FIXED DOSE COMBINATIONS (FDC)

1. Tablet: - Levodopa 100 mg or 250 mg + Carbidopa 10 mg or 25 mg

-Levodopa 100 mg or 250 mg

-Carbidopa 10 mg or 25 mg

A. Indication: Parkinsonism

B) Dose & Route: Started with 1 tab TDS orally. Dosage increased slowly over a periods of
week depending on the response of patient.

C) Justification for using both drugs in FD combination

1) L-dopa is a prodrug, while carbidopa is a peripheral dopa decarboxylase enzyme inhibitor

2) If L- dopa is used alone then more than 95% of it is converted in peripheral tissue to
dopamine (DA) by the peripheral dopa decarboxylase. Therefore only 1 to 2% of L- dopa is
available to cross the blood brain barrier & reach the brain striatal region to produce its
beneficial effect.

3) The peripherally produced DA is responsible for certain side effects –

i) Tachycardia, palpitations ii) Nausea, vomiting

4) Carbidopa, by inhibiting peripheral dopa – decarbaxylase, prevents peripheral conversion of

L- Dopa to DA & therefore permits more amount of L-dopa to enter the brain & thus increases
the therapeutic effect of L- dopa.

5) The FD combination of both drugs has following advantages.

i) Effective dose of L-dopa is reduced by 75%.
ii) Side effects like nausea, vomiting, tachycardia, palpitations are prevented. This permits
more rapid increase in the dosage to optimum levels & also improves patient compliance.
iii) Pyridoxine dose not antagonize the effects of L-dopa.
iv) Control of symptoms is smoother & ‘on –off’ effect is minimized.
v) Degree of improvement is higher, some pts not responding adequately to L-dopa alone, also
improve.

D) Contraindications: i) H/O hypersensitivity to L-dopa &/or carbidopa. ii) Presence of CVS &
Psychiatric diseases.

E) General comments: Clinical documentation justifies the use of this FD combination & it is
included in WHO list of essential drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

2. Tablet: Sulphamethoxazole 400 mg + Trimethoprin 80 mg

- Tablet Sulphamethoxazole 400 mg

-Trimethoprin 80 mg
A) Indications: Dose & route : Given orally used to treat i) Acute urinary tract
infections due to E. coil, proteus. Dose 2 tab BD x 10-14 days. ii) Acute respiratory
tracts infections caused by gram +ve cocci & H. influrenzae. 2 tab BD x 7-10 days.
iii) Typhoid 2 tabs BD,contd for 7 days after fever comes down (i.e. 3+7 = 10 days)
iv) Gonorrhoea 2 tabs BD x 5 days
v) Bacterial diarrhoeas & dysentery due to E coli, Shigella, Campylobacter 2 tabs BD x
5 days vi) Pneumocystis carini infection in AIDs patients.
B) Justification: Each drug is bacteriostatic but combination is bactericidal. Therapeutic
effect is greater than the sum of the effect of each drug. They form supradditive
synergistic combination due to sequential blockade.
Conversion of
to to
PABA Folic acid Folinic acid
Prevented by Prevented by (THFA)
Sulphamethoxazole by Trimethoprin by
inhibiting Folic acid inhibiting dihydrofolate
synthetase reductase

other advantage is bacterial resistance develops slowly to the combination.

C) Precaution –Should NOT be prescribd to pts with hypersensitivity reactions to sulfas
contraindicated in pregnancy.
D) General comments: i) Compliance is improved. ii) Cost is less than the sum of the
individual drug. iii) Clinical documentation justifies the use of the combination. iv) This
Fixed dose drug combination is included in WHO of Essential drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

3. Tablet: Sulphadoxine 500 mg + pyrimethamine 25mg

-Sulphadoxine 500 mg
-Pyrimethamine 25mg

A. Indications: To treat acute attack of malaria especially chloroquine resistant

falciparum malaria.

B. Dose & route: 2-3 tablets single dose orally for adults

C. Justification: Sulphadoxine has some inhibitory effects on the erythrocyte phase

specially of P. falciparum. However, it forms supraddictive syngergistic combination
with phrimethamine due to sequential blockade.

Conversion of

to to
PABA Folic acid Folinic acid
Prevented by Prevented by
Sulphadoxine by Pyrimethamine by
inhibiting Folic acid inhibiting dihydrofolate
synthetase reductase

IV) Precaution: Should NOT be prescribed to patients with H/O hypersensitivity

reactions to sulphonamides. Contraindicated in pregnancy

V) General comment: i) Cost is less than the Sum of the individual drugs

ii) Clinical documentation justifies the use of the combinations.

iii) This Fixed Dose drug combination is included in WHO list of essential Drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

4. Tablet: Isoniazid 300 mg + Thiacetazone 150 mg

- Isoniazid 300 mg &

- Thiacetazone 150 mg

A) Indication: Tuberculosis

B) Dose & Route: 1 tablet daily orally for 8 months after an initial course of 2 months
with INH & Rifampicin (Low cost regime)

C) Justification for giving thiacetazone with INH: Thiacetazone is tuberculostatic; it

delays the development of resistance to INH a tuberculocidal drug.

D) Contraindications: 1. Hepatic diseases, 2. renal failure, 3. Sensitivity to INH &/or

thiacetazone.

E) General comments: 1. Patient compliance is improved

2. This fixed dose drug combination is justifiable & is included in WHO list of essential
drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

5. Tablet: Ethinyl oestradiol 0.03mg +Levonorgestral 0.15 mg

Tablet: -Ethinyl oestradiol 0.03 mg

-Levonorgestral 0.15 mg

A. Indication: For contraception in females.

B. Dose & route: Taken orally. One tablet is taken daily for 21 days starting on 5th
day of menstruation. The next course is after a gap of 7 days. Calendar packs with
21 active & 7 blank pills are available.
C. Justification for using both drugs in combination: Ethinyl oestradiol is mainly
responsible for inhibiting ovulation.
Levonorgestrel 1) Ensures prompt bleeding on withdrawal & reduces the risk of
endometrial carcinoma. 2) Helps in contraception by inhibiting ovulation & by
making the cervical mucus thick, viscid & hostile to sperms.

D. Contraindications: 1. Thromboembolic disorder or H/o it. 2. Moderate to severe

hypertension. 3. Active liver disease or H/O jaundice during post pregnancy. 4.
Suspected / overt malignancy of genitals / breast.

E. General comment: This fixed dose drug combination is justifiable & is included in
WHO list of Essential drug.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

6. Injection: Lignocaine 2% + Adrenaline 1 in 200,000

Injection: Lignocaine 2%

Adrenaline 1 in 200,000

A. Indications: for infiltration & nerve block anesthesia.

B. Route of administration:
1) For Infiltration anesthesia –The local anesthetic solution is infiltrated under the
skin in the area of operation –blocks sensory nerve endings.

2) For nerve block anesthesia the LA solution is injected around nerve trunks or
plexuses.

C) Justification for including Adrenaline:

Adrenaline by constricting blood vessels, Slows the absorption of the LA from the site
of administration & thus
1) Prolongs the duration of action of the LA
2) Decreases the systemic toxicity of the LA i.e. Lignocaine.

D) Precautions:
1) Lignocoine containing Adrenaline injection should NOT be used to treat Ventricular
tachycardia.
2) Lignocaine containing Adrenaline injection should NOT be injected in tissue / sites
supplied by end arteries e.g. Fingers, toes, penis, ears & nose. To do so will result in
ischemic necrosis & gangrene of adrenaline – induced, vasoconstriction of the end
arteries. 3) Lignocaine containing ADR injection should NOT be: used in pts with
myocardial disease (ischemia arrhythmias), hypertension & hyperthyroidism.
E) General Comments: Combination of Lignocaine with adrenaline is rational and this
Fixed Dose Drug combination is included in WHO test of essential Drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

7. Oral rehydration salt

1) Sodium chloride -3.5gm

2) Potassium chloride-1.5 gm

3) Tri sodium citrate dehydrate -2.9 gm

4) Glucose-20gm

A) Indication: To correct dehydration in cases of diarrhoeas, cholera. Helps to restore &

maintain hydration, electrolyte & pH balance.

