The Malaysian Health Authority-National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia released the following new drug safety alerts.
Proton pump inhibitors: Risk of microscopic colitis
Gabapentin is an anticonvulsant or anti epileptic drug which is used to prevent and control seizures along with other medications. It is also used to relieve nerve pain (neuropathic pain) following shingles (a painful rash due to herpes zoster infection) in adults. Gabapentin shows analgesic activities through interactions with descending pain inhibitory pathways in the spinal cord and at higher brain centres.
Dysphagia which is known as a difficulty in swallowing and could be a symptom for underlying disorder. The causes of dysphagia are medical illnesses of neurologic background such as Alzheimer’s disease, neuromuscular disorders or oesophagus obstruction and drug-induced dysphagia.
There are three major mechanisms involved in drug-induced dysphagia–
- Dysphagia identified as a adverse drug reaction of the medicine
- Dysphagia experienced by patient as a complication of the therapeutic action of medicine
- Dysphagia due to oesophageal injury included by medication.
The National Pharmaceutical Regulatory Agency (NPRA) has received information from the European Medicines Agency (EMA) regarding Pharmacovigilance Risk Assessment Committee’s (PRAC) recommendation to all product registration holders of gabapentin to update the package insert with risk of dysphagia.
Underlying mechanism:
Gabapentin molecule has the potential to cause difficulty in swallowing by its inhibitory action on the central nervous system (CNS) which may lead to decreased awareness and reduced control of the voluntary muscle involved in swallowing leading to difficulty in initiating a swallow.
Case reports of Gabapentin-Dysphagia
NPRA has received 377 case reports with 681 adverse events suspected to be related to gabapentin and there were no adverse events reported to local health authority related to dysphagia or difficulty swallowing.
Advice for Healthcare Professionals:
- Caution on symptoms of CNS depression: To advise patients (treated with gabapentin) and their care providers to monitor for sings of difficulty in swallowing.
- To reduce the risk of dysphagia: Suggest patient or patient’s caretaker to administer gabapentin drug in an upright position with adequate amounts of fluid, at least 30 minutes before sleeping.
NPRA has completed a review of this safety issue and Malaysian Drug Control Authority (DCA) has agreed to include dysphagia as adverse drug reaction in the postmarketing experience section of the package insert (product information document) of all gabapentin-containing products.
Proton pump inhibitors: Risk of microscopic colitis
Proton pump inhibitors (PPI) are the group class of medicines which reduce the gastric acid secretion by inhibiting the enzyme present at the stomach wall (responsible for stomach acid production). Some of examples of medicines coming under the class of PPI are pantoprazole, rabeprazole, omeprazole etc.,
PPIs are used widely in the treatment of gastro-oesophageal reflux (GERD), prophylaxis of gastrointestinal ulcer, eradication of infection caused by Helicobacter pylori. They are also used to combat the adverse drug reaction (excessive acid secretion) caused by pain medications, non-steroidal anti-inflammatory drugs (NSAIDs).
Microscopic colitis is the defined as the inflammation of colon (large intestine) that causes persistent watery and non-bloody diarrhoea. The colon tissue might appear normal with a colonoscopy or flexible sigmoidoscopy and inflammatory colon tissue is identifiable only by examining under a microscope (hence this disorder got the name ‘microscopic’)
Types of Microscopic colitis
- Collagenous colitis- colon tissue with a thick layer of protein (collagen).
- Lymphocytic colitis- colon tissue with increased lymphocytes (white blood cells).
- Incomplete microscopic colitis- colon tissue containing mixed features of collagenous and lymphocytic colitis.
The underlying parthenogenesis of PPI induced microscopic colitis is not well understood. However, there are many factors suspected to cause microscopic colitis, including drug consumption and there is consistent increase in the number of global ADR reports of microscopic colitis with PPI use.
Case reports at NPRA:
NPRA has received 30 case reports of diarrhoea associated with the use of PPIs, but not received any adverse drug reaction reports pertaining to microscopic colitis associated with the PPI use.
Microscopic colitis is considered as drug therapeutic class effect of PPI-class of drugs and NPRA has completed a review of this safety issue and Malaysian Drug Control Authority (DCA) has agreed to include microscopic colitis as adverse drug reaction in the postmarketing experience section of the package insert (product information document) of all drugs coming under PPI class.
Advice for Healthcare Professionals
- Caution: Diarrhoea is considered as one of the symptoms of microscopic colitis and all health care professionals are advise to be alert on identification of symptoms for microscopic colitis risk associated with the use of PPI.
- Discontinue: Stop the therapy with PPI class of drugs where appropriate and to avoid unnecessary treatment with PPIs to reduce the possible risk of microscopic colitis.
Health care professionals and consumers are advised to report any suspected adverse reactions or experienced with the use of gabapentin or Proton pump inhibitors (PPI) to the Malaysian health authority by online voluntary reporting facility through ADR web form. This will facilitate in accumulation of the more evident safety data which could expedite the regulatory actions by NPRA.