![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20090118022524im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: November 15, 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.
|
(glimepiride) |
(anastrozole) |
(azelastine HCl) |
(irbesartan) |
|
(irbesartan/hydrochlorothiazide) |
(sulfasalazine) |
|
(lamivudine/zidovudine) |
|
(olsalazine) |
(alprostadil) |
(epoprostenol sodium) |
(alendronate sodium) |
|
(heparin sodium inj. & heparin lock flush) |
(lamotrigene) |
(levofloxacin) |
(fluvoxamine maleate) |
|
(cefepime HCl) |
(multivitamin) |
(paroxetine HCl) |
(rifapentine) |
|
(mesoridazine besylate) |
(nisoldipine) |
(timolol maleate) |
(nitroglycerin) |
|
(dorzolamide HCl) |
(stavudine) |
"In US clinical studies of Amaryl, 414 of 1109 patients were 65 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.
"Comparison of glimepiride pharmacokinetics in NIDDM patients less than or equal to 65 years (n = 49) and those greater than 65 years (n = 42) was performed in a study using a dosing regimen of 6 mg daily. There were no significant differences in glimepiride pharmacokinetics between the two age groups. (See CLINICAL PHARMACOLOGY, Special Populations, Geriatric.) "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.
"In elderly, debilitated, or malnourished patients, or in patients with renal or hepatic insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents. (See CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency; PRECAUTIONS, General; and DOSING AND ADMINISTRATION, Specific Patient Populations.)"
[Other labeling changes not appearing in 2000 PDR: May00]
AVALIDE (irbesartan/hydrochlorothiazide) Tablets
[September 20, 2000: Bristol-Myers Squibb] [Other labeling changes not appearing in 2000 PDR: May00]
"The following have been very rarely reported in post-marketing experience:["Rare cases of" deleted] urticaria; angioedema (involving swelling of the face, lips, pharynx, and/or tongue)["have been reported" deleted]; increased liver function tests; jaundice.
Hyperkalemia has been rarely reported."
"The following have been very rarely reported in post-marketing experience:["Rare cases of" deleted] urticaria; angioedema (involving swelling of the face, lips, pharynx, and/or tongue)["have been reported with irbesartan" deleted]. Hyperkalemia has been rarely reported.
Very rare cases of jaundice have been reported with irbesartan."
" Children, ["two" deleted] six years of age and older:"
Maintenance Therapy: Heading changed to reflect increase in age from 2 to 6 years (new text in italics) -
" Children, ["two" deleted] six years of age and older:"
"Calcium chloride is not recommended in the treatment of asystole and electromechanical dissociation."
"10% Calcium Chloride Injection, USP is administered only by slow intravenous injection (not to exceed 1 mL/min), preferably in a central or deep vein.."
Fourth paragraph added -
"The pediatric dosage in hypocalcemic disorders ranges from 2.7 to 5.0 mg/kg hydrated calcium chloride (or 0.136 to 0.252 mEq elemental calcium per kg, or 0.027 to 0.05 mL of 10% Calcium Chloride Injection per kg). No data from clinical trials is available about repeated dosages, though textbook references recommend repeat dosages q 4 to 6 hours."
"In a double-blind, placebo-controlled study, increased frequency and severity of diarrhea were reported in patients randomized to olsalazine 500 mg B.I.D. with concomitant radiation."
"Of the approximately 1,065 patients who entered the in-office dose-titration period in clinical studies, 25% were 65 years or older. In clinical studies, geriatric patients required, on average, higher minimally effective doses and had a higher rate of lack of effect (optimum dose not determined). Overall differences in safety were not observed between these geriatric patients and younger patients. Geriatric patients should be dosed and titrated according to the same DOSAGE AND ADMINISTRATION recommendations as younger patients, and the lowest possible effective dose should always be used. 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. "
"In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom Flolan therapy was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and returned to baseline values by day 87. The change in furosemide clearance value is not likely to be clinically significant. However, patients on digoxin may show elevations of digoxin concentrations after initiation of Flolan therapy, which may be clinically significant in patients prone to digoxin toxicity."
