![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20090118023205im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: 8/25/99)
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.
|
(tirofiban HCl) |
(methyldopa/ hydrochlorothiazide) |
(cefazolin Na) |
(clarithromycin) |
|
(alprostadil) |
(neomycin and polymyxin B sulfates/ bacitracin zinc/ hydrocortisone)&(neomycin and polymyxin B sulfates/ hydrocortisone acetate) |
(warfarin Na) |
(calcipotriene) |
|
(fluticasone dipropionate) |
|
(eptifibatide) |
(cephalexin HCl) |
|
(terbinafine) |
(levofloxacin) |
(levorphanol tartrate) |
(cefdinir) |
|
|
(milrinonelactate) |
(pyridostigmine Br) |
(delavirdine mesylate) |
|
(risperidone) |
(atenolol/ chlorthalidone) |
(atenolol) |
(ticlopidine HCl) |
|
(tocainide HCl) |
(topiramate) |
(didanosine) |
(stavudine) |
|
(azithromycin) |
"Discard unused solution 24 hours following the start of the infusion."
deleted and replaced with -
"Any unused solution should be discarded."
Directions for Use: Text added as new last paragraph -
"Aggrastat may be administered in the same intravenous line as dopamine, lidocaine, potassium chloride, and Pepcid (famotidine) Injection."
"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 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 gluconate is not recommended."
"For those patients requiring higher doses, one tablet of Aldoril D30 or Aldoril D50 two times a day may be used."
deleted and replaced with -
"Alternatively, one tablet of Aldoril D30 or Aldoril D50 once daily may be used. Hydrochlorothiazide doses greater than 50 mg daily should be avoided."
Second paragraph revised (new text in italics) -
["Patients usually do not require doses of hydrochlorothiazide in excess of 50 mg 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. The usual daily dosage of methyldopa is 500 mg to 2 g. To minimize the sedation associated with methyldopa, start dosage increases in the evening. The maximum daily dose of methyldopa is 3 g."
Third paragraph, last sentence deleted -
"The maximum recommended daily dose of methyldopa is 3 g and of hydrochlorothiazide is 200 mg."
Note: The word "children" has been changed to "pediatric patients" or to a more specific subgroup (e.g., neonates, infants) throughout the package insert.
"The sodium content is ["46" deleted] 48 mg per gram of cefazolin."
"Before therapy with Ancef is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or other drugs. If this product is given to penicillin-sensitive patients, caution should be exercised because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin alergy. If an allergic reaction to Ancef occurs, discontinue treatment with the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated."
"Before reconstitution protect from light and store ["between 15 o and 30 oC (59o and 86oF)." deleted] at Controlled Room Temperature 20o to 25oC (68o to 77oF)."
[Other labeling changes not appearing in 1999 PDR: Jul98, Sep98]
Last paragraph -
"Rarely, erythromycin and clarithromycin have been associated with ventricular arrhythmias, including ventricular tachycardia and torsades de pointes, in individuals with prolonged QT intervals."
deleted and replaced with -
"As with other macrolides, clarithromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes."
[Other labeling changes not appearing in 1999 PDR: Jan99, Mar98]
"The patient should be instructed to immediately report to his physician or, if unavailable, to seek immediate medical assistance for any erection that persists for longer than ["6" deleted] 4 hours."
"The patient must be instructed to immediately report to his physician or, if unavailable, to seek immediate medical assistance for any erection that persists for longer than ["6" deleted] 4 hours"
"Erections that last more than ["6" deleted] 4 hours can cause serious and permanent damage. Call your doctor or seek professional help immediately if you still have an erection ["6" deleted] 4 hours after injection."
[Click Here to see new labeling/package insert for Ointment.]
"Owing to its excellent spreading and penetrating properties, the cream facilitates treatment of hairy and intertriginous areas. It may also be of value in selective cases where lesions are moist."
"This product is contraindicated in tuberculosis, fungal, or viral (for example, herpes simplex or varicella zoster) lesions of the skin. ["(herpes simplex, vaccinia, and varicella.)" deleted]"
"Because of the concern of nephrotoxicity and ototoxicity associated with neomycin, this combination should not be used over a wide area or for extended periods of time."
deleted and replaced with -
"Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk of ototoxicity is greater with prolonged use.
