7 Summary of the safety profile The safety of ziconotide administered as a continuous intrathecal infusion has been evaluated in more than 1,400 patients participating in acute and chronic pain clinical trials. The duration of treatment has ranged from one-hour bolus infusion to continuous use for more than 6 years.
The median exposure time was 43 days. 2 μg/day. In clinical trials, 88% of patients experienced adverse reactions. The most common adverse reactions reported in long-term clinical trials were dizziness (42%), nausea (30%), nystagmus (23%), confusional state (25%), gait abnormal (16%), memory impairment (13%), vision blurred (14%), headache (12%), asthenia (13%), vomiting (11%), and somnolence (10%).
Most adverse reactions were mild to moderate in severity and resolved over time. Tabulated list of adverse reactions Unless otherwise noted the table shows the incidence rates of adverse reactions reported in the intrathecal clinical trials with ziconotide (short- and long-term exposure).
Within each frequency grouping undesirable effects are presented in order of decreasing frequency. Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) System organ class Very common Common Uncommon Not known Infections and infestations sepsis, meningitis Immune system disorders anaphylactic reactiona Metabolism and nutrition disorders appetite decreased, anorexia Psychiatric disorders confusional state anxiety, auditory hallucination, insomnia, agitation, disorientation, hallucination, visual hallucination, depression, paranoia, irritability, depression aggravated, nervousness, affect lability, mental status changes, anxiety aggravated, confusion aggravated delirium, psychotic disorder, suicidal ideation, suicide attempt, thought blocking, abnormal dreams, aggressiveness 8 System organ class Very common Common Uncommon Not known Nervous system disorders dizziness, nystagmus, memory impairment, headache, somnolence dysarthria, amnesia, dysgeusia, tremor, balance impaired, ataxia, aphasia, burning sensation, sedation, paraesthesia, hypoaesthesia, disturbance in attenti on, speech disorder, areflexia, coordination abnorm al, dizziness postural, cognitive disorder, hyperaesthesia, hyporeflexia, ageusia, depressed level of consciousness, dysaesthesia, parosmia, mental impairment incoherence, loss of consciousness, coma, stupor, convulsions, cerebrovascular accident, encephalopathy Eye disorders vision blurred diplopia, visual disturbance, photophobia Ear and labyrinth disorders vertigo, tinnitus Cardiac disorders atrial fibrillation Vascular disorders orthostatic hypotensi on, hypotension Respiratory, thoracic and mediastinal disorders dyspnoea respiratory distress Gastrointestinal disorders nausea, vomiting diarrhoea, dry mouth, constipation, nausea aggravated, upper abdominal pain dyspepsia Skin and subcutaneous tissue disorders pruritus, sweating increased rash Musculoskeletal and connective tissue disorders pain in limb, myalgia, muscle spasms, muscle cramp, muscle weakness, arthralgia, peripheral swelling rhabdomyolysis, myositis, back pain, muscle twitching, neck pain 9 System organ class Very common Common Uncommon Not known Renal and urinary disorders urinary retention, urinary hesitation, dysuria, urinary incontinence acute renal failure General disorders and administration site conditions gait abnormal, asthenia fatigue, pyrexia, lethargy, oedema peripheral, rigors, fall, chest pain, feeling cold, pain, feeling jittery, pain exacerbated difficulty in walking Investigations blood creatine phosphokina se increased, weight decreased electrocardiogram abnormal, aspartate aminotransferase increased, blood creatine phosphokinase MM increased, body temperature increased a.
From spontaneous reporting Description of selected adverse reactions Meningitis Administration of medicinal products by the intrathecal route carries the risk of potential serious infections, such as meningitis, which may be life threatening.
4). Elevations of creatine phosphokinase Elevations in creatine phosphokinase were usually asymptomatic. Monitoring of creatine phosphokinase is recommended. 4). CNS adverse reactions Cognitive and neuropsychiatric adverse reactions are common in patients treated with ziconotide.
Cognitive impairment typically appears after several weeks of treatment. Episodes of acute psychiatric disturbances, such as hallucinations, paranoid reactions, hostility, aggressiveness, delirium, psychosis and manic reactions have been reported in patients treated with ziconotide.
The ziconotide dose should be reduced or discontinued if signs or symptoms of cognitive impairment or neuropsychiatric adverse reactions develop, but other contributing causes should also be considered. The cognitive effects of ziconotide are typically reversible within 1 - 4 weeks after discontinuation of the medicinal product, but may persist in some cases.
The available data do not exclude the possibility of an increased risk of suicide when using ziconotide. 3). 4). 10 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the […]