"In addition to adverse reactions reported from clinical trials, the following events have been identified during post-approval use of Flolan. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Flolan."
"Blood and Lymphatic: pancytopenia, anemia, splenomegaly, hypersplenism.
Endocrine and Metabolic: hyperthyroidism."
"No fatal events have been reported following overdosage of Flolan."
Replaced with -
"In clinical practice, fatal occurrences of hypoxemia, hypotension and respiratory arrest have been reported following overdosage of Flolan."
[Other labeling changes not appearing in 2000 PDR: Jun99, Nov99]
Heparin Lock Flush Solution is intended for maintenance of patency of intravenous injection devices only and is not to be used for anticoagulant therapy.
New third paragraph added -
"Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial prothrombin times (APTTs) compared with patients under 60 years of age."
"Increased Risk in Older Patients, especially Women
A higher incidence of bleeding has been reported in patients, particularly women, over
60 years of age."
Geriatric Use:
[Heparin Lock Flush Solution]
"A higher incidence of bleeding has been reported in patients 60 years of age, especially women (see PRECAUTIONS, General and CLINICAL PHARMACOLOGY)."
[Heparin Sodium Injection]
"A higher incidence of bleeding has been reported in patients 60 years of age, especially women (see PRECAUTIONS, General). Clinical studies indicate that lower doses of heparin may be indicated in these patients (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION)."
"Patients over 60 years of age may require lower doses of heparin."
"To facilitate monitoring fetal outcomes of pregnant women exposed to lamotrigine, physicians are encouraged to register patients, before fetal outcome (e.g., ultrasound, results of amniocentesis, birth, etc.) is known, and can obtain information by calling the Lamotrigine Pregnancy Registry at (800) 336-2176 (toll-free). Patients can enroll themselves in the North American Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll-free)."
Postmarketing and Other Experience: Subsection revised (new text in italics) -
"In adition to the adverse experiences reported during clinical testing of Lamictal, the following adverse experiences have been reported in patients receiving marketed Lamictal ["in other countries" deleted] and from worldwide noncontrolled investigational use. These adverse experiences have not been listed above, and data are insufficient to support an estimate of their incidence or to establish causation.
Blood and Lymphatic: Agranulocytosis, aplastic anemia, disseminated intravascular coagulation, hemolytic anemia, neutropenia, pancytopenia, red cell aplasia.
Gastrointestinal: Esophagitis.
Hepatobiliary Tract and Pancreas: Pancreatitis.
Immunologic: Lupus-like reaction, vasculitis.
Lower Respiratory: Apnea.
Musculoskeletal: Rhabdomyolysis has been observed in patients experiencing hypersensitivity reactions.
Neurology: Exacerbation of parkinsonian symptoms in patients with pre-existing Parkinson's disease, tics.
Non-site Specific: Hypersensitivity reaction, multiorgan failure, progressive immunosuppression."
" Lamictal Added to AEDs [AntiEpileptic Drugs] Other Than EIAEDs [Enzyme Inducing AEDs] and VPA: [Valprioc Acid] The effect of AEDs other than EIAEDs and VPA on the metabolism of Lamictal ["cannot be predicted" deleted] is not currently known. Therefore, no specific dosing guidelines can be provided in that situation. Conservative starting doses and dose escalations (as with concomitant VPA) would be prudent; maintenance dosing would be expected to fall between the maintenance dose with VPA and the maintenance dose without VPA, but with an EIAED. "
Fourth paragraph revised (new text in italics) -
The smallest available strength of Lamictal Chewable Dispersible Tablets is 2 mg, ["5 mg" deleted] and only whole tablets should be administered. If the calculated dose cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet (see HOW SUPPLIED and PATIENT INFORMATION for a description of the Lamictal Chewable Dispersible Tablet available sizes).
Fifth paragraph deleted -
"Pediatric patients who weigh less than 17 kg (37 lb) should not receive Lamictal because therapy cannot be initiated using the dosing guidelines (see Table 8 and Table 9) and the currently available tablet strengths (see warnings)."
