![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20090118022529im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: April 14, 2000)
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 2000 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.
|
(zafirlukast) |
(acetic acid) |
(leflunomide) |
(donepezil) |
|
(dinoprostone) |
(warfarin) |
E.E.S. P.C.E 333mg (erythromycin ethylsuccinate) |
(cromolyn sodium) |
|
(ionosol t) |
(ionosol mb) |
(isoproterenol HCl) |
(levofloxacin) |
|
(cefoxitin) |
(desogestrel/ethinyl estradiol) |
(mitoxantrone) |
(physiosol) |
|
(clopidogrel bisulfate) |
(felodipine) |
|
(pravastatin) |
|
(omeprazole) |
|
(sterile talc powder) |
(silver sulfadiazine) |
|
|
|
|
(efavirenz) |
|
(trientine HCl) |
(tromethamine) |
(multiple electrolyte additive) |
(levonorgestrel/ethinyl estradiol) |
|
(dorzolamide HCl) |
(moexipril HCl) |
(tretinoin) |
(estradiol) |
|
(paricalcitol) |
(lisinopril) |
(cetirizine HCl) |
"Based on cross study comparison, the clearance of zafirlukast is reduced in patients 65 years of age and older such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients (see DOSAGE AND ADMINISTRATION, and CLINICAL PHARMACOLOGY sections).
"A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebo-controlled clinical trials. Of these, 243 patients were elderly (age 65 years and older). No overall difference in adverse events was seen in the elderly patients, except for an increase in the frequency of infection among zafirlukast treated elderly patients compared to placebo treated elderly patients (7.0% vs. 2.9%). The infections were not severe, occurred mostly in the lower respiratory tract, and did not necessitate withdrawal of therapy.
"An open-label, uncontrolled, 4-week trial of 3759 asthma patients compared the safety and efficacy of Accolate 20 mg given twice daily in three patient age groups, adolescents (12-17 years), adults (18-65 years), and elderly (greater than 65 years). A higher percentage of elderly patients (n=384) reported adverse events when compared to adults and adolescents. These elderly patients showed less improvement in the efficacy measures. In the elderly patients, adverse events occurring in greater than 1% of the population included headache (4.7%), diarrhea and nausea (1.8%), and pharyngitis (1.3%). The elderly reported the lowest percentage of infections of all three age groups in this study."
"Clinical studies of 0.25% Acetic Acid Irrigation have not been performed to determine whether patients over 65 years respond differently from younger subjects. Although systemic absorption of this product is unlikely, greater sensitivity of some older individuals cannot be ruled out."
Revisions, some extensive, to:
CLINICAL STUDIES Section - two new tables added providing additional
information regarding the pivotal trials.
WARNINGS Section - addition of Immunosuppression Potential subsection
(moved from PRECAUTIONS Section and revised) and Skin Reaction subsection.
PRECAUTIONS Section - addition of Need for Drug Elimination subsection.
Contact the company for a copy of the new labeling/package insert. Return to Quick Reference
"Voluntary reports of adverse events temporally associated with Aricept that have been received since market introduction that are not listed above, and that there is inadequate data to determine the causal relationship with the drug include the following: abdominal pain, agitation, cholecystitis, confusion, convulsions, hallucinations, heart block, hemolytic anemia, hyponatremia, pancreatitis and rash."
"• Patients in whom oxytoxic drugs are contraindicated or when prolonged contraction of the uterus may be detrimental to fetal safety or uterine integrity such as previous cesarean section or major uterine surgery (See PRECAUTIONS and ADVERSE REACTIONS)."
"Cervidil is contraindicated when prolonged contraction of the uterus may be detrimental to fetal safety and uterine integrity. Therefore Cervidil should not be administered to patients with a history of previous cesarean section or uterine surgery given the potential risk for uterine rupture and associated obstetrical complications."
"In Postmarketing Experience Reports, uterine rupture has been reported in association with the use of Cervidil."
"Patients should remain in the ["supine" deleted] recumbent position for 2 hours following insertion, but thereafter may be ambulatory"
"capecitabine, celecoxib, rofecoxib"
Extensive revisions to "Carcinogensis, Mutagenisis, and Impairment of Fertility," "Pregnancy," "Drug Interaction During Pregnancy," and "Pediatric Use" subsections in the 1999 PDR.
