Baclofen has been shown to have general CNS depressant properties, causing sedation, somnolence, and respiratory and cardiovascular depression.
The most commonly reported adverse events with LIORESAL Intrathecal (baclofen injection) in clinical trials were drowsiness, weakness in the lower extremities, dizziness and seizures.
Adverse drug reactions from clinical trials are listed in the table below according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked under headings of frequency, the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category using the following convention (CIOMS III) is also provided for each adverse drug reaction: very common ( ≥ 1/10); common ( ≥ 1/100, < 1/10); uncommon ( ≥ 1/1,000, < 1/100); rare ( ≥ 1/10,000, < 1/1,000); very rare ( < 1/10,000), including isolated reports.
Adverse events associated with the delivery system (e.g. mass at the tip of the catheter, catheter dislocation with possible complications, pocket infection, meningitis, overdose due to wrong manipulation of the device) have been reported, whereby in some cases a causal relationship with baclofen cannot be excluded (see WARNINGS). These are in addition to those listed below. In a fatal case of a child (causality with baclofen uncertain), inflammatory signs in the posterior horns and signs of arachnoiditis in proximity of the catheter tip were observed. This corresponds to observations in dogs, where chronic inflammatory reactions to the foreign body of the catheter were observed, independently of baclofen concentration.
Incidence of Most Frequent Adverse Events in US Clinical Trials
| Adverse Event | Number of patients reporting events (%) | ||
| Screening (N= 244) |
Titration (N= 214) |
Maintenance (N=214) |
|
| Somnolence | 13 (5.3%) | 11(5.1%) | 18 (8.4%) |
| Weakness, Lower Extremities | 1 (0.4%) | 11(5.1%) | 15 (7.0%) |
| Dizziness | 6 (2.4%) | 5 (2.3%) | 12(5.6%) |
| Convulsion | 1 (0.4%) | 4 (1.9%) | 11 (5.1%) |
| Headache | 0 (0%) | 3 (1.4%) | 9 (4.2%) |
| Nausea/Vomiting | 3 (1.2%) | 5 (2.3%) | 3 (1.4%) |
| Numbness/Itching/Tingling | 2 (0.8%) | 1 (0.5%) | 8 (3.7%) |
| Hypotension | 3 (1.2%) | 0 (0%) | 5 (2.3%) |
| Vision Blurred | 0 (0%) | 2 (0.9%) | 5 (2.3%) |
| Constipation | 0 (0%) | 2 (0.9%) | 5 (2.3%) |
| Hypotonia | 2 (0.8%) | 3 (1.4%) | 2 (0.9%) |
| Dysarthria | 0 (0%) | 1 (0.5%) | 6 (2.8%) |
| Coma (Overdose) | 0 (0%) | 4 (1.9%) | 3 (1.4%) |
| Lethargy | 1 (0.4%) | 0 (0%) | 4 (1.9%) |
| Weakness, Upper Extremities | 1 (0.4%) | 0 (0%) | 4 (1.9%) |
| Hypertension | 1 (0.4%) | 2 (0.9%) | 2 (0.9%) |
| Dyspnea | 1 (0.4%) | 2 (0.9%) | 1 (0.5%) |
In addition to the more common adverse events reported above, the following adverse events were observed during clinical trials elsewhere or reported by clinicians.
Metabolism and nutritional disorders
Uncommon: Dehydration, weight loss, albuminuria and hyperglycemia
Psychiatric disorders
Common: Depression, anxiety, agitation
Uncommon: Suicide ideation and suicide attempt, hallucinations, paranoia, euphoric mood
Nervous system disorders
Common: Confusional state, disorientation, insomnia, sedation, paresthesia, fatigue, lethargy
Uncommon: nystagmus, ataxia, memory impairment.
Eye disorders
Common: Accommodation disorder, diplopia
Cardiac disorders
Uncommon: Bradycardia
Rare: pulmonary embolism.
Vascular disorders
Uncommon: Deep vein thrombosis, flushing, pallor
Gastrointestinal disorders
Common: Dry mouth, diarrhea, decreased appetite, increased salivation
Uncommon: Ileus, hypogeusia, dysphagia
Respiratory, thoracic and mediastinal disorders
Common: Respiratory depression, pneumonia,
Renal and urinary disorders
Common: urinary incontinence, urinary retention.
Reproduction system and breast disorders
Common: Sexual dysfunction
Skin and subcutaneous tissue disorders
Common: Urticaria, pruritus, facial and/or peripheral edema
Uncommon: Alopecia, hyperhidrosis
Musculoskeletal and connective tissue disorders
Common: Hypertonia
General disorders and administration site conditions
Common: Asthenia, pyrexia, chills, pain
Uncommon: Hypothermia
Adverse Drug Reactions From Spontaneous Reports And Literature Cases (frequency not known)
The following adverse drug reactions have been derived from post-marketing experience with LIORESAL Intrathecal via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.
Nervous system disorders: dysphoria
Respiratory, thoracic and mediastinal disorders: bradypnea