Geriatric Use

In worldwide clinical studies of Actigall, approximately 14% of subjects were over 65 years of age (approximately 3% were over 75 years old). In a subgroup analysis of existing clinical trials, patients greater than 56 years of age did not exhibit statistically significantly different complete dissolution rates from the younger population. No age related differences in safety and effectiveness were found. Other reported clinical experience has not identified differences in response in elderly and younger patients. However, small differences in efficacy and greater sensitivity of some elderly individuals taking Actigall cannot be ruled out. Therefore, it is recommended that dosing proceed with caution in this population.

Coadministration of amprenavir and methadone as compared to a non-matched historical control group resulted in a 30%, 27%, and 25% decrease in serum amprenavir AUC, C_max, and C_min, respectively.

Hormonal contraceptives (e.g., birth control pills) because the effectiveness of one or both drugs may be decreased. Talk to your doctor about choosing a different type of contraceptive.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

ALTACE is contraindicated in patients who are hypersensitive to this product or any other angiotensin converting enzyme inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor.

As with other ACE inhibitors, rarely, a mild – in isolated cases severe – reduction in the red blood cell count and hemoglobin content, white blood cell or patelet count may develop. In isolated cases, agranulocytosis, pancyotpenia, and bone marrow depression may occur. Hematological reactions to ACE inhibitors are more likely to occur in patients with collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma) and renal impairment.

However, since the renin-angiotensin system maybe activated in patients with severe liver cirrhosis and/or ascites, particular caution should be exercised in treating these patients.

Clinical Studies of Aminosyn II [3.5% M or 4.25% M in Dextrose Injection, Aminosyn II in Dextrose Injection and Aminosyn II 15% Pharmacy Bulk Package] have not been performed to determine whether patients over 65 years of age 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 kidney, and the risk for adverse 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.

"Due to their concentration, these solutions are not recommended for use in pediatric patients less than 1 year old. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants."

Achilles and other tendon ruptures that require surgical repair or resulted in prolonged disability have been reported with quinolones. Cinoxacin should be discontinued if the patient experiences pain, inflammation, or tendon rupture.

Patients should be advised that convulsions have been reported in patients taking quinolones, including cinoxacin acid, and to notify their physician before taking this drug if there is a history of this condition.

Following a single 500 mg dose of cinoxacin, peak serum

concentrations in geriatric patients were similar to those in all adults. With repeated administration of cinoxacin, no accumulation of drug was found in the twenty patients ages 70-89 (see Geriatric under Clinical Pharmacology). No dosage adjustment is required based on age alone. In geriatric patients with reduced renal function, the dosage should be reduced (see Impaired Renal Function under Dosage and Administration).

Clinical studies of cinoxacin 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.

HIV treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV and HBV. The causal relationship to discontinuation of lamivudine treatment is unknown. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of posttreatment exacerbations of hepatitis.

800 mg once daily has been shown to increase lamivudine exposure (AUC). The effect of higher doses of TMP/SMX on lamivudine pharmacokinetics has not been investigated (see CLINICAL PHARMACOLOGY). No data are available regarding the potential for interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.

Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of COMBIVIR in combination with zalcitabine is not recommended.

Concomitant use of COMBIVIR with stavudine should be avoided since an antagonistic relationship with zidovudine has been demonstrated in vitro. In addition, concomitant use of zidovudine with doxorubicin or ribavirin should be avoided because an antagonistic relationship has been demonstrated in vitro.

See CLINICAL PHARMACOLOGY for additional drug interactions.

Gastrointestinal: Oral mucosal pigmentation, stomatitis.

Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.

A reduction in the daily dose of zidovudine may be necessary in patients with mild to moderate impaired hepatic function or liver cirrhosis. Because COMBIVIR is a fixed-dose combination that cannot be adjusted for this patient population, COMBIVIR is not recommended for patients with impaired hepatic function.

Information for Patients: Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

In patients with a history of liver disease or abnormal ALT, AST and/or bilirubin at baseline, LUMIGAN had no adverse effect on liver function over 24 months.

In a single-dose study, the pharmacokinetics of atovaquone, proguanil, and cycloguanil were compared in 13 elderly subjects (age 65 to 79 years) to 13 younger subjects (age 30 to 45 years). In the elderly subjects, the extent of systemic exposure (AUC) of cycloguanil was increased (point estimate = 2.36, CI = 1.70, 3.28). T_max was longer in elderly subjects (median 8 hours) compared with younger subjects (median 4 hours) and average elimination half-life was longer in elderly subjects (mean 14.9 hours) compared with younger subjects (mean 8.3 hours).

In a single-dose study, the pharmacokinetics of atovaquone, proguanil, and cycloguanil were compared in 13 subjects with hepatic impairment (9 mild, 4 moderate, as indicated by the Child-Pugh method) to 13 subjects with normal hepatic function. In subjects with mild or moderate hepatic impairment as compared to healthy subjects, there were no marked differences (<50%) in the rate or extent of systemic exposure of atovaquone. However, in subjects with moderate hepatic impairment, the elimination half-life of atovaquone was increased (point estimate = 1.28, 90% CI = 1.00 to 1.63). Proguanil AUC, C_max , and its t_1/2 increased in subjects with mild hepatic impairment when compared to healthy subjects (Table 1). Also, the proguanil AUC and its t_1/2 increased in subjects with moderate hepatic impairment when compared to healthy subjects. Consistent with the increase in proguanil AUC, there were marked decreases in the systemic exposure of cycloguanil (C_max and AUC) and an increase in its elimination half-life in subjects with mild hepatic impairment when compared to healthy volunteers (Table 1). There were few measurable cycloguanil concentrations in subjects with moderate hepatic impairment (see DOSAGE AND ADMINISTRATION). The pharmacokinetics of atovaquone, proguanil, and cycloguanil after administration of MALARONE have not been studied in patients with severe hepatic impairment.

