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COMT inhibitors interactions

Posted by jimmygold70 on December 22, 2006, at 3:36:40 [reposted on December 23, 2006, at 12:47:18 | original URL]

In reply to Stimulant @ AD booster-Green Tea?, posted by kelv on December 21, 2006, at 11:50:51

These are the interactions for Entacapone - a COMT inhibitor. Might they hold true for green tea? Exercise caution!

------------------------------

Entacapone
Comtan® Print

Drug Interactions

• Amoxapine
• Ampicillin
Antipsychotics
Anxiolytics, Sedatives, and Hypnotics
Barbiturates
• Buprenorphine
• Butorphanol
• Chloramphenicol
• Cholestyramine
• Dobutamine
• Dopamine
• Dronabinol, THC
• Droperidol
• Ephedra, Ma Huang
• Ephedrine
• Epinephrine
• Erythromycin
• Ethanol
• Furazolidone
• Isocarboxazid
• Isoetharine
• Isoniazid, INH
• Isoproterenol
• Linezolid
• Maprotiline
• Methyldopa
• Mirtazapine
• Nabilone
• Nalbuphine
• Nefazodone
• Norepinephrine
Opiate agonists
• Pentazocine
• Phenelzine
• Pramipexole
• Probenecid
• Procarbazine
• Rasagiline
• Rifampin
• Ropinirole
• Selegiline
• Tranylcypromine
• Trazodone
Tricyclic antidepressants

NOTE: Entacapone is highly protein bound. In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, salicylic acid, phenylbutazone, and diazepam.[5769] In vitro studies have shown that entacapone can inhibit the cytochrome P450 isoenzymes 1A2, 2A6, 2C6, 2C19, 2D6, 2E1 and 3A4, but only at very high entacapone concentrations (> 200 microM) that would not be seen during normal clinical usage.[5769]

It should be noted that entacapone may usually be taken concomitantly with the selective MAO-B inhibitors rasagiline and selegiline.[5769] For example, no drug-drug interactions have been shown between entacapone and selegiline in two multi-dose interaction studies.[5769] Stable doses of entacapone were used together with rasagiline in clinical trials.[9086] The practitioner should be alert to adverse effects and need for dosage titrations.

Patients should not receive entacapone in combination with non-selective monoamine oxidase inhibitors (MAOIs) such as isocarboxazid, phenelzine, or tranylcypromine.[5769] This includes agents with non-selective MAO inhibiting activity like furazolidone [5343], isoniazid, INH [4930], linezolid [5330] or procarbazine [5356]. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of entacapone and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone to avoid potential interactions.

Drugs known to be metabolized by catechol-O-methyltransferase (COMT), such as bitolterol (beta-agonist), dobutamine [6302], dopamine [6393], ephedrine (or ephedra, ma huang) [6994] epinephrine [6234] [6995], isoetharine, isoproterenol [6995], methyldopa [5990], and norepinephrine [6235], regardless of the route of administration (including inhalation) should be administered cautiously in patients receiving entacapone.[5769] Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. When a single 400 mg dose of entacapone was given with intravenous isoproterenol and epinephrine the overall mean maximal changes in heart rate during infusion were about 50% and 80% higher than with placebo for isoproterenol and epinephrine, respectively. Ventricular tachycardia was noted in one healthy volunteer during an interaction study with epinephrine infusion and oral entacapone administration. Treatment with propranolol was required. A casual relationship to entacapone administration seems probable. A pharmacokinetic interaction of apomorphine with catechol-O-methyl transferase inhibitors (COMT inhibitors, e.g., tolcapone or entacapone) is unlikely since apomorphine appears not to be metabolized by COMT.[5392]

As entacapone is primarily excreted in the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidation are given concurrently with entacapone.[5769] These agents include ampicillin, chloramphenicol, cholestyramine, erythromycin, probenecid, and rifampin.[5769]

Entacapone should be given cautiously with other agents that cause CNS depression due to the possibility of additive sedation.[5769] Agents that may cause additive sedation when given concurrently with entacapone include amoxapine, antipsychotics [5022], anxiolytics, sedatives, and hypnotics, opiate agonists, sedating H1-antagonists, barbiturates, buprenorphine, butorphanol, dronabinol, THC, droperidol, ethanol, maprotiline, mirtazapine, nabilone [9044], nalbuphine, nefazodone, pentazocine, pramipexole, ropinirole, trazodone, and tricyclic antidepressants. No pharmacokinetic interaction was noted when entacapone, without levodopa and carbidopa, and imipramine were given together in a single-dose study.

[ Interactions Last Revised: 6/14/2006 3:47:00 PM ]


--------------------------------------------------------------------------------

References

4930. Nydrazid® Injection (isoniazid, INH)package insert. Princeton, NJ: Apothecon; 1997 Aug.
5022. Mellaril® (thioridazine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2000 Jun.

5330. Zyvox™ (linezolid) package insert. Kalamazoo, MI: Pharmacia & Upjohn Company; 2005 Feb.


5343. Furoxone® (furazolidone) package insert. Eatontown, NJ: Roberts Pharmaceutical Corporation; No date.

5356. Matulane® (procarbazine) package insert.Gaithersburg, MD: sigma-tau Pharmaceuticals, Inc.; 2002 July.

5392. Apokyn™ and Apokyn™ Pen (apomorphine) injection package insert. Durham, NC:Mylan Bertek Pharmaceuticals Inc.; 2004 April.


5769. Comtan® (entacapone) package insert. East Hanover, NJ: Novartis Pharmaceuticals; 2000March.


5990. Aldomet® (methyldopa) package insert. West Point, PA: Merck & Co., Inc.;1998 Jul.

6234. Epinephrine injection 1:1000 package insert. Shirley, NY: American Regent, Inc.; 2003 Jan.

6235. Norepinephrine package insert. Irvine, CA: Gensia Sicor Pharmaceuticals; 2002 Apr.

6302. Dobutamine Hydrochloride in 5% Dextrose Injection package insert. Deerfield, IL: Baxter Healthcare Corp.;2002 Jul.


6393. Intropin® (dopamine hydrochloride) injection package insert. Manati, Puerto Rico: Du Pont Pharmaceuticals;1991 Jan.


6994. Renfrew C, Dickson R, Schwab C. Severe hypertension following ephedrine administration in a patient receiving entacapone. Anesthesiology. 2000;93:1562.

6995. Illi A, Sundberg S, Ojala-Karlsson P, et al. The effect of entacapone on the disposition and hemodynamic effects of intravenous isoproterenol and epinephrine. Clin Pharmacol Ther 1995;58:221—7.


9044. Cesamet™ (nabilone) package insert. Costa Mesa, CA: Valeant Pharmaceuticals International; 2006 May.

9086. Goetz CG, Schwid SR, Eberly SW, et al. Safety of rasagiline in elderly patients with Parkinson disease. Neurology. 2006;66:1427—9.


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poster:jimmygold70 thread:715906
URL: http://www.dr-bob.org/babble/alter/20061218/msgs/715910.html