GD — Society for Dermopharmacy

Issue 2 (2004)

Dermatological prescription implies prescription, manufacturing and marketing of pharmaceuticals for external application which are prepared - in general for each individual case - under the responsibility of a pharmacist in a public pharmacy or hospital pharmacy. The prescription is oriented by special circumstances for single patients. In a narrower sense, the term prescription also designates the prescription formula and the prescription drug. Dermatological extemporaneous preparations are often spoken of if prescriptions have proven successful from experience or if rationally justified recommendations in relevant publications, especially collections of corresponding suggestions are reverted to. Particular importance in connection with the standardization of prescription bases and prescription in Germany befits the effective pharmacopoeia - possibly also former issues including the pharmacopoeia of the ex-German Democratic Republic (GDR) – as well as the DAC and the NRF. We speak of individual prescription if such data is not made use of.

As far as pharmaceutical quality and benefit-risk-assessment are concerned, physicians and pharmacists fulfil their responsibility towards their patients in a particular way for dermatological extemporaneous preparations by orienting as far as possible to current principles and transforming them into professional practice. The benefit thereby consists in the treatment of skin organ diseases aiming at their elimination; there may be a risk of local and systemically imparted unwanted drug effects at the patient treated and/or an impact on human environment.

Essential importance in the field of dermatological prescription is attached to the Quality Management. For this the individual physicians and pharmacists bear equally responsibility as chambers, specialized societies, professional associations and drug manufacturers, providing ingredients. The quality of dermatological prescription is to be considered under the aspects of structure-, process and result quality both individually and in its entirety. Measures of internal and external quality control (ring experiments) have to be strived for.

The guideline integrates important demands which had already been formulated with priority from a medical point of view in the form of a commission resolution "Extemporaneous Preparations" of the DDG (see references) in 1997. It combines moreover the interests of dermatological prescription and pharmaceutical therapy with the pharmaceutical possibilities and the principles of the ‘good pharmaceutical practice’ within the frame of effective laws.

1 Therapeutical concept

Extemporaneous preparations open up a wide spectrum for individual approaches within Dermatotherapy. The therapy concept selected by the physician defines the quality requirement to the prescription drug and has to be recognizable in essence from the prescription; this also includes indications regarding the application by the pharmacist. If this is not the case a check back with the physician is required (please refer to chapter 2).

The pharmacist has to support this concept when preparing and dispensing of the prescription. This applies in particular to quality adherence and consideration of the non-objection of the ingredients for the mode of application in question, compatibility, galenical characteristics, hygiene, sufficient preservation, stability, labelling, applicability and packaging. He is to foster the patient's compliance. If necessary, lacks of clarity and objections have to be eliminated jointly by physician and pharmacist.

2 Interdisciplinary cooperation
and error prevention

In order to avoid delays and errors, dermatological prescriptions have to be made out in a precise and unequivocal manner. Salts respectively solvates or derivatives of ingredients have to be named correctly in order to avoid misdosage or inefficacy. In case of recognizable errors, the pharmacist has to eliminate the unclarity by contacting the physician before starting the preparation process. Also in the case that the real intention of the prescribor is sufficiently perceptible, at least subsequent information should follow in order to avoid repetitions.

Furthermore, regular consultations are necessary before preparing of such extemporaneous preparations which contain contested drugs (please refer to chapter 4) which consist partly of ingredients whose quality can only be conditionally secured (please refer to chapter 3). This also applies to extemporaneous preparations the exact mode of application of which is indistinct (please refer to chapters 1 and 10), respectively from which no or only insufficient effectiveness can be expected or their pharmaceutical quality would be insufficient due to various reasons without modifying the prescription formula (please refer to chapters 7 and 9).

A restriction to one or few drug concentrations at ready-to-use drugs for topical application is an essential motive for the prescription of extemporaneous preparations with individually varying concentrations. In this context, deviations from the standard concentration may be intended or based on an error. Due to the fact that drugs at too high a concentration may considerably endanger patients, selected dermatic active substances with so-called upper therapeutically recommended concentrations are listed in the NRF (table 1.6-1) by suggestion of the DDG commission of extemporaneous preparations. If these concentrations in prescriptions are exceeded, the physician is to stress his intention by making an exclamation mark. In case such an indication is missing, the pharmacy has to eliminate the lack of clarity before preparing the drug.

