AEMPS Guidance on Excipients in Medicines in Spain

1. Regulatory Framework

Excipients in medicines must be declared in accordance with EU legislation, primarily Directive 2001/83/EC as amended, and the Guideline on excipients in the labelling and package leaflet of medicinal products for human use (EMA/CHMP/302620/2017 Rev. 1). In Spain, these rules are enforced by the Spanish Agency for Medicines and Medical Devices (AEMPS).

AEMPS Excipientes de medicamentos

2. Mandatory Excipients with Recognized Effects

Certain excipients require specific warnings in the package leaflet (section 2) and labeling due to their potential to cause adverse reactions. The list includes:

• Alcohol (ethanol)
• Benzalkonium chloride
• Benzoic acid and benzoates
• Benzyl alcohol
• Butylated hydroxyanisole (BHA) / Butylated hydroxytoluene (BHT)
• Lactose
• Parahydroxybenzoates (parabens)
• Phosphates
• Potassium
• Propylene glycol
• Sodium
• Sorbitol
• Sulfites
• Wheat starch (gluten content)

Each has defined thresholds triggering declaration and specific warning texts.

AEMPS Excipientes de medicamentos

3. Declaration Requirements

• Quantitative declaration: Required when the amount exceeds a specified threshold (e.g., >1 mmol sodium per dose, >1 g lactose per dose).
• Qualitative declaration: Mandatory for excipients with known effects even below quantitative thresholds.
• Labeling: Warnings on the outer packaging must reference the package leaflet (e.g., “Contiene lactosa. Si su médico le ha indicado que padece una intolerancia a ciertos azúcares, consulte con él antes de tomar este medicamento.”).
• Package leaflet: Full details including warnings, especially for vulnerable populations (e.g., children, pregnant women, patients with specific intolerances).

AEMPS Excipientes de medicamentos

4. Special Cases

• Alcohol: Warning required if >0.5 g per dose.
• Sorbitol: Declaration and warning if >10 g per dose (may cause gastrointestinal effects).
• Sodium: Quantitative declaration if >1 mmol per dose; warning for low-sodium diets.
• Lactose: Warning for patients with rare hereditary problems of galactose intolerance.
• Parabens: Warning for possible allergic reactions.
• Sulfites: Warning if >10 mg/kg or per dose.

For parenteral, topical, and ophthalmic products, all excipients must be qualitatively declared.

AEMPS Excipientes de medicamentos

5. Implementation and Compliance

Marketing authorization holders must update labeling and leaflets during renewal or variation procedures to reflect current excipient guidelines. AEMPS monitors compliance through assessment of applications and post-authorization surveillance.

AEMPS Excipientes de medicamentos

6. Patient Safety Focus

Proper excipient declaration helps patients and healthcare professionals identify risks (e.g., allergies, intolerances) and supports safe use of medicines.

AEMPS Excipientes de medicamentos