What happens when a tablet turns yellow?

Tablet Discoloration to Yellow: Causes and Clinical Significance

Primary Concern: Drug Degradation and Loss of Potency

When a tablet turns yellow, it typically indicates chemical degradation through oxidation or hydrolysis, which can result in loss of therapeutic efficacy and potential formation of toxic degradation products. 1, 2

Mechanisms of Tablet Discoloration

Oxidative Degradation

• Air flow and oxygen exposure accelerate the yellowing process through oxidative degradation, even in light-shielded environments 1
• The discoloration manifests as intensification of yellowish or brownish color, characterized by increasing chroma values while hue angle remains relatively constant 2
• Oxidation occurs primarily on the tablet surface initially, creating heterogeneous discoloration patterns 1

Hydrolytic Degradation

• Moisture can trigger hydrolysis of active pharmaceutical ingredients, producing yellow-colored degradation products 1
• However, humidity alone may not be sufficient—oxidation appears to be the primary driver in most cases 1

Clinical Implications

Loss of Therapeutic Efficacy

• Discolored tablets should be discarded as they have likely lost potency 3
• The yellowing process correlates with chemical breakdown of the active ingredient, rendering the medication less effective or ineffective 1, 2

Specific Drug Examples

• Nitroglycerin tablets deteriorate within one week when carried in a pill box, and unused tablets should be discarded after 5 months even under optimal storage 3
• Furosemide tablets turn yellow through formation of hydrolysate degradation products when exposed to air flow 1

Storage Factors Accelerating Discoloration

Environmental Conditions

• Improper storage temperature increases degradation rates following Arrhenius kinetics 2
• Frequent bottle opening introduces oxygen and moisture, accelerating breakdown 3
• Air circulation from ventilation systems or blowers dramatically increases oxidative degradation 1

Packaging Issues

• Cotton, plastic, or paper stuffing in bottles reduces tablet stability considerably 3
• Loose caps or non-airtight containers allow continuous oxygen exposure 1, 3
• Transfer to pill boxes or non-original containers eliminates protective packaging 3

Patient Management Algorithm

Immediate Actions

1. Instruct patients to discard any yellowed tablets immediately 3
2. Obtain replacement medication from pharmacy with proper storage instructions 3
3. Review storage practices to prevent recurrence 3

Prevention Strategies

• Store tablets in original amber glass bottles with tightly sealed caps 3
• Keep bottles refrigerated when appropriate for the specific medication 3
• Minimize bottle opening frequency—remove only needed doses rather than handling entire supply 3
• Avoid transferring tablets to secondary containers for daily carrying 3
• Discard tablets after manufacturer-specified timeframes regardless of appearance 3

Patient Education Points

• Yellowing indicates the medication is no longer safe or effective to use 1, 2
• Visual inspection should be performed before each dose 2, 4
• Report discoloration to pharmacist or physician immediately 3
• Never use discolored tablets even if expiration date has not passed 1, 2

Common Pitfalls to Avoid

• Do not assume yellowing is merely cosmetic—it represents actual chemical degradation 1, 2
• Do not continue using tablets that show any color change from original white appearance 2, 4
• Avoid storing medications in bathrooms or other high-humidity environments 1
• Do not remove cotton or desiccant packets if originally included in packaging, but do not add cotton to bottles that did not originally contain it 3