![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20081028113912im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: December 3, 1999)
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.
|
(bleomycin sulfate) |
(plegisol) |
(norfloxacin) |
(amiodarone HCl) |
(ethacrynic acid & ethacrynate Na) |
(norethindrone acetate/ ethinyl estradiol) |
(glyburide) |
(peg-3350 & electrolytes) |
(heparin) |
(enoxaparin Na) |
(methrotrexate Na) |
(glyburide) |
(niacin) |
(ritonavir) |
(peg-3350/soduim chloride sodium bicarbonate potassium chloride) |
(pravastatin Na) |
(troglitazone) |
(fluoxetine HCl) |
(paclitaxel) |
(topiramate) |
(tolazamide) |
(remifentanil HCl) |
(didanosine) |
(rofecoxib) |
(nevirapine) |
(latanoprost) |
(sparfloxacin) |
(ranitidine HCl) |
[Other labeling changes not appearing in 1999 PDR: aug99 ]
"Scleroderma-like skin changes have also been reported as part of postmarketing surveillance"
"Clinical studies of Plegisol did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between older and younger patients.
"In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosage range reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease.
"This product is unique in that there is no hepatic or renal excretion and specific adjustments for dosing in the elderly are not known."
Deleted and replaced with -
"Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis."
"Therefore, as with the oral formulation, norfloxacin should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, and other factors which dispose to seizures."
Fourth paragraph revised, adverse effects have been reordered and new text is in italics -
"The following adverse effects have been reported with Tablets Noroxin (norfloxacin tablets). Hypersensitivity Reactions: Hypersensitivity reactions including anaphylactoid reactions, angioedema, arthralgia, arthritis, dyspnea, myalgia, urticaria, vasculitis; Gastrointestinal: Hepatitis, jaundice, including cholestatic jaundice, pancreatitis, pseudomembraneous colitis; Heamatologic: Hemolytic anemia, sometimes associated with glucose-6-phospahte dehydrogenase deficiency, leukopenia, neutropenia, thrombocytopenia; Musculoskeletal: Possible exacerbation of myasthenia gravis, tendinitis, tendon rupture; Nervous System/Psychiatric: Ataxia, CNS effects characterized as generalized seizures and myoclonus; Guillain-Barre syndrome, paresthesia, peripheral neuropathy, psychic disturbances including confusion, depression, psychotic reactions; Renal: Interstitial nephritis, renal failure; Skin: Erythema multiforme and Stevens-Johnson syndrome, exfoliative dermatitis, photosensitivity, rash, toxic epidermal necrolysis; Special Senses: Diplopia, tinnitus, transient hearing loss.
[Other labeling changes not appearing in 1999 PDR: Jan99]
"Food increases the rate and extent of absorption of Cordarone. The effects of food upon the bioavailability of Cordarone have been studied in 30 healthy subjects who received a single 600-mg dose immediately after consuming a high fat meal and following an overnight fast. The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (Cmax) of amiodarone increased by 2.3 (range 1.7 to 3.6) and 3.8 (range 2.7 to 4.4) times, respectively, in the presence of food. Food also increased the rate of absorption of amiodarone, decreasing the time to peak plasma concentration (Tmax) by 37%. The mean AUC and mean Cmax of desethylamiodarone increased by 55% (range 58 to 101%) and 32% (range 4 to 84%), respectively, but there was no change in the Tmax in the presence of food."
Second paragraph, third and fourth sentences deleted -
"The pharmacological activity of this metabolite, however, is not known. During chronic treatment, the plasma ratio of metabolite to parent compound is approximately one."
Replaced with the following text -
"No data are available on the activity of DEA in humans, but in animals, it has significant electrophysiologic and antiarrhythmic effects generally similar to amiodarone itself. DEA's precise role and contribution to the antiarrhythmic activity of oral amiodarone are not certain. The development of maximal ventricular class III effects after oral Cordarone administration in humans correlates more closely with DEA accumulation over time than with amiodarone accumulation."
Third paragraph deleted, replace with the following text (third and fourth paragraphs) -
"Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. Neither amiodarone nor DEA is dialyzable.
