus. Embryolethality was observed in rabbits that received 3.7 g I/kg, but this was considered to have been secondary to maternal toxicity. Adequate and well-controlled studies in pregnant women have not been conducted. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether Ultravist Injection is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast agents are administered to nursing women because of potential adverse reaction, and consideration should be given to temporarily discontinuing nursing.

Pediatric Use

The safety and efficacy of Ultravist Injection have been established in the pediatric population over 2 years of age. Use of Ultravist Injection in these age groups is supported by evidence from adequate and well controlled studies of Ultravist Injection in adults and additional safety data obtained in literature and other reports in a total of 274 pediatric patients. Of these, there were 131 children (2–12 years), 57 adolescents, and 86 children of unreported or other ages. There were 148 females, 94 males and 32 in whom gender was not reported. The racial distribution was: Caucasian 93 (33.9%), Black 1 (0.4%), Asian 6 (2.2%), and unknown 174 (63.5%). These patients were evaluated in intra-arterial coronary angiographic (n=60), intravenous contrast computerized tomography (CT) (n=87), excretory urography (n=99) and 28 other procedures.

In these pediatric patients, a concentration of 300 mg I/mL was employed for intravenous contrast CT or excretory urography. A concentration of 370 mg I/mL was employed for intra-arterial and intracardiac administration in the radiographic evaluation of the heart cavities and major arteries. Most pediatric patients received initial volumes of 1–2 mL/kg.

Optimal doses of Ultravist Injection have not been established because different injection volumes, concentrations and injection rates were not studied. The relationship of the volume of injection with respect to the size of the target vascular bed has not been established. The potential need for dose adjustment on the basis of immature renal function has not been established. In the pediatric population, the pharmacokinetic parameters have not been established.

Pediatric patients at higher risk of experiencing an adverse reaction during and after administration of any contrast agent include those with asthma, a sensitivity to medication and/or allergens, cyanotic and acyanotic heart disease, congestive heart failure, or a serum creatinine greater than 1.5 mg/dL. The injection rates in small vascular beds, and the relationship of the dose by volume or concentration in small pediatric patients have not been established. Exercise caution in selecting the dose.

Safety and effectiveness in pediatric patients below the age of two have not been established.

Geriatric Use

Middle-aged and elderly patients, without significantly impaired renal function, who received Ultravist Injection in doses corresponding to 9–30 g iodine, had mean steady-state volumes of distribution that ranged between 30–40 L. Mean total and renal clearances were between 81–125 mL/min and 70–115 mL/min respectively in these patients, and were similar to the values found in the young volunteers. The distribution phase half-life in this patient population was 0.1 hour, the main elimination phase half-life was 2.3 hours, and the terminal elimination phase half-life was 40 hours. The urinary excretion (97% of the dose) and fecal excretion (2%) was comparable to that observed in young healthy volunteers, suggesting that, compared to the renal route, biliary and/or gastrointestinal excretion is not significant for iopromide.

Renal Impairment

In patients with renal impairment, opacification of the calyces and pelves by iopromide may be delayed due to slower renal excretion of iopromide.

A pharmacokinetic study in patients with mild (n=2), moderate (n=6), and severe (n=3) renal impairment was conducted. The total clearance of iopromide was decreased proportionately to the baseline decrease in creatinine clearance. The plasma AUC increased about 2-fold in patients with moderate renal impairment and 6-fold in patients with severe renal impairment compared to subjects with normal renal function. The terminal half-life increased from 2.2 hrs for subjects with normal renal function to 11.6 hrs in patients with severe renal impairment. The peak plasma concentration of iopromide was not influenced by the extent of renal impairment. Exercise caution and use the lowest necessary dose of ULTRAVIST in patients with renal dysfunction [see Warnings and Precautions (5.2)].

Overdosage

The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

Ultravist Injection binds negligibly to plasma or serum protein and can, therefore, be dialyzed.

Ultravist Injection Description

ULTRAVIST  (iopromide) Injection is a nonionic, water soluble x-ray contrast agent for intravascular administration. The chemical name for iopromide is N,N'-Bis(2,3-dihydroxypropyl) –2,4,6–triiodo–5– [(methoxyacetyl)amino] –N-methyl–1,3-benzenedicarboxamide. Iopromide has a molecular weight of 791.12 (iodine content 48.12%).

Iopromide has the following structural formula:

Ultravist Injection is a nonionic, sterile, clear, colorless to slightly yellow, odorless, pyrogen-free aqueous solution of iopromide, containing 2.42 mg/mL tromethamine buffer and 0.1 mg/mL edetate calcium disodium stabilizer.

