Drug Interaction Risk Assignment

A new antiviral combination medicine called Paxlovid (which contains nirmatrelvir and ritonavir) has recently been approved for the treatment of COVID-19. Given the prevalence of COVID-19 in the community, this medicine is widely used.

1. Question: Based on the results from the phase I drug interaction trials for Formoderal, what are the likely consequences in terms of exposure and response to this medicine if Formoderal is given orally to a patient being treated with Paxlovid?

Pharmacodynamics

A phase III clinical trial is conducted to evaluate the effectiveness of Formoderal in combination with ibuprofen for acute moderate to severe pain in a pre-hospital setting.

2. Question: Making reference to the respective mechanisms of Formoderal (a fictional opioid analgesic) and ibuprofen, explain the rationale for combining these two medicines.

3. Question: In order to treat the same severity of pain, how would the dose of Formoderal in the combination with ibuprofen likely compare to the dose of Formoderal when administered alone? Making particular reference to the pre-hospital context, what is the likely significance of any difference in Formoderal dose?

Adverse Effects

Formoterol is an opioid analgesic that causes an analgesic effect by acting as an agonist at the mu-opioid receptors. Sedation (i.e. feeling sleepy) is reported to be a common ‘on-target’ adverse effect of other drugs from this class such as morphine and fentanyl.

4. Question: Based on these statements, is it likely that sedation will be a common adverse effect with Formoderal? Briefly explain your reasoning. 

Impact on Pre-hospital Care

It is well known that many medications used by patients in the community can impact the efficacy and tolerability of medicines administered by paramedics.

5. Question

Making reference to any potential drug interactions and/or changes in patient physiology, discuss the potential treatment implications in a patient treated with low dose Formoderal for migraines in the community who requires treatment with morphine for severe acute pain in a pre-hospital setting. 

Clinical Use of Opioid Drugs

Ms. Smith is receiving end-of-life care at home from extended care paramedics. She has charted the following oral medications for cancer pain:

6. Question: Explain why the two medications are dosed at different frequencies despite both containing oxycodone, providing a pharmacokinetic and clinical rationale for the prescriber's decision. Assume that the dose and frequency of administration are appropriate. 

Mr. Jones is an aged care resident who has been suffering from mild to moderate pain and was commenced on Codeine Linctus (5 mg/mL) as he is unable to swallow tablets and capsules.

He was given a single 12 mL (60mg) dose of codeine and has had an allergic reaction (the exact nature of the reaction is unimportant). The nurse at the aged care facility mentions that she checked the patient's allergies before charting the codeine and that Mr. Jones only reported an allergy to morphine. The nurse also mentions that a pharmacist did warn her about Mr. Jones reacting to codeine due to his morphine allergy but did not explain why this would be the case. The nurse assumed codeine would be fine since the patient is not allergic to all opioids and has previously used tramadol without issue for osteoarthritic pain.

7. Question: Explain why you might expect an individual who has a known allergy to morphine to be at higher risk of having an allergic reaction to codeine compared to other opioids. 

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