An 87-year-old male PACE participant with hypertension, Parkinson’s BPH, GERD, insomnia, depression, and arthritis has a regimen of 17 medications, including:
- Amlodipine, 10 mg QD
- Omeprazole, 20 mg QD
- Acetaminophen, 500 mg TID
- Buproprion XL, 150 mg QD
- Mirtazapine, 15 mg QD
Upon receipt of a new prescription for zolpidem 5 mg, the CareKinesis pharmacist evaluated the participant’s medication history and noticed that the participant had a trial of melatonin for a few months then switched to mirtazapine 7.5 mg, which did not work, and is now on mirtazapine 15 mg, which is not working either.
The CareKinesis pharmacist reviewed the participant’s Medication Risk Matrix profile in EireneRx and noticed that he was prescribed amlodipine and omeprazole, which are metabolized by CYP3A4, as well. In addition, the pharmacist observed a CYP2D6 metabolized drug, buproprion, and a CYP1A2 metabolized drug, Tylenol, listed in the profile. Because 75% of mirtazapine is metabolized by the three pathways mentioned, there is roughly a two to four fold expected increase in mirtazapine concentration.
If is often thought that higher concentrations of a particular medication will result in a more desirable effect. However, the CareKinesis pharmacist found that in this particular patient’s case, the opposite occurred. At lower doses, mirtazapine has a higher affinity for histamine receptors and causes sedation. As doses get higher, it has the opposite effect and can cause insomnia since it has a higher affinity for serotonergic receptors and less for histamine receptors.
The prescriber and the CareKinesis pharmacist collaborated and agreed to keep the mirtazapine dosage at 15 mg, change times of medication administration to reduce competitive inhibition, and switch medications to non-CYP-metabolized drugs, such as omeprazole to ranitidine. With these changes only buproprion is inhibiting the mirtazapine, which could account for a 1.3 to 2 times increase in mirtazapine concentrations.
Since there is now less competitive inhibition through the 1A2 pathway, the prescriber and the CareKinesis pharmacist also reintroduced melatonin. If the participant continues to have insomnia, the prescriber and the CareKinesis pharmacist plan to decrease the mirtazapine to 7.5 mg before adding any other medications.