Contact the company for a copy of the new labeling/package insert or see the current labeling in the 2000 PDR.
"An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of 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."
"Clinical studies of Isuprel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects in clinical circumstances. There are, however, some data that suggest that elderly healthy or hypertensive patients are less responsive to beta-adrenergic stimulation than are younger subjects. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy."
[Other labeling changes not appearing in 2000 PDR: Jul99]
"Streptococcus pneumoniae (including penicillin-resistant strains*)
*Note: penicillin-resistant strains are those strains with a penicillin MIC value of 2 microgram/mL."
Susceptibility Tests:First paragraph, second and third sentences deleted -
"However, until levofloxacin susceptibility testing is available, the susceptibility of the organism to ofloxacin may be used to predict susceptibility to levofloxacin. While ofloxacin susceptible organisms will be susceptible to levofloxacin, ofloxacin intermediate or resistant organisms may be susceptible to levofloxacin."
"Some quinolones have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. During post-marketing surveillance, extremely rare cases of torsades de pointes, have been reported in patients taking levofloxacin. These reports generally involve patients who had concurrent medical conditions and the relationship to levofloxacin has not been established. Among drugs known to cause prolongation of the QT interval, the risk of arrhythmias may be reduced by avoiding use in the presence of hypokalemia, significant bradycardia, or concurrent treatment with class Ia or class III antiarrhythmic agents."
Information for Patients: Next to last bullet added:
"that concurrent administration of warfarin and levofloxacin has been associated with increases of the International Normalized Ratio (INR) or prothrombin time and clinical episodes of bleeding. Patients should notify their physician if they are taking warfarin."
Drug Interactions: Paragraph revised, new text in italics -
"Warfarin: No significant effect of levofloxacin on the peak plasma concentration, AUC, and other disposition parameters for R- and S- warfarin was detected in a clinical study involving healthy volunteers. ["No significant change in prothrombin time was noted in the presence of levofloxacin." deleted] Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. ["However, since some quinolones have been reported to enhance the effects of oral anticoagulant warfarin or its derivatives in the patient population, the prothrombin time or other suitable coagulation test should be closely monitored if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives." deleted] There have been reports during the post-marketing experience in patients in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding."
"increased International Normalized Ratio (INR)/prothrombin time" and "torsades de pointes"
Across these 8 studies, 18 levofloxacin-treated and 4 non-quinolone comparator-treated patients with community-acquired pneumonia due to penicillin-resistant S. pneumoniae (MIC value for penicillin greater than or equal to 2 microgram/mL) were identified. Of the 18 levofloxacin-treated patients, 15 were evaluable following completion of therapy. Fifteen out of the 15 evaluable levofloxacin-treated patients with community-acquired pneumonia due to penicillin-resistant S. pneumoniae achieved clinical success (cure or improvement). Of these 15 patients, 6 were bacteremic and 5 were classified as having severe disease. Of the 4 comparator-treated patients with community-acquired pneumonia due to penicillin-resistant S. pneumoniae, 3 were evaluable for clinical efficacy. Three out of the 3 evaluable comparator-treated patients achieved clinical success. All three of the comparator-treated patients were bacteremic and had disease classified as severe. "
"While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section is unknown."
The subsequent text of the Microbiology subsection was reordered and revised to read as follows:
"Cefoxitin 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
Staphylococcus aureus, (including penicillinase producing strains)
Staphylococcus epidermidis
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin.
Most strains of enterococci, e.g. Enterococcus faecalis, are resistant.
["Beta hemolytic and other streptococci (most strains of enterococci, e.g., Enterococcus
faecalis [formerly Streptococcus faecalis], are resistant" deleted]
Aerobic gram-negative microorganisms
[" Eikenella corrodens (beta-lactamase negative strains)" deleted]
Escherichia coli
Haemophilus influenzae
Klebsiella species (including K. pneumoniae)
Morganella morganii
Neisseria gonorrhoea (including penicillinase producing strains)
Proteus mirabilis
Proteus vulgaris
Providencia species (including Providencia rettgeri)
Anaerobic gram-positive microorganisms
Clostridium spp.
Peptococcus niger
Peptostreptococcus spp.