Ultravist Injection is available in four strengths:

150 mg I/mL provides 311.7 mg/mL iopromide,

240 mg I/mL provides 498.72 mg/mL iopromide,

300 mg I/mL provides 623.4 mg/mL iopromide,

370 mg I/mL provides 768.86 mg/mL iopromide.

During the manufacture of Ultravist Injection, sodium hydroxide or hydrochloric acid may be added for pH adjustment. Ultravist Injection has a pH of 7.4 (6.5– ) at 25± 2°C, is sterilized by autoclaving and contains no preservatives.

The iodine concentrations (mg I/mL) available have the following physicochemical properties:

* Osmolality was measured by vapor-pressure osmometry. Osmolarity was calculated from the measured osmolal concentrations.
		ULTRAVIST INJECTION	ULTRAVIST INJECTION	ULTRAVIST INJECTION	ULTRAVIST INJECTION
Property		150 mg I/mL	240 mg I/mL	300 mg I/mL	370 mg I/mL
Osmolality*(mOsmol/kg water)	@ 37°C	328	483	607	774
Osmolarity*(mOsmol/L)	@ 37°C	278	368	428	496
Viscosity (cP)	@ 20°C	2.3	4.9	9.2	22
	@ 37°C	1.5	2.8	4.9	10
Density (g/mL)	@ 20°C	1.164	1.262	1.330	1.409
	@ 37°C	1.157	1.255	1.322	1.399

Solutions of Ultravist Injection 150 mg I/mL, 240 mg I/mL, 300 mg I/mL and 370 mg I/mL have osmolalities from approximately 1.1 to 2.7 times that of plasma (285 mOsmol/kg water).

Ultravist Injection - Clinical Pharmacology

Mechanism of Action

Iopromide is a nonionic, water soluble, tri-iodinated x-ray contrast agent for intravascular administration.

Intravascular injection of iopromide opacifies those vessels in the path of flow of the contrast agent, permitting radiographic visualization of the internal structures until significant hemodilution occurs.

Pharmacodynamics

Following ULTRAVIST administration, the degree of contrast enhancement is directly related to the iodine content in the administered dose; peak iodine plasma levels occur immediately following rapid intravenous injection. Iodine plasma levels fall rapidly within 5 to 10 minutes. This can be accounted for by the dilution in the vascular and extravascular fluid compartments.

Intravascular Contrast: Contrast enhancement appears to be greatest immediately after bolus injections (15 seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive two-to-three second scans performed within 30 to 90 seconds after injection (that is, dynamic computed tomographic imaging).

Ultravist Injection may be visualized in the renal parenchyma within 30–60 seconds following rapid intravenous injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1–3 minutes, with optimum contrast occurring within 5–15 minutes.

In contrast CT, some performance characteristics are different in the brain and body. In contrast CT of the body, iodinated contrast agents diffuse rapidly from the vascular into the extravascular space. Following the administration of iodinated contrast agents, the increase in tissue density to x-rays is related to blood flow, the concentration of the contrast agent, and the extraction of the contrast agent by various interstitial tissues. Contrast enhancement is thus due to any relative differences in extravascular diffusion between adjacent tissues.

In the normal brain with an intact blood-brain barrier, contrast is generally due to the presence of iodinated contrast agent within the intravascular space. The radiographic enhancement of vascular lesions, such as arteriovenous malformations and aneurysms, depends on the iodine content of the circulating blood pool.

In tissues with a break in the blood-brain barrier, contrast agent accumulates within interstitial brain tissue. The time to maximum contrast enhancement can vary from the time that peak blood iodine levels are reached to 1 hour after intravenous bolus administration. This delay suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine containing medium within the lesion and outside the blood pool. The mechanism by which this occurs is not clear.

For information on coagulation parameters, fibrinolysis and complement system [see Drug Interactions (7.2)].

Pharmacokinetics

Distribution

After intravenous administration to healthy young volunteers, plasma iopromide concentration time profile shows an initial distribution phase with a half-life of 0.24 hour; a main elimination phase with a half-life of 2 hours; and a terminal elimination phase with a half-life of 6.2 hours. The total volume of distribution at steady state is about 16 L suggesting distribution in to extracellular space. Plasma protein binding of iopromide is 1%.

Iodinated contrast agents may cross the blood-brain barrier [see Warnings and Precautions (5.8)].

Elimination

The amounts excreted unchanged in urine represent 97% of the dose in young healthy subjects. Only 2% of the dose is recovered in the feces. Similar recoveries in urine and feces are observed in middle-aged and elderly patients. This finding suggests that, compared to the renal route, biliary and/or gastrointestinal excretion is not important for iopromide. During the slower terminal phase only 3% of the dose is eliminated; 97% of the dose is disposed of during the earlier phases, the largest part of which occurs during the main elimination phas