B) Dose & Route: Contents of packets dissolved in a liter of water. ORS solution taken
orally at ½ - 1 weight volume, initially 5-7.5% body weight volume equivalent is given
in 2-4 hours. Subsequently taken in amounts & at intervals, sufficient to cover the rate of
loss in stools.

C) Justification for using the ingredients:

1. NaCl, KCL are used to correct the Na, K & Chloride loss respectively.

2. Glucose is added as it facilitates Na reabsorption

(Glucose –Na contransport system is functional) Glucose also provides nutrition.

3. Na citrate is used to correct acidosis.

D) Precaution: Excessive glucose should not be used as it can produce osmotic diarrhea.

E) General comment: This FDC is justifiable & is included in WHO list of essential
drugs

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

8. Ointment Benzoic Acid 6%+ Salicyclic Acid 3%

A) Indication: To treat ringworm Fungal skin Infection, tenia pedis, tenia versicolor &
other dermatomycoses.

B) Route: Ointment applied locally to the affected part BD, TDS or as reqd. It is also
called as Whitfield’s ointment

C) Justification: 1. Benzoic acid has antifungal activity is fungistatic.

2. Salicylic Acid is comparatively a weak antifungal agent but has keratolytic

properties. By its keratolytic action it helps to remove the hyperkeratotic skin tissue &
thus promotes the penetration of Benzoic acid into the lesion & ensures better contact of
Benzoic acid with fungus.

D) Side effects: Points may complain of irritation & burning sensation at site of
application.

E) General comment: This FDC is justifiable & is included in WHO list of Essential
Drugs.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

9. Tablet: - Propranolol HCl 40 mg + Dihydralazine 25 mg +Hydrochlorthiazide 20

mg

Tablet -Propranolol HCl 40 mg

Dihydralazine sulphate 25 mg

Hydrochlorthiazide 20 mg

A) Indication, Dose & route – Moderate to severe hypertension. Given orally. Start with
one tab OD or BD & gradually increase up to 5 tabs daily, until control is achieved.

B) This is a combination of β-blocker, an arteriolar dilator & a diuretic. In the treatment

of moderate to severe hypertension combination of drug is used to:

1) Prevent side effects &

2) To get an additive antihypertensive effects.

Hydrallazine – included (1) Salt & water retention is counteracted by hydrochlorthiazide

(2) tachycardia & palpitations by propranolol

Further the combination of 3 doses is highly effective as 3 different parameters

affecting BP are reduced viz Cardiac output by propranolol, Peripheral resistance by
hydrallazine, plasma volume by hydrochlorothiazide.

C) However, using their 3 doses in fixed dose combination has the following
disadvantages 1) It is NOT possible to alter the dose of any one drug independent of the
other 2) Contraindication to one component (allergy other conditions. Contraindicates
the whole preparation e.g. Propranolol is contraindicated in bronchial
asthmatics.Therefore this FDC preparation cannot be used in hypertensive having
bronchial asthma. Hence using the 3 drugs in a fixed dose combination is NOT
justifiable.

D) General comments: The 3 days should be prescribed & taken separately & SHOULD
NOT be used in fixed Dose combination.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

10. Tablet: Atenolol -50 mg (Aten) +Nifedipine (SR) -20mg (Nif)

Tablet Atenolol -50 mg (Aten)

Nifedipine (SR) -20 mg (Nif)

A) Indications: 1) Moderate to severe hypertension 2) Exertional Angina.

