![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20081028114124im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: 10/1/99, Marinol added: 10/20/99)
Note: The following summaries include only those safety-related sections that have been modified, and therefore do not contain all the information needed for safe and effective prescribing. Contact the manufacturer for the complete labeling/package insert.
NB: Comparison made to 1999 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.
|
(methyldopa/ chlorothiazide) |
(sulfasalazine) |
(dicyclomine HCl) |
(sotalol) |
|
(bleomycin sulfate) |
TOSYLATE |
(diltiazem HCl) |
(cefuroxime axetil) |
|
(neomycin/polymyxin B sulfate) |
(fluocinolone acetonide) |
(flutamide) |
(nitrofurantoin) |
|
(glipizide) |
(miglitol) |
|
(propranolol HCl) |
|
(mefloquineHCl) |
(chlordiazepoxide HCl/ clidinium Br) |
|
(dronabinol) |
|
(norethindrone/ ethinyl estradiol) |
(vincristine sulfate) |
(norethindrone/ ethinyl estradiol) |
(acarbose) |
|
(dinoprostone) |
(trimethoprim) |
(finasteride) |
(acebutolol) |
|
(testolactone) |
(metolazone) |
(simvastatin) |
(ondansetron) |
"When methyldopa and lithium are given concomitantly the patient should be carefully monitored for symptoms of lithium toxicity. Read the prescribing information for lithium preparations.
"Several studies demonstrate a decrease in the bioavailability of methyldopa when it is ingested with ferrous sulfate or ferrous gluconate. This may adversely affect blood pressure control in patients treated with methyldopa. Coadministration of methyldopa with ferrous sulfate or ferrous gluconate is not recommended."
"Azulfidine EN-tabs are contraindicated in: Patients hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates, Pediatric patients under two years of age, Patients with intestinal or urinary obstruction, Patients with porphyria, as the sulfonamides have been reported to precipitate an acute attack."
"Rheumatoid arthritis rarely remits. Therefore, continued administration of Azulfidine EN-tabs ["may be needed" deleted] is indicated. Patients requiring sulfasalazine should follow up with their physicians to determine the need for continued administration."
Carcinogenesis, Mutagenesis, Impairment of Fertility: Last paragraph, first sentence revised (new text in italics) -
"Impairment of male fertility was observed in reproductive studies performed in rats ["and rabbits" deleted] at a dose of 800 mg/kg/day (4800 mg/m2)."
"The following events have been identified during post-approval use of products which contain (or are metabolized to) mesalamine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine:
"Gastrointestinal: Reports of hepatotoxicity, including elevated liver function tests (SGOT / AST, SGPT / ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. One case of Kawasaki-like syndrome, which included hepatic function changes, was also reported."
"The signs and symptoms of overdosage are headache; nausea; vomiting; blurred vision; dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation. A curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
"A 37-year-old female reported numbness on the left side, cold fingertips, blurred vision, abdominal and flank pain, decreased appetite, dry mouth, and nervousness following ingestion of 320 mg daily (four 20 mg tablets QID) for four days. These events resolved after discontinuing the dicyclomine."
"Administration of Betapace within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cmax and AUC of 26% and 20%, respectively and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid two hours after Betapace has no effect on the pharmacokinetics or pharmacodynamics of sotalol."
"Malaise was also reported as part of postmarketing surveillance."
"Patients over 65 years may be at increased risk of developing orthostatic hypotension, especially when the recommended rate of intravenous infusion is exceeded. See DOSAGE AND ADMINISTRATION."
"Clinical studies of bretylium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 drug therapy.
"Intravenous infusion, especially if administered at a rate beyond that recommended in the DOSAGE AND ADMNISTRATION section, may produce an increased risk of orthostatic hypotension in the elderly. See WARNINGS.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. 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, See CLINICAL PHARMACOLOGY."
Second paragraph, last sentence revised (new text in italics) -
"More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension."
