Published: 1 September 2022

Publications

Gathering knowledge from adverse reaction reports: September 2022

Prescriber Update 43(3): 43–45
September 2022

Adverse reaction reporting is an important component of medicine safety monitoring. Case reports can highlight significant safety issues concerning therapeutic products and their use.

The table below presents a selection of recent informative cases from the Centre for Adverse Reactions Monitoring (CARM) database.

Case detailsa,b	Reaction description and data sheet informationb,c
CARM ID: 139501 Age: 77 Gender: Male Medicine(s): Finasteride Reaction(s): Breast cancer male	A patient taking long-term finasteride was diagnosed with male breast cancer.
	The Ricit data sheet states that a small number of cases of male breast cancer have been seen in clinical trials and in the post-market setting, but a causal relationship has not been established. The data sheet also states that physicians should counsel patients to report any breast changes or symptoms during treatment.
CARM ID: 140096 Age: 8 Gender: Male Medicine(s): Montelukast Reaction(s): Epistaxis	The patient experienced epistaxis within hours of commencing montelukast. He had no previous history of nosebleeds.
	Increased bleeding tendency (rare) and epistaxis (uncommon) are listed as adverse reactions in the Montelukast Mylan data sheet.
CARM ID: 143342 Age: 73 Gender: not reported Medicine(s): Tolvaptan Reaction(s): Hepatorenal syndrome, hepatic failure, encephalopathy	Two months after starting tolvaptan, the patient developed mild hepatic impairment. This worsened to severe impairment and tolvaptan was stopped. The patient subsequently developed liver failure, hepato-renal syndrome and hepatic encephalopathy.
	Section 4.4 of the Jinarc data sheet provides detailed safety measures to mitigate the risk of significant and irreversible liver injury. This includes blood testing for hepatic transaminases and bilirubin before initiating treatment and regularly throughout treatment. Monitoring for symptoms of liver injury is also recommended. Treatment must be interrupted at the onset of symptoms or signs consistent with liver injury and may need to be permanently discontinued.
CARM ID: 143508 Age: 66 Gender: Female Medicine(s): Clozapine, codeine phosphate, oxybutynin Reaction(s): Constipation, megacolon	A patient taking long-term clozapine was prescribed oxybutynin and codeine. She was admitted to hospital with a severe bowel obstruction.
	The Clopine and Clozaril data sheets state that clozapine has been associated with varying degrees of impairment of intestinal peristalsis, ranging from constipation to intestinal obstruction, faecal impaction, paralytic ileus, megacolon and intestinal infarction/ischaemia. Particular care is necessary in patients who are receiving concomitant medicines known to cause constipation. Constipation is described as a common side effect in the Codeine phosphate PSM data sheet. There are no approved oxybutynin products in New Zealand. However, the New Zealand Formulary monograph for oxybutynin lists constipation as an adverse effect.
CARM ID: 143793 Age: 61 Gender: Female Medicine(s): Amitriptyline Reaction(s): Blindness, glaucoma	The patient was prescribed daily amitriptyline for an unapproved use. Approximately a year later, she developed acute angle glaucoma in one eye that progressed to permanent blindness.
	Acute glaucoma is listed as a very rare ADR in the Arrow-Amitriptyline data sheet.
CARM ID: 144121 Age: 89 Gender: Female Medicine(s): Nirmatrelvir + ritonavir, felodipine, donepezil, candesartan Reaction(s): Drug interaction, syncope, hypotension, bradycardia	A patient with severe renal impairment was prescribed a full dose of Paxlovid. Concomitant medicines included felodipine, donepezil and candesartan. On day 4 of Paxlovid treatment, she experienced collapse, hypotension and bradycardia. An interaction with felodipine was suspected.
	The Paxlovid data sheet states that the appropriate dose for patients with severe renal impairment has not been determined and it is contraindicated in these patients. Paxlovid inhibits CYP3A and may increase plasma concentrations of medicines that are primarily metabolised by CYP3A. Caution is warranted when Paxlovid is co-administered with calcium channel blockers, including felodipine. Clinical monitoring of patients is recommended, and a dose decrease of the calcium channel blocker may be needed. The Felo ER data sheet states that felodipine is metabolised by CYP3A4. Concomitant administration of medicines which interfere with CYP3A4 may affect plasma concentrations of felodipine.

Notes:

1. Only the medicines suspected to have caused the reaction are listed in the table.
2. The reactions listed in the ‘Case details’ column are coded according to the Medical Dictionary for Regulatory Activities (MedDRA), an internationally used set of standardised terms relating to medical conditions, medicines and medical devices. The reactions listed in the ‘Reaction description’ column are based on what was reported to CARM, and do not always match the MedDRA term.
3. If the suspect medicine’s brand name is not described in the report to CARM, only the data sheet for the funded medicine is included in the table.

Information about suspected adverse reactions reported to CARM is available on the Medsafe website using the Suspected Medicines Adverse Reaction Search (SMARS).

By selecting the ingredient of a medicine, you can find out:

• the number of reports and suspected adverse reactions for that ingredient. The suspected reactions are grouped by body system or organs (Summary report)
• single case reports, listing the medicines involved that contain the ingredient and the suspected adverse reactions (Detail report).