![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20081028100707im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: 12/11/98, Flagyl ER added: 12/17/98)
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 1998 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.
|
(irinotecan HCl) |
(cytarabine) |
(levamisole HCl) |
(metronidazole) |
|
(fluticasone propionate) |
(metformin HCl) |
(lincomyin HCl) |
|
|
(vinorelbine tartrate) |
(cisatracurium besylate) |
(tamoxifen citrate) |
(ritonavir) |
|
(metipranolol) |
(lisinopril/ hydrochlorothiazide) |
(pentazocine lactate) |
(eprosartan mesylate) |
|
(timolol maleate/ hydrochlorothiazide) |
(enalapril maleate/ hydrochlorothiazide) |
Last paragraph in section revised (new text in italics) -
"Acute pancreatitis has been reported to occur in patients being treated with Cytosar-U who have had prior treatment with L-asparaginase.15 There is evidence that this may be schedule dependent.50"
49. Smith GA, Damon LE, Rugo HS, et al: High-Dose Cytarabine Dose Modification Reduces the Incidence of Neurotoxicity in Patients with Renal Insufficiency. J Clin Oncol 1997;15:8333-839.
50. McBride CE, Yavorski RT, Moses FM, et al: Acute Pancreatitis Associated with Continuous Infusion Cytarabine Therapy: A Case Report. Cancer 1996; 77:2588-2591.
"The pharmacokinetics of Ergamisol have not been studied in the dosage regimen recommended with fluorouracil ["nor in patients with hepatic insufficiency" deleted]."
Text added as new last sentence -
"In the presence of cirrhosis the Cmax of Ergamisol is not clearly increased but the AUC increases four-fold."
"Cases of an encephalopathy-like syndrome associated with demyelination have been reported in patients treated with Ergamisol (levamisole hydrochloride). Worldwide postmarketing experience with the combination therapy of Ergamisol and fluorouracil has also included reports of peripheral neuropathy and multifocal inflammatory leukoencephalopathy. The onset of symptoms and the clinical presentation in these cases are quite varied. Symptoms may include coma, confusion, lethargy, memory loss, muscle weakness, paresthesia, seizures, and speech disturbances. This condition has been associated with MRI and CT scan findings of demyelinating lesions in the white matter. If an acute neurological syndrome occurs, Ergamisol and fluorouracil should be discontinued immediately. Patients have generally recovered/improved with drug discontinuation ["and corticosteroid therapy" deleted], but in some cases patients have not recovered/improved and deaths have been reported. Patients are generally treated with corticosteroids, but the efficacy of corticosteroids has not been proven."
Last paragraph, text added as new first sentence -
"In the presence of cirrhosis the Cmax of Ergamisol is not clearly increased but the AUC increases four-fold. Dose modification or discontinuation of Ergamisol may be necessary if adverse experiences are observed."
"Since the AUC of Ergamisol is markedly increased in cirrhotic patients, such patients should be observed closely for adverse effects. dose reduction or discontinuation of Ergamisol may be warranted if adverse experiences are noted."
"Store at controlled room temperature [", 15o-30oC (59o-86oF)" deleted] (59o-77oF/15o-25oC)."
"Flagyl ER has not been studied in pregnant women. Since metronidazole crosses the placental barrier and enters the fetal circulation rapidly, it should not be administered to pregnant patients during the first trimester. No fetotoxicity was observed when metronidazole was administered orally to pregnant mice at 60 mg/m2/day, which is approximately 10% of the human dose when expressed as mg/m2. However, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. There are, however, no adequate and well-controlled studies in pregnant women. (See CONTRAINDICATIONS.)
"Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed."
"Flagyl ER was studied in patients with BV in two randomized, multicenter, well-controlled, investigator blind clinical trials. A total of 557 otherwise healthy nonpregnant patients with BV were randomized to treatment with Flagyl ER once a day for 7 days (n=270) or 2% clindamycin vaginal cream one applicator full (5 grams) once a day for 7 days (n=287)."