Anaerobic gram-negative microorganisms
Bacteroides distasonis
Bacteroides fragilis
Bacteroides ovatus
Bacteroides thetaiotaomicron
Bacteroides spp.
The following in vitro data are available, but their clinical significance is unknown. Cefoxitin exhibits in vitro minimum inhibitory concentrations (MIC's) of 8 micrograms/mL or less for aerobic microorganisms and 16 micrograms/mL or less for anaerobic microorganisms against
Most (greater than or equal to 90%) strains of the following organisms; however, the safety and effectiveness of cefoxitin in treating clinical infectionss due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-negative microorganisms
Eikenella corrodens [non-(-lactamase producers]
Klebsiella oxytoca
Anaerobic gram-positive microorganisms
Clostridium perfringins
Anaerobic gram-negative microorganisms
Prevotella bivia (formerly Bacteroides bivius)
Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa
and enterococci and many strains of Enterobacter cloacae.
["Methicillin resistant staphylococci are almost uniformly resistant to Mefoxin" deleted]
The subsection: Susceptibility Tests has been deleted.
A new subsection: Dilution Techniques (with references) has been added. Contact the company for a copy of the new labeling/package insert to see this subsection.
(4) Gynecological infections,
" Streptococcus agalactiae" added. ["Group B streptococci." Deleted] following
Peptostreptococcus species.
(7) Skin and skin structure infections
" Streptococcus pyogenes and other" added following Staphylococcus epidermidis
a. Myocardial infarction
Third paragraph, sixth sentence added -
"Desogestrel has minimal androgenic activity (see CLINICAL PHARMACOLOGY) and there is some evidence that the risk of myocardial infarction associated with oral contraceptives is lower when the progestogen has minimal androgenic activity than when the activity is greater."
b.Thromboembolism
First paragraph, second sentence revised (new text in italics) -
"Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thromboembolic disease (2,319-24). ["thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease" deleted]
New second paragraph -
"In two case-control studies and one cohort study of venous thromboembolism, third generation oral contraceptives, including those containing desogestrel, were reported to have a relative risk between 1.5 and 2.4 when compared to certain second generation oral contraceptives (103-105). These risks are within the above-mentioned range for deep vein thrombosis and pulmonary embolism. A relative risk of 2 would translate into an additional 1-2 cases of non-fatal venous thromboembolism per 10,000 women-years of use. The risk of venous thromboembolic disease associated with oral contraceptives does not increase with length of use and disappears after pill use is stopped."
d. Dose-related risk of vascular disease from oral contraceptives
Second paragraph, last sentence revised (new text in italics) -
"New acceptors of oral contraceptive agents should be started on preparations containing 0.035 mg or less of estrogen. ["the lowest estrogen content which produces satisfactory results in the individual" deleted]
"Blood clots and blockage of blood vessels are one of the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blockage of the vessel carrying blood to the lungs. These risks may be greater with desogestrel-containing oral contraceptives, such as Mircette, than with other low-dose pills. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision."
"Injection site reactions including phlebitis have been reported infrequently at the site of infusion. There have been rare reports of tissue necrosis following extravasation. Skin discoloration has also been reported."
Replaced with:
Extravasation at the infusion site has been reported, which may result in erythema, swelling, pain, burning, and/or blue discoloration of the skin. Extravasation can result in tissue necrosis with resultant need for debridement and skin grafting. Phlebitis has also been reported at the site of infusion.
Pulmonary: New subsection -
"Interstitial pneumonitis has been reported in cancer patients receiving combination chemotherapy that included Novantrone."
"Clinical studies of Physiosol Irrigation have not been performed to determine whether patients over 65 years respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 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."
"The following events have been reported spontaneously from worldwide postmarketing experience: very rare cases of hypersensitivity reactions including angioedema, bronchospasms, and anaphylactoid reactions."
" CYP3A4 Inhibitors - Felodipine is metabolized by CYP3A4. Co-administration of CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several-fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. These increases in concentration may lead to increased effects (lower blood pressure and increased heart rate). These effects have been observed with co-administration of itraconazole (a potent CYP3A4 inhibitor). Caution should be used when CYP3A4 inhibitors are co-administered with felodipine. A conservative approach to dosing felodipine should be taken. The following specific interactions have been reported:
"Itraconazole - Co-administration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6-fold increase in the Cmax and a 2-fold prolongation in the half-life of felodipine.
