Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI73ZRISW)
  Drug Name Phentermine Drug Info Safinamide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Appetite Depressants Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Phentermine-Safinamide Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Phentermine Safinamide
      Mechanism Monoamine oxidase substrate Monoamine oxidase inhibitor
      Key Mechanism Factor 1
Factor Name Monoamine oxidase Structure Sequence
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Phentermine caused by Safinamide mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Caution and more frequent blood pressure monitoring may be advisable when oral and/or topical sympathomimetic agents are coadministered with MAOIs including safinamide.

References
1 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
2 Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
3 Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5. [PMID: 4685619]
4 Cerner Multum, Inc. "Australian Product Information.".
5 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
6 Cusson JR, Goldenberg E, Larochelle P "Effect of a novel monoamine-oxidase inhibitor, moclobemide on the sensitivity to intravenous tyramine and norepinephrine in humans." J Clin Pharmacol 31 (1991): 462-7. [PMID: 2050833]
7 Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31. [PMID: 8845455]
8 De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
9 Elis J, Laurence DR, Mattie H, Prichard BN "Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure." Br Med J 2 (1967): 75-8. [PMID: 6020852]
10 Fenwick MJ, Muwanga CL "Anaphylaxis and monoamine oxidase inhibitors--the use of adrenaline." J Accid Emerg Med 17 (2000): 143-4. [PMID: 10718244]
11 Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62. [PMID: 14197995]
12 Goulet JP, Perusse R, Turcotte JY "Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic interactions." Oral Surg Oral Med Oral Pathol 74 (1992): 692-7. [PMID: 1359489]
13 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
14 Product Information. Xadago (safinamide). US WorldMeds LLC, Louisville , KY.
15 Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]
16 Sjoerdsma A "Catecholamine-drug interactions in man." Pharmacol Rev 18 (1966): 673-83. [PMID: 5904180]
17 Smookler S, Barmudez AJ "Hypertensive crisis resulting from an MAO inhibitor and an over-the counter appetite suppressant." Ann Emerg Med 11 (1982): 482-4. [PMID: 7114595]
18 Thompson DS, Sweet RA, Marzula K, Peredes JC "Lack of interaction of monoamine oxidase inhibitors and epinephrine in an older patient." J Clin Psychopharmacol 17 (1997): 322-3. [PMID: 9241014]
19 Wright SP "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet 1 (1978): 284-5. [PMID: 74715]