"Syringes containing this product should be labeled "WARNING - ["NAVELBINE" deleted] FOR ["INTRAVENOUS" deleted] IV USE ONLY. FATAL if given intrathecally."
"Vestibular and auditory deficits have been observed with Navelbine, usually when used in combination with cisplatin."
"There is no known antidote for overdoses of Navelbine. ["The primary anticipated complications of overdosage would consist of bone marrow suppression and peripheral neurotoxicity." deleted] Overdoses involving quantities up to ten times the recommended dose (30 mg/m2) have been reported. The toxicities described were consistent with those listed in the ADVERSE REACTIONS section including paralytic ileus, stomatitis, and esophagitis. Bone marrow aplasia, sepsis, and paresis have also been reported. Fatalities have occurred following overdose of Navelbine. If overdosage occurs, general supportive measures together with appropriate blood transfusions, growth factors, and antibiotics should be instituted as deemed necessary by the physician."
"In one intubation study during thiopental anesthesia in which fentanyl and midazolam were administered two minutes prior to induction, intubation conditions were assessed at 120 seconds. The following table displays these results in this study of 51 patients.
"Table 2
Study of Tracheal Intubation Comparing two doses of Cisatracurium
(Thiopental anesthesia)
|
Intubating Conditions |
3x ED95 |
4x ED95 |
|
Excellent and Good |
23/26 (88%) |
24/25 (96%) |
|
Excellent |
8/26 (31%) |
15/25 (60%) |
|
Good |
15/26 (58%) |
9/25 (36%) |
"While GOOD OR EXCELLENT intubation conditions were achieved in the majority of patients in this setting, EXCELLENT intubation conditions were more frequently achieved with the 0.2 mg/kg dose (60%) than the 0.15 mg/kg dose (31%) when intubation was attempted 2.0 minutes following cisatracurium.
"A second study evaluated intubation conditions after 3 and 4X ED95 (0.15 mg/kg and 0.20 mg/kg) following induction with fentanyl and midazolam and either thiopental or propofol anesthesia. This study compared intubation conditions produced by these doses of cisatracurium after 1.5 minutes. The following table displays these results.
"Table 3
Study of Tracheal Intubation Comparing three doses of Cisatracurium
(Thiopental or Propofol Anesthesia)
|
Intubating |
3x ED95 |
3x ED95 |
4x ED95 |
4x ED95 |
|
Excellent and Good Proportion |
29/31 |
28/31 |
28/30 |
27/28 |
|
Excellent Proportion |
18/31 |
17/31 |
22/30 |
16/28 |
|
Good Proportion |
11/31 |
11/31 |
6/30 |
11/28 |
"EXCELLENT intubation conditions were more frequently observed with the 0.2 mg/kg dose when intubation was attempted 1.5 minutes following cisatracurium."
"In two intubation studies using thiopental or propofol and midazolam and fentanyl as co-induction agents, EXCELLENT intubation conditions were most frequently achieved with a 0.2 mg/kg compared to 0.15 mg/kg dose of cisatracurium."
"Recommended Storage: Store Norvir oral solution ["in the refrigerator between 36-46oF (2-8oC) until it is dispensed." deleted] at room temperature 68oF to 77oF (20oC to 25oC). Do not refrigerate. Shake well before each use. Use by product expiration date.
"["Refrigeration of Norvir oral solution by the patient is recommended, but not required if used within 30 days and stored below 77oF (25oC)." deleted] Product should be stored and dispensed in the original container.
"Avoid exposure to excessive heat. Keep cap tightly closed."
"Each mL of OptiPranolol contains 3 mg of metipranolol. INACTIVES: Povidone, Glycerin, Hydrochloric Acid, Sodium Chloride, Edetate Disodium, and Purified Water. Sodium Hydroxide and/or Hydrochloric Acid may be added to adjust pH. The product is produced at pH 5.0-5.8 and osmolality 265 to 330 mOsmol/kg. PRESERVATIVE ADDED: Benzalkonium Chloride 0.004%."
