Should not be CombinedThe reason may be a pharmacodynamic interaction that can have dramatic consequences (unpredictable increase in bleeding risk, serious cardiac arrhythmias, bone marrow suppression, seizures, serotonin syndrome, etc.). It may also be a very strong or unpredictable pharmacokinetic interaction. This can either be a large increase in the concentration (usually more than a fivefold increase) of the affected drug with risk of toxic effects, or a significant decrease in concentration (usually more than 80% reduction) of the affected drug with risk of therapeutic failure.
If the drug is essential (immunosuppressants, warfarin, anti-HIV agents, contraceptives), the consequences of therapeutic failure can be dramatic (rejection of transplanted organs, thrombosis, HIV flare-up, unwanted pregnancy). Sometimes reduced therapeutic effect is far less dramatic (phosphodiesterase inhibitors such as sildenafil, tadalafil and vardenafil for erectile dysfunction), but a reduction of more than 80% in concentration with resulting lack of effect is classified in this category.
Although a drug combination is classified in this group it may sometimes be justifiable or even desirable to combine the drugs. However, this should only be done after a careful risk/benefit assessment on an individual basis.
Take PrecautionsThis category is used if the pharmacodynamic interactions are less dramatic than in the category above, or if the pharmacokinetic interactions lead to an increase in concentration of less than fivefold or a reduction in concentration of less than 80%.
Examples of precautions that may be relevant are:
- adjust the dose of the affected drug
- measure the plasma concentration of the affected drug and adjust the dose if necessary
- bring the patient back for clinical follow-up
- ask the patient to contact you if specific symptoms occur
- monitor relevant laboratory parameters (INR, serum creatinine, hematological parameters, ECG etc.)
Academic InterestA selection of the interactions concerns drugs that can generally be combined without further action. The interactions are still mentioned because they may occasionally produce stronger effects in individual patients, so that it may later be necessary to investigate whether an interaction may be the cause if a patient has an abnormal reaction to a specific drug combination.
