Trombogard

Trombogard may be available in the countries listed below.

Ingredient matches for Trombogard

Aspirin

Acetylsalicylic Acid is reported as an ingredient of Trombogard in the following countries:

• Bulgaria

International Drug Name Search

Somnite

Somnite may be available in the countries listed below.

Ingredient matches for Somnite

Nitrazepam

Nitrazepam is reported as an ingredient of Somnite in the following countries:

• Bahrain


• Cyprus


• Iraq


• Jordan


• Kuwait


• Lebanon


• Libya


• Qatar


• Saudi Arabia


• Sudan


• United Arab Emirates

International Drug Name Search

Cepime

Cepime may be available in the countries listed below.

Ingredient matches for Cepime

Cefepime

Cefepime is reported as an ingredient of Cepime in the following countries:

• Peru

International Drug Name Search

Renvela

Generic Name: sevelamer (Oral route)

se-VEL-a-mer

Commonly used brand name(s)

In the U.S.

• Renagel


• Renvela

Available Dosage Forms:

• Tablet


• Powder for Suspension


• Capsule

Therapeutic Class: Phosphate Binder

Uses For Renvela

Sevelamer is used to treat hyperphosphatemia (too much phosphate in the blood) in patients with chronic kidney disease who are on dialysis.

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

Before Using Renvela

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

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of sevelamer in the elderly. However, elderly patients may start at a lower dose.

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 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.

• Ciprofloxacin


• Levothyroxine


• Mycophenolate Mofetil

Interactions with Food/Tobacco/Alcohol

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

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:

• Bowel blockage—Should not be used in patients with this condition.

• Difficulty with swallowing or other swallowing problems or


• Major surgery on the gastrointestinal tract or


• Stomach or bowel problems (e.g., constipation), severe—Use with caution. May cause serious side effects if the tablet cannot be swallowed completely and properly absorbed.

Proper Use of sevelamer

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

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

Take this medicine with meals.

Follow carefully any diet program your doctor may recommend.

How to use the powder for oral suspension:

• Pour the entire contents of the packet in an empty cup.


• Mix the powder with 2 tablespoons of water for the 0.8 gram dose or 4 tablespoons of water for the 2.4 gram dose.


• Stir the mixture vigorously and drink it as soon as you can or within 30 minutes. Be sure to stir the mixture again before drinking if you decide to wait.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

If you are taking any other medicines, you may be asked to take them at least 1 hour before or 3 hours after you take sevelamer. If you need help deciding the best times to take your other medicines, ask your doctor or pharmacist.

Dosing

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

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

• For high phosphorus levels in the blood:
  
  • For oral dosage forms (suspension or tablets):
    
    • For patients not taking a phosphate binder:
      
      • Renagel®:
        
        • Adults—At first, 800 to 1600 milligrams (mg) three times a day with meals, depending on your blood phosphorus level. Your doctor will adjust your dose as needed.
        
        
        • Children—Use and dose must be determined by your doctor.
        
        
      
      
      • Renvela®:
        
        • Adults—At first, 800 to 1600 mg (1 to 2 tablets) or 0.8 to 1.6 grams (g) of powder for suspension three times a day with meals depending on your blood phosphorus level. Your doctor will adjust your dose as needed.
        
        
        • Children—Use and dose must be determined by your doctor.
        
        
      
      
    
    
    • For patients switching from Renagel® tablets to Renvela® powder for suspension or tablets:
      
      • Adults—Use the same dose in grams. Your doctor will adjust your dose as needed.
      
      
      • Children—Use and dose must be determined by your doctor.
      
      
    
    
    • For patients switching from calcium acetate to sevelamer, your doctor will determine the best dose for you and adjust as needed.
    
    
  
  

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 Renvela

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

If your symptoms do not improve or if they get worse, call your doctor.

Many people with kidney problems need to be on a special diet. To keep your kidney disease from getting worse, it is very important that you follow your special diet and take your medicines regularly, even if you are feeling better.

Renvela 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

• Bloody, black, or tarry stools


• heartburn


• indigestion


• nausea


• severe abdominal or stomach pain, cramping, or burning


• severe constipation


• severe vomiting


• trouble with breathing


• vomiting


• vomiting of material that looks like coffee grounds, severe and continuing

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:

More common

• Acid or sour stomach


• belching


• bloating


• constipation


• diarrhea


• excess air or gas in the stomach or intestines


• full feeling


• passing gas


• stomach discomfort or upset

Incidence not known

• Itching skin


• rash

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: Renvela 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 Renvela resources

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

• Renvela Prescribing Information (FDA)


• Renvela MedFacts Consumer Leaflet (Wolters Kluwer)


• Renvela Consumer Overview


• Sevelamer Professional Patient Advice (Wolters Kluwer)


• Sevelamer Monograph (AHFS DI)


• Renagel Consumer Overview


• Renagel Prescribing Information (FDA)

Compare Renvela with other medications

• Hyperphosphatemia of Renal Failure

Moclobemide

UK matches:

• Moclobemide 150mg Tablets (SPC)

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

N06AG02

CAS registry number (Chemical Abstracts Service)

0071320-77-9

Chemical Formula

C13-H17-Cl-N2-O2

Molecular Weight

268

Therapeutic Category

Antidepressant: Inhibitor of monoamine oxidase type A (MAO-A)

Chemical Name

Benzamide,4-chloro-N-[2-(4-morpholinyl)-ethyl]-

Foreign Names

• Moclobemidum (Latin)
• Moclobemid (German)
• Moclobemide (French)
• Moclobemida (Spanish)

Generic Names

• Moclobemide (OS: USAN, BAN)
• RO 11-1163 (IS: Roche)
• Moclobemid (PH: Ph. Helv. 10)
• Moclobemidum (PH: Ph. Helv. 10)

