Zemplar Capsules

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience

CKD Stages 3 and 4

The safety of ZEMPLAR capsules has been evaluated in three 24-week (approximately six-month), double-blind, placebo-controlled, multicenter clinical studies involving 220 CKD Stages 3 and 4 patients. Six percent (6%) of ZEMPLAR capsules treated patients and 4% of placebo treated patients discontinued from clinical studies due to an adverse event. Adverse events occurring in the ZEMPLAR capsules group at a frequency of 2% or greater and more frequently than in the placebo group are presented in Table 3:

Table 3: Adverse Reactions by Body System Occurring in ≥ 2% of Subjects in the ZEMPLAR-Treated Group of Three, Double-Blind, Placebo-Controlled CKD Stages 3 and 4 Studies

The following additional adverse reactions occurred in < 2% of the ZEMPLAR-treated patients in the above double-blind, placebo-controlled clinical trial.

Gastrointestinal Disorders: Dry mouth

Investigations: Hepatic enzyme abnormal

Nervous System Disorders: Dysgeusia

Skin and Subcutaneous Tissue Disorders: Urticaria

The safety of ZEMPLAR capsules has been evaluated in one multicenter clinical study involving CKD Stages 3 and 4 patients ages 10 to 16 years. A 12-week double-blind, placebo-controlled phase was followed by an open-label phase during which all patients received ZEMPLAR capsules.

During the 12-week blinded phase, a total of 18 patients received ZEMPLAR capsules and 18 patients received placebo. Adverse events occurring more frequently in the ZEMPLAR capsules group than in the placebo group are presented in Table 4.

Table 4: Adverse Reactions by Body System Occurring in the Double-Blind, Placebo-Controlled, CKD Stages 3 and 4 Study in Patients Ages 10 to 16 Years

The following adverse reactions have occurred in ZEMPLAR-treated patients:

Gastrointestinal Disorders: Abdominal pain, constipation, vomiting

Metabolism and Nutrition Disorders: Hypercalcemia and hyperphosphatemia

Nervous System Disorders: Headache

CKD Stage 5

The safety of ZEMPLAR capsules has been evaluated in one 12-week, double-blind, placebo-controlled, multicenter clinical study involving 88 CKD Stage 5 patients. Sixty-one patients received ZEMPLAR capsules and 27 patients received placebo.

The proportion of patients who terminated prematurely from the study due to adverse events was 7% for ZEMPLAR capsules treated patients and 7% for placebo patients.

Adverse events occurring in the ZEMPLAR capsules group at a frequency of 2% or greater and more frequently than in the placebo group are as follows:

Table 5: Adverse Reactions by Body System Occurring in ≥ 2% of Subjects in the ZEMPLAR-Treated Group, Double-Blind, Placebo-Controlled CKD Stage 5 Study

The following adverse reactions occurred in < 2% of the ZEMPLAR-treated patients in the above double-blind, placebo-controlled clinical trial.

Gastrointestinal Disorders: Gastroesophageal reflux disease

Metabolism and Nutrition Disorders: Decreased appetite, hypercalcemia, hypocalcemia

Reproductive System and Breast Disorders: Breast tenderness

Skin and Subcutaneous Tissue Disorders: Acne

The safety of ZEMPLAR capsules has been evaluated in one 12-week, open-label, single-arm, multicenter clinical studies involving 13 CKD Stage 5 patients ages 10 to 16 years of age receiving peritoneal dialysis or hemodialysis.

The following adverse reactions were reported:

Gastrointestinal Disorders: Abdominal pain, diarrhea, nausea, vomiting

Metabolism and Nutrition Disorders: Hypercalcemia, hyperphosphatemia

Three of 13 patients (23%) had hypercalcemia defined as at least 2 consecutive serum calcium values > 10.2 mg/dL (2.55 mmol/L).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ZEMPLAR capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Angioedema (including laryngeal edema)

Investigations: Blood creatinine increased

Excessive administration of ZEMPLAR capsules can cause hypercalcemia, hypercalciuria, and hyperphosphatemia, and over suppression of PTH [see WARNINGS AND PRECAUTIONS].

Treatment Of Overdosage

The treatment of acute overdosage of ZEMPLAR capsules should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. If the drug has passed through the stomach, the administration of mineral oil may promote its fecal elimination. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion, and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and institution of a low-calcium diet are also indicated in accidental overdosage. Due to the relatively short duration of the pharmacological action of paricalcitol, further measures are probably unnecessary. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered depending on the patient's underlying condition. These include the use of drugs such as phosphates and corticosteroids, as well as measures to induce an appropriate forced diuresis.

Paricalcitol is not significantly removed by dialysis.