الدليل الإرشادي لمستحضرات الباراسيتامول السائلة للأطفال

​1.1.          Objective

The Drug Sector in Saudi Food & Drug Authority (SFDA) has developed this document to promote safer use of products containing paracetamol in pediatric under 12 years old by minimizing the potential of paracetamol overdosing and toxicity due to medication errors or accidental ingestion.

1.2.          Background

          Paracetamol is one of the most frequently administered medication to pediatrics worldwide. The current dosing instruction of registered paracetamol label mostly based on age not weight, which are imprecise and may result in inaccurate dosing due to marked variations in the weight of children of the same age. In 2015, a committee of experts led by SFDA has met to review the appropriate dosage labelling of paracetamol in children and infants.

The SFDA committee concluded a number of recommendations including:

Due to availability of different doses for the same child's age/weight, corrective action should be taken for paracetamol dosage labelling, based on child's weight to avoid sub-therapeutic dosing.

Ensuring the availability of a precise measuring device packaged within all marketed products.

Investigate dosage labelling for all paracetamol products that available in the market.

1.3.          Scope

To provide applicants with guidance on the requirements necessary to receive marketing authorization for over the counter (OTC) oral liquid dosage forms containing paracetamol apply to both single-ingredient and combination-ingredient products for pediatric under 12 years of age.

1.4.          Related Guidelines

- This document should be read in conjunction with the following documents:

         - The GCC Guidance for presenting the SPC, PIL and Labeling Information.

        - Guidance for Graphic Design of Medication Packaging.

In Saudi Arabia, paracetamol is available in several dosage forms and concentrations including:

2.1. Strengths  

• - Paracetamol 120mg/5mL

• - Paracetamol 125mg/5mL

• - Paracetamol 100mg/mL

• - Paracetamol 160mg/5mL

2.2. Pharmaceutical Forms

Oral liquid formulation such as solutions, suspensions, syrup, drops and elixir.​

3.1. Patient Information Leaflet (PIL)

In addition to the GCC Guidance for presenting the SPC, PIL and Labeling Information and the guidance for Graphic Design of Medication Packaging, the followings are special considerations for products containing paracetamol as OTC Products:

3.1.1.      Therapeutic Indications  

To relieve mild to moderate pain and to reduce fever in many conditions including headache, toothache, teething, feverishness, colds, influenza, and following vaccination.

3.1.2.      Dosage Direction for Children Under 12 Years

The dose should be weight-related dosing in the label instructions. If the weight of the child is unknown, the age related dosing is provided (See table 1 and 2).

 Table 1: Dosage for children under 12 years of age: 25 mg/mL; 24 mg/mL; 32 mg/mL paracetamol

To minimize dosing errors, paracetamol oral drops solution of 100 mg/mL concentration should not be concurrently labeled for both infants (under 2 years) and children (of 2 years and older). Thus, clear statement of “this product for infants under 2 years" should be available.

Table 2: Dosage of children under 2 years,: 100 mg/mL Paracetamol oral drops​

3.1.3.      Special considerations

The patient information leaflet should include the following:

• The recommended single dose and maximum daily dose in mL, as well as the dosing interval for the product. Maximum daily dose may be expressed as: “Do not take more than x mL or x doses in 24 hours".

• “Seek medical advice before giving to preterm neonate or term neonates <10 days".

• “Repeat 4 – 6 hourly up to 5 times per day if required. No more than 5 doses in any 24-hour period, unless directed by phyisician".

• For 25 mg/mL; 24 mg/mL; 32 mg/mL: “Should not be used for more than 5 days for children ≥2 years and 3 days for infants (<2 years) except on medical advice."

• For 100mg/mL: “Should not be used for more than 3 days at a time except on medical advice."

• “Should not be used with other paracetamol-containing products."

• Instructions specific for oral liquid dosage form, i.e. should not include all dosage forms of paracetamol in one PIL such as (tablet or suppositories,).

3.1.4.      Warnings

• Under section 2 “Before you take or use the product": Liver warning: (should be bold font type): “This product contains paracetamol. Maximum daily dose is (XX mL) in 24 hours. Severe or possibly fatal liver damage may occur if you take more than the recommended dose in 24 hours or with other drugs containing paracetamol."

• “DO NOT USE with other drugs containing paracetamol. If you are not sure whether a drug contains paracetamol, ask a doctor or pharmacist."

• Do not use if you are allergic to paracetamol or any other ingredient in this product

3.2. Outer and Immediate Packaging

In addition to The GCC Guidance for Presenting the SPC, PIL, and Labeling Information, and SFDA Guidance for Graphic Design of Medication Packaging, the following are special considerations for products containing paracetamol as OTC Products:

• The quantitative declaration of the medicinal ingredients (paracetamol) on any panel of the immediate and outer packaging should be prominently displayed and should be further identified by the therapeutic class or indication “paracetamol (analgesic/antipyretic) 32 mg/mL".

• Concentration of paracetamol should appear in bold font type, clear font size and in black text with a white background in the middle of the label.

• It is recommended that the age group for which the medicine is intended should be stated on the outer packaging.

• If there is an image of a child on the outer packaging, the image should be representative of the age range for which the product is suitable.

The immediate and outer packaging should contain the below warnings:

• DO NOT USE with other drugs containing paracetamol. If you are not sure whether a drug contains paracetamol, ask a doctor or pharmacist.

• DO NOT USE if you are allergic to paracetamol or any other ingredient in this product

• For oral suspensions, shake the bottle well before use.

3.3. Pack Size and Container

Packaging should be standard child-resistant to prevent or delay pediatrics from opening bottles, giving caregivers reasonable time to intervene.

3.4. Combination

Marketing authorization holder should apply outside of the labelling standard if they wish to combine paracetamol with medicinal ingredient(s) such as sedative, antitussive, antihistamine. Please note that all labelling requirements for paracetamol is also applies to products combining paracetamol with any other medicinal ingredient.

The statement: “this product Contains paracetamol and other Ingredients" should appear in bold font type and clear font size in the top right corner of the label. In addition, the text for “this product contains paracetamol" should appear in red with a white background.

• For small package sized products: Consideration will be given for products with small package size. However, the text for “Contains paracetamol" should appear prominently in bold font type in red with a white background in the top right corner of the label.

3.5. Delivery Device

• For oral liquid formulations, it is required that an appropriate dosage delivery device be provided, such as a calibrated and labeled oral syringe or dosing cup.

• As the dosing directions should be in milliliters (mL), accordingly the dosage delivery devices should have calibrated units of liquid measurement expressed in milliliters (mL) only.

The following statement should be included with the directions for use: “Use only the measuring device provided", and include instructions that are consistent with the measuring device.​​

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1- Health Canada Revised Guidance Document: Acetaminophen Labelling Standard. September 2016.

2- US Food and Drug Administration. Over-the-Counter Pediatric Oral Liquid Drug Products Containing Acetaminophen: Guidance for Industry. August 2015.​