3. Package Leaflet (PL)

Site: EUPATI Open Classroom
Course: Product information and information to the public
Book: 3. Package Leaflet (PL)
Printed by: Guest user
Date: Monday, 6 February 2023, 8:13 AM

1. Package Leaflet (PL)

Just like the SmPC, the Package Leaflet (PL), as mentioned in the introduction, can be considered a key element in medicines information and is mandated by law. The SmPC does not address patients. Many sections are complicated and contain technical terms. Therefore, the legislation requires a PL to be produced. The PL should contain all information from the SmPC that is necessary and useful for the patient. The basic philosophy in producing a PL is that after reading it, the patient will fully understand what the medicine is, what it is used for and how to use it. The doctor (or, in case of a non-prescription medicine, the pharmacist) may well have explained it all. However, back at home, the patient may need to again read the PL to fully understand the medication and how it is used. For example, are there special conditions under which you should not take the medicine? Should you take the medicine with a meal – or on an empty stomach? What are the potential side effects? What if you forget to take a dose?

As regards the legal background, the primary legislation is Directive 2001/83/EC which stipulates:

  • The inclusion in the packaging of all medicinal products of a package leaflet (PL) shall be obligatory. (Art. 58) 
  • The package leaflet shall be drawn up in accordance with the summary of the product characteristics; it shall include, in the following order …. [it follows the list of items to be included] (Art. 59 (1))
  • The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use. (Art. 59 (3))
  • The PL must be written and designed to be clear and understandable, enabling the users to act appropriately, when necessary, with the help of health care professionals. (Art 63 (2)) [1]


[1] At the time of writing, there are ongoing initiatives to improve the access to the important information in the PL.

 


1.1. PL process


The PLs are drafted by the pharmaceutical companies based on their data and a draft PL must be included in the application dossier in Module 1 (CTD). After submission of the dossier, a number of rounds of review starts involving different actors:

  • Assessors from Member states  
  • EMA
  • Patients

User Testing:
Additionally, user testing is performed during the procedure (a legal requirement since 2005), not only looking at the content but also at the design and layout of the leaflet. Article 59(3) of Directive 2001/83/EC states that the PL shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use (e.g., format, layout, contrast, spacing etc.). This needs to be documented in the applications for marketing authorisations, significant variations to MAs, renewal applications and applications where harmonisation of the PL is undertaken and which must demonstrate compliance with article 59(3). Therefore, the company must consult with target patient groups, and one way to do this is for the company to perform a ‘user test’.

This often follows the recommendations of the ‘readability guideline’: a group of relevant patients is identified (appropriate number, gender, age, treatment naïve/patients?), The group will look at a test package (usually labelling and PL) and answer questions covering key messages (relevant, open questions, expected answers?) discuss the layout and make proposals for amendments where appropriate.

Not all language versions of the PL will undergo user testing. The company chooses the language in which the readability test is carried out. One of the limitations of this method is that the evidence for the positive result in other languages depends on the quality of the translation process. The PL text proposed by the company will be evaluated by the EMA Quality Review of the Documents (QRD) group.

Review of the PL can also occur for medicines already on the market. This can happen due to major changes in the content but also on a regular basis in terms of usability. One example of this would be adapting to new techniques, e.g. the electronic leaflet (for instance in Germany package leaflet (“Gebrauchsinformation 4.0”).


1.2. Structure and content of the PL

As laid out in the QRD template ANNEX III B, the sections of a PL for product X are the following:

Abbreviated quotes from the template are included to illustrate details of the PL, incl. prescriptive text. These quotes are indicated in the following way: [Green text]. They are guidance and explanatory notes only, to be deleted when using the templates.
{text}: Information to be filled in
<text>: Text to be selected or deleted as appropriate

Package leaflet: Information for the <patient> <user> [Heading to be printed]

{(Invented) name strength pharmaceutical form}
{active substance(s)}

[For medicinal products subject to additional monitoring ONLY: The black symbol and the statements should only appear here.]

