Drug interactions program for medical doctors pharmacists and

Drug interactions program for medical doctors, pharmacists and other health care proffesionals Pharm. Dr. Josef Suchopar MUDr. Michal Prokes INFOPHARM a. s. , Prague Czech Republic

Drug interactions: Are they really important? • Metaanalysis of 39 prospective clinical trials has proved: • Adverse Drug Reactions are 4 th most frequent cause of death • Lazarou et al: JAMA 1998 • Analysis of USA National Drug Register has proved: • The cause of 2/3 of ADRs are drug interactions • Phillips et al: JAMA 2001

Different kinds of drug interactions Drug interactions: • • PHARMACOKINETIC PHARMACODYNAMIC Interaction drug - drug Interaction drug - alcohol Interaction drug - foods (and soft drinks) Interaction drug – food supplements All these kinds are divided into: Drug interactions: – clinically relevant – not clinically relevant

Pharmacokinetic drug interactions Drug absorption Transport of the drug inside the body Drug displacement (protein-binding) Drug metabolism (biotransformation) CYP 3 A 4, CYP 2 D 6, CYP 2 C 9… Drug excretion

Example: Changes of biological availability of midazolam caused by coincident medication Inhibitors of CYP 3 A 4 increase bioavailability of midazolam, inducers of CYP 3 A 4 lessen it.

Pharmacodynamic drug interaction • Opposing or antagonistic interaction: – Anticoagulants + vitamin K: Anticoagulant effect opposed • Serotonin syndrome • QT prolongation – can lead to life threatening cardiac arrhytmia torsade de pointes • Disturbances in fluid and electrolyte balance – Kalium loosing diuretics + digoxin: Increased toxicity of digoxin

Probability of drug interaction rises with the number of drugs patient uses

Why doctors cannot keep drug interactions on mind? Too many informations: • 2 700 drug interaction in CR, where coincident therapy is forbidden by manufacturer • 3 100 drug clinical relevant interactions in CR, where coincident therapy may cause serious damage to patient

Solution is to combine these activities: • Education of doctors and pharmacits • Cooperation of doctors and pharmacists to identify high-risk patiens • Feedback to doctors from databases of health insurance funds • Computer program: – alerts doctors when potencial drug-drug interaction occurs – offers the most detailed evidence-based information in the actual time the prescription is written

Questions asked by doctors and pharmacists • Two drugs interact: Is this knowledge theoretical (speculative) or is it proved in humans (not only in mice or in vitro)? How strong is the proof? • Clinical relevance: If the interaction occured in humans, how serious is it? • Has it been described many times or only once? • Are all patients affected or only a few? • Is it best to avoid these two drugs altogether or can the interaction be accommodated in some way (and how)? Dosing of drugs, lab tests, watching for specific signs and symptoms… Stockley´s Drug Interactions, Sixth edition

INFOPHARM program offers (I) • Stratification of the clinical importance of drug interaction (values from 0 to 5, where values 3, 4 and 5 are clinically relevant) • Validation of quality of documentation of drug interaction: – – – poor evidence no EBM proof avilable, only manufacturer´s statement case-report good (more than 3 case-reports or a small study) excelent (study) • Aggregate evaluation of clinical importance and quality of documentation (values from 0 to 5)

INFOPHARM program offers (II) • Information, what happens to patient when the two drugs are applied • Mechanism of drug interaction (if known) • What measures are to be applied to lessen the risk: Decrease dosing, lab tests provided, watching for specific signs and symptoms, or not to apply the two drugs together at all • Comments: Abstracts from medical papers containing all the neccessary information for doctor to know how to deal with the situation • References: Each user can find the primary source of information

The way the information is provided Stratification of quality of documentacion and clinical relevance What happens to patient? Mechanism of interaction What measures are to be made?

Abstracts from medical papers are detailed Sources – to identify the medical papers

Three ways to use INFOPHARM drug interaction program • Isolated use of the program • Drug interaction program is used like a module for other program, such as: – patient notes including medication on PC – pharmacy programs for warehousing activities • Health insurance funds database use the program to provide drug prescription analysis and rational drug prescription support to the doctors

Isolated use of drug interactions program INFOPHARM

Notes (eg. diagnosis, adress of the patient… Name and number of insurance card of the patient Here user writes the name of the medicinal product

Write first 4 letters and list of drugs pops up. Scrool down to find the right drug and then ENTER

List of drugs is being made Number: Clincal relevance of drug interaction Red line: drug interaction Black line: contraindication! Where drug interaction is identified, line is automatically drawn

Program identifies: • Potential drug interactions – red connection-line • Contraindicated drug interactions – black connectionline • No drug interaction – green connection-line (evidence from human studies) • 2 or more drugs with the same active ingredient – blue connection-line • 2 or more drugs with similar active ingredient, when co-prescription is usually erroneous – violet connection-line • 2 or more drugs with marked hepatotoxicity, myelotoxicity or nephrotoxicity, when co-prescription is to be avoided – yellow connection-line

Stratification of the risk of drug interactions in ČR and in other countries In drug-interaction program filters should be implied

Documented evidence in ČR and in other countries

When only clinically relevant interaction are to be identified, press filter button Buttons for saving the patient medical record and opening another one

Now filter is set only for clinical relevant interactions level 4 and 5 To get detailed information on the drug interaction press this button

Examplex of health insurance database report on drug interactions using INFOPHARM program

Drug interactions prescribed to patients which are client of particular general practicioner Upper index: Dr. prescribed both drugs Lower index: Both drug prescribed by specialis

The same GP: drug interactions are sorted by individual patients

INFOPHARM a. s. • • • Adress: Hvozdanska 3 Post code number: 148 00 City: Prague 4 Country: Czech Republic www. drugagency. cz tel. +420 226 211 791 -3, +420 724 375 439 (Prokes Michal, MD) • fax: +420 226 211 794