"Therapy with this product should be limited to 7 days of treatment. (See INDICATIONS AND USAGE.)
"Neomycin sulfate may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical neomycin is not known. Discontinue promptly if sensitization or irritation occurs.
"When using neomycin-containing products to control secondary infection in the chronic dermatoses, such as chronic otitis externa or stasis dermatitis, it should be borne in mind that the skin in these conditions is more liable than is normal skin to become sensitized to many substances, including neomycin. The manifestation of sensitization to neomycin is usually a low-grade reddening with swelling, dry scaling, and itching; it may be manifest simply as a failure to heal. Periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. These symptoms regress quickly on withdrawing the medication. Neomycin-containing applications should be avoided for the patient thereafter."
"As with ["any antibacterial" (Cream) deleted],["any" (Ointment) deleted] other antibiotic (Cream) preparations , prolonged use may result in ["the" (Ointment) deleted] overgrowth of nonsusceptible organisms, including fungi. Treatment should not be continued for longer than 7 days. If the infection is not improved after 1 week, cultures and susceptibility tests should be repeated to verify the identity of the organism and to determine whether therapy should be changed. Allergenic cross-reactions may occur which could prevent the use of any or all of the aminoglycoside antibiotics for the treatment of future infections. ["Appropriate measures should be taken if this occurs." deleted]
"Use of steroids on infected areas should be supervised with care as anti-inflammatory steroids may encourage the spread of infections. If this occurs, steroid therapy should be stopped and appropriate antibacterial drugs used. Generalized dermatological conditions may require systemic corticosteroid therapy."
"Signs and symptoms of exogenous hype adrenocorticism can occur with the use of topical corticosteroids, including adrenal suppression. Systemic absorption of topically applied steroids will be increased if extensive body surface areas are treated or if occlusive dressings are used. Under these circumstances, suitable precautions should be taken when long-term use is anticipated.
"["Specifically, sufficient percutaneous absorption of hydrocortisone can occur in pediatric patients during prolonged use to cause cessation of growth, as well as other systemic signs and symptoms of hyperadrenocorticism." deleted]"
Pediatric Use: Subsection revised (new text in italics) -
"Safety and effectiveness in pediatric patients have not been established. ["(see PRECAUTIONS: General)." deleted] Sufficient percutaneous absorption of hydrocortisone can occur in infants and children during prolonged use to cause cessation of growth, as well as other signs and symptoms of hyperadrenocorticism."
"Therapy with this product should be limited to 7 days."
["There are no significant age-related differences in the pharmacokinetics of racemic warfarin." deleted] Patients 60 years or older appear to exhibit greater than expected PT/INR response to the anticoagulant effects of warfarin. The cause of the increased sensitivity to the anticoagulant effects of warfarin in this age group is unknown. This increased anticoagulant effect from warfarin may be due to a combination of pharmacokinetic and pharmacodynamic factors. Racemic warfarin clearance may be unchanged or reduced with increasing age. Limited information suggests there is no difference in the clearance of S-warfarin in the elderly versus young subjects. However, there may be a slight decrease in the clearance of R-warfarin in the elderly as compared to the young. ["Older patients (60 years or older) appear to exhibit greater than expected PT/INR response to the anticoagulant effects of warfarin." Deleted] Therefore, as patient age increases, ["less warfarin is" deleted] a lower dose of warfarin is usually required to produce a therapeutic level of anticoagulation." ["The cause of this response to warfarin is not known." deleted]
"Prokinetic Agents" was added under Gastrointestinal and "Herbal Medicines" was added as a new class
Within the Table "EXOGENOUS FACTORS: Specific Drugs Reported"
"cisapride", "danshen (Chinese herb)", "fenofibrate", "fluvastatin", and "tramadol" were added.
In the section -
"The following factors, alone or in combination, may be responsible for DECREASED PT/INR
response:
Within the table "EXOGENOUS FACTORS: Specific Drugs Reported"
"atorvastatin" was added.