Brand Names

• Amira
  Alphapharm, Australia



• Apo-Moclob
  Apotex, Czech Republic



• Apo-Moclobemide
  Apotex, Canada; Apotex, New Zealand



• Auromid
  Galenika, Serbia



• Aurorix
  Meda, Austria; Meda, Belgium; Meda, Bulgaria; Meda, Switzerland; Meda, Czech Republic; Meda, Germany; Meda, Denmark; Meda, Finland; Meda, Hungary; Meda, Ireland; Meda, Iceland; Meda, Luxembourg; Meda, Luxembourg; Meda, Netherlands; Meda, Norway; Meda, Portugal; Meda, Sweden; Meda Pharma, Slovakia; Roche, Australia



• Biorix
  CBC, Taiwan



• Clobemix
  Genepharm, Australia



• Clorix
  Pharma Dynamics, South Africa



• Depnil
  Cipla Medpro, South Africa



• Eutac
  Taiwan Biotech, Taiwan



• GenRX Moclobemide
  Apotex, Australia



• Inpront
  Chile, Chile



• Manerix
  Meda, Spain; Meda, United Kingdom; Meda, Ireland



• Maorex
  Torrex, Hungary



• Maosig
  Sigma, Australia



• Mobemid
  Jelfa, Poland



• Mobemide
  Trima Unipharm, Singapore; Unipharm, Israel



• Moclamine
  Biocodex, France



• Moclix
  Hexal, Luxembourg



• Moclo A
  Sandoz, Switzerland



• Moclobemid Actavis
  Actavis, Finland; Actavis, Sweden



• Moclobemid AL
  Aliud, Germany



• Moclobemid Alternova
  Alternova, Austria; Alternova, Denmark; Alternova, Finland; Alternova, Sweden



• Moclobemid Hexal
  Hexal, Germany



• Moclobemid real
  Dolorgiet, Germany



• Moclobemid Sandoz
  Sandoz, Germany



• Moclobemid Stada
  Stada, Germany



• Moclobemid Torrex
  Torrex, Slovenia; Torrex, Slovakia



• Moclobemid
  Actavis, Norway; ratiopharm, Norway



• Moclobemid-1A Pharma
  1A Pharma, Germany



• Moclobemida Genedec
  Genedec, Portugal



• Moclobemida Teva
  Teva, Spain



• Moclobemide Actavis
  Actavis, Netherlands



• Moclobemide CF
  Centrafarm, Netherlands



• Moclobemide EG
  Eurogenerics, Luxembourg



• Moclobemide Merck
  Mylan, Netherlands



• Moclobemide Mylan
  Mylan, Belgium



• Moclobemide PCH
  Pharmachemie, Netherlands



• Moclobemide ratiopharm
  ratiopharm, Netherlands



• Moclobemide Sandoz
  Sandoz, Belgium; Sandoz, Netherlands



• Moclobemid-neuraxpharm
  Neuraxpharm, Germany



• Moclobemid-Puren
  Actavis, Germany



• Moclobemid-ratiopharm
  Ratiopharm, Germany; Ratiopharm, Finland



• Moclobemid-Teva
  Teva, Germany



• Moclobeta
  Betapharm, Germany



• Moclod
  CCPC, Taiwan



• Moclostad
  Pharmacodane, Denmark



• Mocloxil
  Anpharm, Poland



• Mocrim
  Apotex, Hungary



• Mohexal
  Sandoz, Australia



• Moklar
  Biovena, Poland



• Nu-Moclobemide
  Nu-Pharm, Canada



• PMS-Moclobemide
  Pharmascience, Canada



• Rimarex
  Sun, India

International Drug Name Search

Glossary

BAN	British Approved Name
IS	Inofficial Synonym
OS	Official Synonym
PH	Pharmacopoeia Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
SPC	Summary of Product Characteristics (UK)
USAN	United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Sertraline Ranbaxy

Sertraline Ranbaxy may be available in the countries listed below.

Ingredient matches for Sertraline Ranbaxy

Sertraline

Sertraline hydrochloride (a derivative of Sertraline) is reported as an ingredient of Sertraline Ranbaxy in the following countries:

• France


• Netherlands

International Drug Name Search

Moexipril

In the US, Moexipril (moexipril systemic) is a member of the drug class angiotensin converting enzyme inhibitors and is used to treat Diabetic Kidney Disease, Heart Attack, Heart Failure, High Blood Pressure and Left Ventricular Dysfunction.

US matches:

• Moexipril


• Moexipril and hydrochlorothiazide


• Moexipril Hydrochloride

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

C09AA13

CAS registry number (Chemical Abstracts Service)

0103775-10-6

Chemical Formula

C27-H34-N2-O7

Molecular Weight

498

Therapeutic Categories

Antihypertensive agent

ACE inhibitor

Chemical Name

(3S)-2-[(2S)-N-[(1S)-1-Carboxy-4-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid, 2-ethyl ester

Foreign Names

• Moexiprilum (Latin)
• Moexipril (German)
• Moexipril (French)
• Moexipril (Spanish)

Generic Names

• Moexipril (OS: BAN, DCF)
• RS 10085 (IS: Syntex)
• Moexipril Hydrochloride (OS: USAN, BANM)
• CI 925 (IS)
• RS 10085-197 (IS: Syntex)
• SPM 925 (IS)

Brand Names

• Cardiotensin
  Schwarz, Poland



• Enulid 15 (Moexipril and Hydrochlorothiazide)
  Rottapharm, Italy



• Femipres plus (Moexipril and Hydrochlorothiazide)
  UCB, Italy



• Femipres
  Schwarz, Italy



• Fempress
  Actavis, Germany



• Fempress plus (Moexipril and Hydrochlorothiazide)
  Actavis, Germany



• Moex
  Schwarz, Czech Republic; Schwarz, Hong Kong; Schwarz, Russian Federation; UCB, France



• Moexipril Hydrochloride and Hydrochlorthiazide (Moexipril and Hydrochlorothiazide)
  Paddock, United States; Teva USA, United States



• Moexipril Hydrochloride
  Apotex, United States; Paddock, United States; Teva USA, United States



• Perdix
  Schwarz, Israel; Schwarz, Oman; UCB Pharma, United Kingdom



• Renoprotec
  Merck, Mexico



• Uniretic (Moexipril and Hydrochlorothiazide)
  Schwarz, United States



• Univasc
  Adeka, Turkey; Pharos, Indonesia; Schwarz, Philippines; Schwarz, United States; UCB, Indonesia

International Drug Name Search

Glossary

BAN	British Approved Name
BANM	British Approved Name (Modified)
DCF	Dénomination Commune Française
IS	Inofficial Synonym
OS	Official Synonym
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Carindacilline

Carindacilline may be available in the countries listed below.