3 Quality of ingredients

The quality of prescription ingredients called for by pharmaceutical laws has to be ascertained and documented by the pharmacist. This is why in principle only raw materials and preparations, marketable ready-to-use drugs or substances or preparations prescribed in formulations provided with a test certificate according to §§ 6 and 11 ApBetrO (Pharmacists' Rules and Regulations), or furnished with complete pharmaceutical quality documentation or substances and preparations produced in pharmacies according to the generally recognized pharmaceutical rules may be prescribed, processed or marketed.

4 Concerns and
pharmacologic-toxicologically contested ingredients

Physicians and pharmacists are to consider the current state of knowledge in medical and pharmaceutical science when assessing concerns as it can - among other sources - be extracted from statements of the BfArM respectively AMK and AKdÄ as well as from scientific articles in professional journals. The monographs which have been made known in public in connection with the subsequent approval of ready-to-use drugs by processing of scientific findings have to be considered for the assessment. In case of doubt, information has to be obtained, e.g. from institutions of chambers, specialized societies, professional associations or competent authorities.

It is not allowed to prescribe, prepare nor dispense questionable prescriptions. Concerns - among other causes – can directly result from the pharmacologic-toxicological properties of certain medicinal substances respectively other prescription ingredients or develop from the interplay of ingredients or come about in the context of intended doses, concentrations, mode and duration of application.

A benefit-risk-assessment for pharmacologic-toxicologically contested components respectively prescriptions has to be established in view of therapeutical alternatives. For negative monographs or otherwise prevailing negatively classified ingredients (or prescriptions), a benefit-risk assessment has to be carried out individually for each isolated case. Above all an exceptionally positive judgement should be documented in writing, e.g. by means of the pattern according to NRF, illustration 1.5-1. Economical aspects are not to be considered in this context.

5 Medicinal agents and drug combinations

Extemporaneous preparations should be composed in accordance with rationally comprehensible aspects and always contain medicinal agents in therapeutically effective concentrations. Two or more pharmaceutically effective substances should only be combined in well-founded exceptions for drugs used for topical application.

In times of a permanently increasing number of medicinal agents, the use of multiple combinations does not only pose an incremental difficulty in rational comprehension but their pharmaceutical quality is moreover complicated to assess and safeguard. This refers in particular to the preparation of ready-to-use drugs in a prescription (please refer to chapter 9).

The packing of extemporaneous preparations has to be performed in a way to ensure the required drug quality within the designated application period and allow a safe use of the drug according to its intended purpose. Packaging recommendations by the AMK, the NRF and the ZL are to be considered. If available, primary packing material with certification according to up-to-date specific standards should be used, e.g. pursuant to annex H of the DAC or the ZL-packaging regulations.

7 Preservation and hygiene

Dermatologic extemporaneous preparations have to be prepared in a hygienically unobjectionable manner and also stay in this state during the application period, i.e. in certain cases sterility, in general a germ number limitation of not exceeding 100 germs per gram respectively millilitre under exclusion of certain indicator organisms and pathogenic agents. This is why only hygienically safe base substances (including water) as well as packing materials and only approved working techniques may be used. The GD guideline and relevant guidelines concerning quality assurance by the Bundesapothekerkammer (Federal Chamber of Pharmacy) are to be considered. As a matter of principle, extemporaneous preparations susceptible to microbes should be protected from microbial perishing by adding a suited preservative. In case preservation should not be employed, the physician has to make an explicit note ("preservation free").

Contained preservations have to be marked (please refer to chapter 10).

8 Stability

Missing long-term stability may be responsible for the lack of ready-to-use drugs with certain medicinal agents or base on certain dermatic bases. This may be an essential reason for the prescription of such extemporaneous preparations. Extemporaneous preparations only have to be stable during the designated application period.

For ready-to-use drugs, the term of stability and use-up deadline at the patient's have to be distinguished. Concerning ad hoc prepared prescriptions, however, prescription, preparation, sale and starting of use normally coincide in such a short period of time that here stability before use besides use-up deadline are merely relevant for sterile drug types. Prescriptions should be marked with a definite final date of the term of use for sale (please refer to NRF, paragraph 1.4, general indications, especially tables 1.4.-2 and 1.4.3), e.g. "not to be used after”.....

Drug master preparations and dermatic bases used in pharmacies are subject to different systematics (see NRF). The use of opened packs of ready-to-use drugs for prescription purposes in pharmacies is to be limited in time in a reasonable way; for example the NRF approximate values for terms of consumption as starting of use may be alternatively used without, however, overstepping the expiry date stipulated by the manufacturer.

9 Avoidance of incompatibilities and standardized prescriptions

Incompatibilities between prescription ingredients and prescriptions and their primary packaging materials can be avoided when limiting to ready-to-use drugs and standardized instructions, e.g. according to SR or NRF. As far as ready-to-use drugs or analogous NRF-prescriptions are available, individually composed prescriptions should only be made out in particularly justified cases.