"Patients 60 years or older appear to exhibit greater than expected PT/INR response to the anticoagulant effects of warfarin (see CLINICAL PHARMACOLOGY). Coumadin is contraindicated in any unsupervised patient with senility. Caution should be observed with administration of warfarin sodium to elderly patients in any situation or physical condition where added risk of hemorrhage is present. Low initiation doses of warfarin are recommended for elderly patients (see DOSAGE AND ADMINISTRATION)."
[Other labeling changes not appearing in 1999 PDR: Dec98]
"Use the Rotadisk blisters within 2 months after opening of the moisture-protective foil overwrap or before the expiration date, whichever comes first. Place the sticker provided with the product on the tube and enter the 2-month use date on the sticker."
"Show your family members and others where you keep this kit and how to use it. They need to know how to use it before you need it. They can practice giving a Shot by giving your normal insulin shots. It is important that they practice. A person who has never given a shot probably will not be able to do it in an emergency."
[Other labeling changes not appearing in the 1999 PDR: Sep98]
"Table 1 shows the effects of ["on platelet function and bleeding time" deleted] the two doses of eptifibatide used in the two principal clinical studies on ex vivo platelet aggregation induced by 20 microMolar ADP in PPACK-anticoagulated platelet-rich plasma and on bleeding time."
Pharmacodynamics:
Table 1
"Platelet Inhibition and Bleeding Time" -
"IMPACT II 135/0.5 and PURSUIT 180/2.0" revised with the addition of asterisks as follows:
"IMPACT II 135/0.5* and PURSUIT 180/2.0** "
Text added immediately below Table 1 -
" * 135 ug/kg bolus followed by a continuos infusion of 0.5 ug/kg/min"
** 180 ug/kg/bolus followed by a continuos infusion of 2.0 ug/kg/min"
"Serum creatinine >/= 2.0 mg/dL (for the 180 ug/kg bolus and the 2 ug/kg/min infusion) or >/= 4.0 mg/dL (for the 135 ug/kg bolus and the 0.5 ug/kg/min infusion)."
deleted and replaced with -
"Serum creatinine >/= 4.0 mg/dL. In patients with serum creatinine levels between 2.0 mg/dL and 4.0 mg/dL, the 135 ug/kg bolus and 0.5 ug/kg/min infusion should be administered."
"The aPTT should be maintained between 50 and 70 seconds unless PCI is to be performed. ["During PCI, the ACT shoudl be maintained between 300 and 350 seconds. The aPTT should be checked prior to arterial sheath removal. The sheath should not be removed unless the aPTT is < 45 seconds." deleted] In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT. Table 6 displays the risk of major bleeding according to the maximum aPTT attained within 72 hours in the PURSUIT study."
Text added after Table 6 -
"During PCI, the PURSUIT study stipulated a target ACT between 300 and 350 seconds. Patients receiving an eptifibatide 180 ug/kg bolus followed by a 2 ug/kg/min infusion experienced an increased incidence of bleeding relative to placebo, primarily at the femoral access site.
"The aPTT or ACT should be checked prior to sheath removal. The sheath should not be removed unless the aPTT is < 45 seconds or the ACT < 150 seconds."
Renal Insufficiency: Text added as new second sentence -
"For patients with serum creatinine > 2.0 and < 4.0 mg/dL, eptifibatide should be administered as a 135 ug/kg bolus followed by a 0.5 ug/kg/min infusion."
"Intracranial hemorrhage was rare in the PURSUIT clinical study, with only 3 patients in the placebo group, 1 patient in the group treated with eptifibatide 180/1.3 and 5 patients in the group treated with eptifibatide 180/2.0 experiencing a hemorrhagic stroke within 30 days of randomization. The overall incidence of stroke was 0.5% in patients receiving eptifibatide 180/1.3, 0.7% in patients receiving eptifibatide 180/2.0, and 0.8% in placebo patients within 30 days of randomization."
"Vials should be stored refrigerated at 2-8oC (36-46oF). Vials may be transferred to room temperature storage* for a period not to exceed 2 months. Upon transfer, vial cartons must be marked by the dispensing pharmacist with a "DISCARD BY" date (2 months from the transfer date or the labeled expiration date, whichever comes first).
