SIDE EFFECTS

Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Extraneal (icodextrin peritoneal dialysis solution) was originally studied in controlled clinical trials of 493 patients with end-stage renal disease who received a single daily exchange of Extraneal (icodextrin peritoneal dialysis solution) for the long dwell (8-to 16- hours). There were 215 patients exposed for at least 6 months and 155 patients exposed for at least one year. The population was 18-83 years of age, 56% male and 44% female, 73% Caucasian, 18% Black, 4% Asian, 3% Hispanic, and it included patients with the following comorbid conditions: 27% diabetes, 49% hypertension and 23% hypertensive nephropathy.

Rash was the most frequently occurring Extraneal (icodextrin peritoneal dialysis solution) -related adverse event (5.5%, Extraneal (icodextrin peritoneal dialysis solution) ; 1.7% Control). Seven patients on Extraneal (icodextrin peritoneal dialysis solution) discontinued treatment due to rash, and one patient on Extraneal (icodextrin peritoneal dialysis solution) discontinued due to exfoliative dermatitis. The rash typically appeared within the first three weeks of treatment and resolved with treatment discontinuation or, in some patients, with continued treatment.

Female patients reported a higher incidence of skin events, including rash, in both Extraneal (icodextrin peritoneal dialysis solution) and dextrose control treatment groups.

Table 1 shows the adverse events reported in these clinical studies, regardless of causality, occurring in ≥ 5% of patients and more common on Extraneal (icodextrin peritoneal dialysis solution) than control.

Table 1 - Adverse Experiences in ≥ 5 % of Patients and More Common on EXTRANEAL (icodextrin peritoneal dialysis solution)

Adverse reactions reported with an incidence of > 5% and at least as common on dextrose control included pain, asthenia, exit site infection, infection, back pain, hypotension, diarrhea, vomiting, nausea/vomiting, anemia, peripheral edema, hypokalemia, hyperphosphatemia, hypoproteinemia, hypervolemia, arthralgia, dizziness, dyspnea, skin disorder, pruritis.

Additional adverse events occurring at an incidence of < 5% and that may or may not have been related to Extraneal (icodextrin peritoneal dialysis solution) include: pain on infusion, abdominal enlargement, cloudy effluent, ultrafiltration decrease, postural hypotension, heart failure, hyponatremia, hypochloremia, hypercalcemia, hypoglycemia, alkaline phosphatase increase, SGPT increase, SGOT increase, cramping, confusion, lung edema, facial edema, exfoliative dermatitis, eczema, vesicobullous rash, maculopapular rash, erythema multiforme. All reported events are included in the list except those already listed in Table 1 or the following two paragraphs, those not plausibly associated with Extraneal (icodextrin peritoneal dialysis solution) , and those that were associated with the condition being treated or related to the dialysis procedure.

Extraneal (icodextrin peritoneal dialysis solution) was additionally studied in a subpopulation of 92 high average/high transporter APD patients in a two-week controlled clinical trial where patients received a single daily exchange of Extraneal (icodextrin peritoneal dialysis solution) (n=47) or dextrose control (n=45) for the long dwell (14 ±2 hours). Consistent with the data reported in the original trials of Extraneal (icodextrin peritoneal dialysis solution) , rash was the most frequently occurring event.

Peritoneal Dialysis-Related

Adverse events common to the peritoneal dialysis, including peritonitis, infection around the catheter, fluid and electrolyte imbalance, and pain, were observed at a similar frequency with Extraneal and Controls (See PRECAUTIONS).

Changes in Alkaline Phosphatase and Serum Electrolytes

An increase in mean serum alkaline phosphatase has been observed in clinical studies of ESRD patients receiving Extraneal (icodextrin peritoneal dialysis solution) . No associated increases in other liver chemistry tests were observed. Serum alkaline phosphatase levels did not show progressive increase over a 12-month study period. Levels returned to normal approximately two weeks after discontinuation of Extraneal (icodextrin peritoneal dialysis solution) .

Decreases in serum sodium and chloride have been observed in patients using Extraneal (icodextrin peritoneal dialysis solution) . The declines in serum sodium and chloride may be related to dilution resulting from the presence of icodextrin metabolites in plasma. Although these decreases have been small and clinically unimportant, monitoring of patients' serum electrolyte levels as part of routine blood chemistry testing is recommended.

Post-Marketing

The following adverse reactions have been identified during post-approval use of Extraneal (icodextrin peritoneal dialysis solution) . Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Adverse reactions are listed by MedDRA System Order Class (SOC), followed by Preferred Term in order of severity.

INFECTIONS AND INFESTATIONS: Fungal peritonitis, Peritonitis bacterial, Catheter site infection, Catheter related infection

BLOOD AND LYMPHATIC SYSTEM DISORDERS: Thrombocytopenia, Leukopenia, Leukocytosis

IMMUNE SYSTEM DISORDERS: Leukocytoclastic vasculitis, Serum sickness, Hypersensitivity

METABOLISM AND NUTRITION DISORDERS: Shock hypoglycemia, Fluid overload, Dehydration, Fluid imbalance

NERVOUS SYSTEM DISORDERS: Hypoglycemic coma, Burning sensation

EYE DISORDERS: Vision blurred

RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Bronchospasm, Stridor

GASTROINTESTINAL DISORDERS: Sclerosing encapsulating peritonitis, Aseptic peritonitis, Peritoneal cloudy effluent, Ileus, Ascites, Inguinal hernia, Abdominal discomfort

SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Erythema multiforme, Angioedema, Urticaria generalized, Toxic skin eruption, Swelling face, Periorbital edema, Exfoliative rash, Skin exfoliation, Prurigo, Rash (including macular, papular, erythematous, exfoliative), Dermatitis (including allergic and contact), Drug eruption, Erythema, Onychomadesis, Dry skin, Skin chapped, Blister

MUSCULOSKELETAL, CONNECTIVE TISSUE DISORDERS: Arthralgia, Back pain, Musculoskeletal pain

REPRODUCTIVE SYSTEM AND BREAST DISORDERS: Penile edema, Scrotal edema

GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS: Discomfort, Pyrexia, Chills, Malaise, Drug effect decreased, Drug ineffective, Catheter site erythema, Catheter site inflammation, Infusion related reaction (including Infusion site pain, Instillation site pain)

Drug Abuse And Dependence

There has been no observed potential of drug abuse or dependence with Extraneal (icodextrin peritoneal dialysis solution) .

Read the entire FDA prescribing information for Extraneal (Icodextrin Peritoneal Dialysis Solution) »