Principles and Practice of Pharmaceutical Medicine

labeling elsewhere in the world, this regulation
emphasizes drug tolerability, consistent with the
approach taken with much of regulatory affairs in
Japan. The visual presentation of the precautions
subsections goes further to make this point: Warn-
ings are printed in red within a red box, whereas
contraindications are printed in black, and again
within a red box. Lastly, contraindications for
co-administered drugs must be printed as a table
within a red box.
Japanese labeling regulations require that ani-
mal data and data from other members of the same
chemical or pharmacological class of drugs should
be included, even when these allude to adverse
effects that have not actually been observed for
the product that is labeled. When direct drug attri-
butability of an adverse event has not been estab-
lished, it remains a requirement that other
indirectly obtained information must still be

included; this would include epidemiological

information or pharmacodynamic effects obse-

rved in normal volunteer studies. Adverse event

frequencies (Section 38.4, Table 38.1) may be

presented in a table, usually for all adverse event

types reported with frequencies>5%, between

0.1–5 and<0.1%.

38.3 Drug labeling in the United

States

The Food and Drug Administration (FDA) is,

among other things, probably the most stringent

controller of drug labeling of all the world’s reg-

ulatory authorities. Typically, drug labels are

agreed with pharmaceutical companies at meetings

shortly before product approval, where the pro-

posed label is debated line by line. Such meetings

Table 38.1 Subtitles that must appear in Japanese drug labeling, and the order in which they appear

(after Article 52, Item 1 of the Pharmaceutical Affairs Law)

1. Date of preparation or revision of label 11. Precautions


2. Japanese Standard Commodity Number 12. Pharmacokinetics


3. Therapeutic category (e.g. bronchodilator) 13. Clinical studies


4. Regulatory Classification (e.g. ‘Designated Drug’) 14. Pharmacology


5. Brand name 15. Physicochemistry


6. Warning(s) 16. Precautions for handling


7. Contraindications 17. Conditions for approval


8. Composition and description 18. Packaging


9. Indications 19. References and how to order


10. Dosage and administration 20. Identity of manufacturer
    (etc.)

Table 38.2 Subsections of ‘precautions’ in Japanese drug labeling

1. Warnings 7. Use in the elderly


2. Contraindications (Do not administer 8. Use in pregnancy, delivery
   to the following types of patients). and lactation


3. Careful administration (Administer with 9. Pediatric use
   care to the following patients)


4. Important precautions 10. Effects on clinical


5. Drug interactions: laboratory tests
   (i) Contraindicated co-administrations 11. Overdosage
   (ii) Precautions for coadministration


6. (i) Clinically significant adverse events 12. Precautions concerning use
   (ii) Other adverse events 13. Other precautions

530 CH38 DRUG LABELING