At doses above 50 mg, reversible neutropenias and thrombocytopenias were observed, and particularly evident in heavily pretreated patients. These side-effects are shared by most chemotherapies, including alkylating agents in general. Drug interactions
No drug interaction studies have been reported. Several in vitro studies indicate that melphalan flufenamide may be successfully combined with standard chemotherapy or targeted agents. Therapeutic efficacy
In a Phase 1/2 trial, in solid tumor patients refractory to standard therapy, response evaluation showed disease stabilization in a majority of patients. In relapsed and refractory multiple-myeloma (RRMM) patients, promising activity was seen in heavily pre-treated RRMM patients where conventional therapies had failed; the median Progression-Free Survival was 9.4 months and the Duration of Response was 9.6 months. An overall response rate of 41% and a clinical benefit rate of 56% were also shown, with similar results seen across patient populations regardless of their refractory status. Hematologic toxicity was common, but manageable with cycle prolongations, dose modifications and supportive therapy, and non-hematologic treatment-related adverse events were infrequent. History
Efficacy was evaluated in HORIZON (NCT02963493), a multicenter, single-arm trial. Eligible patients were required to have relapsed refractory multiple myeloma. Patients received melphalan flufenamide 40 mg intravenously on day 1 and dexamethasone 40 mg orally (20 mg for patients ≥75 years of age) on day 1, 8, 15 and 22 of each 28-day cycle until disease progression or unacceptable toxicity.
For long-term treatment, the drug is also contraindicated in people with peptic ulcers, severe osteoporosis, severe myopathy, certain viral infections, glaucoma, and metastasizing tumours.There are no contraindications for use in emergency medicine. Side effects
Side effects of triamcinolone are similar to other corticoids. In short-term treatment up to ten days, it has very few adverse effects; however, sometimes gastrointestinal bleeding is seen, as well as acute infections (mainly viral) and impaired glucose tolerance.Side effects of triamcinolone long-term treatment may include coughing (up to bronchospasms), sinusitis, metabolic syndrome–like symptoms such as high blood sugar and cholesterol, weight gain due to water retention, and electrolyte imbalance, as well as cataract, thrush, osteoporosis, reduced muscle mass, and psychosis. Triamcinolone injections can cause bruising and joint swelling. Symptoms of an allergic reaction include rash, itch, swelling, severe dizziness, trouble breathing, and anaphylaxis. Overdose
No acute overdosing of triamcinolone has been described. Interactions
Drug interactions are mainly pharmacodynamic, that is, they result from other drugs either adding to triamcinolones corticoid side effects or working against its desired effects. They include:
Atropine and other anticholinergics can substantially increase pressure in the eyes. Antidiabetic drugs can become less effective because triamcinolone causes diabetes-like symptoms. Aspirin and other NSAIDs, as well as anticoagulants such as warfarin, add to the risk of gastrointestinal bleeding. Diuretics that excrete potassium (such as loop diuretics and thiazides) can increase the risk of hypokalemia and thus lead to abnormal heart rhythm. Cardiac glycosides may have more adverse effects due to reduced potassium levels in the blood.