This section refers to combinations of drugs in a single pharmaceutical formulation. It does not refer to concomitant drug therapy, e.g. in infections, hypertension and in cancer, when several drugs are given separately.
Fixed-dose drug combinations are appropriate for:
• Convenience, with improved patient compliance. This is particularly appropriate when two drugs are used at constant dose, long term, for an asymptomatic condition, e.g. a thiazide plus a (3-adrenoceptor blocker in mild or moderate hypertension. The fewer tablets the patients have to take, the more reliably will they use them, especially the elderly—who as a group receive more drugs because they have multiple pathology.
• Enhanced effect. Single-drug treatment of tuberculosis leads to the emergence of resistant mycobacteria; this effect is prevented or delayed by using two or more drugs simultaneously. Combining isoniazid with rifampicin (Rifinah, Rimactazid) ensures that single drug treament cannot occur; treatment has to be two drugs or no drug at all. Oral contraception (with an oestrogen and progestogen combination) is used for the same reason.
• Minimisation of unwanted effects. Combining levodopa with benserazide (Madopar) or with carbidopa (Sinemet) slows its metabolism outside the central nervous system so that smaller amounts of levodopa can be used; this reduces adverse effects.
Fixed-dose drug combinations are inappropriate:
• When the dose of one or more of the component drugs may need to be adjusted independently. A drug with a wide dose-range that must be adjusted to suit the patient's response is unsuitable for combination with a drug that has a narrow dose range.
• If the time course of drug action demands different intervals between administration of the components.
• If irregularity of administration, e.g. in response to a symptom such as pain or cough, is desirable for some ingredients but not for others.
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