"Do not use beyond the labeled expiration date. Protect from light until administration. Discard any unused portion left in the vial.
"*USP Controlled Room Temperature: 25oC (77oF) with excursions permitted between 15-30oC (59-86oF)."
[Labeling changes for other formulations not appearing in the 1999 PDR: Jan99]
[Other labeling changes not appearing in 1999 PDR: Dec98]
"The mechanism of action of levofloxacin and other flouroquinolone antimicrobials involves inhibition of ["DNA gyrase (bacterial topoisomerase II), an enzyme" deleted] bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.
Third paragraph revised (new text in italics) -
"Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and Beta-lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to ["Beta-lactam antibiotics" deleted] these antimicrobials."
Fifth paragraph revised (new text in italics) -
"Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:
"Aerobic gram-positive microorganisms
Enterococcus faecalis (many strains are only moderately susceptible)
Staphylococcus aureus (methicillin-susceptible strains)
Staphylococcus saprophyticus
Streptococcus pneumoniae (penicillin-susceptible strains)
Streptococcus pyogenes"
Sixth paragraph revised (new text in italics) -
"The following in vitro data are available, but their clinical significance is unknown. Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC's) of 2 ug/mL or less against most (>/= 90%) strains of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.
"Aerobic gram-positive microorganisms
Staphlococcus epidermidis (methicillin-susceptible strains)
Streptococcus (Group C/F)
Streptococcus (Group G)
Streptococcus agalactiae
Streptococcus pneumoniae (penicillin-resistant strains)
["Staphylococcus saprophyticus" deleted]
Viridans group streptococci
"Aerobic gram-negative microorganisms (two text revisions as follows):
["Acinetobacter anitratus" deleted]
Citrobacter (diversus) koseri"
"The safety and efficacy of levofloxacin in ["children" deleted] pediatric patients, adolescents (under the age of 18 years), pregnant women, and sursing women have not been established.
"-that antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamins preparations with zinc or Videx, (didanosine), chewable/buffered tablets or the pediatric powder for oral solution should be taken at least two hours before or two hours after levofloxacin administration. (See Drug Interactions)."
(Tablets and Injection)
New bullet added -
"-that convulsions have been reported in patients taking quinolones, including levofloxacin, and to notify their physician before taking this drug if there is a history of this condition."
Drug Interactions: Antacids, Sucralfate, Metal Cations, Multi-Vitamins:
(Tablets)
Second sentence revised (new text in italics) -
"Tablets with antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamins preparations with zinc or Videx, (didanosine) chewable/buffered tablets or the pediatric powder for oral solution may substantially interfere with the gastrointestinal absorption of levofloxacin resulting in systemic levels considerably lower than desired."
(Injection)
Text revised (new text in italics) -
"There are no data concerning an interaction of Intravenous quinolones with oral antacids, sucralfate, multivitamins, Videx (didanosine), or metal cations. However, no quinolone should be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line. (See DOSAGE AND ADMINISTRATION.)"
Geriatric Use (new subsection):
"In phase 3 clinical trials, 898 levofloxacin-treated patients (26%) were >/= 65 years of age. Of these, 514 patients (15%) were between the ages of 65 and 74 and 384 patients (11%) were 75 years or older. No overall differences in safety or 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.
"The pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. However since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug 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."
"Oral doses should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamins preparations with zinc or Videx, (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution."
(Injection)
Levaquin injection premix in single-use flexible container: First paragraph, last sentence,
revised (new text in italics) -
"Consequently each 50 mL and 100 mL PREMIX flexible container already contains a dilute solution with the equivalent of 250 mg and 500 mg of levofloxacin, respectively (5 mg/mL) in 5% Dextrose (D5W)."
"Tablets should be stored at ["59o to 86oF" deleted] 25oC (77oF); excursion permitted to
15o C - 30oC (59o F to 86o F).
Dispense in tight containers as defined in USP/NF.
Parenteral dosage forms should be stored at ["59o to 86o F" deleted] 25o C (77o F); excursion permitted to 15oC - 30oC (59oF to 86oF)."