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects, you may get. See the end of section 4 for how to report side effects. >

[For medicines available only on prescription:]

<Read all of this leaflet carefully before you start <taking> <using> this medicine because it contains important information for you.

  • -        Keep this leaflet. You may need to read it again.
  • -        If you have any further questions, ask your <doctor> <,> <or> <pharmacist> <or nurse>.
  • <-  This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.> [Do not include this statement in case of hospital use.]
  • -        If you get any side effects, talk to your <doctor> <,> <or> <pharmacist> <or nurse>. This includes any possible side effects not listed in this leaflet. See section 4.>

[For medicines available without a prescription:]

<Read all of this leaflet carefully before you start <taking> <using> this medicine because it contains important information for you.

Always <take> <use> this medicine exactly as described in this leaflet or as your <doctor> <,> <or>

<pharmacist> <or nurse> <has> <have> told you.

  • -          Keep this leaflet. You may need to read it again.
  • -          Ask your pharmacist if you need more information or advice.
  • -          If you get any side effects, talk to your <doctor> <,> <or> <pharmacist> <or nurse>. This includes any possible side effects not listed in this leaflet. See section 4.
  • -          You must talk to a doctor if you do not feel better or if you feel worse <after {number of} days>.>

What is in this leaflet [User testing to date has indicated that most patients value a content listing in the package leaflet. In order for this to be most useful it needs to be prominently displayed where it appears.]

  1. What X is and what it is used for.
  2. What you need to know before you <take> <use> X.
  3. How to take <use> X.
  4. Possible side effects.
  5. How to store X.
  6. Contents of the pack and other information

1. What X is and what it is used for

[(Invented) name, active substance(s) and pharmacotherapeutic group as per section 1 and 2 of the SmPC, e.g. “X contains the active substance Y”.]

[Therapeutic indications in line with section 4.1 of the SmPC, in which age group the medicine is indicated, specifying the age limits, e.g. “X is used to treat {indication} in <adults> <new-born babies> <babies> <children> <adolescents> <aged {x to y}> <years> <months>”].

[Information on the benefits of using this medicine [On a case-by-case basis, information on the benefits of the treatment, as long as it is compatible with the SmPC, useful for the patient, and to the exclusion of any element of a promotional nature, e.g. entitled “How X works”.

<You must talk to a doctor if you do not feel better or if you feel worse <after {number of} days>].

2. What you need to know before you <take> <use> X

Do not <take> <use> X

[All contraindications from section 4.3 of the SmPC in the same order as in the SmPC]

Warnings and precautions

Talk to your doctor <or> <pharmacist> <or nurse> before <taking> <using> X
[All warnings and precautions for use from section 4.4 of the SmPC; it should also be made clear for each warning or precaution for use, what action the patient should take to minimise the potential risk]

Children <and adolescents>

[When the indicated in children, warnings and precautions specific to this population (identified as such in section 4.4 of the SmPC), if not, information should reflect the paediatric subsection of section 4.2 of the SmPC, e.g. “Do not give this medicine to children between the ages of x and y <years> <months> because <of the risk of […]> <it does not work> <the potential benefits are not greater than the risks>, <it is unlikely to be safe>”].

Other medicines and X

<Tell your <doctor> <or> <pharmacist> if you are <taking> <using>, have recently <taken> <used> or might <take> <use> any other medicines.>

[The effects of other medicines on the medicine in question and vice versa as per section 4.5 of the SmPC. Where it may be helpful to the patient, describe in brief terms the consequence of the interaction, e.g. distinguish the medicine which must not be used with the medicine: “Do not take X with Y (a medicine used for Z) as this may result in the <loss of its effect><side effect>”]

X with <food> <and> <,> <drink> <and> <alcohol>

[Interactions not related to medicines, e.g. patients should not consume milk in combination with tetracyclines and no alcohol should be consumed during treatment with benzodiazepines].

Pregnancy <and> <,> breast-feeding <and fertility>

[conclusion summary of the information in section 4.6 of the SmPC, in addition to the following optional statement: <If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your <doctor> <or> <pharmacist> for advice before taking this medicine.>]

[If contraindicated in pregnancy and/or breast-feeding the same information should be presented in both subsections (“Do not take/use X” and “Pregnancy, breast-feeding and fertility”) of the leaflet]

Driving and using machines

[Where there is cautionary advice in section 4.7 of the SmPC this should be translated into meaningful colloquial language for the patient and should include an explanation as to why the patient is advised not to drive or undertake these tasks, and whether or not to discuss this with their doctor.]

<X contains {name the excipient(s)}>

[If appropriate, warnings of those excipients knowledge of which is important for the safe and effective use of the medicine as per section 4.4 of the SmPC. This subsection should be omitted when the medicine does not contain any excipients of known effect.]

3. How to <take> <use> X

[In simple cases, the following 3 items can be combined as one paragraph.]

[For medicines available on prescription only:]

<Always <take> <use> this medicine exactly as your doctor <or pharmacist> has told you. Check with your <doctor> <or> <pharmacist> if you are not sure.>

<The recommended dose is ...>

 

[For medicines available without prescription:]

<Always <take> <use> this medicine exactly as described in this leaflet or as your <doctor> <,> <or>

<pharmacist> <or nurse> <has> <have> told you. Check with your <doctor> <or> <,> <pharmacist>

<or nurse> if you are not sure.>

<The recommended dose is ...>

<Use in children <and adolescents>>

[When the medicine is indicated in different age groups with a different dose, method of administration, frequency of administration or duration of treatment, specific instructions for use for each age group should be clearly identified.]

 

Route(s) and/or method of administration

[(SmPC section 4.2)

Route(s) of administration according to “Standard Terms” published by the Council of Europe and an additional patient-friendly explanation if necessary.

Method of administration: e.g. “Do not swallow”, “Shake well before use” (user testing experience has shown it is useful to state the reasons for the inclusion of such a statement, e.g. “Do not break or crush the tablet(s). If you do, there is a danger you could overdose because this medicine will be absorbed into your body too quickly”).

Where relevant, guidance should always be included to clarify if the medicine must be taken with food, during/before meals, or clearly state if food/meals have no influence, etc.]

<The score line is only there to help you break the tablet if you have difficulty swallowing it whole.>

<The tablet can be divided into equal doses.>

<The score line is not intended for breaking the tablet.>

[Duration of treatment (SmPC section 4.2) If appropriate, especially for medicines available without prescription, precise statements should be included on:

  • the usual duration of the therapy;
  • the maximum duration of the therapy;
  • the intervals with no treatment;
  • the cases in which the duration of treatment should be limited.]

[For some medicines it may be necessary to include some additional information in this section although this need not be covered in all cases. The following headings can be used as a guide:]

<If you <take> <use> more X than you should

[Describe how to recognise symptoms if someone has taken an overdose and what to do as per SmPC section 4.9.]

<If you forget to <take> <use> X>

[Make clear to patients what they should do after irregular use of a medicine, e.g.: if information is available, try to include information on the maximum interval the missed dose can be caught up as per SmPC section 4.2.]

<Do not take a double dose to make up for a forgotten <tablet> <dose> <…>.>

<If you stop <taking> <using> X>

[Indicate withdrawal effects and how to minimise them as per SmPC section(s) 4.2 and/or 4.4.]

<If you have any further questions on the use of this medicine, ask your <doctor> <,> <or><pharmacist> <or nurse>.>

4. Possible side effects

[Begin this section with]

Like all medicines, this medicine can cause side effects, although not everybody gets them.

[The section should generally be divided into two sections bearing in mind that there should be sufficient patient-friendly description of the overt clinical signs and symptoms to enable the patient to recognise all side effects which may occur as set out in section 4.8 of the SmPC:

1) the most serious side effects need to be listed prominently first with clear instructions to the patients on what action to take (e.g. to stop taking the medicine and/or seek urgent medical advice. The use of the words “straight away” or “immediately” may be helpful in this context).