B. Other Ventricular Arrhythmias: 1. Intravenous Use: Second paragraph, second sentence revised (new text in italics) -
"More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension."
"Store at controlled room temperature 59-86oF (15-30oC)."
deleted and replaced with -
"Store at 25oC (77oF); excursions permitted to 15-30oC (59-86oF) [see USP Controlled Room Temperature]."
"The safety and effectiveness of Cortisporin Otic Solution in otitis externa have been established in the pediatric age group 2 years to 16 years of age. There is inadequate data to establish safety and effectiveness in otitis externa for pediatric patients under 2 years of age."
Geriatric Use: Existing text deleted and replaced with -
"Clinical studies of Cortisporin Otic Solution 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."
[Click Here to see new labeling.]
[Other information regarding these changes: Letter]
"Serum transaminase levels should be measured prior to starting treatment with flutamide. Flutamide is not recommended in patients whose ALT values exceed twice the upper limit of normal. Serum transaminase levels should then be measured monthly for the first 4 months of therapy, and periodically thereafter. Liver function tests also should be obtained at the first signs and symptoms suggestive of liver dysfunction, e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, hyperbilirubinuria, jaundice or right upper quadrant tenderness. If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, flutamide should be immediately discontinued with close follow-up of liver function tests until resolution."
"No information on the pharmacokinetics of flutamide in hepatic impairment is available (see BOXED WARNINGS, Hepatic Injury)."
Women, Pediatrics (new subsection):
"Flutamide has not been studied in women or pediatric subjects."
Stage B2-C Prostatic Carcinoma: First paragraph revised (new text in italics) -
"The effects of hormonal treatment combined with radiation was studied in 466 patients (231 Eulexin + ["LHRH-A" deleted] goserelin acetate implant+ radiation, 235 radiation alone) with ..."
"Treatment with Eulexin and the ["LHRH agonist" deleted] goserelin acetate implant should start eight weeks ..."
"Eulexin capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment)."
"Hepatic injury: SEE BOXED WARNING
"Use in Women: This product has no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions.
"Fetal toxicity: Flutamide may cause fetal harm when administered to a pregnant woman (see Pregnancy).
"Aniline toxicity: One metabolite of flutamide is 4-nitro-3-fluoro-methylaniline. Several toxicities consistent with aniline exposure, including methemoglobinemia, hemolytic anemia and cholestatic jaundice have been observed in both animals and humans after flutamide administration. In patients susceptible to aniline toxicity (e.g., persons with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease and smokers), monitoring of methemoglobin levels should be considered."
"In clinical trials, gynecomastia occurred in 9% of patients receiving flutamide together with medical castration."
Laboratory Tests: Second paragraph deleted -
"Since transaminase abnormalities and rarely jaundice have been reported with the use of Eulexin, periodic liver function tests should be considered, e.g., when the patient has jaundice or laboratory evidence of liver injury in the absence of liver metastases. Eulexin therapy should be discontinued. Abnormalities are usually reversible upon discontinuation. See WARNINGS, Hepatic Injury above."
Animal Toxicology (new subsection):
"Serious cardiac lesions were observed in 2/10 beagle dogs receiving 25 mg/kg/day for 78 weeks and 3/16 receiving 40 mg/kg/day for 2-4 years. These lesions, indicative of chronic injury and repair processes, included chronic myxomatous degeneration, intra-arterial fibrosis, myocardial acidophilic degeneration, vasculitis and perivasculitis. The doses at which these lesions occurred were associated with 2-hydroxyflutamide levels that were 1 to 12-fold greater than those observed in humans at therapeutic levels."
Pregnancy: Pregnancy Category D:
Existing text -
"See WARNINGS section."
deleted and replaced with -
"There was decreased 24-hour survival in the offspring of pregnant rats treated with flutamide at doses of 30, 100, or 200 mg/kg/day (approximately 3, 9, and 19 times the human dose). A slight increase in minor variations in the development of the sternabrae and vertabrae was seen in fetuses of cats treated with higher doses. Feminization of the male cats also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day, equal 1.4 times the human dose)."