"In clinical studies of 2 to 7 days, clearance of amiodarone after intravenous administration in patients with VT and VF ranged between 220 and 440 mL/hr/kg. Age, sex, renal disease, and hepatic disease (cirrhosis) do not have marked effects on the disposition of amiodarone or DEA. Renal impairment does not influence the pharmacokinetics of amiodarone. After a single dose of intravenous amiodarone in cirrhotic patients, significantly lower Cmax and average concentration values are seen for DEA, but mean amiodarone levels are unchanged. Normal subjects over 65 years of age show lower concentrations (about 100 ml/hr/kg) than younger subjects (about 150 ml/hr/kg) and an increase in t1/2 from about 20 to 47 days. In patients with severe left ventricular disposition the pharmacokinetics of amiodarone are not significantly altered but the terminal disposition t1/2 of DEA is prolonged. Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with Cordarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction."
Fifth paragraph, new first sentence -
"Following single dose administration in 12 healthy subjects, Cordarone exhibited multi-compartmental pharmacokinetics with a mean apparent plasma terminal elimination half-life of 58 days (range 15 to 142 days) for amiodarone and 36 days (range 14 to 75 days) for the active metabolite (DEA)."
"Clinical studies of Cordarone Tablets 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."
"Because of the food effect on absorption, Cordarone should be administered consistently with regard to meals (see "Clinical Pharmacology")."
"Store in a tightly closed container at 25 oC (77 oF); excursions permitted to 15-30 oC (59-86 oF). [see USP Controlled Room Temperature]
[Other labeling changes not appearing in 1999 PDR: May99]
Contact the company for a copy of the new labeling/package insert.
"Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see DOSAGE AND ADMINISTRATION).
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function."
"GoLYTELY is contraindicated in patients known to be hypersensitive to any of the components."
[IMPORTANT NOTE: The following labeling changes differ from the class labeling for the 10 USP Units/mL]
"FOR IV FLUSH ONLY"
In title section and throughout the text, the syringe is identified as:
"Ansyr(tm) Unit of Use Plastic Syringe"
It may interfere with laboratory tests in blood samples withdrawn from such devices, unless the volume of in situ heparin-saline, equal to that of the priming volume of the catheter, is aspirated and discarded before such samples are taken.
"To prevent clot formation in a central venous catheter or peripherally inserted central venous catheter following its proper insertion, Heparin Lock Flush Solution, 100u/mL is injected into the catheter (or into each unused lumen of a multiple-lumen catheter) in a quantity sufficient to fill the entire catheter or lumen of a multiple-lumen catheter to the tip (see catheter manufacturer's labeling for specific catheter lumen volumes). This solution should be replaced each time the catheter (or catheter lumen in a multiple lumen catheter) is used. Aspirate before administering any solution in order to confirm catheter patency. If the drug to be administered is incompatible with heparin, the entire catheter or catheter lumen should be flushed with sterile water or normal saline before and after the medication is administered. Following the second flush, Heparin Lock Flush Solution may be reinstilled into the set. The catheter manufacturer's instructions should be consulted for specifics concerning the catheter in use at a given time."
"Repeated flushing of a catheter device with Heparin 100 USP units/mL may result in a systemic anticoagulant effect."
"Not for multiple dosing. After single use, discard unused portion in the Ansyr(tm) unit of use 5 mL plastic syringe (100 USP Units/mL)."
Pediatric Use:
"Safety and effectiveness of the 100 USP Units/mL Heparin Lock Flush Solution, USP, in pediatric patients have not been established."
Second paragraph added:
"Heparin Lock Flush Solution, USP 100 USP Units/mL, is injected as a single dose into an intravenous injection device using a volume of solution equivalent to that of the indwelling venipuncture device (see catheter manufacturer's labeling for specific catheter lumen volumes).
Third paragraph, second and fourth sentences added:
"After each use of the indwelling venipuncture device for injection or infusion of medication, or withdrawal of blood samples, another dose (using a volume of solution equivalent to that of the indwelling venipuncture device) - should be injected to restore the effectiveness of the heparin lock." "The amount of heparin solution in each single dose is sufficient to prevent clotting within the lumen of indwelling venipuncture devices for up to twenty-four hours."
Fifth paragraph (new text in italics) -
"When the indwelling device is used for repeated withdrawal of blood samples for laboratory analyses and the presence of heparin or saline is likely to interfere with or alter results of the desired blood tests, the in situ heparin flush solution should be cleared from the device by aspirating and discarding a volume of solution equivalent to that of the indwelling venipuncture device before the desired blood sample is drawn, See PRECAUTIONS."
