"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates in clinical practice.
A total of 1254 adult patients received PRIALT as a continuous infusion in acute and severe chronic pain trials with an exposure of 662 patient-years. The mean duration of treatment was 193 days with 173 patients (14%) treated for at least 1 year. The average final dose was 17.6 mcg/day (0.73 mcg/hr).
The most frequently reported adverse reactions ( ≥ 25%) in clinical trials were dizziness, nausea, confusional state and nystagmus. Slower titration of PRIALT may result in fewer serious adverse reactions and discontinuation of PRIALT for adverse reactions [see Clinical Studies and DOSAGE AND ADMINISTRATION].
Adverse reactions during the slow titration placebo-controlled trial that occurred in 5% or greater of patients and more commonly with PRIALT than with placebo are summarized in Table 1.
Table 1: Incidence of Adverse Reactions in Slow
Titration Placebo-Controlled Trial by Percent (Events That Occurred in ≥ 5%
of Patients and More Commonly with PRIALT than with Placebo)
|MedDRA System Organ Class
MedDRA Preferred term
|Percentage of Patients|
|Ear and Labyrinth Disorders|
|General Disorders and Administration Site Conditions|
|Infections and Infestations|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|Pain in Limb||5||2|
|Nervous System Disorders|
|Renal and Urinary Disorders|
|Skin and Subcutaneous Disorders|
Other Adverse Reactions Observed During Clinical Studies Of PRIALT
The following adverse reactions assessed as related to PRIALT have been reported in 2% or greater of patients participating in the clinical studies:
EYE DISORDERS: diplopia, visual disturbance
GASTROINTESTINAL DISORDERS: abdominal pain, constipation, dry mouth, nausea aggravated
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: fall, fatigue, lethargy, edema peripheral
INVESTIGATIONS: blood creatine phosphokinase increased
METABOLISM AND NUTRITION DISORDERS: appetite decreased
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: muscle cramp, muscle weakness, myalgia, pain in limb
NERVOUS SYSTEM DISORDERS: aphasia, areflexia, balance impaired, burning sensation, coordination abnormal, disturbance in attention, dizziness postural, dysarthria, dysgeusia, hypoaesthesia, mental impairment, paraesthesia, sedation, speech disorder
PSYCHIATRIC DISORDERS: agitation, anxiety, cognitive disorder, confusional state, depression, depression aggravated, disorientation, hallucination, hallucination auditory, hallucination visual, insomnia, irritability, mood disorder, nervousness, paranoia
RENAL AND URINARY DISORDERS: dysuria, urinary hesitation
VASCULAR DISORDERS: hypotension, orthostatic hypotension.
The following medically important adverse reactions occurred in less than 2% of patients were assessed by the clinical investigators as related to PRIALT: acute renal failure, atrial fibrillation, cerebrovascular accident, sepsis, meningitis, psychotic disorder, suicidal ideation, respiratory distress, rhabdomyolysis, electrocardiogram abnormal, stupor, loss of consciousness, clonic convulsion and grand mal convulsion. Fatal aspiration pneumonia and suicide attempt were reported in less than 1% of patients.
The following adverse events have been reported during post-approval use of PRIALT. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypersensitivity reactions including angioedema, serious skin reactions including bullous dermatitis, skin ulcers, skin exfoliation, and burning skin sensation.
Read the Prialt (ziconotide) Side Effects Center for a complete guide to possible side effects
Formal PK drug-drug interaction studies have not been performed with PRIALT. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, intrathecal administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Further, as ziconotide is not highly bound in plasma (approximately 50%) and has low plasma exposure following intrathecal administration, clinically relevant plasma protein displacement reactions involving ziconotide and co-administered medications are unlikely.
Over 90% of patients treated with intrathecal PRIALT used systemic opiates and in the slow titration study, 98% of patients received opioids.
The combination of PRIALT with intrathecal opiates has not been studied in placebo-controlled clinical trials and is not recommended.
Interaction With CNS Depressants
Almost all patients in the PRIALT clinical trials received concomitant non-intrathecal medication. Most patients received several concomitant drugs, including antidepressants (66%), anxiolytics (52%), antiepileptics (47%), neuroleptics (46%), and sedatives (34%). The use of drugs with CNS-depressant activities may be associated with an increased incidence of CNS adverse reactions such as dizziness and confusion [see WARNINGS AND PRECAUTIONS].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/5/2016
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