Zelnorm side effects of medication benefit and dosage by Ray Sahelian, M.D.
March 15 2016

Handb Clin Neurol. 2014. Commonly used gastrointestinal drugs. This chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threatening extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod Zelnorm have been grave enough to lead to their withdrawal from many world markets.

Zelnorm is a prescription medication used for the short-term treatment of women who have irritable bowel syndrome (IBS) with constipation (hard stools or difficulty passing stools) as their main bowel problem. IBS is a disorder that interferes with the normal functions of the large intestine (colon). Symptoms may include cramps, abdominal pain, bloating, constipation, and/or diarrhea. Zelnorm is made by the pharmaceutical giant Novartis. We understand Zelnorm has been taken off the market.

Beginning in April 2007, Swiss pharmaceutical maker Novartis AG stopped selling Zelnorm drug to relieve constipation after it was linked to higher chance of heart attack, stroke and worsening heart chest pain that can become a heart attack. Novartis agreed to withdraw Zelnorm at the FDA's request. Zelnorm, also called tegaserod maleate, is a prescription medication approved for short-term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 with chronic constipation. Doctors who prescribe Zelnorm should work with their patients and transition them to other therapies as appropriate.

Mechanism of action
Zelnorm increases the action of serotonin (a body chemical) in the intestines. This speeds the movement of stools (bowel movements) through the bowels. Zelnorm is used to treat severe, chronic, irritable bowel syndrome (IBS) in women who have constipation as their main bowel problem (constipation-predominant). Zelnorm has not been shown to be helpful for men with irritable bowel syndrome. Zelnorm works by increasing the movement of stools through the bowels. For those patients who are helped, Zelnorm reduces pain and discomfort in the abdominal area, bloating, and constipation. Zelnorm is not a cure for IBS and does not work for all women who use it. FDA does not have evidence that Zelnorm is effective in men with IBS.

 Aggarwal A1, Bhatt M2.Author informationAbstractThis chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threating extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod have been grave enough to lead to their withdrawal from many world markets. Awareness and recognition of the neurotoxicity of gastrointestinal drugs is essential to help weigh the benefit of their use against possible adverse effects, even if uncommon. Furthermore, as far as possible, drugs such as metoclopramide and others that can lead to tardive dyskinesias should be used for as short time as possible, with close clinical monitoring and patient education.

Questions
Q. I suffer from severe Irritable Bowel Syndrome that responds somewhat (although not completely satisfactory) to a serotonin mimetic called Zelnorm. Do you have any thoughts on taking a supplement of 5htp for boosting the serotonin in my GI tract?
     A. 5-HTP does convert to serotonin, but we don't have any experience using 5-Hydroxytryptophan for IBS.