Table 8 revised to incorporate dosing with the new 2 mg tablet -
|
Weeks 1 and 2 |
0.15 mg/kg/day in one or two divided doses, rounded down to the nearest whole tablet. Only whole tablets should be used for dosing |
||
|
Weeks 3 and 4 |
0.3 mg/kg/day in one or two divided doses, rounded down to the nearest whole tablet |
||
|
Weight based dosing can be achieved by using the following guide: |
|||
|
If the patient's weight is |
Give this daily dose, using the most appropriate combination of Lamictal 2 mg and 5 mg tablets |
||
|
Greater than |
And less than |
Weeks 1 and 2 |
Weeks 3 and 4 |
|
6.7 kg |
14 kg |
2 mg every other day |
2 mg every day |
|
14.1 kg |
27 kg |
2 mg every day |
4 mg every day |
|
27.1 kg |
34 kg |
4 mg every day |
8 mg every day |
|
34.1 kg |
40 kg |
5 mg every day |
10 mg every day |
|
Usual maintenance dose: 1 to 5 mg/kg/day (maximum 200 mg/day in one or two divided doses). To achieve the usual maintenance dose, subsequent doses should be increased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose. |
|||
Table 9 revised to incorporate dosing with the new 2 mg tablet -
|
Weeks 1 and 2 |
0.6 mg/kg/day in two divided doses, rounded down to the nearest whole tablet. |
|
Weeks 3 and 4 |
1.2 mg/kg/day in two divided doses, rounded down to the nearest whole tablet. |
|
Usual maintenance dose: 5 to 15 mg/kg/day (maximum 400 mg/day in two divided doses). To achieve the usual maintenance dose, subsequent doses should be increased every 1 to 2 weeks as follows: calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose. |
|
Patients Over 12 Years of Age: New second paragraph added -
" Lamictal Added to AEDs Other Than EIAEDs and VPA: The effect of AEDs other than EIAEDs and VPA on the metabolism of Lamictal ["cannot be predicted" deleted] is not currently known. Therefore, no specific dosing guidelines can be provided in that situation. Conservative starting doses and dose escalations (as with concomitant VPA) would be prudent; maintenance dosing would be expected to fall between the maintenance dose with VPA and the maintenance dose without VPA, but with an EIAED. "
"Store at ["15° to 25°C (59° to 77°F)" deleted] 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature] in a dry place." "...and protect from light." [for the 100, 150 and 200 mg tablets]"
Text below the graphics are shown below:
" NOTE: The pictures above show actual tablet shape and size and the wording describes the color and printing that is on each strength of Lamictal Tablets and Chewable Dispersible Tablets. Before taking your medicine, it is important to compare the tablets you receive from your doctor or pharmacist with these pictures to make sure you have received the correct medicine."
"Three hundred ninety-nine patients were enrolled in an open-label, randomized, comparative study for complicated skin and skin structure infections. The patients were randomized to receive either levofloxacin 750 mg QD (IV followed by oral), or an approved comparator for a median of 10 ± 4.7 days. As is expected in complicated skin and skin structure infections, surgical procedures were performed in the levofloxacin and comparator groups. Surgery (incision and drainage or debridement) was performed on 45% of the levofloxacin treated patients and 44% of the comparator, either shortly before or during antibiotic treatment and formed an integral part of therapy for this indication.
Among those who could be evaluated clinically 2-5 days after completion of study drug, overall success rates (improved or cured) were 116/138 (84.1%) for patients treated with levofloxacin and 106/132 (80.3%) for patients treated with the comparator.
"Success rates varied with the type of diagnosis ranging from 68% in patients with infected ulcers to 90% in patients with infected wounds and abscesses. These rates were equivalent to those seen with comparator drugs."
"The multiple-dose pharmacokinetics of fluvoxamine were determined in male and female children (ages 6-11) and adolescents (ages 12-17). Steady-state plasma fluvoxamine concentrations were 2-3 fold higher in children than in adolescents. AUC and Cmax in children were 1.5- to 2.7 higher than that in adolescents (see table below). As in adults, both children and adolescents exhibited nonlinear multiple-dose pharmacokinetics. Female children showed significantly higher AUC (0-12) and Cmax compared to male children and, therefore, lower doses of Luvox tablets may produce therapeutic benefit (see table below). No gender differences were observed in adolescents. Steady-state plasma fluvoxamine concentrations were similar in adults and adolescents at a dose of 300 mg/day, indicating that fluvoxamine exposure was similar in these two populations (see table below). Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit."
Comparison of Mean (SD) fluvoxamine pharmacokinetic parameters between children, adolescents and adults
|
Pharmaco-kinetic Parameter (body weight corrected) |
Dose = 200 mg/day (100 mg bid) |
Dose = 300 mg/day (150 mg bid) |
||
|
Children (n=10) |
Adolescent (n=17) |
Adolescents (n = 13) |
Adults (n = 16) |
|
|
AUC 0-12 (ng.h/ml/kg) |
155.1 (160.9) |
43.9 (27.9) |
69.6 (46.6) |
59.4 (40.9) |
|
Cmax (ng/ml/kg |
14.8 (14.9) |
4.2 (2.6) |
6.7 (4.2) |
5.7 (3.9) |
|
Cmin ng/ml/kg |
11.0 (11.9) |
2.9 (2.0) |
4.8 (3.8) |
4.6 (3.2) |
Comparison of Mean (SD) fluvoxamine pharmacokinetic parameters between male and female children (6-11 years)
|
Pharmacokinetic Parameter (body weight corrected) |
Dose = 200 mg/day (100 mg bid) |
|
|
Male Children (n = 7) |
Female Children (n = 3) |
|
|
AUC 0-12 (ng.h/ml/kg) |
95.8 (83.9) |
293.5 (233.0) |
|
Cmax (ng/ml/kg) |
9.1 (7.6) |
28.1 (21.1) |
|
Cmin (ng/ml/kg) |
6.6 (6.1) |
21.2 (17.6) |
Clinical Trials
Pediatric OCD Study:
First paragraph, third sentence revised (new text in italics) -
"All patients ["Patients in these studies" deleted] had moderate-to-severe OCD (DSM-III-R) with mean baseline ratings on the Children's Yale-Brown Obsessive Compulsive Scale (CY BOCS), total score of 24."
Second paragraph revised (new text in italics) -
"Post hoc expoloratory analyses for gender effects on outcomes did not suggest any differential responsiveness on the basis of gender. Further exploratory analyses revealed a prominent treatment effect in the 8-11 age group and essentially no effect in the12-17 age group. While the significance of these results is not clear, the 2-3 fold higher steady state plasma fluvoxmaine concentrations in children compared to adolescents (see Pharmacokinetics) is suggestive that decreased exposure in adolescents may have been a factor, and dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit."
"Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder and with aging, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences.
"Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence.
"The table below displays the incidence of sexual side effects reported by at least 2% of patients taking Luvox in placebo controlled trials in depression and OCD."
| Luvox N=892 | Placebo N=778 | |
| Abnormal Ejaculation* | 8% | 1% |
| Impotence* | 2% | 1% |
| Decreased Libido | 2% | 1% |
| Anorgasmia | 2% | 0% |
| * Based on the number of male patients. |
"There are no adequate and well-controlled studies examining sexual dysfunction with fluvoxamine treatment.
"Fluvoxamine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae and upon discontinuation of fluvoxamine.
"While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRI's, physicians should routinely inquire about such possible side effects."
"The recommended starting dose for Luvox tablets in pediatric populations (ages 8-17 years) is 25 mg, administered as a single daily dose at bedtime. In a controlled clinical trial establishing the effectiveness of Luvox tablets in OCD, pediatric patients (ages 8-17) were titrated within a dose range of 50 to 200 mg/day. ["The dose should be increased in 25 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved, not to exceed 200 mg per day." Deleted] Physicians should consider age and gender differences when dosing pediatric patients. The maximum dose in children up to age 11 should not exceed 200 mg/day. Therapeutic effect in female children may be achieved with lower doses. Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit. The dose should be increased in 25 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved. It is advisable that a total daily dose of more than 50 mg should be given in two divided doses. If the two divided doses are not equal, the larger dose should be given at bedtime."