Ingredient matches for Carindacilline

Carindacillin

Carindacilline (DCF) is also known as Carindacillin (Prop.INN)

International Drug Name Search

Glossary

DCF	Dénomination Commune Française
Prop.INN	Proposed International Nonproprietary Name (World Health Organization)

Click for further information on drug naming conventions and International Nonproprietary Names.

Cadco

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Cadco

Pyrantel

Pyrantel tartrate (a derivative of Pyrantel) is reported as an ingredient of Cadco in the following countries:

• United States

International Drug Name Search

Oxinest

Oxinest may be available in the countries listed below.

Ingredient matches for Oxinest

Oxybuprocaine

Oxybuprocaine hydrochloride (a derivative of Oxybuprocaine) is reported as an ingredient of Oxinest in the following countries:

• Brazil

International Drug Name Search

Baclofen Polpharma

Baclofen Polpharma may be available in the countries listed below.

Ingredient matches for Baclofen Polpharma

Baclofen

Baclofen is reported as an ingredient of Baclofen Polpharma in the following countries:

• Czech Republic

International Drug Name Search

Fosemyk

Fosemyk may be available in the countries listed below.

Ingredient matches for Fosemyk

Fluprednidene

Fluprednidene 21-acetate (a derivative of Fluprednidene) is reported as an ingredient of Fosemyk in the following countries:

• Greece

Miconazole

Miconazole nitrate (a derivative of Miconazole) is reported as an ingredient of Fosemyk in the following countries:

• Greece

International Drug Name Search

Normocard

Normocard may be available in the countries listed below.

Ingredient matches for Normocard

Atenolol

Atenolol is reported as an ingredient of Normocard in the following countries:

• Poland

International Drug Name Search

Magnopyrol

Magnopyrol may be available in the countries listed below.

Ingredient matches for Magnopyrol

Metamizole

Metamizole magnesium (a derivative of Metamizole) is reported as an ingredient of Magnopyrol in the following countries:

• Mexico

Metamizole sodium monohydrate (a derivative of Metamizole) is reported as an ingredient of Magnopyrol in the following countries:

• Peru

International Drug Name Search

Magnobal

Magnobal may be available in the countries listed below.

Ingredient matches for Magnobal

Magnesium Hydrogen Aspartate

Magnesium Hydrogen Aspartate dihydrate (a derivative of Magnesium Hydrogen Aspartate) is reported as an ingredient of Magnobal in the following countries:

• Germany

International Drug Name Search

Medisamin

Medisamin may be available in the countries listed below.

Ingredient matches for Medisamin

Tranexamic Acid

Tranexamic Acid is reported as an ingredient of Medisamin in the following countries:

• Vietnam

International Drug Name Search

Raniver

Raniver may be available in the countries listed below.

Ingredient matches for Raniver

Ranitidine

Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Raniver in the following countries:

• Turkey

International Drug Name Search

Tetraciclina

Tetraciclina may be available in the countries listed below.

Ingredient matches for Tetraciclina

Tetracycline

Tetraciclina (DCIT) is known as Tetracycline in the US.

International Drug Name Search

Glossary

DCIT	Denominazione Comune Italiana

Click for further information on drug naming conventions and International Nonproprietary Names.

Panzynorm

Panzynorm may be available in the countries listed below.

Ingredient matches for Panzynorm

Pancreatin

Pancreatin is reported as an ingredient of Panzynorm in the following countries:

• Austria


• Czech Republic


• Estonia


• Georgia


• Germany


• India


• Russian Federation

International Drug Name Search

Fortrans

Fortrans may be available in the countries listed below.

Ingredient matches for Fortrans

Macrogol

Macrogol 4000 (a derivative of Macrogol) is reported as an ingredient of Fortrans in the following countries:

• Slovakia

International Drug Name Search

Ekybyl

Ekybyl may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Ekybyl

Acetyl Methionine

Acetyl Methionine is reported as an ingredient of Ekybyl in the following countries:

• France

International Drug Name Search

Ratinal

Ratinal may be available in the countries listed below.

Ingredient matches for Ratinal

Ranitidine

Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Ratinal in the following countries:

• Indonesia

International Drug Name Search

Differin Lotion

adapalene

Dosage Form: lotion
FULL PRESCRIBING INFORMATION

Indications and Usage for Differin Lotion

Differin Lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older.

Differin Lotion Dosage and Administration

Apply a thin film of Differin Lotion to the entire face and other affected areas of the skin once daily, after washing gently with a mild soapless cleanser. Dispense a nickel size amount of Differin Lotion (3-4 actuations of the pump) to cover the entire face. Avoid application to the areas of skin around eyes, lips and mucous membranes.

Differin Lotion is for topical use only and not for oral, ophthalmic, or intravaginal use.

Dosage Forms and Strengths

Each gram of the lotion contains 1 mg (0.1%) adapalene in an oil-in-water emulsion.

Contraindications

None.

Warnings and Precautions

Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be avoided during the use of Differin Lotion. Patients with high levels of sun exposure and those with inherent sensitivity to sun should be warned to exercise caution. Use of sunscreen products and protective apparel (e.g. hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with Differin Lotion.

Local Cutaneous Reactions

Signs and symptoms of local skin irritation (such as erythema, scaling, dryness, stinging/burning) may be experienced with use of Differin Lotion. These are most likely to occur during the first 2 weeks of treatment, are mostly mild to moderate in severity, and usually lessen with continued use of Differin Lotion. Depending upon the severity of these side effects, patients should be instructed to use a moisturizer, reduce the frequency of the application of Differin Lotion 0.1%, or discontinue use.

