Can Nurofen Plus (ibuprofen and codeine) be used with sertraline?

Can Nurofen Plus Be Used With Sertraline?

Nurofen Plus (ibuprofen 200mg + codeine 12.8mg) can be used with sertraline, but requires caution due to two distinct safety concerns: increased bleeding risk from the ibuprofen-sertraline combination and reduced codeine efficacy due to sertraline's CYP2D6 inhibition. 1, 2

Critical Safety Considerations

Bleeding Risk (Most Clinically Significant)

• The combination of sertraline (an SSRI) with ibuprofen (an NSAID) significantly increases the risk of gastrointestinal bleeding through additive antiplatelet effects 2, 3
• Patients should be cautioned about concomitant use of sertraline and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation, as combined use has been associated with increased bleeding risk 2
• This interaction is well-documented across multiple SSRIs and NSAIDs, with evidence from both controlled trials and case reports 3

Reduced Codeine Efficacy

• Sertraline is a moderate inhibitor of CYP2D6, which can reduce codeine's conversion to morphine and thereby decrease its analgesic effectiveness 1, 4
• Codeine requires metabolism by CYP2D6 to morphine to exert its pain-relieving effect, and this metabolic pathway is impaired by sertraline 1, 4
• Clinical studies confirm that antidepressants with moderate-to-strong CYP2D6 inhibition should be avoided in patients receiving codeine for optimal pain control 4

Absolute Contraindications (Not Applicable Here)

• Codeine is absolutely contraindicated with MAOIs (phenelzine, tranylcypromine, selegiline, linezolid) due to risk of serotonin syndrome and hypertensive crisis, but sertraline is an SSRI, not an MAOI 1
• A 2-week washout period is required when switching between MAOIs and other medications 1

Clinical Management Algorithm

If the patient requires both medications:

1. Monitor closely for bleeding signs (bruising, nosebleeds, gastrointestinal bleeding, prolonged bleeding from cuts) 2

2. Consider gastroprotection with a proton pump inhibitor to reduce NSAID-induced gastrointestinal adverse effects 5

3. Anticipate reduced pain relief from the codeine component and be prepared to adjust pain management strategy 1, 4

4. Limit duration of concurrent use to the shortest period necessary, as chronic use increases interaction risks 3

Alternative approaches to consider:

• For pain management: Consider acetaminophen-based analgesics instead of ibuprofen-codeine combinations, as acetaminophen does not increase bleeding risk with SSRIs 5

• For antidepressant therapy: Escitalopram has minimal effects on CYP450 enzymes and lower propensity for drug interactions, making it a safer option if codeine therapy is essential 1

• For combination therapy: If both NSAID and opioid analgesia are needed, consider using them separately rather than in fixed combination to allow dose optimization 6, 7

Additional Safety Points

• The ibuprofen-codeine combination itself is pharmacokinetically compatible with no interaction between the two components 8
• Both drugs have similar half-lives (2-2.5 hours), making them suitable for fixed combination formulations 8
• The analgesic efficacy of ibuprofen 400mg + codeine 60mg is superior to either component alone, particularly in the first few hours after administration 7
• Short-term use (≤12 weeks) of combination analgesics carries lower risk than chronic use 3