"Treatment with Eulexin and the ["LHRH agonist" deleted] goserelin acetate implant did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multi-center clinical trial comparing Eulexin + ["LHRH-A" deleted] goserelin acetate implant + radiation versus radiation alone."
Stage D2 Metastatic Carcinoma: Fifth paragraph, second sentence deleted -
"No causal relatedness of these reactions to drug treatment has been made, and some of the adverse experiences reported are those that commonly occur in elderly patients."
Paragraph beginning - "In addition, the following spontaneous adverse experiences have been reported..."
First sentence: - "sulfhemoglobinemia" added.
Last sentence revised (new text in italics) - "The hepatic conditions were ["usually" deleted] often reversible after discontinuing therapy... "
Last paragraph -
Text deleted and replaced with -
"Malignant breast neoplasms have occurred rarely in male patients being treated with Eulexin."
Text deleted -
"Two reports of malignant breast neoplasms occurring in male patients being dosed with Eulexin Capsules have been reported. One involved a pre-existing nodule which was first detected 3-4 months before initiation of Eulexin monotherapy. After excision, this nodule was diagnosed as a poorly differentiated ductal carcinoma. The other report involved gynecomastia and a breast nodule noted 2 and 6 months, respectively, after initiation of Eulexin monotherapy. The nodule was excised and diagnosed as a moderately differentiated invasive ductal tumor."
"Since flutamide is highly protein bound, dialysis may not be of any use as treatment for overdose."
deleted and replaced with -
"Flutamide is highly protein bound and is not cleared by hemodialysis."
[Click Here to see new labeling.]
"Dilution Techniques:
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of nitrofurantoin powder. The MIC values should be interpreted according to the following criteria:
|
Microorganism |
MIC (mcg/mL) |
|
E. coli ATCC 25922 |
4-16 |
|
S. aureus ATCC 29213 |
8-32 |
|
E. faecalis ATCC 29212 |
4-16 |
"A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
"Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard nitrofurantoin powder should provide the following MIC values:
|
MIC (mcg/mL) |
Interpretation |
|
# 32 |
Susceptible (S) |
|
64 |
Intermediate (I) |
|
$ 128 |
Resistant (R) |
"Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 300 mcg nitrofurantoin to test the susceptibility of microorganisms to nitrofurantoin.
"Reports from the laboratory providing results of the standard single-disk susceptibility test with a 300 mcg trimethoprim disk should be interpreted according to the following criteria:
|
Zone diameter (mm) |
Interpretation |
|
$ 17 |
Susceptible (S) |
|
15-16 |
Intermediate (I) |
|
# 14 |
Resistant (R) |
"Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for nitrofurantoin.
"As with standardized dilution techniques, diffusion methods require the use of the laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 300 mcg nitrofurantoin disk should provide the following zone diameters in these laboratory test quality control strains:
|
Microorganism |
MIC (mcg/mL) |
|
E. coli ATCC 25922 |
20-25 |
|
S. aureus ATCC 25923 |
18-22 |
"A determiniation has not been made whether controlled clinical studies of Glucotrol included sufficient numbers of subjects aged 65 and over to define a difference in response 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 patinet 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."
"Elderly: The pharmacokinetics of miglitol were studied in elderly and young males (n = 8 per group). At a dosage of 100 mg 3 times daily for 3 days, no differences between the two groups were found."
"Of the total number of subjects in clinical studies of Glyset in the United States, patients valid for safety analyses included 24 percent over 65, and 3 percent over 75. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. The pharmacokinetics of miglitol were studied in elderly and young males (n=8 per group). At the dosage of 100 mg 3 times daily for 3 days, no differences between the two groups were found."
"Patients over 60 years of age, following similar doses of heaprin, may have higher plasma levels of heparin and longer activated partial thromboplastin times (APTTs) compared with patients under 60 years of age."
"A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age."