Differin Lotion should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of “waxing” as a depilatory method should be avoided on skin treated with Differin Lotion.

Avoid concomitant use of other potentially irritating topical products (abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes).

Adverse Reactions

Clinical Studies Experience

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

A total of 2141 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks. Of these, 1068 were exposed to Differin Lotion during the clinical trials. A total of 1057 subjects completed at least one post treatment evaluation.

Related adverse reactions that were reported in at least 1% of patients treated with Differin Lotion or with the Vehicle Lotion are presented in Table 1.

The majority of cases was transient, mild to moderate in severity and was managed with moisturizers.

Table 1: Adverse Reactions Reported in Clinical Trials by At Least 1% of Patients

System Term	Organ	Class/Preferred	Adapalene Lotion 0.1% N = 1068	Vehicle Lotion N = 1073
Subjects with Related AR(s)			10.2%	4.6%
Dry Skin			7.7%	3.0%
Skin Irriitation			1.5%	0.7%
Skin burning/skin discomfort			0.9%	0.0%
Sunburn			0.6%	0.6%

Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials. Erythema, scaling, dryness, burning/stinging were assessed:

Table 2: Incidence of Local Cutaneous Irritation, for Subjects Whose Irritation Score was Higher than at Baseline, in Controlled Clinical Studies Adverse Reactions (Differin Lotion Group N = 1057* )

Combined Study 1 and Study 2	Maximum Severity During Treatment (N = 1057)			Week 12 Treatment Severity (N = 950)
* Data from 11 subjects with missing data are not included.
Local Cutaneous Irritation (skin irritation)	Mild	Moderate	Severe	Mild	Moderate	Severe
Erythema	21.8%	8.0%	0.2%	7.9%	2.6%	0.2%
Scaling	25.3%	6.5%	0.1%	5.3%	1.1%	0
Dryness	36.1%	7.3%	0.3%	7.6%	2.0%	0
Stinging/burning	22.1%	7.0%	0.9%	4.6%	1.0%	0.4%

Local tolerability scores for erythema, scaling, dryness, burning/stinging rose during the first two weeks of treatment and generally decreased thereafter.

Drug Interactions

Concomitant Topical Medications

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. Caution should be exercised in using preparation containing sulfur, resorcinol or salicylic acid in combination with Differin Lotion.

No formal drug-drug interaction studies were conducted with Differin Lotion.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with Differin Lotion. Therefore, Differin Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies have not been conducted with Differin Lotion. Furthermore, such studies are not always predictive of human response.

Human Data

In clinical trials involving Differin Lotion, 0.1% in the treatment of acne vulgaris, women of childbearing potential initiated treatment only after a negative pregnancy test. Two women became pregnant while using Differin Lotion, 0.1%. One patient delivered a healthy full term baby and the other patient electively terminated her pregnancy.

Animal Data

No teratogenic effects were observed in rats treated with oral doses of 0.15 to 5.0 mg adapalene/kg/day, up to 25 times (mg/m2/day) the maximum recommended human dose (MRHD) of 2 grams of Differin Lotion. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of ≥ 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day [25-59 times (mg/m2) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.

Systemic exposure (AUC 0-24h) to adapalene at topical doses (6.0 mg/kg/day) in rats represented 101 times the exposure to adapalene in patients with acne treated with Differin Lotion applied to the face, chest and back (2 grams applied to 1000 cm² of acne-involved skin).

Nursing Mothers

It is not known whether adapalene is excreted in human milk following use of Differin Lotion. Because many drugs are excreted in human milk, caution should be exercised when Differin Lotion is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Differin Lotion in pediatric patients under the age of 12 have not been established.

Geriatric Use

Clinical studies of Differin Lotion did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Differin Lotion Description

DIFFERIN (adapalene) Lotion, 0.1% for topical use, is an adapalene-based product.

Adapalene is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene is (6-[3-(1-adamantyl)-4-meghoxyphenyl]-2-naphthoic acid). Adapalene has the following structural formula:

Adapalene:

Molecular formula:  C28H28O3       Molecular weight: 412.5

Differin Lotion contains the following inactive ingredients: carbomer 941, disodium edetate, medium chain triglycerides, methylparaben, phenoxyethanol, poloxamer 124, polyoxyl-6-polyoxyl-32 palmitostearate, PPG-12/SMDI copolymer, propylene glycol, propylparaben, sodium hydroxide, stearyl alcohol, and purified water.

Differin Lotion - Clinical Pharmacology

Mechanism of Action

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Pharmacodynamics

Pharmacodynamics of Differin Lotion is unknown.

Pharmacokinetics

Systemic exposure of adapalene following a topical application of Differin Lotion was studied in one clinical study. Fourteen subjects at 18-29 years of age with severe acne were treated with 2 g of Differin Lotion once daily for 30 days to approximately 1000 cm2 of acne involved skin. Serial plasma samples were collected for 24 or 72 hours following application on days 1, 15 and 30. All plasma concentrations for 12 out of 14 patients were below the limit of quantification (LOQ=0.1 ng/mL). One patient had one sample above LOQ at day 30 and the other patient had four plasma samples above LOQ on both days 1 and 15, which ranged from 0.102 and 0.131 ng/mL. Due to the limited number of available data points, PK analysis was not undertaken.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity and impairment of fertility studies were conducted with Differin Lotion.

Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m2/day), and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3.0, and 9.0 mg/m2/day). In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of 2 grams of Differin Lotion. In the rat study, an increased incidence of benign and malignant pheochromocytomas in the adrenal medulla of male rats was observed.

No photocarcinogenicity studies were conducted with adapalene. However, animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g. retinoids) when exposed to UV irradiation in the laboratory or sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources.

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test).

In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

Clinical Studies

The safety and efficacy of Differin Lotion applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing Differin Lotion to the Lotion vehicle in acne subjects.

In Study 1, 1075 subjects were randomized to Differin Lotion or vehicle. The median age of these subjects was 16.7 years old and 53.1% were females. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions. The majority of subjects (91.0%) had a baseline IGA score of ‘Moderate’.

