Substitutability criteria

Each drug is assessed individually, but the criteria remain the same.
Medicines should:

• be approved as such,
• contain the same active ingredient(s),
• contain the active ingredients in same amounts,
• have the same dosage form,
• have been judged to be bioequivalent/therapeutically equivalent.

Common barriers to substitution

Even where two drugs meet the basic substitutability criteria, they may not be substitutable. Some differences affect the properties of medicines, the method of administration, or the user’s perception to such a degree that they render in-pharmacy substitution inappropriate.

Common differences that may present an obstacle include:

• The active substance having what is termed a narrow therapeutic range, meaning that relatively small changes to its level in the individual’s blood may be of major clinical significance. This applies, for example, to drugs used to treat epilepsy and those administered after a transplant to prevent tissue rejection.
• A significant section of the product information is missing or contradictory. Even where medicines are otherwise pharmaceutically equivalent, contradictory information on the package leaflet may cause uncertainty for the patient. Product information is assessed in its entirety, but special focus is placed on pregnancy warnings, for example.
• Major differences in administration, e.g. in the case of drugs that require a certain breathing technique to be used, those contained in injection pens, or other drugs that come with a dispensing aid.
• Some differences in drug properties, e.g. significant differences in tablet size. This is especially true where tablets cannot be divided, crushed, or dissolved.
• Drugs mainly intended for children that have a different flavour. For example, a banana-flavoured drug is not substitutable for a raspberry-flavoured one. However, the flavour does not have to be completely identical for substitution to be accepted, as a raspberry-flavoured product can be replaced with one having a different raspberry flavour.
• Medicinal products for topical use, in particular ointments and creams, the excipients of which vary greatly in fat and water content.

Differences that are typically of no hindrance to substitution

There may also be differences between two drugs that are not crucial from the point of view of substitutability.

• Drugs containing different salts of the active substance.

For practical reasons, it is common practice to make a salt of the active substance. The substance’s name, whose last component may for instance be 'chloride' or 'bromide', identifies the salt in question. Where drugs are bioequivalent, it has been shown that different salts behave in the same way in the body and that the difference in salt form is of no significance.

• Drugs being available in tablet or capsule form.

The Swedish MPA is of the opinion that tablets and capsules are generally so similar from the point of view of use that they do not preclude substitutability.

• Drugs being scented or unscented.

The presence or absence of a scent may or may not excite the user’s senses, but this criterion has no effect on medical treatment. For allergy sufferers, the prescriber should refuse substitution on medical grounds.

• Drugs containing various colourants.

If the colour is crucial for recognition or in case of an allergy to any colourant, the prescriber should refuse substitution on medical grounds.

• Drugs being packed in blister packs or bottles.

When assessing substitutability, the Swedish MPA does not take packaging into account. Depending on hand strength or mobility, some individuals may have difficulty opening bottles or blister packs. If justified, the prescriber or pharmacist may refuse substitution.

• Differences in the intended use of drugs

The drug should always be used according to the prescriber’s instructions. As a result of the freedom to prescribe, the instructions for use on the prescription outweigh recommended indications or dosages in the product information. This presupposes other essential information being provided and not leading to major differences in dosage recommendations.

Depot preparations

A depot preparation is a drug whose active substance is released over an extended period. This makes assessment of medical equivalence more complex, as the effects of food intake and repeat dosing, for example, may have greater relevance.

If small differences in uptake by the body are likely to have an impact on the drug’s efficacy and safety, the release principle, i.e. how the active substance is released into the body, will be assessed. If that is the case, the Swedish MPA will, for precautionary reasons, take the view that various release principles present an obstacle to the substitutability of depot preparations.

Some substitution groups have subgroups

Some substitution groups have several subgroups. This may be due, for example, to the substance having a narrow therapeutic range, there being significant differences in product information, or medicines primarily intended for children having different flavour profiles.

These subgroups are named active substance, dosage form, and strength and they are typically assigned a letter designation, e.g. group A, B, or C. This means that the drugs in group A are substitutable with each other, but not with drugs in groups B or C.