"Heparin Lock Flush Solution, USP, 100 USP Units/mL, 5 mL fill, in a 5 mL Ansyr Unit of Use plastic syringe, LifeShield with male Luer Lock adapter (LIST 3454)."
[Other labeling changes not appearing in 1999 PDR: Dec98, Apr99]
Last paragraph revised (new text in italics) -
Other reports include: local reactions at the injection site (i.e., skin necrosis, nodules, inflammation, oozing), systemic allergic reactions (i.e., pruritis, urticaria, anaphylactoid reactions), vesiculobullous rash, purpura, and thrombocytosis. Very rare cases of hyperlipidemia have been reported, with one case of hyperlipidemia, with marked hypertriglyceridemia, reported in a diabetic pregnant woman; causality has not been determined.
"All patients should be evaluated for a bleeding disorder before ["prophylactic" deleted] administration of Lovenox Injection, unless the medication is needed urgently."
Administration: Subcutaneous Injection Technique:
Second sentence revised (new text in italics) -
"To avoid the loss of drug when using the 30 and 40 mg prefilled syringes, do not expel the air bubble from the syringe before the injection"
[Other information regarding these changes: Letter]
"Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis."
"If necessary, this could include the use of leucovorin calcium and/or acute, intermittent hemodialysis with a high-flux dialyzer."
Drug Interactions: Eighth paragraph -
"Patients receiving concomitant therapy with methotrexate and etretinate or other retiniods should be monitored closely for possible increased risk of hepatotoxicity."
Deleted and replaced with -
"The potential for increased hepatotoxicity when methotrexate is administered with other hepatotoxic agents has not been evaluated. However, hepatotoxicity has been reported in such cases. Therefore, patients receiving concomitant therapy with methotrexate and other potential hepatotoxins (e.g., azathioprine, retinoids, sulfasalazine) should be closely monitored for possible increased risk of hepatotoxicity."
", soft tissue necrosis and osteonecrosis."
Adverse Reactions in Psoriasis: Last sentence added:
"Rarely, painful plaque erosions may appear (Pearce, HP and Wilson, BB: Am Acad Dermatol 35:835-838, 1996)."
" Generally speaking, neither hemodialysis nor peritoneal dialysis have been shown to improve metotrexate elimination. However, effective clearance of metotrexate has been reported with acute, intermittent hemodialysis using a high-flux dialyzer (Wall, SM et al: Am J Kidney Dis 28(6): 846-854, 1996)."
"If necessary, acute, intermittent hemodialysis with a high-flux dialyzer may also be beneficial in these patients."
"Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see DOSAGE AND ADMINISTRATION).
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function."
[Other labeling changes not appearing in 1999 PDR: Sep99]
[Other labeling changes not appearing in the 1999 PDR: Jun99, May99, Apr99, Oct98, Feb98]
"Concomitant use of Norvir with lovastatin or simvastatin is not recommended. Caution should be exercised if HIV protease inhibitors, including Norvir, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (e.g., atorvastatin or cerivastatin). The risk of myopathy including rhabdomyolysis may be increased when HIV protease inhibitors, including Norvir, are used in combination with these drugs.
"NuLYTELY is contraindicated in patients known to be hypersensitive to any of the components. NuLYTELY is contraindicated in patients with ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis or toxic megacolon."
[Other labeling changes not appearing in 1999 PDR: Aug98
"Clinical and pathologic studies have shown that elevated levels of total cholesterol (Total-C), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B ["(a membrane transport complex for LDL)" deleted] (Apo B - a membrane transport complex for LDL) promote human atherosclerosis."
"Pravacol is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, Apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Frederickson type IIa and IIb)7."
[Other information regarding these changes: Letter]
[Other labeling changes not appearing in 1999 PDR: Jun99, May99]
"U.S. fluoxetine clinical trials (10,782 patients) included 687 patients equal to or greater than 65 years of age and 93 patients equal to or greater than 75 years of age. The efficacy in geriatric patients has been established (see Clinical Trials under Clinical Pharmacology). For pharmacokinetic information in geriatric patients see Age under Clinical Pharmacology. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. As with other SSRIs, fluoxetine has been associated with cases of clinically significant hyponatremia in elderly patients (see Hyponatremia under Precautions)."
[Other labeling changes not appearing in 1999 PDR: Jun98, Apr98
"Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see DOSAGE AND ADMINISTRATION).