2) then a list of all other side effects, listed by frequency and starting with the most frequent (without repeating the most serious included above).

 

Within each section mentioned above, side effects should be arranged by frequency. The following frequency convention is recommended:

Very common: may affect more than 1 in 10 people Common: may affect up to 1 in 10 people Uncommon: may affect up to 1 in 100 people

Rare: may affect up to 1 in 1,000 people

Very rare: may affect up to 1 in 10,000 people

Not known: frequency cannot be estimated from the available data

This frequency convention should not appear before the list of side effects as this takes up space and has shown in user testing to be misleading to patients.

In any case, when expressing the likelihood of side effects, it is important to include verbal terms and numerical data, as far as possible. Bear in mind that user testing has shown that double sided expressions such as “affects more than 1 in 100 but less than 1 in 10” are not well understood and should not be used.

System organ class listings should not be used. However, patient-friendly terms for parts of the body may be used as headings where the frequency is not known.]

<Additional side effects in children <and adolescents >>

[If appropriate (and in line with information stated in section 4.8 of the SmPC), a subsection should highlight any clinically relevant differences in terms of side effects in any relevant subset of the paediatric population compared to another or to the adult population.]

 

[For ALL medicinal products: The following sub-heading should appear at the end of section 4:]

Reporting of side effects

If you get any side effects, talk to your <doctor> <or> <,> <pharmacist> <or nurse>. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store X

Keep this medicine out of the sight and reach of children.

[Expiry date]

Do not use this medicine after the expiry date which is stated on the <label> <carton> <bottle> <...>

<after {abbreviation used for expiry date}.> <The expiry date refers to the last day of that month.>

 

[Storage conditions]

[Information in accordance with section 6.4 of the SmPC]

[Where applicable, shelf life after reconstitution, dilution or after first opening the container in accordance with section 6.3 of the SmPC.]

[Where appropriate, warnings against certain visible signs of deterioration]

<Do not use this medicine if you notice {description of the visible signs of deterioration}.>

<Do not throw away any medicines via wastewater <or household waste>. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.>

 

6. Contents of the pack and other information

What X contains

[The active substance(s) (expressed qualitatively and quantitatively) and the other ingredients (expressed qualitatively as given in sections 2 and 6.1 of the SmPC.]

- The active substance(s) is (are)… [e.g. “Each <tablet> <capsule> contains x <gram>

<milligram>…{active substance}”.]

-  The other <ingredient(s)> <(excipient(s))> is (are)...

 

What X looks like and contents of the pack

[The pharmaceutical form should be stated according to the full “Standard Terms” published by the Council of Europe and an additional patient-friendly explanation may be given if necessary. It is recommended to include a physical description, e.g. shape, colour, texture, imprint, etc. as per section 3 of the SmPC.]

[All pack sizes as per section 6.5 of the SmPC, if appropriate indicate that not all pack sizes may be marketed. A cross-reference to other pharmaceutical forms and strengths may be included.]

Marketing Authorisation Holder and Manufacturer

{Name and address}

<{tel}>

<{fax}>

<{e-mail}>

A mobile technology feature may be included in the packaging material and/or the package leaflet, and its location should take into account the overall readability.

See if you can find any differences in a PL you have at home.

The company cannot change the PL without submitting a variation application for the SmPC. Such changes could be initiated by the company. However, the regulators may also request changes, for example, in case of new knowledge on product safety or efficacy. Such regulatory initiatives may arise from what are known as referrals (see text below).

A referral is a procedure used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral, the EMA conducts a scientific assessment of a particular medicine or class of medicines on behalf of the European Union (EU).
The medicine, or the class or medicines, is 'referred' to the EMA for making a recommendation for a harmonised position across the EU.

Reasons why a referral may be started, range from concerns over the safety of a class of medicine to disagreements among Member States on the use of the medicine: