Fixed dose combinations (FDCs) combine two or more active pharmaceutical ingredients into a single medicine. FDCs can be rational when the ingredients have different mechanisms of action, decrease resistance, increase efficacy, decrease adverse effects or toxicity, increase compliance by reducing pill burden, and decrease total therapy costs. Rational FDCs provide benefits like better therapeutic efficiency, reduced adverse effects, convenience of dosing, and improved patient compliance. However, irrational FDCs can also be harmful, so strict evaluation of safety, efficacy and pharmacokinetic drug interactions is needed to ensure FDCs developed in India are rational.

1. Abdul Basit
2nd Prof
1666

2. DEFINITION
It is a combination of two or more
active pharmaceutical ingredient or
compounds formulated as a single
medicine irrespective of its dosage
form designed ..

3. According to Drug and Cosmetic Act 1940 , every new FDC’s should
be considered as a new drug and should be allowed for marketing only
after submission of relevant preclinical and clinical trial data
The recent 20th model list of essential drugs prepared by the
WHO (2017) includes medications between 334 and 580 , of
which 25 are fixed dose combination drugs

4. The development of FDC’s is becoming increasingly important
from a public health perspective .
They are being used in the treatment of a wide range of conditions
and are particularly useful in the management of HIV virus / AIDS ,
MALARIA , T.B , which are considered to be the foremost
infectious disease threats in the wold today

5. Rational Fixed Dose Combination
The rational drug use stands for provision of appropriate medicines in right
manner ( dose , route , frequency of administration , duration ) in the right
patient , at right cost and right time
The main concept of rational drug therapy focuses on —
Safety.
Efficacy
Good quality of drug

6. As a rule —— a) Two drugs to be combined should
have approximately equal half life
b) The ratio of doses of each component should depend
on apparent volume of distribution and plasma
concentration

7. According to WHO Guidelines , FDC’s are rational when
they had :
Active pharamacological ingredients with different mechanism of
action
Decrease the occurrence of resistance of antimicrobial agents
Increase the efficacy of combination ( oestrogen + progesterone)

8. Decrease the incidence of ADR or toxicity ( Amiloride may prevent
hypokalemia caused by hydrochlorthiazide )
Increase the compliance of drug therapy with decrease pill burden
Dose of each API should be appropriate for defining or larger group of
population
Decrease the total cost of therapy.

9. Heart
disease
Hypertension
Obesity
Diabetes Hyperlipidemia
Co - morbid
Conditions
Treats different ailments in
the same patient ( co -
morbidity) at the same
time and with one pill
Allows for synergistic combination

10. Advantages of Rational FDC’s
Better therapeutic efficiency
Reduced adverse effects (levodopa + carbidopa)
Convenience of dose
Better patient compliance

11. Rational FDC drugs
Generic Combination Category
Amoxicillin + Clavulinic
acid
Antibiotic
Neomycin+ Bacitracin Antibiotic
Ceftazidime +
Tazobactam
Antibiotic
Levodopa + Carbidopa Antiparkinsonism

12. Ferrous salt + folic
acid
Antianaemic
Sulfamethoxazole+
trimethoprim
Antibacterial
Sulfadoxime+
pyrimethamine
Antimalarial

13. Isoniazid +
Rifampicin
Antitubercular
Benzoic acid +
Salicylic acid
Antifungal
Tannic acid +
Glycerine
Antiseptic
Al. hydroxide + Mg
hydroxide
Antiacid

14. Conclusion
Rational combinations can be of immense help to
health care system and they improve the quality of
life …………….
But Irrational fixed dose combination products are considered to be equally
harmful

15. Some Suggestions for making FDC rational in India are:
ADR Reporting should be made mandatory as they are in developed country
Pharmacokinetic drug interaction study and investigation on the safety profile shall be
an integral part of all studies on FDC Product
Medical students and post-graduate colleges must take the responsibilities of training
students and young Doctors , how to assess new drug combination more logically
Pharmaceutical Companies have to conduct detailed studies on such Combination

16. Thank You
For your Attention