When processing drugs in single composed dermatic bases from recognized and generally accessible instructions (for example from DAB, DAC, SR or NRF), possible incompatibilities may be predicted to a great extent and can be avoided by switching to alternatives.

Formulations on the basis of brand bases or ready-to-use drugs should only be prescribed if experimentally secured data concerning the physical, chemical and microbiological quality and stability on the part of the producers of pharmaceuticals can be presented for the scheduled treatment over an appropriate period.

Priority should be given as far as possible to those prescriptions which are contained in approved and generally accessible instructions (for instance DAB, DAC, SR, NRF, standardized approvals or ADKA-regulations) within a given context.

10 Labeling and patient information

Extemporaneous preparations in prescriptive preparation are to be labelled by the pharmacy according to ApBetr0 (pharmacy operation regulation). In specifying and completing the mentioned obligatory declarations therein, it is recommendable to indicate the information in German language.

The designation of medicinal agents may not be abbreviated or stated in a way that the patient respectively consignee might be deceived or mislead about the content. Drugs for topical applications containing glucocorticoids are to be marked "containing cortisone!"

Pharmaceutically effective ingredients have to be marked as to type and quantity. Other ingredients are to be labelled according to the effective stipulations. The information has to suffice for a repetition of the prescription in identical composition.

11 Unwanted effects of pharmaceuticals

Physicians and pharmacists are to document observations about unwanted drug effects also for extemporaneous preparations und inform the pharmaceutical commissions accordingly. It is recommendable to deposit a copy in the pharmacy respectively doctor's practice.

12 Dermatological and pharmaceutical continuous training

An appeal is made to the institutions of chambers, professional associations, specialized societies and drug producers to incorporate the actual state of knowledge regarding a rational handling of dermatological extemporaneous preparations into university studies and continuous professional training of physicians, pharmacists and assistant professions concerned as well as to further interdisciplinary cooperation.

13 Glossar

ABDA: ABDA - Bundesvereinigung Deutscher Apothekerverbände (Federal Association of German Pharmacist Unions).
ADKA: Bundesverband Deutscher Krankenhausapotheker (Federal Association of Hospital Pharmacists).
AKdÄ: Arzneimittelkommission der deutschen Ärzteschaft (Drug Commission of the German Medical Profession)
AMG: Arzneimittelgesetz (Drug Act)
AMK: Arzneimittelkommission der Deutschen Apotheker (Drug Commission of German Pharmacists)
ApBetrO: Apothekenbetriebsordnung (Pharmacies' Rules and Regulations)
BfArM Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Drugs and Medicinal Products)
DAB: Deutsches Arzneibuch (German Pharmacopoeia).
DAC: Deutscher Arzneimittel-Kodex (German Drug Code)
DDG: Deutsche Dermatologische Gesellschaft (German Dermatological Society).
GD: Gesellschaft für Dermopharmazie (Society for Dermopharmacy)
RF: Neues Rezeptur-Formularium (New Prescription Formulary)
SR: Standardrezepturen 1990 (DDR) (Standard Prescriptions 1990 (GDR))
Standardzulassungen (Standard Approvals): Sammlung von Monographien zu Arzneimitteln gemäß § 36 AMG, die von der Pflicht zur Einzelzulassung befreit sind (Collection of Monographs concerning drugs in accordance with § 36 AMG, which are exempted from individual registration)
ZL: Zentrallaboratorium Deutscher Apotheker (Central Laboratory of German Pharmacists).

14 References:

1. Meigel, W.N., Altmeyer, P., Jahn, S., und die DDG-Kommission "Magistrale
Rezepturen", Empfehlungen zu "Magistralen Rezepturen" erarbeitet, Hautarzt 48,
702 (1997). Siehe auch Dt. Derm. 45, 600 (1997).

2. ABDA - Bundesvereinigung Deutscher Apothekerverbände (Hrsg.), Neues
Rezeptur-Formularium (NRF), Kapitel Allgemeine Hinweise, Abbildung I.5-1 sowie
Tabellen I.2.-1, I.4.-2, I.4-3 and I.6-1 Govi-Verlag, Eschborn /Deutscher
Apothekerverlag , Stuttgart.

3. Hygiene-Richtlinie für die Herstellung von nicht sterilen pharmazeutischen Zubereitungen in der Apotheke vom 19.01.2000 in der Fassung vom 25.11.2002, Fachgruppe „Magistralrezepturen“ der GD, www.gd-online.de.