"In controlled studies of patients with intraocular pressure greater than 24 mmHg at baseline, OptiPranolol Ophthalmic Solution reduced the average intraocular pressure approximately 20-26%.
"The onset of action of OptiPranolol Ophthalmic Solution, as measured by a reduction in intraocular pressure, occurs within 30 minutes after a single administration. The maximum effect occurs at about 2 hours. A reduction in intraocular pressure can be demonstrated 24 hours after a single dose. Clinical studies in patients with glaucoma treated for up to two years indicate that an intraocular pressure lowering effect is maintained."
"OptiPranolol Ophthalmic Solution is indicated in the treatment of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit; including patients with ocular hypertension, and patients with chronic open angle glaucoma."
deleted and replaced with -
"OptiPranolol Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma."
Second and third paragraphs beginning "In controlled studies ..." and "The onset of action ..." moved to CLINICAL PHARMACOLOGY section - see above.
Fourth paragraph beginning "In clinical trials..." moved to DOSAGE AND ADMINISTRATION section - see below.
"Patients should be advised that OptiPranolol contains benzalkonium chloride which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following OptiPranolol administration."
"In clinical trials, OptiPranolol Ophthalmic Solution was safely used during concomitant therapy with pilocarpine, epinephrine or acetazolamide."
"Lisinopril is an effective treatment of hypertension in once-daily doses of 10-80 mg, while hydrochlorothiazide is effective in doses of ["25-100 mg" deleted] 12.5-50 mg."
"The safety and efficacy of Talwin as preoperative or preanesthetic medication have been established in pediatric patients 1 to 16 years of age. Use of Talwin in these age groups is supported by evidence from adequate and well controlled studies in adults with additional data from published controlled trials in pediatric patients. The safety and efficacy of Talwin as a premedication for sedation have not been established in pediatric patients less than one year old. Information on the safety profile of Talwin as a postoperative analgesic in children less than 16 years is limited."
"The recommended single parenteral dose as premedication for sedation is 0.5 mg/kg by intramuscular route."
"Blood pressure control is maintained with once- or twice-daily dosing over a 24-hour period and in some patients is maintained with a single daily dose."
Clinical Trials: Second paragraph split into two paragraphs and revised (new text in italics) -
"The antihypertensive effects of Teveten were demonstrated principally in ["four" deleted] five placebo-controlled trials (["8" deleted"] 4 to 13 weeks' duration) ["using" deleted] including dosages of 400 mg to 1200 mg given once daily (["one study" deleted"] two studies), 25 mg to 400 mg twice daily (two studies), and one study comparing total daily doses of 400 mg to 800 mg given once daily or twice daily. The ["four" deleted] five studies included ["988" deleted] 1111 patients randomized to eprosartan and ["275" deleted] 395 patients randomized to placebo. The studies showed dose-related antihypertensive responses.