ND = not determined due to lack of quantifiable data.

* Ratio of geometric means.

† Mean difference.

Among subjects who received MALARONE for prophylaxis of malaria in clinical trials with an active comparator, adverse experiences occurred in a similar or lower proportion of subjects receiving MALARONE than an active comparator (Table 3). The mean durations of dosing and the periods for which the adverse experiences are summarized in Table 3, were 28 days (Study 1) and 26 days (Study 2) for MALARONE, 53 days for mefloquine, and 49 days for chloroquine plus proguanil (reflecting the different recommended dosing regimens). Fewer neuropsychiatric adverse experiences occurred in subjects who received MALARONE than mefloquine. Fewer gastrointestinal adverse experiences occurred in subjects receiving MALARONE than chloroquine/proguanil. Compared with active comparator drugs, subjects receiving MALARONE had fewer adverse experiences overall that were attributed to prophylactic therapy (Table 3). Prophylaxis with MALARONE was discontinued prematurely due to a treatment-related adverse experience in 7 of 1,004 travelers.

*Adverse experiences that started while receiving active study drug.

Two active-controlled studies were conducted in non-immune travelers who visited a malaria-endemic area. The mean duration of travel was 18 days (range 2 to 38 days). Of a total of 1,998 randomized patients who received MALARONE or control drug, 24 discontinued from the study before follow-up evaluation 60 days after leaving the endemic area. Nine of these were lost to follow-up, 2 withdrew because of an adverse experience and 13 were discontinued for other reasons.) The studies were not large enough to allow for statements of comparative efficacy. In addition, the true exposure rate to P. falciparum malaria in both studies is unknown.

In a malaria challenge study conducted in healthy US volunteers, atovaquone alone prevented malaria in 6 of 6 individuals, whereas 4 of 4 placebo-treated volunteers developed malaria.

In patients with impaired renal function (creatinine clearance ≤60 mL/min), the dose of MAXIPIME should be adjusted to compensate for the slower rate of renal elimination. Because high and prolonged serum antibiotic concentrations can occur from usual dosages in patients with renal insufficiency or other conditions that may compromise renal function, the maintenance dosage should be reduced when cefepime is administered to such patients. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms. (See specific recommendations for dosing adjustment in DOSAGE AND ADMINISTRATION.) During postmarketing surveillance, serious adverse events have been reported including life-threatening or fatal occurrences, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and/or renal failure (See ADVERSE REACTIONS: In Postmarketing Experience). Most cases occurred in patients with renal impairment who received doses of cefepime that exceeded recommendations in Table 13 of DOSAGE AND ADMINISTRATION. Symptoms of neurotoxicity resolved after discontinuation of cefepime and/or after hemodialysis.

Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of cefepime from the body. Accidental overdosing has occurred when large doses were given to patients with impaired renal function. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and neuromuscular excitability. (See PRECAUTIONS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.)

Store at 25° C (77° F); excursions permitted to 15° - 30° C (59° - 86° F) [see USP Controlled Room Temperature]. Protect from temperatures above 40° C (104° F).

Clinical studies of MONOPRIL 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 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.

Store at 25° C (77° F); excursions permitted to 15° C - 30° C (59° F - 86° F) [see USP Controlled Room temperature]. Protect from moisture by keeping bottle tightly closed.

Clinical studies of Nafcillin Injection 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.

Nafcillin Injection contains 76.6 mg (3.33 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 230 and 460 mg/day (10.0 and 20.0 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

Clinical studies of Oxacillin Injection 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.

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.

Oxacillin Injection contains 92.4 mg (4.02 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 92.4 and 554 mg/day (4.02 and 24.1 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

In elderly patients, the mean peak enoxacin plasma concentration was 50% higher than that in young adult volunteers receiving comparable single doses of enoxacin. (See CLINCAL PHARMACOLOGY.) Enoxacin is known to be excreted by the kidney and the risk of adverse reactions may be greater in patients with impaired renal function. The dosage should be reduced in patients with renal impairment. (See DOSAGE AND ADMINISTRATION.)

Clinical studies of Penicillin G Injection 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.

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.

Penicillin G Injection contains 23.5 mg (1.02 mEq) of sodium per million units. At the usual recommended doses, patients would receive between 23.5 and 564 mg/day (1.02 and 24.5 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

Clinical studies of Proloprim (trimethoprim) Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience ^4,5 has not identified differences in response 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.

Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfaethoxazole have been published.⁶ Trimethoprim 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 potassium concentrations and to monitor renal function by calculating creatinine clearance.

Geriatric use:

Clinical studies of Stimate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. However, other post-marketing experience has reported the occurrence of hyponatremia with the use of desmopressin acetate and fluid overload.

Therefore, in elderly patients fluid intake should be adjusted downward in an effort to decrease the potential occurrence of water intoxication and hyponatremia. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures, which could lead to coma.

Patients who do not have need of antidiuretic hormone for its antidiuretic effect should be cautioned to ingest only enough fluid to satisfy thirst, in an effort to decrease the potential occurrence of water intoxication and hyponatremia.

As for all patients, dosing for geriatric patients should be appropriate to their overall situation.

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of theseevents are currently unknown. A causal relationship has not been established.

PRECAUTIONS / Information for Patients (See Patient Information Leaflet.) section:

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.