" Erythromycin - Co-administration of felodipine (Plendil) with erythromycin resulted in approximately 2.5-fold increase in the AUC and Cmax, and about 2-fold prolongation in the half-life of felodipine.
" Grapefruit juice - Co-administration of felodipine with grapefruit juice resulted in more than 2-fold increase in the AUC and Cmax, but no prolongation in the half-life of felodipine.
" Cimetidine - Co-administration of felodipine with cimetidine (a non-specific CYP-450 inhibitor) resulted in an increase of approximately 50% in the AUC and the Cmax, of felodipine."
"An evaluation of current literature revealed no clinical experience identifying differences between 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.
Potassium ions are 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."
[Other labeling changes not appearing in 2000 PDR: Oct99, Jan00]
Replaced with:
"In one primary (West of Scotland Coronary Prevention Study - WOS)1 and two secondary (Long Term Intervention with Pravastatin In Ischemic Disease - LIPID2 and the Cholesterol and Recurrent Events - CARE3) prevention studies. Pravachol has been shown to reduce cardiovascular morbidity and mortality across a wide range of cholesterol levels (see Clinical Studies)."
Secondary Prevention of Cardiovascular Events
New subsection -
"In the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID)2 study, the effect of Pravachol, 40 mg daily, was assessed in 9014 patients (7498 men; 1516 women; 3514 elderly patients [age equal to or greater than 65 years]; 782 diabetic patients) who had experienced either an MI (5754 patients) or had been hospitalized for unstable angina pectoris (3260 patients) in the preceding 3-36 months. Patients in this multicenter, double-blind, placebo-controlled study participated for an average of 5.6 years (median of 5.9 years) and at randomization had total cholesterol between 114 and 563 mg/dL (mean 219 mg/dL), LDL-C between 46 and 274 mg/dL (mean 150 mg/dL), triglycerides between 35 and 2710 mg/dL (mean 160 mg/dL), and HDL-C between 1 and 103 mg/dL (mean 37 mg/dL). At baseline, 82% of patients were receiving aspirin and 76% were receiving anti-hypertensive medication. Treatment with Pravachol significantly reduced the risk for total mortality by reducing coronary death (see Table 1). The risk reduction due to treatment with Pravachol on CHD mortality was consistent regardless of age. Pravachol significantly reduced the risk for total mortality (by reducing CHD death) and CHD events (CHD mortality or nonfatal MI) in patients who qualified with a history of either MI or hospitalization for unstable angina pectoris."
|
Number (%) of Subjects |
||||
|
Event |
Pravastatin
N = 4,512 |
Placebo
N = 4,502 |
Risk
Reduction |
P-value |
|
287 (6.4) |
373 (8.3) |
24% |
0.0004 |
CHD mortality or non-fatal MI Myocardial revascularization
|
498 (11.0) 557 (12.3) 584 (12.9) |
633 (14.1) 715(15.9) 706 (15.7) |
23% 24% 20% |
Less than 0.0001 Less than 0.0001 Less than 0.0001 |
Non-hemorrhagic Cardiovascular mortality |
|
204 (4.5) 196 (4.4) 433 (9.6) |
19% 23% 25% |
0.0477 0.0154 Less than 0.0001 |
"Therapy with Pravachol (pravastatin sodium) ["lipid altering agents" deleted] should be considered in those individuals at increased risk for atherosclerosis-related clinical events as a function of cholesterol level, the presence or absence of coronary heart disease, and other risk factors."
Secondary Prevention of Cardiovascular Events
Reordered and revised to read as follows:
"In patients with clinically evident coronary heart disease, Pravachol (pravastatin sodium) is indicated to:
- Reduce the risk of total mortality by reducing coronary death
- Reduce the risk of myocardial infarction
- Reduce the risk of undergoing myocardial revascularization procedures
- Reduce the risk of stroke and stroke/transient ischemic attack (TIA)
- Slow the progression of coronary atherosclerosis
Replaced with:
"In three large, placebo-controlled trials (West of Scotland Coronary Prevention study [WOS], Cholesterol and Recurrent Events study [CARE], and Long-term Intervention with Pravastatin in Ischemic Disease study [LIPID]) involving a total of 19,768 patients treated with Pravachol (N=9895) or placebo (N=9873), the safety and tolerability profile in the pravastatin group was comparable to that of the placebo group over the median 4.8 to 5.9 years of follow-up." "
"Omeprazole was administered to over 2000 elderly individuals (greater than or equal to 65 years of age) in clinical trials in the US and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.
"Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly. (See CLINICAL PHARMACOLOGY.)"
"Clinical studies of Ringer's Irrigation have not been performed to determine whether patients over 65 years respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 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."
"It has been suggested that success of the pleurodesis is related to ["even distribution of talc over the pleural surfaces, and to" deleted] the completeness of the drainage of the pleural fluid, as well as full reexpansion of the lung, ["all" deleted] both of which will promote symphysis of the pleural surfaces "
"An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions 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."
"An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions 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."
"Clinical studies of Sorbitol-Manitol Irrigation did not include sufficient numbers patients aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 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 WARNINGS."
"Sustiva (efavirenz) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on two clinical trials of at least one year duration that demonstrated prolonged suppression of HIV-RNA. ["This indication is based on analyses of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA with Sustiva.] deleted]."
"In addition, the following adverse reactions have been reported in marketed use: dystonia, muscular spasm, myasthenia gravis."
"Clinical studies of Tham solution did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions 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."
"An evaluation of current literature revealed no clinical experience identifying differences in response between 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.
"Sodium ions and phosphorous are known to be substantially secreted 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."
"Clinical studies of Univasc 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 therapy."
"Of the total number of subjects in clinical studies of Vesanoid, 21.4% were 60 and over. 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."
"A long-term, open-label safety study of 164 CRF patients (mean dose of 7.5 mcg three times per week), demonstrated that mean serum Ca, P, and Ca x P remained within clinically appropriate ranges with PTH reduction (mean decrease of 323 pg/mL at 13 months)."
"Zemplar has been evaluated for safety in clinical studies in 454 ["270" deleted] CRF patients."
Last sentence added -
"Safety parameters (changes in mean Ca, P, Ca x P) in an open-label safety study up to 13 months in duration support the long-term safety of Zemplar in this patient population."
"In two placebo controlled, 12-week clinical studies using doses of Zestril up to 20 mg, Zestril as adjunctive therapy to digitalis and diuretics improved the following signs and symptoms due to congestive heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distension."
Last sentence added -
"A large (over 3000 patients) survival study, the ATLAS Trial, comparing 2.5 and 35 mg of lisinopril in patients with heart failure, showed that the higher dose of lisinopril had outcomes at least as favorable as the lower dose.
"In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse events were not different between the low and high groups, either in total number of discontinuation (17-18%) or in rare specific events (less than 1%). The following adverse events mostly related to ACE inhibition, were reported more commonly in the high dose group:
%of patients_____________High Dose_____Low Dose
Events_________________(N=1568)______(N=1596)
Dizziness ________________ 18.9__________12.1
Hypotension______________ 10.8___________6.7
Creatinine increased _________9.9___________7.0
Hyperkalemia ______________6.4___________3.5
NPN* increased ____________9.2 __________ 6.5
Syncope __________________7.0 __________ 5.1
*NPN = non-protein nitrogen
"The usual effective dosage range is 5 to 40 mg per day administered as a single daily dose. The dose of Zestril can be increased by increments of no greater than 10 mg, at intervals of no less than 2 weeks to the highest tolerated dose, up to a maximum of 40 mg daily. Dose adjustment should be based on the clinical response of individual patients."
"In placebo-controlled trials, 186 patients aged 65 to 94 years received doses of 5 to 20 mg of Zyrtec per day. Adverse events were similar in this group to patients under age 65. Subset analysis of efficacy in this group was not done."
Replaced with -
"Of the total number of patients in clinical studies of Zyrtec, 186 patients were 65 years and older, and 39 patients were 75 years and older. No overall differences in safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. With regard to efficacy, clinical studies of Zyrtec for each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.
"Zyrtec 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 Geriatric Patients and Renal Impairment subsections in CLINICAL PHARMACOLOGY)."
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