Daily defined doses, Pharmacovigilance Notes Unit 2 B.Pharm 8 Semester
Defined Daily Dose (DDD)
Definition and introduction
The basic definition of the defined daily dose (DDD) is:
The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults.
The DDD is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Therapeutic doses for individual patients and patient groups will often differ from the DDD as they will be based on individual characteristics (such as age, weight, ethnic differences, type and severity of disease) and pharmacokinetic considerations.
Only one DDD is assigned per ATC code and route of administration (e.g. oral formulation). The DDD is nearly always a compromise based on a review of available information including doses used in various countries when this information is available. The DDD is sometimes a “dose” that is rarely if ever prescribed, because it might be an average of two or more commonly used doses.
Drug utilization data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. DDDs provide a fixed unit of measurement independent of price, currencies, package size and strength enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups.
General principles for DDD assignment
DDDs are only assigned to drugs with an ATC code and a DDD will normally not be assigned for a substance before a product is approved and marketed in at least one country.
The basic principle is to assign only one DDD per route of administration within an ATC code.
DDDs for single substances are normally based on monotherapy. Exceptions to this rule are given in the guidelines of the relevant ATC groups.
For substances indicated for rare disorders with highly individual dosing schedules, the Working Group could decide not to assign a DDD.
DDDs are not established for topical products, sera, vaccines, antineoplastic agents, allergen extracts, general and local anesthetics and contrast media.
When a new DDD is assigned, various sources are used to get the best overview of the actual or expected use of a substance. The assigned DDD is based on the following principles:
- The average adult dose recommended for the main indication as reflected by the ATC code. When the recommended dose refers to body weight, an adult is considered to be a person of 70 kg. It should be emphasised that even special pharmaceutical forms mainly intended for children (e.g. mixtures, suppositories) are assigned the DDD used for adults. Exceptions are made for some products only used by children, e.g. growth hormones and fluoride tablets.
- The recommended maintenance dose (long term therapeutic dose) is usually preferred when establishing the DDD. The initial dose may differ from the maintenance dose but this is not reflected in the DDD. If the approved dose recommendation provides limited information about maintenance dose, the DDD will usually be the average of the maintenance dose range. Examples of interpretation of approved dose titration recommendations:
- “Titrate up to a high dose if it is tolerated”: the high dose would normally be chosen as the DDD.
- “Consider to increase the dose only if efficacy is not satisfactory with initial dose”: the DDD would normallybe based on the initial dose.
- For some groups of medicinal products specific principles for DDD assignment are established (e.g. the DDDs for the selective serotonin agonists in the treatment of migraine are based on the approved initial dose). These principles are given in the guidelines for the relevant ATC groups.
- The treatment dose is generally used. If, however, prophylaxis is the main indication, this dose is used, e.g. for fluoride tablets (A01AA01) and some antimalarials.
- A DDD is usually established according to the declared content (strength) of the product. Various salts of a substance are usually not given different DDDs. Exceptions are described in the guidelines for the relevant ATC groups. For example, the DDDs for antimalarials are expressed as the base.
- Different stereoisomeric forms are normally assigned separate DDDs and ATC codes. The DDDs for stereoisomeric forms are described in the respective ATC groups.
- Prodrugs, which have not been given a separate ATC code, are normally not given a separate DDD.
- The DDD is often identical for various dosage forms of the same drug. Different DDDs can be established when the bioavailability is substantially different for various routes of administration (e.g. oral and parenteral administration of morphine) or if the dosage forms are used for different indications. When the use of parenteral formulations represents only a minor fraction of the total use for a specific indication, these products have normally not received a separate DDD even if the bioavailability of the oral form is substantially different. This principle has not been strictly followed in recent years. Parenteral antibacterials are for example mainly used in hospitals and often for more severe infections than in primary care. The DDDs are frequently used as indicators for antibacterial use in hospitals, and it has been decided that assigning different DDDs for oral and parenteral formulations could be important in some cases to improve the usefulness of the methodology in drug utilization monitoring and research.
- Parenteral products with different routes of administration (e.g. i.v. and i.m.) have the same DDD.
DDDs for combinations products
The DDDs assigned for combination products are based on the main principle of counting the combination as one daily dose, regardless of the number of active ingredients included in the combination. If a treatment schedule for a patient includes e.g. two single ingredient products, then the consumption will be measured by counting the DDDs of each single ingredient product separately. If, however, a treatment schedule includes a combination product containing two active ingredients, then the calculated consumption measured in DDDs will normally be lower since the DDD for the combination will be counted.
Example I:
Treatment with two products, each containing one active ingredient:
Product A:
Tablets containing 20 mg of substance X (DDD = 20 mg)
Product B:
Tablets containing 25 mg of substance Y (DDD = 25 mg)
The dosing schedule 1 tablet of A plus 1 tablet of B daily will be calculated as a consumption of 2 DDDs.
Example II:
Treatment with a combination product containing two active ingredients:
Product C:
Tablets containing 20 mg of substance X and 12.5 mg of substance Y. The DDD of the combination products is assigned as 1 UD = 1 tablet.
The dosing schedule 1 tablet of C daily will be calculated as 1 DDD (even though it will be equivalent to 1.5 DDD of the single active ingredients).
The following principles for assigning DDDs to combination products apply:
- For combination products (other than the combination products used in hypertension, see point 2 below) where the ATC code identifies the main ingredient (i.e. for the 50- and 70-series combinations and for some 4thlevel combinations), the DDD for the combination product should be equal to the DDD for the main active ingredient.
2.For combination products used for treatment of hypertension (i.e. ATC group C02, C03, C07, C08 and C09), DDDs are based on the average number of dosing intervals per day. This means that: 1 tablet is the DDD for combinations given once daily, whereas 2 tablets is the DDD for combinations given twice daily and 3 tablets is the DDD for combinations given three times daily etc. This principle means that the assigned DDDs may differ from the DDD assigned for the main active ingredient (according to ATC code).
For all combination products where the DDD assigned deviates from the principles given above, a list of DDDs are available on this website List of DDDs combined products.
MCQ on Pharmacovigilance given at the end of Lecture (see above lecture)
Pharmacovigilance Lectures Playlist
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