Background Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine. Aims To document the incidence of potentially harmful CIGH in the UK. Method We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992–2017. Results There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died. Deaths averaged 1 per year 1992–1999, 5 per year 2000–2009 and 15 per year 2010–2017. Those who died were older (median 52 years v. 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years v. 4.8 years), but there was no difference in prescribed dose. Within the first 4 years of clozapine treatment, there were 169 reports of CIGH, of which 3% (n = 5) were fatal. At 10–14 years there were 63 reports of CIGH, of which 25% (n = 16) were fatal. Among the deaths, males were younger (median 51, range 22–89 v. median 57, range 24–89 years) with higher clozapine doses (median 450, range 100–900 v. median 300, range 12.5–800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (n = 92). The procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma and proctosigmoidectomy. Clozapine dosage was reduced in 6 patients, stopped and restarted in 23, ‘continued’ in 6 and discontinued permanently in at least 76 patients. Conclusions The risk of serious morbidity/mortality from CIGH is substantial. The need to actively monitor bowel function and give laxatives to patients treated with clozapine is clear.

Novel herbal drug delivery system opens new vistas for delivery of herbal drugs at right place, at right concentration, for right period of time and also gives scientific angle to verify the standardization of herbal drug. Herbal Transdermal patches can develop valuable assessment and drug safety by additional site specific the way and temporal position in the body’s imperative to reduce the number and size of doses required to achieve the objective of systemic medication during topical application to the intact skin surface. Rheumatoid Arthritis (RA) is a chronic, progressive autoimmune disease of unknown cause. It is characterized by persistent inflammation that primarily affects the peripheral joints. In the present study, herbal transdermal patch was developed by using ethanolic extract of leaves of Cardiospermum halicacabum and rhizomes of Drynaria quercifolia that had already been widely used for the treatment of arthritis in conventional dosage forms. Evaluation of the developed patch for the effectiveness against RA was done by in vitro methods in terms of inhibition of albumin denaturation, measurement of Interleukin-6 cytokines by Enzyme-Linked Immuno Assay (ELISA). IC-50 value was determined from albumin denaturation inhibition assay. The herbal patch significantly and dosedependently inhibited Interleukin–6 cytokines. The present study revealed that the formulated polyherbal Transdermal patch will be the better drug of choice for the treatment of Rheumatoid Arthritis as compared to the conventional dosage forms.