"At study endpoint, patients treated with Teveten at doses of ["200 mg to 400 mg" deleted] 600 mg to 1200 mg given once ["twice" deleted] daily experienced significant decreases in sitting systolic and diastolic blood pressure at trough, with differences from placebo of approximately ["7-10/4-6" deleted] 5-10/3-6 mmHg. ["In one study, once daily dosing at doses up to 800 mg had only small trough effects (about 2-3 mmHg) on diastolic pressure. A 1200 mg single daily dose had a persistent effect of 9/3 mmHg, but there is little overall experience with this dose." deleted] Limited experience is available with the dose of 1200 mg administered once daily. In a direct comparison of 200 mg to 400 mg b.i.d. with 400 mg to 800 mg o.d. of Teveten, effects at trough were similar. Patients treated with Teveten at doses of 200 mg to 400 mg given twice daily experienced significant decreases in sitting systolic and diastolic blood pressure at trough, with difference from placebo of approximately 7-10/4-6 mmHg. ["In general, Teveten should be initiated as a b.i.d. regimen." deleted]"
Previous third paragraph, now the fourth paragraph revised (new text in italics) -
"Peak (1 to 3 hours) effects were uniformly, but moderately, larger than trough effects with b.i.d. dosing, with the trough-to-peak ratio for diastolic blood pressure 65% to 80%. In the ["o.d." deleted] once-daily dose-response ["study" deleted] studies, trough-to-peak response of < or = ["40%" deleted] 50% were observed at ["all" deleted] some doses (including 1200 mg), suggesting attenuation of effect at the end of the dosing interval. ["In the study comparing once- and twice-daily dosing, however, both dosing regimens resulted in trough-to-peak ratios of greater than 60% with twice-daily dosing still producing larger trough-to-peak ratios." deleted]
"In ["one" deleted] a study of only patients ["aged 65 years and older" deleted] over the age of 65, Teveten at 200 mg twice daily (and increased optionally up to 300 mg twice daily) decreased diastolic blood pressure on average by ["2" deleted] 3 mmHg (placebo ["subtracted" deleted] corrected)."
"Patients were rarely withdrawn from Teveten because of laboratory test results."
Creatinine, Blood Urea Nitrogen: Last sentence revised (new text in italics) -
"["Six" deleted] Two patients were withdrawn from clinical trials for elevations in serum creatinine and ["two for increases in" deleted] BUN, and three additional patients were withdrawn for increases in serum creatinine."
Hemoglobin: Last sentence revised (new text in italics) -
"["Eight" deleted] Two patients were withdrawn from clinical trials for anemia."
Neutropenia: Last sentence revised (new text in italics) -
"["One" deleted] No patient was withdrawn from any clinical trials for neutropenia."
Thrombocytopenia: second sentence revised (new text in italics) -
"["Three" deleted] Four patients receiving Teveten in clinical trials were withdrawn for thrombocytopenia."
Serum potassium: Last sentence revised (new text in italics) -
"["Two patients were" deleted] One patient was withdrawn from clinical trials for hyperkalemia and ["five" deleted] three for hypokalemia."
"The usual starting dose of Tevetan in patients who are not volume depleted is 200 mg twice daily. If additional antihypertensive effect is required, the dosage of Teveten may be increased to 400 mg twice daily. A diuretic may be added if blood pressure is still not adequately controlled, but there is no experience with doses above 400 mg twice daily in combination with a diuretic. Achievement of maximum blood pressure reduction in most patients may take 2 to 3 weeks. In patients with adequate blood pressure control at trough on twice-daily therapy, it may be possible to maintain control with once-daily therapy at the same total daily dose. There is limited experience with doses beyond 800 mg/day."
Text added as new first and second paragraphs -
"The usual recommended starting dose of Teveten is 600 mg once daily when used as monotherapy in patients who are not volume depleted (See WARNINGS, Hypotension in Volume-and/or Salt-Depleted Patients). Teveten can be administered once or twice daily with total daily doses ranging from 400 mg to 800 mg. There is limited experience with doses beyond 800 mg/day.
"If the anti-hypertensive effect measured at trough using once-daily dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. Achievement of maximum blood pressure reduction in most patients may take 2 to 3 weeks."
Previous second paragraph, now third paragraph, second sentence revised (new text in italics) -
"Discontinuation of treatment ["of" deleted] with eprosartan ..."
"The recommended starting and maintenance dosage is 1 tablet twice a day or 2 tablets once a day. ["Patients usually do not require doses in excess of 50 mg hydrochlorothiazide daily when combined with other antihypertensive agents." deleted] Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. If the antihypertensive response is not satisfactory, another nondiuretic antihypertensive agent may be added."
"The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses; hydrochlorothiazide is effective in doses of ["25 to 100 mg" deleted] 12.5 to 50 mg daily."
