Table 3.

Structured assessment of drug–drug interactions: categories of clinical relevance [27,36]

Category	Description	Examples
A	No or insignificant clinical effect	Increased drug level without clinical symptoms
		Failure of therapy with digoxin
		Atrial ectopics
		INR increase up to 4
B	Transient inconvenience (<2 days) without residual symptoms	Fatigue, headache, nausea, amnesia
		Adverse reactions from increased bioavailability of dihydropyridine calcium channel blockers
C	Prolonged inconvenience (2–7 days) without residual symptoms	Adverse reactions resulting from increased biovailability of antiepileptics or ciclosporin
	Failure of therapy for nonserious diseases	Decreased effects of methadone or thyroxine
D	Prolonged (>7 days) or permanent residual symptoms or invalidity	Toxic effects of aminoglycosides, lithium, methotrexate, digoxin
		INR increase >6
	Failure of therapy for serious but nonfatal diseases	Failure of therapy with loop diuretics (leading to hospitalization because of heart failure)
E	Increased risk of dying	Gastric haemorrhage
		Prolongation of QT interval
		Rhabdomyolysis
	Failure of life-saving therapy	Failure of therapy with antiretroviral drugs, quinidine, ciclosporin
	Increased risk of pregnancy without risk factors for mother or child	Failure of contraceptives due to enzyme induction
F	Death	Fatally ending insult
	Potentially fatal adverse effects	Torsades de points
		Serotonin syndrome
	Increased risk of pregnancy with risk factors for the child

INR, International Normalized Ratio.