4. Bundesapothekerkammer, Leitlinien zur Qualitätssicherung. Herstellung und Prüfung der nicht sterilen Rezeptur- und Defekturarzneimittel, Revision 6.5.2003, www.abda.de/ABDA/download/Qualitaetssicherung/Nicht_sterile_Rez.pdf.

5. Bedenkliche Rezepturarzneimittel (Stand Dezember 2002), Stellungnahme der Arzneimittelkommission der Deutschen Apotheker, Pharm. Ztg. 148 (2003)1236-1237, www.amk.de und www.akdae.de.

15 Procedures of reaching a consensus

Pharmacist Rosemarie Eifler-Bollen*, Dr. Holger Reimann*, Prof. Dr. med. Peter
Altmeyer (1), Kreispharmaziedirektorin Sylvia Demelius (2), Prof. Dr. Volker
Dinnendahl (3), Dr. Herbert Döben (4), Ministerialrat Walter Frie (5), Dr. Bernd
Fröhlingsdorf (6), Dr. med. Klaus Gerecht (7), Prof. Dr. med. Max Gloor (8), Dr.
Bernhard Hoffmann (9), Dr. Bernd Hünerbein (10), Dr. Ulrich Knie (11), Prof. Dr.
med. Hans Christian Korting (12), Prof. Dr. Christel Müller-Goymann (13), Dr. Jochen
Norwig (14), Prof. Dr. Dietrich Schnädelbach (14), Apothekerin Michaela
Tünnermann (8), Dr. Petra Zagermann-Muncke (3), Prof. Dr. med. Achim Zesch (14),
Prof. Dr. Jochen Ziegenmeyer (14).

* Vorsitz (chair), Pharmazeutisches Laboratorium des Neuen Rezeptur-Formulariums
(Pharmaceutical Laboratory of the New Prescription-Fomulary), Eschborn 1: Klinik für
Dermatologie und Allergologie, Ruhr-Universität Bochum, (Clinic for Dermatology and
Allergology)
2: BapÖD - Bundesverband der Apotheker im Öffentlichen Dienst (Federal
Association of Pharmacists in Civil Service); Arbeitsgemeinschaft der Pharmazieräte
Deutschlands (Working Group of Pharmacy Counsellors Germany);
Kreisgesundheitsamt (District Public Health Department), Recklinghausen;
3: Arzneimittelkommission der Deutschen Apotheker ABDA (Pharmaceutics
Commission of German Pharmacists), Bundesvereinigung Deutscher
Apothekerverbände (Federal Association of German Pharmacist Federations),
Eschborn 4: Deutschherren-Apotheke, Bonn
5: Ministerium für Gesundheit, Soziales, Frauen und Familie des Landes Nordrhein-
Westfalen, Düsseldorf (Ministry for Health, Social Welfare, Womankind and Family of
the Land North-Rhine Westfalia)
6: Firma Caesar & Loretz, Hilden
7: Sonderreferat Dermatologische Rezepturen beim Berufsverband der Deutschen
Dermatologen, Kempen (Special Department of Dermatological Prescription at the
Occupational Association of German Dermatologists)
8: GD-Fachgruppe Magistralrezepturen (GD-Department Extemporaneous
Preparations)
9: Landesinstitut für den Öffentlichen Gesundheitsdienst Nordrhein-Westfalen,
Münster 10: Löwen-Apotheke, Naumburg/Saale (State Institute for the Public Health
Service North-Rhine Westfalia)
11: Firma Dr. August Wolff Arzneimittel, Bielefeld
12: Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-
Universität München (Clinic and Polyclinic for Dermatology and Allergology)
13: Institut für Pharmazeutische Technologie der Technischen Universität,
Braunschweig (Institute for Pharmaceutical Technology at the University of
Technology)
14: Bundesinstitut für Arzneimittel und Medizinprodukte - BfArM, Bonn (Federal
Institute for Pharmaceuticals and Medicinal Products)

For the authors:
pharmacist Dr. Bernd Hünerbein, Löwen-Apotheke, Naumburg/Saale, pharmacist
Rosemarie Eifler-Bollen, Pharmazeutisches Laboratorium des Neuen Rezeptur-
Formulariums, Eschborn (Pharmaceutical Laboratory of the New Prescription
Formulary)

The guideline has been established on behalf of the GD Gesellschaft für
Dermopharmazie e.V. by the a. m. expert group as consensus paper.
Creation date: 18.11.1998
Last revision: 01.04.2003
Released for publication: 01.11.2003
Revision planned: 2006

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