Fixed Dose Combinations

(FDCs)
Department of Pharmacology
Ashwini Rural Medical College,
Hospital & Research Center,
Kumbhari, Solapur
1
Tab Syndopa ( Levodopa 100 mg,
Carbidopa 10 mg)

2
 Tab Syndopa ( Levodopa 100 mg, Carbidopa 10 mg)
The fixed dose combination Syndopa is rational.
Indication for this FDC is - Parkinsonism
Justification :
▪ Carbidopa is a peripheral decarboxylase (DC)
inhibitor, when combined with levodopa, it will
inhibit DC in periphery and thereby prevent
conversion of levodopa to dopamine in peripheral
circulation.
▪ This action increases the entry of levodopa in CNS
and also prevents side effects that occur due to
accumulation of DA in periphery.
▪ This also allows reduction in the dose of levodopa &
there is better patient compliance.
▪ Cost of medication is also reduced. 4

▪ Therefore, this FDC is rational & included in WHO list

 tab Catapress (Atenolol 50 mg,
Nifedipine 20 mg)

5
The fixed dose combination Tab. Catapress is
irrational.
Indications for this FDC are hypertension,
angina pectoris

6
 Tab CATAPRESS
Justification :
Atenolol is cardioselective β1-blocker, while
nifedipine is dihydropyridine class of calcium
channel blocker. Combination is rational but
FDC is irrational.
Nifedipine & Atenolol have different
mechanisms of action in hypertension & angina
& therefore exhibit synergism.
Nifedipine induced reflex tachycardia, is
counteracted by β blocker-Atenolol.
Doses of individual drugs can be minimized
when they are used in combination.
Therefore , their dose related side effects are
minimized.
Therefore the combination is rational.
But the dose of individual drug can not be
titrated according to clinical response of the 7
patient.
Therefore, the fixed dose combination of drugs
 TAB Ditide
(Triamterene 50 mg, Benzthiazide 25
mg)

8
The fixed dose combination Ditide is irrational.

Indications for this FDC are- treatment of

hypertension, edema.

9
 Tab Ditide
Justification :

Triameterene is K+ sparing diuretic, while

benzthiazide is a thiazide diuretic. The important
adverse effect of benzthiazide is hypokalemia
which is counteracted by K+ sparing drug
triamterene.
Combination provides additive diuretic activity &
antihypertensive effects & minimizes potassium
depletion. Therefore, this drug combination is
rational.
But, individual drugs can not be titrated
according to patients clinical response. 10
Therefore, this fixed dose combination is
irrational.
Ascoril C Syrup containing :
Codiene 10 mg/5ml
chlorpheniramine 4 mg/5 ml

Indications for this FDC are - Dry cough

associated with common cold, flu etc.

11
The fixed dose combination Ascoril C syrup is
irrational.

12
 Syrup Ascoril C

Justification :
Codeine is a central cough suppressant, while
chlorpheniramine is antihistaminic H1 blocker.
Chlorpheniramine causes reduced airway
secretions by its antihistaminic actions.
For treatment of dry cough only codeine is
sufficient, there is no rationale for addition of
chloropheniramine.
The combination increases adverse effects as
well as cost of treatment.
Therefore, this FDC is irrational. 13
 Inj. Xylocaine 1%
(Lignocaine 1% with Adrenaline)

14
The fixed dose combination Xylocaine is
rational.
Indications for this FDC are nerve block &
infiltration anaesthesia.

15
 Inj. Xylocaine 1%

Justification :
Lignocaine is a local anesthetic while adrenaline
is a sympathomimetic drug. Addition of
adrenaline in topical preparations of lignocaine
helps in following ways :
Adrenaline induced vasoconstriction reduces
systemic absorption of lignocaine & helps in
avoiding systemic toxicity of lignocaine.
It increases duration of action of lignocaine at the
site of application, by causing vasoconstriction.
Dose of lignocaine for local action can be reduced
16
with the addition of adrenaline.
 Inj. Xylocaine 1%

Therefore, this FDC is rational & included in

WHO list of essential medicines.

C/I : This combination is contraindicated for

use at places which are supplied by end
arteries (Finger tips, penis, tip of nose etc.)

17
 Asthalin expectorant
(Salbutamol 2 mg, Guaphenesin 100 mg/10
ml)

18
The fixed dose combination asthalin
expectorant is irrational.
Indications for this FDC are – Cough and
bronchoconstriction/congestion caused by the
common cold, bronchitis, emphysema & other
broncho-pulmonary disorders.