Pharmacodynamics: First paragraph revised (new text in italics) -
"In patients with heart failure due to depressed myocardial infarction, Primacor produced prompt dose and plasma concentration related increase in cardiac output and decrease in pulmonary capillary wedge pressure and vascular resistance, ["without a significant increase in heart rate." deleted] which were accompanied by mild-to-moderate increases in heart rate. Additionally, there is no increased effect on myocardial oxygen consumption. ["These hemodynamic improvements were dose and plasma milrinone concentration related." deleted] In uncontrolled studies, hemodynamic improvement during intravenous therapy with Primacor was accompanied by clinical symptomatic improvement, ["as measured by changes in New York Heart Association classification" deleted] but the ability of Primacor to relieve symptoms has not been evaluated in controlled clinical trials. The great majority of patients experience improvements in hemo-dynamic function within 5 to 15 minutes of initiation of therapy."
Second paragraph, third sentence deleted -
"The heart rate was generally unchanged (increases of 3, 3 and 10 percent, respectfully)."
Third paragraph, second sentence deleted -
"Patients have been maintained on infusions of Primacor for up to 5 days"
"Whether given orally or by continuous or intermittent intravenous infusion, Primacor has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure. In a multicenter trial of 1088 patients with Class III and IV heart failure, long-term oral treatment with Primacor was associated with no improvement in symptoms and an increased risk of hospitalization and death. In this study, patients with Class IV symptoms appeared to be at particular risk of life-threatening cardiovascular reactions. There is no evidence that Primacor given by long term continuous or intermittent infusion does not carry a similar risk. "The use of Primacor both intravenously and orally has been associated with increased frequency of ventricular arrhythmias, including nonsustained ventricular tachycardia. Long-term oral use has been associated with an increased risk of sudden death. Hence, patients receiving Primacor should be observed closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias."
"Primacor is indicated for the short-term intravenous treatment of ["congestive heart failure" deleted] patients with acute decompensated heart failure. Patients receiving Primacor should be observed closely with appropriate electrocardiographic equipment. The facility for immediate treatment for cardiac events, which may include life threatening ventricular arrhythmias, must be available. The majority of experience with intravenous Primacor has been in patients receiving digoxin and diuretics. ["In some patients injections of Primacor and oral Primacor have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. Patients receiving Primacor should be closely monitored during infusion." deleted] There is no experience in controlled trials with infusions of Primacor for periods exceeding 48 hours."
"Each mL contains 5 mg of pyridostigmine bromide compounded with 1% benzyl alcohol, which is not intended for use in newborns, as the preservative."
"Pyridostigmine is mainly excreted unchanged by the kidney1,2,3. Therefore, lower doses may be required in patients with renal disease, and treatment should be based on titration of drug dosage to effect1,2"
Pediatric Use (new subsection):
"Safety and effectiveness in pediatric patients has not been established."
"The safety and effectiveness of Regonol in pediatric patients has not been established, therefore no dosing recommendations can be made (see PRECAUTIONS)."
"1. Cronnelly R, Stanski DR, Miller RD, Sheiner LB. Pyridostigmine, kinetics with and without renal function. Clin Pharmacol Ther 1980;28:78-81.
2. Miller RD. Pharmacodynamics and pharmacokinetics of anticholinesterase. In:Ruegheimer E, Zindler M, eds. Anaesthesiology. Amsterdam, Netherlands: Excerpta Medica; 1981:222-223.
3. Breyer-Plaff U, Maier U, Brinkman AM, Schumm F. Pyridostigmine kinetics in healthy subjects and patients with myasthenia gravis. Clin Pharmacol Ther 1985;5:494-501."
"Coadministration of Rescriptor Tablets with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, calcium channel blockers, ergot alkaloid preparations, amphetamines, cisapride, and sildenafil, may result in potentially serious and/or life-threatening adverse events due to possible effects of Rescriptor on the hepatic metabolism of certain drugs (see PRECAUTIONS section)."