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function."
[Other labeling changes not appearing in 1999 PDR: Jul99
[Other labeling changes not appearing in 1999 PDR: Jul99
[Other information regarding these changes: Letter]
[Other labeling changes not appearing in 1999 PDR: Sep98]
[Other information regarding these changes: Letter]
Replaced with the following text -
"SEVERE, LIFE-THREATENING SKIN REACTIONS, INCLUDING FATAL CASES, HAVE OCCURRED IN PATIENTS TREATED WITH VIRAMUNE(r). THESE HAVE INCLUDED CASES OF STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, AND HYPERSENSITIVITY REACTIONS CHARACTERIZED BY RASH, CONSTITUTIONAL FINDINGS, AND ORGAN DYSFUNCTION. PATIENTS DEVELOPING SIGNS OR SYMPTOMS OF SEVERE SKIN REACTIONS OR HYPERSENSITIVITY REACTIONS MUST DISCONTINUE VIRAMUNE(r) AS SOON AS POSSIBLE. (see WARNINGS)"
"(See PRECAUTIONS, Drug Interactions, for recommendations regarding rifampin, rifabutin, oral contraceptives and methadone)"
Replaced with the following text -
"Severe, life threatening skin reactions, including fatal cases, have occurred in patients treated with Viramune. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions (including, but not limited to, severe rash or rash accompanied by fever, blisters, oral lesions, conjunctivitis, facial edema, muscle or joint aches, general malaise and/or significant hepatic abnormalities) must discontinue Viramune as son as possible. (See PRECAUTIONS, Information for Patients; ADVERSE REACTIONS)"
"Methadone: Based on the known metabolism of methadone, nevirapine may decrease plasma concentrations of methadone by increasing its hepatic metabolism. Narcotic withdrawal syndrome has been reported in patients treated with Viramune and methadone concomitantly. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly."
Information for Patients: New second sentence -
"Fatal skin reactions have been reported."
Fifth sentence revised (new text in italics) -
"Any patient experiencing severe rash or hypersensitivity reactions (rash accompanied by constitutional ["symptoms" deleted] findings such as fever, blistering, oral lesions, conjunctivitis, ["swelling" deleted] facial edema , muscle or joint aches, ["or" deleted]general malaise, or significant hepatic abnormalities) should immediately discontinue medication and consult a physician."
Last paragraph, new sixth and seventh sentences -
"Based on the known metabolism of methadone, nevirapine may decrease plasma concentrations of methadone by increasing its hepatic metabolism. Narcotic withdrawal syndrome has been reported in patients treated with Viramune and methadone concomitantly. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly."
Antiretroviral Pregnancy Registry (new subsection):
"To monitor maternal-fetal outcomes of pregnant women exposed to Viramune, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling (800) 258-4263."
[Other labeling changes not appearing in 1999 PDR: Mar99, Jun98]
"No overall differences in safety or effectiveness have been observed between elderly and younger patients."
"In a covariate analysis, age did not have a statistically significant contribution to the change in QTc recorded in patients taking sparfloxacin. However, in controlled clinical trials, QTc interval prolongation was more frequently reported as an adverse event in patients equal to or greater than 65 years of age than in younger patients. In these clinical trials, QTc interval prolongation was reported more frequently as an adverse event (defined as QTc equal to or greater than 0.440 sec or equal to or greater than 15% change from baseline) in elderly patients treated with sparfloxacin than in elderly patients treated with a comparator drug. During post marketing surveillance, cardiovascular events including torsades de pointes and other arrhythmias were more frequent in the elderly than in younger patients treated with sparfloxacin although a history of underlying cardiac disease in this population was more common. Sparfloxacin is contraindicated in patients with known QTc prolongation (see CONTRAINDICATIONS)."
Eighth paragraph - "CHILDREN" deleted and replaced with "PEDIATRIC PATIENTS"
"• that sucralfate or magnesium- and aluminum-containing antacids or Videx (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution may be taken 4 hours after sparfloxacin administration. (See PRECAUTIONS): Drug Interactions);"
Eleventh bullet added -
"• that convulsions have been reported in patients taking quinolones, including sparfloxacin, and to notify their physician before taking this drug if there is a history of this condition."
