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Published: June 2006

Watching Briefs - June 2006

Prescriber Update 27(1): 2-3.
June 2006

Medsafe Pharmacovigilance Team

SSRI-TCA interactions and serotonin syndrome
Colchicine – safe use is critical
Nitrofurantoin – monitor lung function in long-term use
Proton pump inhibitors and interstitial nephritis

SSRI-TCA interactions and serotonin syndrome

Prescribers are reminded of the potential for interactions to occur when a selective serotonin reuptake inhibitor (SSRI) antidepressant is co-prescribed with a tricyclic antidepressant (TCA).  Concurrent use of SSRIs can elevate TCA plasma levels 2-4 fold, with resultant toxicity. Reported symptoms include constipation, urinary hesitancy, seizures and delirium.1  Serotonin syndrome is another potential consequence of concurrent therapy.  While TCAs and SSRIs can separately cause serotonin syndrome due to their serotonergic properties, this risk is increased when they are used together.  Serotonin syndrome is a dose-dependent toxic state caused by excess serotonin within the CNS and is characterised by mental, autonomic and neuromuscular changes.  Clinical features include confusion, agitation, hyperactivity, sweating, tachycardia, ataxia, hypertonia and tremor.  Prompt withdrawal of the suspect medicines and supportive care are key to the treatment of serotonin syndrome.2

The long half-life of fluoxetine in particular (7-15 days) means that the potential for interactions can persist for days or weeks after withdrawal of this antidepressant.  The mechanism for the increased TCA plasma levels involves SSRI inhibition of cytochrome P450 isoenzyme CYP2D6, which results in decreased TCA metabolism with resultant TCA accumulation.  Should the decision be made to concurrently prescribe an SSRI and TCA, it is recommended that the dose of TCA be decreased and that the patient be closely monitored for signs of TCA toxicity and serotonin syndrome.1  Patients should also be informed about these possible drug interactions and the warning symptoms to look out for.

References
  1. Tricyclics, SSRIs and antidepressants.  In Stockley IH (Ed) Stockley's Drug Interactions 6th Edn. 2003: Great Britain, p.845-850.
  2. Hall M, Buckley N.  Serotonin Syndrome.  Australian Prescriber 2003;26(3):62-63.

Colchicine – safe use is critical

Colchicine in overdose is extremely toxic and has resulted in fatalities.  Prescribers are reminded that colchicine is now indicated as second-line therapy in the treatment of acute gout, after non-steroidal anti-inflammatory drugs.  Corticosteroids are recommended where both are contraindicated.1

Due to the risk of dose-related serious adverse effects, the use of high doses of colchicine to treat acute gout is no longer appropriate, especially in elderly patients, patients with impaired hepatic or renal function, and patients who weigh less than 50kg.  The dosing interval for colchicine has been increased from 2-3 hourly to six hourly.  For otherwise healthy adults the maximum dose of colchicine in the first 24 hours is 2.5mg and the total dose given in an acute attack should not exceed 6mg over four days.  Furthermore, it is no longer considered safe or appropriate to continue dosing until gastrointestinal adverse effects occur.1

Prescribers should be aware that patients might still have supplies of colchicine at home with previous dosage advice, including instructions to continue dosing until diarrhoea occurs.  Prescribers need to inform patients of the revised dosage advice for colchicine, and stress the importance of not exceeding the lowered maximum doses.  Clear dosage advice (including the maximum daily and cumulative doses) should be written on the prescription so that this information can be included on the pharmacy label that is read by the patient.  Patients should be warned of the symptoms of colchicine toxicity and advised to immediately discontinue therapy and see their doctor if symptoms occur.

Reference
  1. Medsafe Pharmacovigilance Team.  Colchicine: Lower doses for greater safety.  Prescriber Update 2005;26(2):26-27. www.medsafe.govt.nz/profs/PUArticles/colchdose.htm

Nitrofurantoin – monitor lung function in long-term use

Information on this subject has been updated. Read the most recent information.

An earlier Prescriber Update article reported a case of fatal interstitial lung disease resulting from long-term nitrofurantoin therapy.1  CARM continues to receive reports of acute and chronic pulmonary adverse reactions associated with nitrofurantoin.  Acute pulmonary reactions typically have hypersensitivity-type features and occur 1-2 weeks after initiation of nitrofurantoin.  Chronic pulmonary reactions mainly involve older persons, are often insidious in onset and associated with therapy of six months or longer.  Interstitial lung disease and pulmonary fibrosis may develop so it is important to avoid any delay in the recognition of nitrofurantoin-induced lung changes.

The pulmonary function of patients undergoing prolonged nitrofurantoin therapy should be monitored.  This involves careful vigilance for early features of emerging pulmonary toxicity, which may be evidenced by cough or shortness of breath, indicating the need for prompt withdrawal and further investigation including chest x-ray and spirometry.  Patients should be informed of the warning symptoms and encouraged to report these early.  Patients who have experienced pulmonary toxicity with nitrofurantoin should not be re-exposed.

Reference
  1. Tatley M.  Pulmonary reactions with nitrofurantoin.  Prescriber Update 2002;23(2):24-25. www.medsafe.govt.nz/profs/PUarticles/nitrofurant.htm

Proton pump inhibitors and interstitial nephritis

Acute renal impairment caused by interstitial nephritis is a recognised complication of treatment with omeprazole.  Presenting symptoms may be non-specific and include malaise, fever, nausea, lethargy, weight loss, rash and eosinophilia.  Patients known to be taking omeprazole who exhibit these symptoms should undergo urine microscopy and assessment of renal function.  If either or both are abnormal, omeprazole should be withdrawn pending nephrology assessment.1  Interstitial nephritis should also be considered if there is an unexpected rise in serum creatinine.

Since publishing information about omeprazole-induced interstitial nephritis in 2000,1 there have been 21 further cases reported to CARM; nine were reported in 2005 alone.  Interstitial nephritis has also been reported with pantoprazole2 and lansoprazole3; CARM has received three such reports for pantoprazole.  This reaction is thought to be rare but proton pump inhibitors are now believed to be the commonest cause of interstitial nephritis in the Auckland region, perhaps due to their widespread use.4  This suggests that prescribers should be vigilant for this adverse reaction when using omeprazole or other proton pump inhibitors.

References
  1. Savage R.  Omeprazole-induced interstitial nephritis.  Prescriber Update 2001;No.20(Feb):11-13. www.medsafe.govt.nz/profs/PUarticles/omeprazole.htm
  2. Pfizer New Zealand Ltd.  Somac (pantoprazole) tablets data sheet 4 April 2005.  www.medsafe.govt.nz/profs/Datasheet/s/somacHeartBurnRelieftab.pdf
  3. Wyeth (NZ) Limited.  Zoton (lansoprazole) capsules data sheet 17 May 2002.
  4. Simpson IJ, Marshall MR, Pilmore H, et al.  Proton pump inhibitors and acute interstitial nephritis – report and analysis of 15 cases.  Nephrology (In Press).

 

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