Acetaminophen, diphenhydramine, and phenylephrine and Eliglustat

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Before using eliglustat, you should have received a test to determine your CYP450 2D6 genotype, which lets the doctor know whether or not you can take the medication and at what dosage. Depending on your CYP450 2D6 genotype and what other medications you may be on, using eliglustat together with diphenhydrAMINE may not be recommended at all, or a dosage adjustment of eliglustat may be needed. Treatment with diphenhydrAMINE can significantly increase the blood levels of eliglustat. This may increase the risk of serious and potentially life-threatening cardiac side effects such as irregular heart rhythm, heart block, and cardiac arrest. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the interaction, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, slow heart rate, weak pulse, or heart palpitations during treatment with eliglustat. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

CONTRAINDICATED: Coadministration with inhibitors of CYP450 2D6 may significantly increase the plasma concentrations of eliglustat, which is primarily metabolized by CYP450 2D6 and, to a lesser extent, CYP450 3A4. Eliglustat at substantially elevated plasma concentrations is predicted to cause prolongation of the PR, QTc and QRS cardiac intervals, which may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes. In 30 subjects who were CYP450 2D6 extensive metabolizers (EMs), eliglustat peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 7.0- and 8.0-fold, respectively, following coadministration of eliglustat (84 mg twice daily) with the potent CYP450 2D6 inhibitor paroxetine (30 mg once daily). Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that paroxetine may increase eliglustat Cmax by 2.1-fold and AUC by 2.3-fold in CYP450 2D6 intermediate metabolizers (IMs). When the moderate CYP450 2D6 inhibitor terbinafine was used, PBPK modeling predicted a 3.8-fold increase in eliglustat Cmax and 4.5-fold increase in AUC for EMs, and a 1.6-fold increase each in Cmax and AUC for IMs. The magnitude of interaction is expected to increase further with the addition of a CYP450 3A4 inhibitor like ketoconazole. Simulations using PBPK models suggest that the combination of paroxetine (30 mg once daily) and ketoconazole (400 mg once daily) may increase eliglustat Cmax by 16.7-fold and AUC by 24.2-fold in EMs given eliglustat 84 mg twice daily. For IMs, the estimated increases in eliglustat Cmax and AUC are 7.5- and 9.8-fold, respectively. When a less potent combination of CYP450 2D6 (terbinafine) and 3A4 (fluconazole) inhibitors were used, PK modeling predicted a 10.2-fold increase in eliglustat Cmax and 13.6-fold increase in AUC for EMs given eliglustat 84 mg twice daily, and a 4.2-fold increase in eliglustat Cmax and 5.0-fold increase in AUC for IMs.

MANAGEMENT: The use of eliglustat in combination with one or more drugs that may result in moderate or potent inhibition of both CYP450 2D6 and 3A4 is considered contraindicated in CYP450 2D6 intermediate metabolizers (IMs) and extensive metabolizers (EMs). In the absence of a concomitant CYP450 3A4 inhibitor, eliglustat may be prescribed at a reduced dosage of 84 mg once daily to IMs and EMs treated with a potent or moderate CYP450 2D6 inhibitor. Poor metabolizers are not affected by CYP450 2D6 inhibition (since they already have minimal functional levels of the isoenzyme) and may also receive the reduced dosage of eliglustat, so long as they are not treated with a CYP450 3A4 inhibitor. Potent and moderate CYP450 3A4 inhibitors include azole antifungal agents, protease inhibitors, aprepitant, ciprofloxacin, clarithromycin, cobicistat, conivaptan, crizotinib, delavirdine, diltiazem, dronedarone, erythromycin, fusidic acid, idelalisib, imatinib, lomitapide, mibefradil, mifepristone, nefazodone, ranolazine, telithromycin, and verapamil. Potent and moderate CYP450 2D6 inhibitors include abiraterone, bupropion, celecoxib, cimetidine, cinacalcet, clobazam, darifenacin, diphenhydramine, duloxetine, fluoxetine, methotrimeprazine, mirabegron, panobinostat, paroxetine, propoxyphene, quinidine, ranolazine, rolapitant, sertraline, stiripentol, and terbinafine. Some drugs such as abiraterone, cimetidine, ranolazine, and stiripentol are dual CYP450 2D6 and 3A4 inhibitors, and they should probably not be used with eliglustat in any patient regardless of their CYP450 2D6 metabolizer status. In addition, antiarrhythmics such as amiodarone, dronedarone, flecainide, propafenone, and quinidine can inhibit CYP450 2D6 and cause significant prolongation of the QT interval. These agents should not be used with eliglustat in any patient.

Acetaminophen, diphenhydramine, and phenylephrine

Generic Name: acetaminophen / diphenhydramine / phenylephrine

Brand name: Benadryl Allergy & Sinus Headache, Delsym Cough Plus Cold Night Time, Mucinex Fast-Max Night Time Cold and Flu, Robitussin Nighttime Multi-Symptom Cold, Sudafed PE Severe Cold, Theraflu Severe Cold & Cough Nighttime, Theraflu Warming Flu & Sore Throat, Theraflu Warming Sinus & Cold, Theraflu Warming Severe Cold Nighttime, Benadryl Allergy & Cold, Sudafed PE Nighttime Cold, Tylenol Allergy Multi-Symptom Nighttime, Theraflu Nighttime Severe Cough & Cold, Children's Delsym Cough Plus Cold Night Time, Children's Mucinex Night Multi-Symp Cold, Children's Dimetapp Multi-Symptom Cold & Flu, Theraflu ExpressMax Nighttime Severe C&C, Theraflu PowerPods Nighttime Severe Cold, Benadryl Allergy/Cold, Tylenol Allergy Multi-Symptom, Theraflu Warming Relief Nighttime Severe Cold

Synonyms: n.a.

What is Acetaminophen, diphenhydramine, and phenylephrine?

Eliglustat

Generic Name: eliglustat

Brand name: Cerdelga

Synonyms: n.a.

What is Eliglustat?