Geriatric Use (new subsection):
"A higher incidence of bleeding has been reported in patients over 60 years of age, especially women (see PRECAUTIONS, General). Clinical studies indicate that lower doses of heparin may be indicated in these patients (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION)."
"Patients over 60 years of age may require lower doses of heparin."
"Clinical studies of propranolol 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 the decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy."
"Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia, and confusion while receiving Librax. These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated (see DOSAGE.). Librax is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (see CONTRAINDICATIONS)."
"Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 Librax capsules per day, to be increased gradually as needed and tolerated."
"In clinical studies, patients over 65 years showed decreased lidocaine clearance. This was partly due to the tendency of elderly patients to have lower body weight and the increased risk of cardiac failure in these patients."
"The safety and effectiveness of lidocaine has not been established in pediatric patients (neonates to adolescents)."
Geriatric Use (new subsection):
"Clinical studies of Lidocaine HCl did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Lidocaine is substantially excreted by the kidney and clearance of Lidocaine is decreased in the elderly (see CLINICAL PHARMACOLOGY). 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 renal or cardiac function, and of concomitant disease or other drug therapy."
"Patients over 65 years may benefit from dosing based upon body weight."
" Tear outer wrap at notch and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually."
Preparation for Administration:
Paragraphs 6, 7, 8, and 9 -
"6. Attach venipuncture device to set.
7. Open clamp to expel air from set and venipuncture device. Close clamp.
8. Perform venipuncture.
9. Regulate rate of administration with flow control clamp."
deleted and replaced with -
"6. Open flow control clamp and clear air from set. Close clamp.
7. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
8. Regulate rate of administration with flow control clamp."
Second paragraph -
"Protect from freezing and extreme heat. Do not store above 40(C (104F()."
deleted and replaced with -
"Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25(C); however, brief exposure up to 40(C does not adversely affect the product."
"Marinol (dronabinol) should be packaged in a well-closed container and stored in a cool environment between 8o and 15oC (46o and 59o F). Protect from freezing. No particular hazard to health care workers handling the capsules has been identified.
"Access to abusable drugs such as Marinol presents an occupational hazard for addiction in the health care industry. Routine procedures for handling controlled substances developed to protect the public may not be adequate to protect health care workers. Implementation of more effective accounting procedures and measures to appropriately restrict access to drugs of this class may minimize the risk of self-administration by health care providers."
deleted and replaced with -
"Marinol (dronabinol) should be packaged in a well-closed container and stored in a cool environment between 8 C and 15 C (46 and 59 F) and alternatively could be stored in a refrigerator. Protect from freezing.
"A meta-analysis of 54 studies found a small increase in the frequency of having breast cancer diagnosed for women who were currently using combined oral contraceptives or had used them within the past ten years. This increase in the frequency of breast cancer diagnosis, within ten years of stopping use, was generally accounted for by cancers localized to the breast. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of use."
deleted and replaced with -
"A meta-analysis of 54 studies reports that women who are currently using combined oral contraceptives or had used them in the past 10 years are at slightly increased risk of having breast cancer diagnosed although the additional cancers tend to be localized to the breast. There is no evidence of an increased risk of having breast cancer diagnosed 10 or more years after cessation of use."
Last paragraph, first sentence - "intraepithelial" added to the description of cervical neoplasia. [Note: this change appears in the 1999 PDR.]
4. Hepatic Neoplasia: Second paragraph modified to read -
"Studies have shown an increased risk of developing hepatocellular carcinoma in oral contraceptive users. However, these cancers are rare in the U.S." [Note: this change appears in the 1999 PDR.]
12. Pediatric Use (new subsection):
"Safety and efficacy of Ortho-Novum Tablets and Modicon Tablets has been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated." [Note; this change appears in the 1999 PDR.}]
"Concurrent administration of vincristine sulfate with itraconazole (a known ["inhibitor of the metabolic pathway" deleted] CYP 3A enzyme) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects (see Adverse Reactions)."
"Of the total number of subjects in clinical studies of Precose in the United States, 27 percent were 65 and over, while 4 percent were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant."
