Safety update

Anthony Ormerod

Why is safety important?

• Clinical trial / European directive• MHRA / governance• Severe disease• Patients have large burden of co-morbidities• Patients with PG are more likely to die• Drugs used in therapy are toxic

Pragmatic trial

• Driven by clinical judgement• Would you normally be comfortable

Weight

• Ciclosporin 4mg/kg• Prednisolone 0.75mg/kg

• Since Sept 2011• Ceiling of 100kg• Maximum ciclosporin 400mg/d• Maximum prednisolone 75mg/ day

Neoral contra-indications

• Impaired renal function• Uncontrolled hypertension• Infection• Malignancy

SPC Neoral what’s new?

• Creatinine 2 weekly for first 3 months• Lipids before and at 1 month• Hepato-toxicity in transplants– Cholestasis – Jaundice– Hepatitis– Liver failure

Neoral Interactions• P glycoprotein PgP inhibited• Aliskiren levels increased• Myositis rhabdomyolysis with statins– Lovastatin– Simvastatin– Atorvastatin– Pravastatin– Fluvastatin– Reduce dose

• Digoxin (toxicity)• Colchicine (peripheral neuropathy, myositis)

Alisikiren??• The Medicines and Healthcare products Regulatory Agency (MHRA)

has recommended that doctors review the treatment of all patients taking aliskiren (Rasilez) for raised blood pressure. This advice follows the results of a study of diabetic patients taking both aliskiren and an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). With this combination the study showed patients were unlikely to benefit from aliskiren and also reported higher than expected incidence of non-fatal stroke, kidney complications, high blood potassium levels and low blood pressure. Doctors have been advised to review the treatment of all patients currently taking aliskiren. In particular, if patients are diabetic and also taking an ACE inhibitor or ARB, then their treatment with aliskiren should be stopped and alternative treatments considered.

Prednisolone• Abdominal distension• Acute pancreatitis• Dypepsia• Nausea• Increased appetite• Oesophageal candidiasis• Oesophageal ulceration• Peptic ulceration – perforation and haemorrhage

• Perforation of small bowel– Especially patients with inflammatory bowel disease

What to do

• Keep good records• Ask about adverse events• Is it related to intervention?• Is it severe?• Is it expected?• If related report Adverse Reactions• If severe (SAE) report in 24 hours of becoming

aware