19
 Asthalin Expectorant
Justification :
Salbutamol is β2 receptor agonist, while
guaphenesin is an expectorant.
Salbutamol is a bronchodilator, acts by β2 agonistic
action in bronchial smooth muscles which
improves airflow.
Expectorant guaphensin increases secretions in
respiratory tract, loosens the thick bronchial
secretions thus improving mucociliary clearance in
the airways.
Therefore, when there is mucus plug formation
associated with bronchoconstriction, combination is
useful.
However if the combination is used 20
indiscriminately in all patients of cough, patients
unnecessarily get exposed to the adverse effects of
 Tab Combiflam
(Ibuprofen 400 mg, Paracetamol 325 mg)

21
The fixed dose combination Combiflam is
irrational.
Indications for this FDC are – headache, body
ache, stiff joints, dental ache, back pain & joint
pain.

22
 Tab Combiflam
Justification :
Ibuprofen is propionic acid derivative &
paracetamol is paraamino phenol derivative, both
belong to the same class of drugs i.e. NSAIDs.
Ibuprofen is primarily indicated as anti-
inflammatory/analgesic while paracetamol is used
as antipyretic and analgesic.
This combination is irrational because both drugs
act by similar mechanism, the combination doesn’t
give any additional benefits & increases the toxicity
as they have common side effects eg. peptic ulcer,
nephrotoxicity. Therefore monotherapy with
individual drug is sufficient depending on the
situation.
23
The fixed dose combination increases ADRs and cost
of therapy.
Tab Mala-D (Norgestrel 0.3 mg,
Ethinyl estradiol 30 μg )

24
 Tab Mala-D (Norgestrel 0.3 mg,
Ethinyl estradiol 30
μg )

The fixed dose combination Mala-D is rational.

Indication for this FDC : Oral contraceptive to
prevent pregnancy.

25
 Tab Mala - D
Justification :
Mala- D is an OC pill that contains combination of
the hormones estrogen & progestin.
These prevent pregnancy by reducing the release of
the luteinizing hormone (LH) & follicle stimulating
hormone (FSH) from the pituitary by negative
feedback inhibition.
As a result follicle fails to develop, doesn’t rupture &
therefore ovulation doesn’t occur.
Progestin inhibits sperm penetration through the
cervix into the upper genital tract by decreasing the
water content & increasing the viscosity of the
cervical mucus.
Therefore, the combination has synergistic action as
contraceptive, more efficacious than the individual 26
drugs.
Therefore, this FDC is rational & included in WHO
Tab Ovral
(Levonorgestrel 0.25 mg,
Ethinyl estradiol 50 μg)

27
 Tab Ovral
(Levonorgestrel 0.25 mg,
Ethinyl estradiol 50 μg)

The fixed dose combination Ovral is rational.

Indication for this FDC : Oral contraceptive to
prevent pregnancy.

28
 Tab Ovral
Justification :
Ovral is an OC pill that contains combination of the
hormones estrogen & progestin.
These prevent pregnancy by reducing the release of
the luteinizing hormone (LH) & follicle stimulating
hormone (FSH) from the pituitary by negative
feedback inhibition.
As a result follicle fails to develop, doesn’t rupture &
therefore ovulation doesn’t occur.
Progestin inhibits sperm penetration through the
cervix into the upper genital tract by decreasing the
water content & increasing the viscosity of the
cervical mucus.
Therefore, the combination has synergistic action as
contraceptive, more efficacious than the individual 29
drugs.
Therefore, this FDC is rational & included in WHO
Augmentin inj.
Amoxicillin 1g
Clavulanic acid 200mg

30
31
Clavulanic acid is a ‘progressive’ inhibitor:
binding with β-lactamase is reversible initially,
but becomes covalent later—inhibition
increasing with time. Called a ‘suicide’ inhibitor,
it gets
inactivated after binding to the enzyme.
It permeates the outer layers of the cell wall of
gram-negative bacteria and inhibits the
periplasmically located β-lactamase.

32
Addition of clavulanic acid re-establishes
the activity of amoxicillin against β-lactamase
producing resistant Staph. aureus (but not MRSA
that have altered PBPs), H. influenzae,
N. gonorrhoeae, E. coli, Proteus, Klebsiella,
Salmonella and Shigella.

33
Clotrimoxazole tab
Sulfamethoxazole 400mg
Trimethoprim 80mg

34
The fixed dose combination of trimethoprim
and sulfamethoxazole is called cotrimoxazole.
Trimethoprim is a diaminopyrimidine related to
the antimalarial drug pyrimethamine which
selectively inhibits bacterial dihydrofolate
reductase (DHFRase). Cotrimoxazole introduced
in 1969 causes sequential block of folate
metabolism.

35
36
Individually, both sulfonamide and trimethoprim
are bacteriostatic, but the combination becomes
cidal against many organisms.

37
Fancidar tab
Sulfadoxine 500mg
Pyrimethamine 25mg

38