Paricalcitolside effects

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.

6.1 Clinical

Trials Experience CKD Stages 3 and 4 Adults The safety of Paricalcitol 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 Paricalcitol Capsules treated patients and 4% of placebo treated patients discontinued from clinical studies due to an adverse event. Adverse events occurring in the Paricalcitol 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 Paricalcitol Capsules-Treated Group of Three, Double-Blind, Placebo-Controlled CKD Stages 3 and 4 Studies Number (%) of Subjects Adverse Events a Paricalcitol Capsules (n = 107) Placebo (n =113) Overall 88 (82%) 86 (76%) Ear and Labyrinth Disorders Vertigo 5 (5%) 0 (0%) Gastrointestinal Disorders Abdominal Discomfort 4 (4%) 1 (1%) Constipation 4 (4%) 4 (4%) Diarrhea 7 (7%) 5 (4%) Nausea 6 (6%) 4 (4%) Vomiting 5 (5%) 5 (4%) General Disorders and Administration Site Conditions Chest Pain 3 (3%) 1 (1%) Edema 6 (6%) 5 (4%) Pain 4 (4%) 4 (4%) Immune System Disorders Hypersensitivity 6 (6%) 2 (2%) Infections and Infestations Fungal Infection 3 (3%) 0 (0%) Gastroenteritis 3 (3%) 3 (3%) Infection 3 (3%) 3 (3%) Sinusitis 3 (3%) 1 (1%) Urinary Tract Infection 3 3%) 1 (1%) Viral Infection 8 (7%) 8 (7%) Metabolism and Nutrition Disorders Dehydration Musculoskeletal and Connective Tissue Disorders 3 (3%) 1 (1%) Arthritis 5 (5%) 0 (0%) Back Pain 3 (3%) 1 (1%) Muscle Spasms 3 (3%) 0 (0%) Nervous System Disorders Dizziness 5 (5%) 5 (4%) Headache 5 (5%) 5 (4%) Syncope 3 (3%) 1 (1%) Psychiatric Disorders Depression 3 (3%) 0 (0%) Respiratory, Thoracic and Mediastinal Disorders Cough 3 (3%) 2 (2%) Oropharyngeal Pain 4 (4%) 0 (0%) Skin and Subcutaneous Tissue Disorders Pruritus 3 (3%) 3 (3%) Rash 4 (4%) 1 (1%) Skin Ulcer 3 (3%) 0 (0%) Vascular Disorders Hypertension 7 (7%) 4 (4%) Hypotension 5 (5%) 3 (3%) a. Includes only events more common in the Paricalcitol treatment group. Additional Adverse Reactions The following additional adverse reactions, occurred in <2% of the Paricalcitol-treated adult 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 Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (Paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. CKD Stage 5 Adults The safety of Paricalcitol 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 Paricalcitol Capsules and 27 patients received placebo. The proportion of patients who terminated prematurely from the study due to adverse events was 7% for Paricalcitol Capsules treated patients and 7% for placebo patients. Adverse events occurring in the Paricalcitol Capsules group at a frequency of 2% or greater and more frequently than in the placebo group are as follows: Table 4. Adverse Reactions by Body System Occurring in ≥ 2% of Subjects in the Paricalcitol Capsules-Treated Group, Double-Blind, Placebo-Controlled CKD Stage 5 Study Number (%) of Subjects Adverse Events a Paricalcitol Capsules (n = 61) Placebo (n =27) Overall 43 (70%) 19 (70%) Gastrointestinal Disorders Constipation 3 (5%) 0 (0%) Diarrhea 7 (11%) 3 (11%) Vomiting 4 (7%) 0 (0%) General Disorders and Administration Site Conditions Fatigue 2 (3%) 0 (0%) Edema peripheral 2 (3%) 0 (0%) Infections and Infestations Nasopharyngitis 5 (8%) 2 (7%) Peritonitis 3 (5%) 0 (0%) Sinusitis 2 (3%) 0 (0%) Urinary Tract Infection 2 (3%) 0 0%) Metabolism and Nutrition Disorders Fluid overload 3 (5%) 0 (0%) Hypoglycemia 2 (3%) 0 (0%) Nervous System Disorders Dizziness 4 (7%) 0 ( 0%) Headache 2 (3%) 0 (0%) Psychiatric Disorders Anxiety 2 (3%) 0 (0%) Insomnia 3 (5%) 0 (0%) Renal and Urinary Disorders Renal failure Chronic 2 (3%) 0 (0%) a. Includes only events more common in the Paricalcitol treatment group. Additional Adverse Reactions The following adverse reactions, occurred in <2% of the Paricalcitol Capsules- 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 Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (Paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

6.2 Postmarketing

Experience The following additional adverse reactions have been reported during post-approval use of Paricalcitol 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 casual relationship to drug exposure.

Immune System Disorders: Angioedema (including laryngeal edema) Investigations: Blood creatinine increased The most common adverse reactions (> 5% and more frequent than placebo) include diarrhea, nasopharyngitis, dizziness, vomiting, hypertension, hypersensitity, nausea, and edema. To report SUSPECTED ADVERSE REACTIONS, contact Marksans at 1-877-376-4271 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch