GLEOLAN SIDE EFFECTS

SIDE EFFECTS

Clinical Trial 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 observed in practice.

The safety of Gleolan is supported by data from 5 open label clinical studies, which included 527 patients with glioma who received ALA HCl. Adverse reactions that occurred in > 1% of patients in the week following surgery were pyrexia, hypotension, nausea, and vomiting. Adverse reactions occurring in the first 6 weeks after surgery in < 1% of patients were: chills, photosensitivity reaction, solar dermatitis, hypotension, abnormal liver function test, and diarrhea. One patient experienced respiratory failure due to drug overdose.

Neurologic Events

Nervous system disorders occurred in 29% of patients within the first week after surgery. Events occurring in > 1% of patients included aphasia (8%), hemiparesis (7.8%), hemianopsia (3.2%), headache (2.7%), seizure (1.9%), hemiplegia (1.9%), monoparesis (1.3%) and hypoesthesia (1.1%). Brain edema occurred in < 1 % of patients in the first 6 weeks after surgery. In a randomized clinical trial (Study 3), the numbers of serious neurologic adverse events in the post operative period were higher in patients randomized to ALA fluorescence arm compared to the control arm. An imbalance was notable for the adverse events aphasia, ataxia, convulsion and hemianopsia, and is likely related to the higher amount of brain resection performed in the ALA arm. At longer follow up periods, the numbers between the two arms appeared similar.

Elevated Liver Enzymes

Worsening of ≥ 2 Common Toxicity Criteria (CTC) grades in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) occurred in (15.8% and 11.6%, respectively) within the first week after surgery. Absolute levels ranged from 2 times to greater than 10 times the upper limit of normal (ULN) for each parameter. At 6 weeks, ALT remained elevated in 2.9% of patients (range 2 to greater than 5 × ULN), and GGT was elevated in 7.5% of patients (range 2 to greater than 10 × ULN). No cases of liver failure occurred.

Post Marketing Experience

The following adverse reactions are among those that have been identified during post-approval use of Gleolan outside of the United States. 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.

Immune Disorders: anaphylactic shock, angioedema, drug eruption, urticaria, erythema.

Metabolism and Nutrition Disorders: metabolic acidosis.

SRC: NLM .