B) Dose & Route: Given Orally 1 tab daily: increased to 2 tabs daily if required.

C) This combination of the cardio selective β1 receptor blockers Aten & the CCB Nif,
an arteriolar dilator, is used as it provides

1) An additive antihypertensive effect – Aten decreases CO & Nif decreases Peripheral

Resistance.

2) An additive Antianginal effect –the 2 drugs their myocardial O2 requirement by

acting different mechanisms viz Aten HR & FOC by blocking cardiac β1 receptors Nif
decreases after load by dilating arterioles. Further, Aten counteracts Nif- induced reflex
tachycardia & Palpitations.

D) However using the 2 drugs in FD comb has following disadvantages: 1) It is Not

possible to alter the dose one drug independent of the other 2) H/O hypersensitivity to
any one of the drug contraindicates the FD comb tablet.3) Contraindication to any one
drug contraindicates the FDC tab. eg Aten is contraindicated in pts having associated
CHF, sinus bradycardia, AV blocks. Therefore this FDC tab cannot be used these
associated diseases. Hence using the 2 drugs in a Fixed Dose comb is NOT justifiable.

E) General Comments: The 2 drug should be prescribed & taken separately & should
NOT be used in a Fixed Dose Combination form.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

11. Enalapril – 10 mg (Ena )+ Hydrochlorthiazide – 25 mg (HCT)

Enalapril – 10 mg (Ena)

Hydrochlorothiazide – 25 mg (HCT)

A) Indications: 1) Moderate to severe hypertension.

2) Congestive cardiac failure

B) Dose & Route: 1 tab daily increasing to 2 tabs once daily if reqd , orally

C) Advantages of using both drugs are: 1. They produce an additive effect & 2.Thiazide
induced hypokalemia is counteracted by enalapril.

D) However, using the 2 drugs in Fixed dose combination is Not justified as:- 1. It is Not
possible to alter the dose of one drug independent of the other. 2. To avoid first dose
severe hypotensive effect of enalapril it is usually started in small doses of 2.5 mg or 5
mg daily & the thiazide diuretic is usually stopped. The diuretic therapy is restarted later
if read. One cannot take this precaution if fixed dose combinartion tablet is used. 3.
Enapril is preferred in pts having associated diabetes mellitus; gout while HCT is to be
avoided. Therefore such FD comb tablet cannot be used in pts having associated diseases
like diabetes mellitus & gout.

E) Contraindicated in Pregnancy in pts with bilateral renal artery stenosis & in pts
suffering from persistent cough.

F) General Comment: The 2 drug should be prescribed & taken separately & NOT used
as fixed Dose combination tablet.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

12. Tablet: - Ibuprofen 400 mg (Ibu) + Paracetamol 325 mg (par)

Ibuprofen 400 mg (Ibu)

Paracetamol 325 mg (par)

A) Indications: 1. Rheumatoid arthritis

2. Osteoaarthiritis

3. Ankylosing spondylitis

4. Musculo-skeletal disorders

5. To relieve postoperative, postpartum pain, toothache.

B) Dose & Route: 1 Tab TDS orally after meals to avoid GTI Side effects, or as reqd

C) This is a FD combination of an analgesic – anti-inflammatory drug IBU with an

analgesic antipyretic drug Par.

D) Using both drugs in FD combination is NOT justified as

1. In the above stated conditions in majority of pts Ibu alone in adequate dosage will
relieve the pain & inflammation.

2. In an occasional pt, if pain is not adequately relieved by Ibu alone then Par can be
prescribed & taken separately to provide an extra pain relief.

3. In majority of pts giving both drugs in FD comb leads to wastage of Par &
unnecessarily increases the cost of treatment.

E) Contraindications: i) H/O hypersensitivity to Ibu &/or Par. ii) Active peptic ulcer.

F) Special precautions: i) Br. Asthma ii) Renal Hepatic or bleeding disorders iii) Those
receiving coumarin anticoagulanants iv) Pregnancy

G) General comments: 1. Contraindications to one component eg. H/O hypersensitivity

to Ibu or Par, Contraindicates the Whole preparations. 2. This FD Combination is not
rational & hence NOT justifiable.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

13. Tablet: - 1. Folic acid - 750 microgram 2. Vitamin B12 - 7.5 microgram 3.
Ferrous fumarate - 200 mg

Tablet1. Folic acid - 750 microgram

2. Vitamin B12 - 7.5 microgram

3. Ferrous fumarate - 200 mg

A) Indications to treat anemias due to Folic acid, Vit. B12 & Iron deficiency

B) Dose & Route: 1 tab td safer food, orally

C) Using all 3 drugs in a fixed dose combination is NOT justified as

1. It is rare for a person to suffer from Folic acid, Vit. B12 & Iron deficiency at the same
time.

2. If the person for e.g. is suffering from Iron deficiency anemia only then simultaneous
administration of folic acid & Vit B12 is of no use. It only Leads to wastage of drug &
unnecessarily increases the cost of treatment.

3) If the person for e.g. is suffering from vit B12 deficiency only then simultaneous
administration of folic acid can prove harmful. Folic acid by diverting Vit. B12 for
erythropoises reduces the availability of Vit B12 for nervous tissue & this aggravates
peripheral neuritis.

D) Side effect: Constipation or GI upsets due to Fe fumarate.

E) General Comment: Depending on the cause of anemia a single specific drug should
only be used & such type of shotgun therapy using multiple haematinics in fixed dose
combination should be avoided.

Vimp for SN on ‘Shot Gun haematinic preps’ or therapy refer Trip P 541 ‘Shot Gun
antianemia preps’ – Write this matter & include marked portion of this sheet, Others
disadvantages of using Fe, Folic acid & Vit B12 in a FDC are : Points 1, 2 & 3. Hence
using such FDCs in NOT recommended.

Department of Pharmacology, BKLWRMC, Sawarde

 FIXED DOSE COMBINATIONS (FDC)

14. Tablet: Norfloxacin 400 mg (Nor) + Tinidazole 600 mg (Tin)

Tablet: Norfloxacin 400 mg (Nor)

Tinidazole 600 mg (Tin)

A) Indications, Dose & Route: 1. Diarrhoea, or dysentery of bacterial, amoebic or mixed

origin. One tab twice daily for 5 days, orally.

2. This is a FD combination if an antibacterial drug Nor with an antiamoebic drug Tin. 3.

Using both drugs in FD combination is Not justified as i) Only occasionally a patient
suffers from both bacterial & amoebic dysenteries at the same time. ii) If the patient is
suffering from bacterial dysentery only then Norflox alone is useful & simultaneous
administration of tin leads to wastage of tin & unnecessarily increases the cost of
treatment. Similarly, if the pt is suffering from amoebic dysentery only then Tin alone is
useful & simultaneous adm of Nor leads to wastage of Nor & unnecessarily increases
the cost of treatment.

3. H/O hypersensitivity to Nor or Tin contraindications the FD Combination preparation.

4. Nor is avoided in chidren because of risk of arthropathy. Therefore this FDC cannot
be used in children.

5. Both drugs share common AEs eg GI distress & CNS effects – Headache, dizziness.
Therefore unnecessary use of both drugs in FD combination subjects the patient to an
increased risk of these AEs .

D) Contraindications: i) H/O hypersensitivity to Nor &/ Or Tin, ii) Pregnancy

E) Special precautions: i) Patients predisposed to seizures, having neurological

disorders. ii) Avoid alcohol (as Disulfiram like reactions to Tin will occur if taken)

F) General comments: In the occasional adult pt suffering from both amoebic &
bacillary dysenteries this FDC preparation may be used.

However its routine use for every case of pure amoebic or bacillary dysentery is NOT
rational & hence NOT recommended.

Department of Pharmacology, BKLWRMC, Sawarde