"Safety and effectiveness in pediatric patients have not been established."
"Dilution Techniques
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of trimethoprim powder. The MIC values should be interpreted according to the following criteria:
|
MIC (mcg/mL) |
Interpretation |
|
# 8 |
Susceptible (S) |
|
$ 16 |
Resistant (R) |
"A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
"Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard trimethoprim powder should provide the following MIC values:
|
Microorganism |
MIC (mcg/mL) |
|
S. aureus ATCC 29213 |
1-4 |
|
E. faecalis ATCC 29212 |
# 1 |
|
E. coli ATCC 25922 |
0.5-2 |
|
P. aeruginosa ATCC 27853 |
>64 |
"Diffusion Techniques
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5 mcg trimethoprim to test the susceptibility of microorganisms to trimethoprim.
"Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 mcg trimethoprim disk should be interpreted according to the following criteria:
|
Zone diameter (mm) |
Interpretation |
|
$ 16 |
Susceptible (S) |
|
11-15 |
Intermediate (I) |
|
# 10 |
Resistant (R) |
"Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for trimethoprim.
"As with standardized dilution techniques, diffusion methods require the use of the laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5 mcg trimethoprim disk should provide the following zone diameters in these laboratory test quality control strains:
|
Microorganism |
Zone Diameter (mm) |
|
E. coli ATCC 25922 |
21-28 |
|
S. aureus ATCC 25923 |
19-26 |
"["The safety of trimethoprim in" deleted] Safety and effectiveness in pediatric patients below the age of ["under" deleted] 2 months have not been established ["of age has not been demonstrated" deleted]. The effectiveness of trimethoprim as a single agent has not been established in pediatric patients under 12 years of age."
"The effectiveness of trimethoprim has not been established in pediatric patients under 12 years of age."
"Percent free PSA (free to total PSA ratio) is not significantly decreased by Proscar. The ratio of free to total PSA remains constant even under the influence of Proscar. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing finasteride therapy, no adjustment to its value appears necessary."
"Clinical studies of Sectral and other reported clinical experience is inadequate to determine whether there are differences in safety or effectiveness between patients above or below age 65.
"Elderly subjects evidence greater bioavailability of acebutolol (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism), presumably because of age-related reduction in first-pass metabolism and renal function. Therefore, it may be appropriate to start elderly patients at the low end of the dosing range (see DOSAGE AND ADMINISTRATION - Use in Older Patients)."
"Safety and effectiveness in pediatric patients have not been established and such use is not recommended."
deleted and replaced with -
"Safety and effectiveness in pediatric patients have not been established in controlled clinical trials. There is limited experience with the use of Zaroxolyn in pediatric patients with congestive heart failure, hypertension, bronchopulmonary dysplasia, nephrotic syndrome, and nephrogenic diabetes insipidus. Doses used generally ranged from 0.05 to 0.1 mg/kg administered once daily and usually resulted in a 1 to 2.8 kg weight loss and 150 to 300 cc increase in urine output. Not all patients responded and some gained some weight. Those patients who did respond did so in the first few days of treatment. Prolonged use (beyond a few days) was generally associated with no further beneficial effect or a return to baseline status and is not recommended.
"There is limited experience with the combination of Zaroxolyn and furosemide in pediatric patients with furosemide-resistant edema. Some benefitted while others did not or had an exaggerated response with hypovolemia, tachycardia, and orthostatic hypotension requiring fluid replacement. Severe hypokalemia was reported and there was a tendency for diuresis to persist for up to 24 hours after Zaroxolyn was discontinued. Hyperbilirubinemia has been reported in 1 neonate. Close clinical and laboratory monitoring of all children treated with diuretics is indicated. See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS."
"Store at ["room temperature" deleted] 25oC (77Fo); excursions permitted to 15-30oC (59-86Fo) [See USP Controlled Room Temperature]. ["Dispense in a tight-light resistant container." deleted]. Protect from light. Keep out of the reach of children."
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