Questions to ask about fixed-dose combination preparations

Questions to ask

Answer for oxycodone-with-naloxone controlled-release (CR) tablets

Is it a sensible combination?

Will the drug combination have an additive or synergistic effect, or does one drug counteract the adverse effects of the other?

The naloxone is intended to counteract the constipation caused by the oxycodone.

Is the combination bioequivalent to the individual components?

Accepted as bioequivalent to similar doses of oxycodone CR tablets.

Is the dosing compatible?

Are the pharmacokinetics similar (e.g. absorption, duration of action)?

Oxycodone and naloxone are released at similar rates from the controlled-release tablets. Under acute parenteral dosing, oxycodone has a longer duration of action than naloxone. In healthy individuals, systemic exposure to naloxone from the tablets is very low.

How likely are dose changes?

Oxycodone dose requirements are likely to increase over time for many people (e.g. disease progression), but within the dosage range of the tablets, the appropriate naloxone dose increases in line with this.

Will increasing the dose of one component result in an unnecessary dose increase in the other component?

No — the fixed dose ratio is appropriate across the approved dose range.

What will be the impact on adverse effects?

Will there be more adverse effects?

Adverse effects appear similar to those of the individual components. Some people may experience withdrawal symptoms on initiation, but the incidence is low.

There are few data regarding long-term or rare adverse effects of chronic oral naloxone.

Will it be possible to identify which drug is causing adverse effects?

Most adverse effects are ascribed to oxycodone.

If the naloxone component is suspected of causing adverse effects, patients can switch directly to oxycodone CR tablets.

What is the place in therapy of the combination preparation?

Should this combination therapy be used for initiating therapy?*

This preparation may be appropriate as initial therapy for some patients.

Would the components be the drugs of choice as separate medicines?

An oxycodone CR preparation is appropriate for some patients with severe chronic pain.

Naloxone is not available in another oral formulation for preventing opioid-induced constipation.

Does the patient need both medicines?

Opioid-induced constipation is common and about 25% of people with established constipation may benefit.

Does evidence show advantages for the combination compared with monotherapy?

Yes. There was a modest reduction in the rate of constipation.

What is the potential for confusion and medication error?

What will be the consequences for the patient?

Patients switching from other opioid formulations (e.g. oxycodone CR tablets) must avoid double-dosing with old and newly prescribed drugs, which could lead to a dangerous opioid overdose.

* There are some occasions when prescribing of a combination preparation as initial therapy is necessary — for example, combined oral contraceptive preparations, some combination antibiotics, some medicines for Parkinson's disease