"As with other cephalosporins, anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranolocytosis and thrombocytopenia have been reported."
"Unlike the adult formulation, M.V.I. 12, this product contains phytonadione (vitamin K1)."
"The use of a multivitamin product obviates the need to speculate on the status of individual vitamin nutriture,"
Paragraph five, last sentence added -
"Blood vitamin concentrations should be monitored to ensure maintenance of adequate levels, particularly in patients receiving parenteral multivitamins as their sole source of vitamins for long periods of time."
"Known hypersensitivity to any of the vitamins or excipients in this product or a pre-existing hypervitaminosis."
" Caution should be exercised when administering this multivitamin formulation to patients on warfarin sodium-type anticoagulant therapy. In such patients, vitamin K may antagonize the hypoprothrombinemic response to anticoagulant drugs. Therefore, periodic monitoring of prothrombin time is essential in determining the appropriate dosage of anticoagulant therapy."
Third paragraph revised (new text in italics) -
"Studies have shown that vitamin A may adhere to plastic, resulting in inadequate vitamin A administration in the doses recommended with M.V.I. Pediatric. Additional vitamin A supplementation may be required, especially in low birth weight infants."
New fifth and sixth paragraphs added -
"In patients receiving parenteral multivitamins, blood vitamin concentrations should be periodically monitored to determine if vitamin deficiencies or excesses are developing.
"Polysorbates have been associated with the E-Ferol syndrome (thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension, and metabolic acidosis) in low birth weight infants."
Physical Incompatibilities
"M.V.I. Pediatric is not physically compatible with alkaline solutions or moderately alkaline drugs such as Diamox (Acetazolamide), Diuril Intravenous Sodium (Chlorothiazide sodium), Aminophylline or sodium bicarbonate. M.V.I. Pediatric is not physically compatible with ampicillin and it may not be physically compatible with Achromycin (tetracycline HCl). It has also been reported that folic acid is unstable in the presence calcium salts such as calcium gluconate. Direct addition of M.V.I. Pediatric to intravenous fat emulsions is not recommended. Consult appropriate references for listings of physical compatibility of solutions and drugs with the vitamin infusion. In such circumstances, admixture or Y-site administration with vitamin solutions should be avoided.
"Several vitamins have been reported to decrease the activity of certain antibiotics. Thiamine, riboflavin, pyridoxine, niacinamide, and ascorbic acid have been reported to decrease the antibiotic activity of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin. Bleomycin is inactivated in vitro by ascorbic acid and riboflavin.
"Some of the vitamins in M.V.I. Pediatric may react with vitamin K bisulfite or sodium bisulfate; if bisulfite solutions are necessary, patients should be monitored for vitamin A and thiamine deficiencies."
Clinical Interactions
"A number of interactions between vitamins and drugs have been reported which may affect the metabolism of either agent. The following are example of these types of interactions.
"Folic acid may lower the serum concentration of phenytoin resulting in increased seizure frequency. Conversely, phenytoin may decrease serum folic acid concentrations and, therefore, should be avoided in pregnancy. Folic acid may decrease the patient's response to methotrexate therapy.
"Pyridoxine may decrease the efficacy of levodopa by increasing its metabolism. Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements.
"In patients with pernicious anemia, the hematologic response to vitamin B12 therapy may be inhibited by concomitant administration of chloramphenicol.
"Vitamin K may antagonize the hypoprothrombinemic effect of oral anticoagulants (see bolded statement above).
"Consult appropriate references for additional specific vitamin-drug interactions."
Drug-Laboratory Test Interactions New subsection -
"Ascorbic acid in the urine may cause false negative urine glucose determinations."
" There have been rare reports of anaphylactic reactions following parenteral multivitamin administration.
Revisions to the Allergic subsection (new text in italics) -
"Allergic - urticaria, shortness of breath, wheezing, and angioedema ["periorbital and digital edema, lip edema" deleted].
"Voluntary reports of adverse events in patients taking Paxil (paroxetine hydrochloride) that have been received since market introduction and not listed above that may have no causal relationship with the drug include...'status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, ventricular tachycardia (including torsade de pointes), ["thrombocytopenia" moved from text in the sentence above"], hemolytic anemia, and events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis).'"
