Overall, side effects occurred in 6% with ramelteon and 2% with placebo in clinical trials. Side effects leading to discontinuation occurred in 1% or fewer people. Rarely, anaphylactic reactions, abnormal thinking, and worsening of depression or suicidal thinking in patients with pre-existing depression may occur with ramelteon. Ramelteon has been found to slightly increase prolactin levels in women (+34% vs. –4% with placebo) but not in men and to decrease free testosterone levels (by 3–6% in younger men and by 13–18% in older men).Ramelteon has not been shown to produce dependence and has shown no potential for abuse. The withdrawal and rebound insomnia that is typical with GABAA receptor positive modulators like benzodiazepines and Z-drugs is not present in ramelteon.Increased incidence of liver and testicular tumors have been observed with ramelteon in rodents but only at doses equivalent to at least 20 times greater than the recommended dose in humans. Overdose
Ramelteon has been assessed at doses of up to 64 mg in clinical studies. Interactions
Ramelteon has been evaluated for potential drug interactions with the following medications and showed no significant effects: omeprazole, theophylline, dextromethorphan, and midazolam, digoxin and warfarin. There were no clinically meaningful effects when ramelteon was coadministered with any of these drugs.A drug interaction study showed that there were no clinically meaningful effects or an increase in adverse events when ramelteon and the SSRI Prozac (fluoxetine) were coadministered. When coadministered with ramelteon, fluvoxamine (strong CYP1A2 inhibitor) increased AUC approximately 190-fold, and the Cmax increased approximately 70-fold, compared to ramelteon administered alone.
This can affect both genders and includes a variety of manifestations of varying severity. Type 3: Autoimmune manifestations primarily limited to the GI tract. This can affect both genders and may also be considered IPEX-like. There is considerable overlap in these disorders, and it is often unclear how to properly distinguish between them as the responsible genes are generally poorly understood at this time. Treatment
Medical therapy is commonly used, most typically with corticosteroids (budesonide and prednisone). However, some patients are refractory to corticosteroids, and in these patients immunosuppressive therapy with azathioprine, cyclophosphamide, tacrolimus, cyclosporine and infliximab has been described. An intravenous nutrition such as total parenteral nutrition and/or a special diet may be necessary. Hematopoietic stem cell transplantation may be curative. References
Further reading
Montalto, Massimo; DOnofrio, Ferruccio; Santoro, Luca; Gallo, Antonella; Gasbarrini, Antonio; Gasbarrini, Giovanni (January 2009). "Autoimmune enteropathy in children and adults". Scandinavian Journal of Gastroenterology. 44 (9): 1029–1036. doi:10.1080/00365520902783691. PMID 19255930. S2CID 33004674. "Autoimmune Enteropathy". Cincinnati Childrens.