 - Relevant history or presence of pulmonary disorders especially COPD, cardiovascular disorders, neurological disorders especially seizures and migraine, psychiatric disorders, gastro-intestinal disorders, renal disorders renal failure determined as an estimated Glomerular Filtration Rate eGFR below 50 mlmin MDRD-based, hepatic disorders Child-Pugh B or C, hormonal disorders especially diabetes mellitus, coagulation disorders. 