The next sentence revised with new text in italics - "There have been spontaneous reports that ["abrupt" deleted] discontinuation (particularly when abrupt) may lead to symptoms such as dizziness, sensory disturbances, agitation or anxiety, nausea and sweating; these events are generally self-limiting."
Commonly reported adverse events associated with paroxetine overdosage include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including torsade de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention."
"Clinical studies of Priftin 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. (See ACTIONS/CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations - Elderly)."
"Clinical studies of nisoldipine 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. Patients over 65 are expected to develop higher plasma concentrations of nisoldipine. 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."
"Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. There have been no reports of exacerbation of rebound hypertension with ophthalmic timolol maleate."
Geriatric Use:
[for Timoptic-XE]
Previous subsection deleted and replaced with the following:
"No overall differences in safety or effectiveness have been observed between elderly and younger patients."
"Clinical studies of transdermal nitroglycerin 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 frquency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy."
"Choriodal detachment has been reported with administration of aqueous suppressant therapy (e.g., dorzolamide) after filtration procedures."
"choroidal detachment following filtration surgery"
"FATAL AND NONFATAL PANCREATITIS HAVE OCCURRED DURING THERAPY WHEN ZERIT WAS PART OF A COMBINATION REGIMEN THAT INCLUDED DIDANOSINE, WITH OR WITHOUT HYDROXYUREA, IN BOTH TREATMENT-NAÏVE AND TREATMENT-EXPERIENCED PATIENTS, REGARDLESS OF DEGREE OF IMMUNOSUPPRESSION (SEE WARNINGS)."
"An increased risk of hepatotoxicity, which may be fatal, may occur in patients treated with Zerit in combination with didanosine and hydroxyurea compared to when Zerit is used alone. Patients treated with this combination should be closely monitored for signs of liver toxicity."
3. Pancreatitis: Fatal and nonfatal pancreatitis have occurred during therapy when Zerit was part of a combination regimen that included didanosine, with or without hydroxyurea, in both treatment-naïve and treatment-experienced patients, regardless of degree of immunosuppression. The combination of Zerit and didanosine (with or without hydroxyurea) and any other agents that are toxic to the pancreas should be suspended in patients with suspected pancreatitis.
"Patients should be informed that when Zerit is used in combination with other agents with similar toxicities, the incidence of adverse events may be higher than when Zerit is used alone. An increased risk of pancreatitis, which may be fatal, may occur in patients treated with the combination of Zerit and didanosine, with or without hydroxyurea. Patients treated with this combination should be closely monitored for symptoms of pancreatitis. An increased risk of hepatotoxicity, which may be fatal, may occur in patients treated with Zerit in combination with didanosine and hydroxyurea. Patients treated with this combination should be closely monitored for signs of liver toxicity. "
Nursing Mothers
"Subsection revised with revisions incorporated below -
"The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV. Studies in lactating rats demonstrated that stavudine is excreted in milk. Although it is not known whether stavudine is excreted in human milk, there exists the potential for adverse effects from stavudine in nursing infants. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving Zerit".
Geriatric Use: New subsection -
"Clinical studies of Zerit did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. Greater sensitivity of some older individuals to the effects of Zerit cannot be ruled out.
" In a monotherapy Expanded Access Program for patients with advanced HIV infection, peripheral neuropathy or peripheral neuropathic symptoms were observed in 15 of 40 (38%) elderly patients receiving 40 mg BID and 8 of 51 (16%) elderly patients receiving 20 mg BID. Of the approximately 12,000 patients enrolled in the Expanded Access Program, peripheral neuropathy or peripheral neuropathic symptoms developed in 30% of patients receiving 40 mg BID and 25% of patients receiving 20 mg BID. Elderly patients should be closely monitored for signs and symptoms of peripheral neuropathy.
"Zerit 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, it may be useful to monitor renal function. Dose adjustment is recommended for patients with renal impairment (see DOSAGE AND ADMINISTRATION: Dosage Adjustment)."
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