6 ADVERSE REACTIONS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Hypercalcemia [see Warnings and Precautions (5.1)]
- Adynamic Bone Disease [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
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.
The safety of Paricalcitol Injection has been established from adequate and well-controlled studies of another paricalcitol injection product [see Clinical Studies (14)]. Below is a display of the adverse reactions of paricalcitol injection in these adequate and well-controlled studies.
Four placebo-controlled, double-blind, multicenter studies were conducted in 113 patients (51% male, 10% Caucasian, 81% African-American and 9% Hispanic, ranging in age from 18 to 90 years). Sixty-two patients were exposed to paricalcitol injection and the average dose at the end of treatment was 0.12 mcg/kg/dose with a mean number of 55 days of dosing across the studies. Discontinuation of therapy due to any adverse reaction occurred in 6.5% of patients treated with paricalcitol injection and 2.0% of patients treated with placebo. Adverse reactions occurring with greater frequency in the group treated with paricalcitol injection and at a frequency of 2% or greater are presented in Table 3.
| Adverse Reaction | Placebo (n = 51) % | Paricalcitol Injection (n = 62) % |
|---|---|---|
| Nausea | 8 | 13 |
| Vomiting | 6 | 8 |
| Edema | 0 | 7 |
| Gastrointestinal Hemorrhage | 2 | 5 |
| Chills | 2 | 5 |
| Pyrexia | 2 | 5 |
| Pneumonia | 0 | 5 |
| Sepsis | 2 | 5 |
| Influenza | 4 | 5 |
| Arthralgia | 4 | 5 |
| Palpitations | 0 | 3 |
| Dry Mouth | 2 | 3 |
| Malaise | 0 | 3 |
Other Adverse Reactions
The following adverse reactions occurred in less than 2% of the patients treated with paricalcitol injection in the above-mentioned studies and in additional double-blind, active-controlled and open-label studies:
Blood and Lymphatic System Disorders: Anemia, lymphadenopathy
Cardiac Disorders: Arrhythmia, atrial flutter, irregular heart rate, cardiac arrest, chest discomfort, chest pain, edema peripheral
Ear and Labyrinth Disorders: Ear discomfort
Endocrine Disorders: Hypoparathyroidism
Eye Disorders: Conjunctivitis, glaucoma, ocular hyperemia
Gastrointestinal Disorders: Abdominal discomfort, constipation, diarrhea, dysphagia, gastritis, intestinal ischemia, rectal hemorrhage
General Disorders: Asthenia, condition aggravated, fatigue, feeling abnormal, pain, swelling
Infections: Nasopharyngitis, upper respiratory tract infection, vaginal infection
Injection Site Reactions: Injection site extravasation, injection site pain
Laboratory Abnormalities: Hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, increased aspartate aminotransferase, prolonged bleeding time
Metabolism and Nutrition Disorders: Decreased appetite, thirst, decreased weight
Musculoskeletal and Connective Tissue Disorders: Joint stiffness, muscle twitching, myalgia
Neoplasms Benign, Malignant and Unspecified: Breast cancer
Nervous System Disorders: Cerebrovascular accident, dizziness, dysgeusia, headache, hypoesthesia, myoclonus, paresthesia, syncope, unresponsive to stimuli, gait disturbance
Psychiatric Disorders: Agitation, confusional state, delirium, insomnia, nervousness, restlessness
Reproductive System and Breast Disorders: Breast pain, erectile dysfunction
Respiratory, Thoracic and Mediastinal Disorders: Cough, dyspnea, orthopnea, pulmonary edema, wheezing
Skin and Subcutaneous Tissue Disorders: Alopecia, blister, hirsutism, night sweats, rash pruritic, pruritus, skin burning sensation
Vascular Disorders: Hypertension, hypotension
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of paricalcitol injection. 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.
Allergic reactions including rash, urticaria, and angioedema (including laryngeal edema) have been reported.