Summary of Product Characteristics (SPC) and Patient Information Leaflet (PIL)

1. Summary of Product Characteristics (SPC) and Patient Information Leaflet (PIL)

2. 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. IIARev3, September 1999 WHO – Guideline - SPC: according to the EU guideline http://mednet3.who.int/prequal/

3. SPCUsage and use of amedicinal product 4. Clinical particulars • Therapeutic indications • Posology and method of administration

4. 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.

5. SPCUsage and use of amedicinal 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)

6. SPCUsage and use of amedicinal 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

7. SPCChanging use of amedicinal 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)

8. SPCChanging use of amedicinal 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

9. SPCChanging use of amedicinal 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

10. SPCChanging use of amedicinal 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

11. SPCChanging use of amedicinal 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: • identify patients at risk • prevent the occurrence or • detect early the onset or worsening of noxious conditions

12. SPCChanging use of amedicinal 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

13. SPCChanging use of amedicinal 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

14. SPCPossible consequences arising from use of a medicinal product • 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)

15. SPCPossible consequences arising from use of a medicinal product 4. 7 Effects on ability to drive and use machines Specify: - no or negligible influence - minor or moderate influence - major influence

16. SPCPossible 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

17. SPCPossible 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

18. SPCPossible 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

19. SPCPossible 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

20. SPCPossible consequences arising from use of a medicinal product • Annex II (SPC guide-line) The Medical Dictionary for Regulatory Activities Terminology (MedDRA)

21. SPCPossible consequences arising from use of a medicinal product • 4. 9 Overdose Describe: - acute symptoms and signs and potential sequelae - management of overdose

22. SPCRelevant Scientific information • 5.1 Pharmacodynamic properties • 5.2 Pharmacokinetic properties • 5.3 Preclinical safety data (not part of this presentation)

23. SPCRelevant Scientific information • 5.1 Pharmacodynamic properties Describe: - Pharmacotherapeutic group (ATC code) - Mechanism of action - Pharmacodynamic effects - Clinical efficacy

24. SPCRelevant Scientific information • 5.2 Pharmacokinetic properties • General characteristics - absorption - Distribution - Biotransformation - Elimination - Linearity/non-linearity

25. SPCRelevant Scientific information • Characteristics in patients ( PK variations regarding e.g. age, gender, polymorphic metabolism, concomitant diseases) • PK/PD relationship(s)

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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:

32. 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)