"Coadministration of Rescriptor with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, calcium channel blockers, ergot alkaloid preparations, amphetamines, cisapride, and sildenafil may result in potentially serious and/or life-threatening adverse events."
Table 1. Selected Drugs that are Predicted to Have Plasma Concentrations Increased by Delavirdine:
"sildenafil" added to the "Other" category Erectile Dysfunction Agents: Sildenafil (new subsection):
"Caution should be used when prescribing sildenafil in patients receiving delavirdine, because delavirdine inhibits CYP3A4 which may result in an increase of sildenafil concentrations. Patients receiving delavirdine and sildenafil should be advised that they may be at an increased risk for sildenafil-associated adverse events, including hypotension, visual changes, and prolonged erection, and should report these symptoms promptly to their physician. Currently, there are no safety and efficacy data available from the use of this combination. If delavirdine and sildenafil are used concomitantly, a single sildenafil dose or 25 mg in a 48-hour period should not be exceeded. This recommendation is based on data from a ritonavir/sildenafil drug-interaction study."
Protease Inhibitors: Amprenavir (new subsection):
"Delavirdine has the potential to increase serum concentrations of amprenavir."
"Clinical studies of Risperdal did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, a lower starting dose is recommended for an elderly patient, reflecting a decreased pharmacokinetic clearance in the elderly, as well as a greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy ["and a greater tendency to postural hypotension" deleted] (See CLINICAL PHARMACOLOGY and DOSAGE ADMINISTRATION). While elderly patients exhibit a greater tendency to orthostatic hypotension, its risk in the elderly may be minimized by limiting the initial dose to 0.5 mg BID followed by careful titration (See PRECAUTIONS). Monitoring of orthostatic vital signs should be considered in patients for whom this is a concern.
"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. 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 DOSAGE AND ADMINISTRATION)."
Orthostatic Hypotension: Section revised (new text in italics) -
"Risperdal (risperidone) may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflecting its alpha-adrenergic antagonistic properties. Syncope was reported in 0.2% (6/2607) of Risperdal treated patients in phase 2-3 studies. The risk of orthostatic hypotension and syncope may be minimized by limiting the initial dose to 2 mg total (either QD or 1 mg BID) in normal adults and 0.5 mg BID in the elderly and patients with renal or hepatic impairment (See DOSAGE AND ADMINISTRATION). Monitoring of orthostatic vital signs should be considered in patients for whom this is a concern. A dose reduction should be considered if hypotension occurs. Risperdal should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormal- ities), cerebrovascular disease, and conditions which would predispose patients to hypotension e.g., dehydration and hypovolemia. Clinically significant hypotension has been observed with concomitant use of Risperdal and antihypertensive medication."
Dysphagia (new subsection):
"Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. Risperdal and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia."
"During postmarketing experience with Tenormin, the following have been reported in temporal relationship to the use of the drug: elevated liver enzymes and/or bilirubin, hallucinations, headache, impotence, Peyronie's disease, postural hypotension which may be associated with syncope, psoriasiform rash or exacerbation of psoriasis, psychosis, purpura, reversible alopecia, thrombocytopenia, visual disturbances, and dry mouth. Tenormin, like other beta blockers, has been associated with the development of antinuclear antibodies (ANA) and lupus syndrome."
"One case of thrombotic thrombocytopenic purpura was ["not seen" deleted] reported during clinical trials ["but" deleted] Based on postmarketing data, US physicians reported about 100 cases between 1992 and 1997."
"Safety and effectiveness in ["children" deleted] pediatric patients have not been established "
Geriatric Use (new subsection):
"Clinical studies of Tonocard 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."
First paragraph revised (new text in italics) -
"Prepare the initial solution of Zithromax (azithromycin for injection) by adding 4.8 mL of Sterile Water for Injection to the 500 mg vial until all of the drug is dissolved. Since Zithromax (azithromycin for injection) is supplied under vacuum, it is recommended that a standard 5 ml (non-automated) syringe be used to ensure that the exact amount of 4.8 ml of Sterile Water is dispensed. Each ml of reconstituted solution contains 100 mg azithromycin. Reconstituted solution is stable for 24 hours when stored below 30oC or 86oF."
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