Drug Interactions: New third sentence:
"Similarly, the oral bioavailability of sparfloxacin may be reduced when Videx, (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution is administered between 2 hours before and 2 hours after sparfloxacin administration."
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: New second paragraph -
"In a study of repeated exposure (5 days per week for 40 weeks) of hairless albino mice (SKH-1) to a low dose (0.272 Caucasian human minimal erythema dose [MED]) of solar stimulated UV radiation, skin tumors were induced with a median onset time of 43 weeks. As expected for this model, the gross appearance of the tumors in this study was consistent with squamous cell carcinoma or its precursors. When sparfloxacin (6.0 or 12.5 mg/kg/day) was administered by the oral route, the median tumor onset time was reduced to 38 and 32 weeks, respectively. This reduction in median onset time was similar to that observed when mice were exposed to a higher dose (0.476 Caucasian human MED) of solar simulated UV radiation alone. At a dose level of 12.5 mg/kg/day, mice had skin sparfloxacin concentrations (± SD of approximately 1.8 µg/g (± 0.26, N=6). Following a 400 mg dose of sparfloxacin, skin levels measured in human subjects averaged 5.5 µg/g (±6.5, N=11). A similar effect on the time to the development of skin tumors has been observed in this mouse strain with some other fluoroquinolone antibiotics. The clinical significance of these findings to humans is unknown."
Mutagenesis: New second paragraph -
"When Chinese hamster ovary cells were incubated with sparfloxacin in the presence of solar simulated UV radiation, chromosome aberrations were induced at concentrations of sparfloxacin that were not associated with aberrations in the absence of UV. The low level of UV used in the experiment, approximately 375 mJ/cm2, was not, by itself, associated with chromosome aberrations, while the high level of UV used in the experiment, approximately 750 mJ/cm2, induced fewer aberrations than sparfloxacin plus low or high dose UV."
Geriatric Use: New subsection:
"In controlled clinical trials conducted in the United States and Europe, sparfloxacin tablets have been administered to approximately 458 elderly (equal to or greater than 65 years of age) patients. It is known that the QTc interval increases with increasing age. In a covariate analysis, age did not have a statistically significant contribution to the change in QTc recorded in patients taking sparfloxacin. However, in controlled clinical trials, QTc interval prolongation was more frequently reported as an adverse event in patients equal to or greater than 65 years of age than in younger patients. In addition, QTc interval prolongation was reported more frequently as an adverse event (defined as QTc equal to or greater than 0.440 sec or equal to or greater than 15% change from baseline) in sparfloxacin treated elderly patients (7/314) than elderly patients treated with a comparator drug (0/301). Finally, the majority of patients with postmarketing cardiovascular events were elderly; however, it is not possible to exclude the roles of other contributing factors such as underlying cardiovascular diseases and concomitant medications. There were no other apparent overall differences in safety and efficacy observed between the elderly and younger individuals in controlled clinical trials. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Sparfloxacin is known to be excreted renally and the risk of adverse 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, DOASGE AND ADMINISTRATION and WARNINGS)
"The pharmacokinetic parameters of sparfloxacin in the elderly were consistent with those observed in normal healthy subjects. (See CLINICAL PHARMACOLOGY: Special Populations.)"
"Antacids containing magnesium and aluminum or sucralfate or Videx, (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution may be taken 4 hours after administration of Zagam (sparfloxacin)."
"In a ranitidine-triazolam drug-drug interaction study, triazolam plasma concentrations were higher during b.i.d. dosing of ranitidine than triazolam given alone. The mean area under the triazolam concentration-time curve (AUC) values, in 18 to 60 year old subjects were 10% and 28% higher following administration of 75-mg and 150-mg ranitidine tablets, respectively, than triazolam given alone. In subjects older than 60 years of age, the mean AUC values were approximately 30% higher following administration of 75-mg and 150-mg ranitidine tablets. It appears that there were no changes in pharmacokinetics of triazolam and a-hydroxytriazolam, a major metabolite, and in their elimination. Reduced gastric acidity due to ranitidine may have resulted in an increase in the availability of triazolam. The clinical significance of this triazolam and ranitidine pharmacokinetic interaction is unknown."
Pediatric Use: Section extensively revised - Contact the company for a copy of the new labeling/package insert.
"In normal volunteers, SGPT values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg q.i.d. intravenously for 7 days, and in 4 of 24 subjects receiving 50 mg q.i.d. intravenously for 5 days."
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