Pharmacokinetic interactions are manifested by undesirably reduced, or increased action of the drug from the expected effects, occurring due to changes in its blood concentration when co-administered with one or more other drugs. Consequently, adverse reactions due to pharmacokinetic interactions are characterized by increased or reduced pharmacological effect of the drug. In assessing the probable cause of side effects in clinical use of a drug, the patient's comedication, comorbidity, and individual genetic diversity in the activities of enzymes and transporters involved in the elimination and excretion of "active" form of the drug and its metabolites from the body have to be taken into account. Therefore, the assessment of causes of adverse reactions in clinical use of a drug is very complex. Due to the population aging and polypharmacy, drug interactions are common and can lead to severe or serious adverse events, and be the cause of hospitalization. Most of the pharmacokinetic (PK) interactions can be predicted and prevented, usually by adjusting the dosage or by reducing or increasing the dose of a particular drug in clinical use, and avoiding or even contraindicating co-administration of two specific drugs that can enter into a significant interaction. Additionally, special precaution is needed when administering the narrow therapeutic/critical dose drugs. The aim of this paper is to present reported adverse effects in year 2013. in Croatia and to provide an overview of the mechanisms of PK drug interactions and emphasize the predictability and the possibility of avoiding certain PK interaction and consequent occurrence of side effects in order to increases the safety of clinical drug administration, highlighting the narrow therapeutic index drugs.