Combining two or more rational drugs is advantageous in case of some very few, selected drugs and sometimes is even necessary. Let us briefly see the scientific rationale of such selected few drug combinations and their particular examples.

1. Synergism: Two drugs are said to have synergism when they facilitate each other’s pharmacological action and hence total effect is greater when given together compound to the sum of their independent actions. For example : sulfamethoxazole+trime-thoprim - the great invention in the field of antimicrobials; thiazide diuretic with ganglion-blocking antihypertensive agent; Benzoic acid+saliacylic acid (for treatment of superficial fungal infection of the skin); Levodopa + Carbidopa (for treatment of parkinsonism); Oestrogen + Progesterone in oral contraceptive pills; glucose + sodium chloride in Oral Rehydration Solution.
   
2. Enhanced Efficacy: this is also a kidn fo synergism, but there is either no linking of other’s pharamco-chemical actions or such a linkage is still not clear. For example " Aspirin _ Coderinel isonex + thiacetazone / P.A.S. / Rifampicin / Ethambutal (to reduce the emergence of drug-resistance to isoinex in the treatment of Tuberculosis); Calcium with Vitamin D (for better absorption); Ferrous Sulfate + Folic acid - (haemoglobin levels would not rise above a 11gms% by Iron alone if there is simultaneous Folic acid deficiency and is not simultaneously met).
   
3. Combined nature of the problem: Vitamin ‘B complex’, multivitamin, Ferrous sulfate + Folic Acid, Vit A + Vit D. Vitamin B deficiency is generally that of all the components of Vitamin ‘B complex’. Many times there is simultaneous deficiency of all the Vitamins in framine conditions, in generalized undernourishment and hence a multivitamin preparation is justified in such cases. Deficiency of iron and Folic acidm, and sometimes of Vit. A and Vit D coexists since their dietary sources are similar, hence their respective F.D. combinations are justified.
   
4. Reduction of side effects or toxicity: isonex + Vitamin B6 (Vitamin B6 prevents Peripheral Neuritis caused by prolonged use of Isonex); Ephedrine + Phenobarbitone - as antiasthmatic (Phenobarbitone counters the central nervous system stimulation caused by Ephedrine); Phenobarbitone+Phenvotoin Sodium as anticonvulsant (reduction of dose both individual drugs due to combination and hence reduction of their toxicity); Magnesium hydroxide+Aluminium hydroxide as antacid (the latter tends to cause constipation; the former is a laxative).
   There could be a few more rational F.D. combinations. But the simple, general rule is that a F.D. combination is justified only when there is a loss in the therapeutic advantage in not combing the two drugs. All other drug-combinations are irrational and should not be allowed.

Source : R.S. Anant, Irrational Drugs and irrational Drug Combinationsm in Amit Sen Gupta (Ed.) op.cit.