Ratinal may be available in the countries listed below.
Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Ratinal in the following countries:
International Drug Name Search
Differin Lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older.
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.
Each gram of the lotion contains 1 mg (0.1%) adapalene in an oil-in-water emulsion.
None.
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.
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).
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.
| 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:
| Combined Study 1 and Study 2 | Maximum Severity During Treatment (N = 1057) | Week 12 Treatment Severity (N = 950) | ||||
|---|---|---|---|---|---|---|
| ||||||
| 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.
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.
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).
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.
Safety and effectiveness of Differin Lotion in pediatric patients under the age of 12 have not been established.
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 (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.
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 of Differin Lotion is unknown.
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.
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.
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.
| 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%) |
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.
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
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 | ||||||||||||||||||||||||||
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| 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 | |
In the US, Tipranavir (tipranavir systemic) is a member of the drug class protease inhibitors and is used to treat HIV Infection.
US matches:
Rec.INN
J05AE09
0174484-41-4
C31-H33-F3-N2-O5-S
602
Antiviral agent, HIV protease inhibitor, nonpeptidic
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)
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 |
Levomet may be available in the countries listed below.
Carbidopa is reported as an ingredient of Levomet in the following countries:
Levodopa is reported as an ingredient of Levomet in the following countries:
International Drug Name Search
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.
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.
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.
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.
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.
A previous hypersensitivity reaction to any penicillin or to procaine is a contraindication.
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.
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.
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.
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.
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.
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.
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.
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.
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.
No long-term animal studies have been conducted with these drugs.
(See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections.)
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.
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.
Penicillin in overdosage has the potential to cause neuromuscular hyperirritability or convulsive seizures.
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.
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.
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.
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.
Prescribing Information as of January 2010
Manufactured and Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620
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| 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) |
Minocyclin Hexal may be available in the countries listed below.
Minocycline hydrochloride (a derivative of Minocycline) is reported as an ingredient of Minocyclin Hexal in the following countries:
International Drug Name Search
Generic Name: botulism immune globulin (BOT ue lizm im MYOON GLOB yoo lin)
Brand Names: BabyBIG
Botulism immune globulin is a sterilized solution made from human plasma. It contains the antibodies to help your body protect itself against infection caused by botulism toxin type A and B.
Botulism immune globulin is used to treat infant botulism caused by toxin type A or B. This medication is used in children who are younger than 1 year old.
Botulism immune globulin may also be used for other purposes not listed in this medication guide.
Before your baby receives botulism immune globulin, tell your doctor if the baby has kidney disease, diabetes, a life-threatening infection, or if the baby is dehydrated, or has recently received any vaccinations.
Botulism immune globulin can be harmful to the kidneys, and these effects are increased when this medication is used together with other drugs that can harm the kidneys. Before your baby is treated with botulism immune globulin, tell your doctor if the baby is receiving chemotherapy, medicines to treat a bowel disorder, medication to prevent organ transplant rejection, antiviral medications, pain medicines, or any IV antibiotics.
To be sure this medication is not causing harmful effects, your baby may need blood tests. Do not miss any follow-up appointments after treatment with botulism immune globulin.
If your baby has certain conditions, he or she may need a dose adjustment or special tests to safely use this medication. Before your baby receives botulism immune globulin, tell your doctor if the baby has:
diabetes;
a life-threatening infection;
if the baby is dehydrated; or
if the baby has recently received any vaccinations.
To best participate in the care of your baby while he or she is being treated with botulism immune globulin, carefully follow all instructions provided by your baby's caregivers.
Botulism immune globulin is given as an injection through a needle placed into a vein. Your baby will receive this injection in a clinic or hospital setting. The medicine must be given slowly through an IV infusion, and can take over an hour to complete.
To be sure this medication is not causing harmful effects, your baby may need blood tests.
Since botulism immune globulin is usually given as a single IV infusion, your baby is not likely be on a daily dosing schedule.
Since botulism immune globulin is given in a controlled medical setting by a healthcare professional, an overdose is not likely to occur.
If your baby was recently vaccinated before treatment with botulism immune globulin, he or she may need to be vaccinated again to be fully protected. Follow your doctor's instructions.
trouble breathing, blue lips, pale skin;
urinating less than usual, fewer wet diapers than usual;
fever with headache, neck stiffness, sleepiness, sensitivity to light, vomiting;
trouble swallowing, noisy breathing, slow breathing;
vomiting, diarrhea, more wet diapers than usual; or
feeding problems, white patches in the mouth.
Less serious side effects may include:
mild skin rash or redness on the baby's face, chest, back, or stomach;
fussiness, excessive crying; or
stuffy nose, cough, chills.
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.
Usual Pediatric Dose for Botulism:
Less than one year of age with infant botulism caused by toxin type A or B:
2 mL/kg (100 mg/kg), given as a single intravenous infusion as soon as the clinical diagnosis of infant botulism is made. Add 2 mL sterile water for injection to the 100 mg vial, resulting in 50 mg/mL solution. Infusion should begin within 2 hours after reconstitution is complete and should be concluded within 4 hours of reconstitution. The infusion should begin slowly. Administration should start at 0.5 mL per kg body weight per hr (25 mg/kg/hr). If no untoward reactions occur after 15 minutes, the rate may be increased to the maximum infusion rate of 1 mL/kg/hr (50 mg/kg/hr). At the recommended rates, infusion of the indicated dose should take 127.5 minutes total elapsed time.
Botulism immune globulin can be harmful to the kidneys, and these effects are increased when this medication is used together with other drugs that can harm the kidneys. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.
Before your baby is treated with botulism immune globulin, tell your doctor about all other medications your baby is receiving, especially:
chemotherapy;
medicines to treat a bowel disorder;
medication to prevent organ transplant rejection;
antiviral medications;
pain or arthritis medicines, including aspirin or ibuprofen (Advil, Motrin); or
any IV antibiotics.
This list is not complete and there may be other drugs that can interact with botulism immune globulin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
Antigreg may be available in the countries listed below.
Ticlopidine hydrochloride (a derivative of Ticlopidine) is reported as an ingredient of Antigreg in the following countries:
International Drug Name Search
RAN-Zopiclone may be available in the countries listed below.
Zopiclone is reported as an ingredient of RAN-Zopiclone in the following countries:
International Drug Name Search
