2. Definition
Incompatibility is the result of prescribing
two or more substances which are
antagonistic in nature and result in
undesirable products or results which
may affect the safety, efficacy and quality
of the products.
Incompatibles are substances which have
opposite medicinal properties, or
substances when mixed together, react
chemically to produce other substances.
An understanding of incompatibilities can
save the pharmacist valuable time in
compounding as well as ensure the
4. Physical Incompatibilities
Physical incompatibilities are often called
Pharmaceutical incompatibilities and produce a
mixture which is unacceptable in appearance and
taste and may result in non-uniform dosage form.
1. Incomplete solution: Gums are insoluble in
alcohol, resins are insoluble in water
2. Precipitation: Resins are precipitated from
alcoholic solution when water is added
Camphor and volatile oils are salted out from
their aromatic water when soluble salts are
added
3. Immiscible liquids. Eg oil & Water
4. Eutexia: eg formation of Eutectic mixture
5. Chemical Incompatibilities
This type of incompatibility exists when
agents are prescribed that react
chemically when mixed, altering the
composition of one or more of the
constituents.
Examples
- Formation of precipitate
- Evolution of gas
- Colour change
6. 1. Alkaloidal Incompatibility
i. Alkaloidal salts with alkaline substances
ii. Alkaloidal salts with soluble iodides
iii. Alkaloidal salts with Tannins
iv. Alkaloidal salts with salicylates
v. Alkaloidal salts with soluble iodides &
bromides
Rx
Caffeine citrate
Sodium Salicylate
Water qs
Make a Mixture
Rx
Strychnine Hcl solution
Aromatic spirit of
Ammonia
Water qs
Make a Mixture
7. 2. Soluble Salicylates
Incompatibilities
i. Soluble salicylates with ferric salt
ii. Soluble salicylates with alkali
bicarbonates
iii. Soluble salicylates and benzoates with
acids Rx
Sodium Salicylate
Lemon syrup
Water qs
Make a Mixture
Rx
Ferric chloride solution
Sodium salicylate
Water qs
Make a Mixture
8. 3.Soluble Iodides Incompatibility
Rx
Quinine sulphate
Dilute sulphuric
acid
Potassium iodide
Water qs
i. Oxidation of iodides with ferric salts
ii. Oxidation of iodides with potassium
chlorates
iii. Oxidation of iodides with Quinine Sulphate
Rx
Ferric chloride
solution
Potassium iodide
Potassium citrate
Water qs
9. 4. Evolution of CO2 Gas
Rx
Sodium bicarbonate
Borax
Phenol
Glycerine
Water qs
Make a Spray Solution
i. Sodium bicarbonate with soluble calcium
or magnesium salts
ii. Bismuth subnitrate with sodium
bicarbonate
iii.Borax with sodium bicarbonate and
glycerin
10. Miscellaneous
Eg.: Soluble Barbiturates with Ammonium
bromide
Rx
Phenobarbitone sodium 600mg
Ammonium bromide 8 gm
Water qs 100 ml
Make a Mixture
Label: Two teaspoonful to be taken at night
11. Therapeutic Incompatibility
Error in dosage
Wrong Dose or dosage form
Contra-indicated drugs
Synergistic and Antagonistic drugs
Drug Interactions
12. Error in dosage
Rx
Codeine phosphate 0.5 g
Prepare 10 dose
Direction: One dose to be taken at bed time
Note:
As Codeine phosphate is a potent drug hence the dose
shows in large quantity.
May be the intention of the physician is to prescribe 5mg
and by mistake prescribed as 0.5 g in the prescription. So
prescription may be referred back to the physician
informing with the dose to be corrected.
14. Contra-indicated drugs
Pregnancy & Lactation
Renal failure
Liver Cirrhosis
The Penicillins and Sulpha drugs are
contra-indicated to the patients who are
allergic to it
Corticosteroids are contra-indicated in
patients having an active peptic ulcer
Barbiturates and morphine should not be
given to asthmatic patients
contd
15. Category Unsafe/Uncertain Safe Alternative
Anti-Amoebic Metrondiazole,
Tinidazole,
Quinidochlor
Diloxanide
furoate,
Loperamide
Antimalarial Artemether
Primaquine
Chloroquine
Mefloquine
Anthelmintic Albendazole
Mebendazole
Ivermectin
Pyrantel pamoate
Piperazine citrate
Niclosamide
Antihypertensiv
e
ACE inhibitor
Propranolol
Metoprolol
Atenolol
AntiDiabetic Sulfonyl ureas
Metformin
Repaglinide
Human Insulin
List of Contra-indicated drugs during
Pregnancy
16. DRUG-DRUG INTERACTION
Drug-drug interactions occur when a drug
interacts, or interferes, with another drug.
This can alter the way of one or both of the
drugs act in the body, or cause unexpected
side effects.
-Synergistic (when the drug's effect is
increased) or
-Antagonistic (when the drug's effect is
decreased) or a new effect can be produced.
Examples
*Use of Codeine with Paracetamol to increase
its analgesic effect.
*Combination of Clavulanic acid with Amoxicillin
in order to overcome bacterial resistance to
17. DRUG-FOOD INTERACTION
A drug-food interaction happens when the food
we eat affects the ingredients in a medicine we
are taking so the medicine cannot work the way
it should.
Example
1. Consumers taking digoxin for heart failure or
ACE inhibitors for high blood pressure should be
careful with salt substitutes, which most often
replace sodium with potassium.
2. Blood-thinning drugs such as Coumadin®
(warfarin) interfere with vitamin K-dependent
clotting factors. Eating too much green leafy
vegetables, which are high in vitamin K, can
decrease the ability of blood-thinners to prevent
clotting.
3. Tetracycline should not be taken with milk
18. HOW TO PREVENT DRUG
INTERACTIONS?
We should tell our doctor about everything
we are taking, including prescription drugs,
OTC medications, vitamins and herbal
supplements.
We should read the consumer information
sheet with our prescriptions and read it
carefully.
We should read the labels on OTC
medications, paying special attention to the
“Warnings”section.
Before buying a new OTC medication,
vitamin or herbal supplement, we should ask
1.Note:
2. Note: Caffeine citrate is an equal mixture of caffeine and citric acid. The citric acid present in caffeine citrate reacts with sodium salicylate to liberate salicylic acid which get precipitated. If caffeine is used alone instead of caffeine citrate it forms a soluble cmplex with sodium salicylates. Hence substitute caffeine citrate with half as much caffeine to form a clear mixture.
1.Note: Ferric salt reacts with sodium salicylate to liberate ferric salicylate which gets separated as indiffusible ppt, hence follow method B
3.Note: Lemon syrup contains citric acid which reacts with Sodium salicylate, separates salicylic acid as indiffusible ppt. The prescription can be dispensed in two methods, 1.follow method B or 2. Replace lemon syrup with Tincture of lemon & Simple syrup.
* Boric acid from hydrolysis of the borax reacts with the glycerol producing monobasic glyceryl-boric acid which liberates carbon dioxide from the bicarbonate. Hasten the reaction with hot water
Note: It forms indiffusible ppt. of Phenobarbitone, hence substituting Ammonium bromide with an equivalent amount of Sodium bromide the indiffusible ppt can be avoided and therapeutic effect can be achieved.
