Therapeutic incompatibility arises as a result of prescribing certain categories of drugs to patients with a sole intention of achieving a specific degree of pharmacological action. However, the nature or intensity of the resultant activity is quite different from that intended by the prescriber. Therapeutic incompatibility results due to the following reasons:

1. Error in dosage form
2. Wrong dose or dosage form
3. Contra indicated drugs
4. Synergistic and antagonistic drugs
5. Drug interactions
6. Prescribing drugs with wrong direction

1. Error in dosage form: The errors in writing or scientific interpretation of the prescription order often leads to therapeutic incompatibilities.Over dosing or under dosing in dispensing medication are the most serious forms leading to therapeutic incompatibility.It is highly essential on the part of the pharmacist to check for the scientific correctness of the prescription before dispensing. Example: R_x   Atropine sulfate0.006 g Phenobarbitone0.015 g Aspirin0.300 g Prepare 10 capsulesIn the given example, the amount of atropine sulfate prescribed for each capsule is more than its recommended dose, which is 0.25 to 2 mg. So, the prescription has to be referred back to the physician or prescriber to correct the dose of the atropine sulfate. Example: R_x   Codeine phosphate0.5 g Prepare 10 powdersDirection: One powder to be taken at bed time.In the given example, the physician is supposed to prescribe 5 mg but recommended 500 mg in the prescription, which is a clear indication of over dosage. The physician might have prescribed the high dose by over sight, so the prescription needs to be referred back to the prescriber to correct the over dosage of codeine phosphate.
2. Wrong dose or dosage form: There are number of drugs that are having identical names and pronunciation resulting in dispensing the wrong drug. This creates problem both to the physician as well as pharmacist.Examples: prednisolone, prednisone and digoxin and digitoxin.Also, we have drugs available in different dosage forms. So, clarity should be maintained while writing the prescription or during dispensing.
3. Contra-indicated drugs: Contra-indicated drugs are those which are not to be prescribed in certain disease condition or to a particular patient who is allergic to it.Example: As such corticosteroids do not cause peptic ulcer but may enhance the ulcer producing effect of NSAIDs in patients having a history of peptic ulcer.Care should be taken in case of patients who are allergic to penicillin and sulfa drugs. Example: R_x   Sulfadiazine250 mg Sulfamerazine250 mg Ammonium chloride250 mg Direction: Take two capsules after six hours.Ammonium chloride which is a urinary acidifier causes deposition of sulfonamide crystals in the kidney. So, the prescription should be referred back to the prescriber for correction.
4. Synergistic and antagonistic drugs: There are drugs which show synergism and antagonism when administered in combination. Whenever two drugs are prescribed together, sometimes there will be an increase in the activity of each other showing synergistic activity. Such synergistic combinations are purposely prescribed by the physician to enhance the therapeutic activity of the drugs.Examples: Combination of antibiotics such as penicillin and streptomycin increases the antibacterial activity.In certain cases, drugs when administered in combinations lead to adverse reactions. In such conditions, the prescription should be referred back to the prescriber for correction. Example: R_x   Amphetamine sulfate20 mg Ephedrine sulfate100 mg Syrup up to100 ml Make a mixtureIn this example, there are two sympathomimetic drugs that show additive effect. So, it is necessary to reduce the dose of each drug. Hence, the prescription has to be referred back to the prescriber.There are drugs which show antagonistic pharmacological effects when prescribed in combination. Example: R_x   Acetophenetidin150 mg Acetyl salicylic acid200 mg Caffeine30 mg Prepare 10 capsulesAcetophenetidin and acetyl salicylic acid are analgesics drugs. Acetophenetidin shows side effect such as central nervous system (CNS) depressant activity, caffeine acts as a CNS stimulant that neutralizes the side effect of acetophenetidin. This kind of incompatibility reaction is needed to get the desired action and hence such kind of prescription can be dispensed as it is without correction (positive antagonism). Example: R_x   Tetracycline hydrochloride250 mg Prepare 10 capsulesDirection: Take one capsule every six hours with milk.Calcium present in the milk inactivates the tetracycline present in the capsule. Hence, milk should be avoided during administration of tetracycline. This kind of prescription is an example for therapeutic incompatibility, which should be avoided. So, the prescription should be referred back to the prescriber to correct the direction (negative antagonism).
5. Drug interactions: Physicians today are prescribing drugs in combinations. These drugs may modify the response to each other by interactions between them.Example:
   • Prescribing ampicillin with allopurinol increases the incidence of skin rashes.
   • Furosemide with amino glycoside antibiotics enhances ototoricity.
   • Indomethacin and related drugs can reduce the antihypertensive effect of captopril.
6. Prescribing drugs with wrong direction: In certain prescriptions, the directions written by the prescriber makes it extremely difficult for the pharmacist as well as patient to understand and execute the prescription. Such prescriptions are deemed as wrong prescriptions.Examples:
   •  In case of tetracycline capsulesDirection: One capsule need to be taken for every six hours along with milk. Calcium present in the milk inactivates the tetracycline present in the capsule leading to therapeutic incompatibility.
   • In case of ointmentDirection: To be applied two to three times in a day to eyes.Skin ointments are not sterilized, which is taken as prime consideration for eye ointments leading to therapeutic incompatibility.
   • In case of non-sterile solutionsDirection: Inject 5 ml intra muscularly (i.m).Maintenance of sterility and isotonicity is taken as the foremost requirement for injectable formulations. So, the given examples show therapeutic incompatibility, which can be traced out easily by the pharmacists if they had gone through the prescription thoroughly and can avoid occurrence of therapeutic hazards.