Summary of Product
Characteristics (SPC)
and
Patient Information Leaflet
(PIL)
SPC and PIL
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Guidelines available
EU – Guidelines
-
A guideline on Summary of Product Characteristics
- Notice to applicants; Rev0, December 1999)
-
Guideline on the readability of the label and package leaflet of
medicinal products for human use – Notice to applicants;
Vol. IIA Rev3, September 1999
WHO – Guideline
- SPC: according to the EU guideline
http://mednet3.who.int/prequal/
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SPC
Usage and use of a medicinal product
4. Clinical particulars


Therapeutic indications
Posology and method of administration
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4.1 Therapeutic indications
- Indication(s) should define the target disease
treatment
primary prevention
secondary prevention
diagnostic indications
Indication(s) should relate as precisely as possible to
the results of clinical trials. Global description
should be avoided.
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SPC
Usage and use of a medicinal product
4.2 Posology and Method of administration
 Dosage has to be clearly specified
- for each method/route of administration
- for each indication
 Dose recommendation has to be clearly specified:
- per dose interval
- per age group
- per patient group (adults, elderly, children)
- per specific patient groups (according to the
patients included in the studies)
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SPC
Usage and use of a medicinal product






Include need for dose titration
Include maximum recommended dose
Include duration of use and restriction on duration
Include relation to food intake
Mention interactions relevant for dose adjustment
Describe correct administration/use
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SPC
Changing use of a medicinal product




4.3 Contraindications
4.4 Special warnings and special precautions
for use
4.5 Interaction with other medicinal
products and other form of interactions
4.6 Pregnancy and lactation (not part of this
presentation)
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SPC
Changing use of a medicinal product

4.3 Contraindications
-
Absolute contraindications (e.g. particular clinical
-
-
diagnosis, concomitant diseases)
contraindicated combinations ( medicine which
should be specifically avoided)
Patient populations not studied where a safety issue
can be predicted
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SPC
Changing use of a medicinal product
-
-
Patient populations excluded from studies on
serious grounds of safety
Hypersensitivity to the substance and to any of the
excipients
Relative contraindications such as patient not studied
in the clinical trials should be included in section 4.4
of the SPC
Exception: if pregnancy is strictly contraindicated
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SPC
Changing use of a medicinal product
4.4 Special warnings and precautions for use
Preferred order:
relative contraindications
warnings
precautions


Special patient groups likely to experience product
related adverse events
Circumstances where incidence or severity of
adverse reactions differ in particular populations
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SPC
Changing use of a medicinal product




Accentuation of frequently serious adverse
reactions
Clinically relevant interactions with other
concomitant administered drugs
Particular risk associated with starting and stopping
the administration of the medicinal product
Any measures to:



SPC and PIL
identify patients at risk
prevent the occurrence or
detect early the onset or worsening of noxious conditions
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SPC
Changing use of a medicinal product

4.5 Interaction with other medicinal products and
other forms of interaction
Preferred order:
Interactions
- affecting the use of this product
- of this drug on others
- referred to in other sections
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SPC
Changing use of a medicinal product
Describe/mention:
 Recommendations regarding concomitant use
(cross refer to 4.3 or 4.4) and precautions including
dose adjustments (cross refer to 4.2 or 4.4)
 Effects on plasma levels and AUC, laboratory
parameters
 Mechanism
 Interactions with food or pharmacologically active
substance not used for medical purpose
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SPC
Possible consequences arising from use of a medicinal product


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
4.7 Effects on ability to drive and use
machines
4.8 Undesirable effects
4.9 Overdose
5. Pharmacological properties
– 5.1 Pharmacodynamic properties
– 5.2 Pharmacokinetic properties
– 5.3 Preclinical safety data (not part of this
presentation)
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SPC
Possible consequences arising from use of a medicinal product
4. 7 Effects on
Specify:
-
SPC and PIL
ability to drive and use machines
no or negligible influence
minor or moderate influence
major influence
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SPC
Possible consequences arising from use of a medicinal product

4.8 Undesirable effects
Comprehensive information on all adverse reactions
attributed to the medicinal product with at least
reasonable suspicion.
Preferred structure:


Generally description
Table
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SPC
Possible consequences arising from use of a medicinal product

Table (cont.)
Adverse reactions arranged according to
- standard system organ class (e.g. MedDRA, Annex
II of the SPC guideline)
- frequency according to the convention:
- very common (>1/10)
-
common (>1/100, <1/10)
uncommon (>1/1,000, < 1/100)
rare (>1/10,000, <1/1,000)
very rare (<1/10.000) incl. isolated reports
- seriousness
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SPC
Possible consequences arising from use of a medicinal product

Additional information
- reversibility or time of onset
- mechanism of reaction
- action to be taken
- dose relationship
- attribution to the substance class
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SPC
Possible consequences arising from use of a medicinal product


Not in this section:
- measures to be taken to avoid specific adverse
reactions (in section 4.4)
No tabulated presentation:
- if there are only few adverse reactions
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SPC
Possible consequences arising from use of a medicinal product

Annex II (SPC guideline)
The Medical Dictionary
for Regulatory
Activities Terminology
(MedDRA)
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SPC
Possible consequences arising from use of a medicinal product

4. 9 Overdose
Describe:
- acute symptoms and signs and potential sequelae
- management of overdose
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SPC
Relevant Scientific information

5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

5.3 Preclinical safety data (not part of this
presentation)
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SPC
Relevant Scientific information
5.1 Pharmacodynamic properties
Describe:

-
Pharmacotherapeutic group (ATC code)
Mechanism of action
Pharmacodynamic effects
Clinical efficacy
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SPC
Relevant Scientific information


5.2 Pharmacokinetic properties
General characteristics
- absorption
- Distribution
- Biotransformation
- Elimination
- Linearity/non-linearity
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SPC
Relevant Scientific information

Characteristics in patients
( PK variations regarding e.g. age, gender,
polymorphic metabolism, concomitant diseases)

PK/PD relationship(s)
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PIL

Patient information leaflet = PIL
Synonyms:
Package leaflet (PL)
Package insert
Principally, a separate leaflet for each
product of different quantitative strength
and pharmaceutical form
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PIL


Content must be in accordance with the
SPC, but the wording must be phrased so
that it is readily and understandable for the
patient
An explanation should be given where
scientific or specialised term is used
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PIL

Example: Model Leaflet

1. What /…/ is and what it is used for
– Pharmaceutical form, contents,
pharmacotherapeutic group
– Contents by weight, volume, no. of doses, pack
size
– Therapeutic indications
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PIL

2. Before you take/use /…/
- Do not take/use /…/
- Take special care with /…/
- Taking/using /…/ with food and drink
- Pregnancy
- Breast-feeding
- Driving and using machines
- Important information about some ingredients
-Taking/using other medicines
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PIL

3. How to take/use /…/
- If you take/use more /…/ than you should
- If you forget to take /…/
- Effects when treatments with /…/ is
stopped
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PIL

4. Possible side effects
Like all medicines, /…/ can have side effects
- Stop taking /…/ and tell your doctor immediately
- Tell your doctor immediately or got to the casualty
department
- Tell yor doctor if you notice any of the following:
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SPC + PIL
Examples for SPC and PIL of substances
indicated for the treatment and/or
prophylaxis of malaria:

Riamet (artemether / lumefantrine)

Malarone (Atovaquone / Proguanil
hydrochloride)
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