In Study 2, 1066 subjects were randomized to Differin Lotion or vehicle. The median age of subjects was 16.7 years old and 53.7% were females. At baseline subjects had the same inclusion criteria as in Study 1 and 95.7% of subjects had a baseline IGA score of ‘Moderate’.

The outcome of the two studies is presented in Table 3.

Table 3: Clinical Study Primary Efficacy Results at Week 12

Study 1
	DIFFERIN Lotion (N = 533)	Vehicle Lotion (N = 542)
IGA Success	140 (26.3%)	94 (17.3%)
Total Lesions: Mean Absolute (Percent) Change	37.9 (51.5%)	26.7 (37.1%)
Inflammatory Lesions: Mean Absolute (Percent) Change	14.7 (54.9%)	10.6 (40.3%)
Non-inflammatory Lesions: Mean Absolute (Percent) Change	23.2 (49.6%)	16.1 (35.7%)

Study 2
	DIFFERIN Lotion (N = 535)	Vehicle Lotion (N = 531)
IGA Success	129 (24.1%)	87 (16.4%)
Total Lesions: Mean Absolute (Percent) Change	32.4 (44.6%)	23.4 (32.8%)
Inflammatory Lesions: Mean Absolute (Percent) Change	12.7 (46.0%)	10.2 (36.9%)
Non-inflammatory Lesions: Mean Absolute (Percent) Change	19.6 (43.1%)	13.1 (30.2%)

How Supplied/Storage and Handling

DIFFERIN (adapalene) Lotion, 0.1%, is packaged in a 2 oz (59 mL) bottle which is equipped with a Lotion dispensing pump.

The Differin Lotion is supplied as follows:

  2 oz bottle pump 0299-5912-02

Storage and handling

• 
  

  Store at controlled room temperature, 20 - 25°C (68 - 77°F); excursions permitted to 15 – 30°C (59 – 86°F).

  
  


• 
  

  Do not freeze.

  
  


• 
  

  Do not refrigerate.

  
  


• 
  

  Protect from light.

  
  


• 
  

  Keep out of reach of children.

  
  


• 
  

  Keep away from heat.

  
  


• 
  

  Keep bottle tightly closed.

  
  

Patient Counseling Information

• 
  

  Apply a thin film of Differin Lotion to the affected areas of the skin once daily, after washing gently with a mild soapless cleanser. Dispense a nickel size amount of Differin Lotion (3-4 actuations of the pump) to cover the entire face. Avoid application to the areas of skin around eyes, lips and mucous membranes. Differin Lotion may cause irritation such as erythema, scaling, dryness, stinging or burning.

  
  


• 
  

  Advise patients to cleanse the area to be treated with a mild or soapless cleanser; pat dry. Apply Differin Lotion to the entire face or other acne affected areas as a thin layer, avoiding the eyes, lips and mucous membranes.

  
  


• 
  

  Exposure of the eye to this medication may result in reactions such as swelling, conjunctivitis and eye irritation.

  
  


• 
  

  Patients should be advised not to use more than the recommended amount and not to apply more than once daily as this will not produce faster results, but may increase irritation.

  
  


• 
  

  Advise patients to minimize exposure to sunlight including sunlamps. Recommend the use of sunscreen products and protective apparel (e.g., hat) when exposure cannot be avoided.

  
  


• 
  

  Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided.

  
  


• 
  

  This medication should not be applied to cuts, abrasions, eczematous, or sunburned skin.

  
  


• 
  

  Wax depilation should not be performed on treated skin due to the potential for skin erosions.

  
  


• 
  

  This product is for external use only.

  
  

Marketed by:

GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USA

Manufactured by:

Galderma Production Canada Inc., Baie d’Urfé, QC, H9X 3S4 Canada

Made in Canada.

GALDERMA is a registered trademark.

P51503-0

PACKAGE LABEL

Rx Only

NDC 0299-5912-02

Differin®

(adapalene) Lotion 0.1%

For External

Use Only

2 FL OZ

(59 mL)

GALDERMA

For external use only.

Not for ophthalmic oral or intravaginal use.

Usual dosage: Apply a thin film on the entire face and other affected areas of the skin once daily. See package insert for complete prescribing information.

Each gram contains: adapalene 1 mg (0.1%) in an aqueous based lotion consisting of the following inactive ingredients:

carbomer 941, disodium edetate, medium chain triglycerides, methylparaben, phenoxyethanol, poloxamer 124, polyoxyl-6-polyoxyl-32 palmitostearate, PPG-12/SMDI copolymer, propylene glycol, propylparaben, sodium hydroxide, stearyl alcohol, and purified water.

Storage: Store at controlled room temperature 68° - 77°F (20° - 25°C) with excursions permitted between 59° - 86°F (15° - 30°C). Do not freeze or refrigerate.

Marketed by:

GALDERMA LABORATORIES, L.P.

14501 North Freeway

Fort Worth, Texas 76177 USA

Manufactured by:

Galderma Production Canada Inc.

Baie d’Urfé, QC, H9X 3S4 Canada

Made in Canada.

GALDERMA is a registered

trademark.

P51638-1

DIFFERIN   adapalene  lotion

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0299-5912 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Adapalene (Adapalene) Adapalene 1 mg  in 1 g

Inactive Ingredients Ingredient Name Strength Carbomer Homopolymer Type A   Edetate Disodium   Medium-chain Triglycerides   Methylparaben   Phenoxyethanol   Poloxamer 124   Propylene Glycol   Propylparaben   Sodium Hydroxide   Stearyl Alcohol   Water

Product Characteristics Color WHITE (white to off-white) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0299-5912-02 57.9 g In 1 BOTTLE, PUMP None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA022502	03/31/2010

Labeler - Galderma Laboratories, L.P. (047350186)

Establishment
Name	Address	ID/FEI	Operations
Galderma Production Canada Inc		251676961	MANUFACTURE

Revised: 03/2010Galderma Laboratories, L.P.

More Differin Lotion resources

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

Compare Differin Lotion with other medications

• Acne

Tipranavir

In the US, Tipranavir (tipranavir systemic) is a member of the drug class protease inhibitors and is used to treat HIV Infection.

US matches:

• Tipranavir


• Tipranavir Solution

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

J05AE09

CAS registry number (Chemical Abstracts Service)

0174484-41-4

Chemical Formula

C31-H33-F3-N2-O5-S

Molecular Weight

602

Therapeutic Category

Antiviral agent, HIV protease inhibitor, nonpeptidic

Chemical Names

2-Pyridinesulfonamide, N-(3-((1R)-1-((6R)-5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenethyl)-6-propyl-2H-pyran-3-yl)propyl)phenyl)-5-(trifluormethyl)-

2-Pyridinesulfonamide, N-(3-(1-(5,6-dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl)propyl)phenyl)-5-(trifluormethyl)-, (R-(R*,R*))-

3'-[(1R)-1-[(6R)-5,6-dihydro-4-hydroxy-2-oxo-6-phenethyl-6-propyl-2H-pyran-3-yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide (WHO)

N-(3-{(1R)-1-[(6R)-4-Hydroxy-2-oxo-6-(2-phenethyl)-6-propyl-5,6-dihydro-2H-pyran-3-yl]propyl}phenyl)-5-(trifluormethyl)-2-pyridin-2-sulfonamid (IUPAC)

Foreign Names

• Tipranavirum (Latin)
• Tipranavir (German)
• Tipranavir (French)
• Tipranavir (Spanish)

Generic Names

• Tipranavir (OS: BAN)
• PNU-140690 (IS: PharmaciaUpjoh)
• U-140690 (IS: PharmaciaUpjoh)

Brand Names

• Aptivus
  Boehringer Ingelheim, Argentina; Boehringer Ingelheim, Australia; Boehringer Ingelheim, Belgium; Boehringer Ingelheim, Canada; Boehringer Ingelheim, Switzerland; Boehringer Ingelheim, Czech Republic; Boehringer Ingelheim, Germany; Boehringer Ingelheim, Denmark; Boehringer Ingelheim, Spain; Boehringer Ingelheim, Finland; Boehringer Ingelheim, France; Boehringer Ingelheim, United Kingdom; Boehringer Ingelheim, Hungary; Boehringer Ingelheim, Ireland; Boehringer Ingelheim, Italy; Boehringer Ingelheim, Mexico; Boehringer Ingelheim, Netherlands; Boehringer Ingelheim, Norway; Boehringer Ingelheim, Portugal; Boehringer Ingelheim, Sweden; Boehringer Ingelheim, Slovenia; Boehringer Ingelheim, Slovakia; Boehringer Ingelheim, United States; Boehringer Ingelheim International, Austria; Boehringer Ingelheim International, Luxembourg



• Atripla
  Boehringer Ingelheim, Ireland

International Drug Name Search

Glossary

BAN	British Approved Name
IUPAC	International Union of Pure and Applied Chemistry
IS	Inofficial Synonym
OS	Official Synonym
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
WHO	World Health Organization

Click for further information on drug naming conventions and International Nonproprietary Names.

Levomet

Levomet may be available in the countries listed below.

Ingredient matches for Levomet

Carbidopa

Carbidopa is reported as an ingredient of Levomet in the following countries:

• Singapore

Levodopa

Levodopa is reported as an ingredient of Levomet in the following countries:

• Singapore

International Drug Name Search

Bicillin C-R 900/300

Generic Name: penicillin g benzathine and penicillin g procaine

Dosage Form: injection, suspension
Bicillin® C-R 900/300

(penicillin G benzathine and penicillin G procaine injectable suspension)

2 mL Syringe

for deep IM injection only

WARNING: NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH. Prior to administration of this drug, carefully read the WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling.

Rx Only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin C-R 900/300 and other antibacterial drugs, Bicillin C-R 900/300 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Bicillin C-R 900/300 (penicillin G benzathine and penicillin G procaine injectable suspension) contains the equivalent of 900,000 units of penicillin G as the benzathine and 300,000 units of penicillin G as the procaine salts. It is available for deep intramuscular injection.

Penicillin G benzathine is prepared by the reaction of dibenzylethylene diamine with two molecules of penicillin G. It is chemically designated as (2S ,5R,6R )-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compound with N,N'-dibenzylethylenediamine (2:1), tetrahydrate. It occurs as a white, crystalline powder and is very slightly soluble in water and sparingly soluble in alcohol. Its chemical structure is as follows:

Penicillin G procaine, (2S ,5R,6R )-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compound with 2-(diethylamino)ethyl p-aminobenzoate (1:1) monohydrate, is an equimolar salt of procaine and penicillin G. It occurs as white crystals or a white, microcrystalline powder and is slightly soluble in water. Its chemical structure is as follows:

Each 2 mL syringe contains the equivalent of 1,200,000 units of penicillin G as follows: penicillin G benzathine equivalent to 900,000 units of penicillin G and penicillin G procaine equivalent to 300,000 units of penicillin G in a stabilized aqueous suspension with sodium citrate buffer; and as w/v, approximately 0.5% lecithin, 0.55% carboxymethylcellulose, 0.55% povidone, 0.1% methylparaben, and 0.01% propylparaben.

Bicillin C-R 900/300 injectable suspension is viscous and opaque. Read CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections prior to use.

CLINICAL PHARMACOLOGY

General

Penicillin G benzathine and penicillin G procaine have a low solubility and, thus, the drugs are slowly released from intramuscular injection sites. The drugs are hydrolyzed to penicillin G. This combination of hydrolysis and slow absorption results in blood serum levels much lower but more prolonged than other parenteral penicillins. Intramuscular administration of 1,200,000 units of Bicillin C-R 900/300 in patients weighing 100 to 140 lbs. usually produces average blood levels of 0.24 units/mL at 24 hours, 0.039 units/mL at 7 days, and 0.024 units/mL at 10 days.

Approximately 60% of penicillin G is bound to serum protein. The drug is distributed throughout the body tissues in widely varying amounts. Highest levels are found in the kidneys with lesser amounts in the liver, skin, and intestines. Penicillin G penetrates into all other tissues and the spinal fluid to a lesser degree. With normal kidney function, the drug is excreted rapidly by tubular excretion. In neonates and young infants and in individuals with impaired kidney function, excretion is considerably delayed.

Microbiology

Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci.

The following in vitro data are available, but their clinical significance is unknown. Penicillin G exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (Groups A, C, G, H, L, and M), and pneumococci. Other organisms susceptible to penicillin G are Neisseria gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, Clostridia species, Actinomyces bovis, Streptobacillus moniliformis, Listeria monocytogenes, and Leptospira species. Treponema pallidum is extremely susceptible to the bactericidal action of penicillin G.

Susceptibility Test: If the Kirby-Bauer method of disc susceptibility is used, a 10-unit penicillin disc should give a zone greater than 28 mm when tested against a penicillin-susceptible bacterial strain.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin C-R 900/300 and other antibacterial drugs, Bicillin C-R 900/300 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Bicillin C-R 900/300 is indicated in the treatment of infections as described below that are susceptible to serum levels characteristic of this particular dosage form. Therapy should be guided by bacteriological studies (including susceptibility testing) and by clinical response.

Bicillin C-R 900/300 is indicated in the treatment of the following in pediatric patients:

Moderately severe to severe infections of the upper-respiratory tract, scarlet fever, erysipelas, and skin and soft-tissue infections due to susceptible streptococci.

NOTE: Streptococci in Groups A, C, G, H, L, and M are very susceptible to penicillin G. Other groups, including Group D (enterococci), are resistant. Penicillin G sodium or potassium is recommended for streptococcal infections with bacteremia.

Moderately severe pneumonia and otitis media due to susceptible pneumococci.

NOTE: Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, and arthritis of pneumococcal etiology are better treated with penicillin G sodium or potassium during the acute stage.

When high, sustained serum levels are required, penicillin G sodium or potassium, either IM or IV, should be used. This drug should not be used in the treatment of venereal diseases, including syphilis, gonorrhea, yaws, bejel, and pinta.

CONTRAINDICATIONS

A previous hypersensitivity reaction to any penicillin or to procaine is a contraindication.

WARNINGS

WARNING: NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH. Prior to administration of this drug, carefully read the WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling.

The combination of penicillin G benzathine and penicillin G procaine should only be prescribed for the indications listed in this insert.

Anaphylaxis

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH BICILLIN C-R CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, BICILLIN C-R SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated with diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Bicillin C-R 900/300, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Method of Administration

Do not inject into or near an artery or nerve.

Injection into or near a nerve may result in permanent neurological damage.

Inadvertent intravascular administration, including inadvertent direct intra-arterial injection or injection immediately adjacent to arteries, of Bicillin C-R and other penicillin preparations has resulted in severe neurovascular damage, including transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding the injection site. Such severe effects have been reported following injections into the buttock, thigh, and deltoid areas. Other serious complications of suspected intravascular administration which have been reported include immediate pallor, mottling, or cyanosis of the extremity both distal and proximal to the injection site, followed by bleb formation; severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity. The above-described severe effects and complications have most often occurred in infants and small children. Prompt consultation with an appropriate specialist is indicated if any evidence of compromise of the blood supply occurs at, proximal to, or distal to the site of injection.1-9 (See PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections.)

Do not inject intravenously or admix with other intravenous solutions. There have been reports of inadvertent intravenous administration of penicillin G benzathine which has been associated with cardiorespiratory arrest and death. (See DOSAGE AND ADMINISTRATION section.)

Quadriceps femoris fibrosis and atrophy have been reported following repeated intramuscular injections of penicillin preparations into the anterolateral thigh.

PRECAUTIONS

General

Prescribing Bicillin C-R 900/300 in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of a development of drug-resistant bacteria.

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.

Care should be taken to avoid intravenous or intra-arterial administration, or injection into or near major peripheral nerves or blood vessels, since such injections may produce neurovascular damage. (See WARNINGS, and DOSAGE AND ADMINISTRATION sections.)

A small percentage of patients are sensitive to procaine. If there is a history of sensitivity, make the usual test: Inject intradermally 0.1 mL of a 1 to 2 percent procaine solution. Development of an erythema, wheal, flare, or eruption indicates procaine sensitivity. Sensitivity should be treated by the usual methods, including barbiturates, and procaine penicillin preparations should not be used. Antihistaminics appear beneficial in treatment of procaine reactions.

The use of antibiotics may result in overgrowth of nonsusceptible organisms. Constant observation of the patient is essential. If new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken.

Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy.

In prolonged therapy with penicillin, and particularly with high-dosage schedules, periodic evaluation of the renal and hematopoietic systems is recommended.

Information for Patients

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs including Bicillin C-R 900/300 should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Bicillin C-R 900/300 is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Bicillin C-R 900/300 or other antibacterial drugs in the future.

Laboratory Tests

In streptococcal infections, therapy must be sufficient to eliminate the organism; otherwise, the sequelae of streptococcal disease may occur. Cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.

Drug Interactions

Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided.

Concurrent administration of penicillin and probenecid increases and prolongs serum penicillin levels by decreasing the apparent volume of distribution and slowing the rate of excretion by competitively inhibiting renal tubular secretion of penicillin.

Pregnancy Category B

Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Soluble penicillin G is excreted in breast milk. Caution should be exercised when penicillin G benzathine and penicillin G procaine are administered to a nursing woman.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been conducted with these drugs.

Pediatric Use

(See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections.)

Geriatric Use

Clinical studies of penicillin G benzathine and penicillin G procaine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function (see CLINICAL PHARMACOLOGY). Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions

As with other penicillins, untoward reactions of the sensitivity phenomena are likely to occur, particularly in individuals who have previously demonstrated hypersensitivity to penicillins or in those with a history of allergy, asthma, hay fever, or urticaria.

The following have been reported with parenteral penicillin G:

General: Hypersensitivity reactions including the following: skin eruptions (maculopapular to exfoliative dermatitis), urticaria, laryngeal edema, fever, eosinophilia; other serum sickness-like reactions (including chills, fever, edema, arthralgia, and prostration); and anaphylaxis including shock and death. Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, penicillin G should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to therapy with penicillin G. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.

Gastrointestinal: Pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. (See WARNINGS section.)

Hematologic: Hemolytic anemia, leukopenia, thrombocytopenia.

Neurologic: Neuropathy.

Urogenital: Nephropathy.

The following adverse events have been temporally associated with parenteral administrations of penicillin G benzathine, although a causal relationship has not necessarily been established:

Body as a Whole: Hypersensitivity reactions including allergic vasculitis, pruritus, fatigue, asthenia, and pain; aggravation of existing disorder; headache.

Cardiovascular: Cardiac arrest; hypotension; tachycardia; palpitations; pulmonary hypertension; pulmonary embolism; vasodilation; vasovagal reaction; cerebrovascular accident; syncope.

Gastrointestinal: Nausea, vomiting; blood in stool; intestinal necrosis.

Hemic and Lymphatic: Lymphadenopathy.

Injection Site: Injection site reactions including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, and skin ulcer. Neurovascular reactions including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, and neurovascular damage.

Metabolic: Elevated BUN, creatinine, and SGOT.

Musculoskeletal: Joint disorder; periostitis; exacerbation of arthritis; myoglobinuria; rhabdomyolysis.

Nervous System: Nervousness; tremors; dizziness; somnolence; confusion; anxiety; euphoria; transverse myelitis; seizures; coma. A syndrome manifested by a variety of CNS symptoms such as severe agitation with confusion, visual and auditory hallucinations, and a fear of impending death (Hoigne's syndrome), has been reported after administration of penicillin G procaine and, less commonly, after injection of the combination of penicillin G benzathine and penicillin G procaine. Other symptoms associated with this syndrome, such as psychosis, seizures, dizziness, tinnitus, cyanosis, palpitations, tachycardia, and/or abnormal perception in taste, also may occur.

Respiratory: Hypoxia; apnea; dyspnea.

Skin: Diaphoresis.

Special Senses: Blurred vision; blindness.

Urogenital: Neurogenic bladder; hematuria; proteinuria; renal failure; impotence; priapism.

OVERDOSAGE

Penicillin in overdosage has the potential to cause neuromuscular hyperirritability or convulsive seizures.

DOSAGE AND ADMINISTRATION

Streptococcal Infections

Group A infections of the upper-respiratory tract, skin and soft-tissue infections, scarlet fever, and erysipelas: A single injection of Bicillin C-R 900/300 is usually sufficient for the treatment of Group A streptococcal infections in pediatric patients.

Pneumococcal Infections (except pneumococcal meningitis)

One Bicillin C-R 900/300 repeated at 2- or 3-day intervals until the temperature is normal for 48 hours. Other forms of penicillin may be necessary for severe cases.

Method of Administration

Bicillin C-R is intended for Intramuscular Injection ONLY. Do not inject into or near an artery or nerve, or intravenously or admix with other intravenous solutions. (See WARNINGS section).

Administer by DEEP INTRAMUSCULAR INJECTION in the upper, outer quadrant of the buttock. In neonates, infants and small children, the midlateral aspect of the thigh may be preferable. When doses are repeated, vary the injection site.

Because of the high concentration of suspended material in this product, the needle may be blocked if the injection is not made at a slow, steady rate.

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

HOW SUPPLIED

Bicillin® C-R 900/300 (penicillin G benzathine and penicillin G procaine injectable suspension) is supplied in 2 mL size syringes in packages of 10 syringes as follows:

1,200,000 units per syringe (21 gauge, thin-wall 1 inch needle for pediatric use), NDC 60793-602-10.

Store in a refrigerator, 2° to 8°C (36° to 46°F).

Keep from freezing.

REFERENCES

1. SHAW, E.: Transverse myelitis from injection of penicillin. Am. J. Dis. Child., 111:548, 1966.


2. KNOWLES, J.: Accidental intra-arterial injection of penicillin. Am. J. Dis. Child., 111:552, 1966.


3. DARBY, C. et al: Ischemia following an intragluteal injection of benzathine-procaine penicillin G mixture in a one-year-old boy. Clin. Pediatrics, 12:485, 1973.


4. BROWN, L. & NELSON, A.: Postinfectious intravascular thrombosis with gangrene. Arch. Surg., 94:652, 1967.


5. BORENSTINE, J.: Transverse myelitis and penicillin (Correspondence). Am. J. Dis. Child., 112:166, 1966.


6. ATKINSON, J.: Transverse myelopathy secondary to penicillin injection. J. Pediatrics, 75:867, 1969.


7. TALBERT, J. et al: Gangrene of the foot following intramuscular injection in the lateral thigh: A case report with recommendations for prevention. J. Pediatrics, 70:110, 1967.


8. FISHER, T.: Medicolegal affairs. Canad. Med. Assoc. J., 112:395, 1975.


9. SCHANZER, H. et al: Accidental intra-arterial injection of penicillin G. JAMA, 242:1289, 1979.

Prescribing Information as of January 2010

Manufactured and Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620

Label Graphic1

LabelGraphics2

Bicillin C-R 900/300  penicillin g benzathine and penicillin g procaine  injection, suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 60793-602 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PENICILLIN G BENZATHINE (PENICILLIN G) PENICILLIN G 900000 [iU]  in 2 mL PENICILLIN G PROCAINE (PENICILLIN G) PENICILLIN G 300000 [iU]  in 2 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 60793-602-10 10 SYRINGE In 1 PACKAGE contains a SYRINGE 1 2 mL In 1 SYRINGE This package is contained within the PACKAGE (60793-602-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA050138	05/18/1953

Labeler - King Pharmaceuticals, Inc. (809587413)

Revised: 07/2011King Pharmaceuticals, Inc.

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