Details of Drug Interaction | MecDDI

Drug General Information (ID: DDINIG0P67)
Drug Name			Aminophylline		Drug Info		Peginterferon beta-1a		Drug Info
Drug Type		Small molecule				Interferons
Therapeutic Class		Bronchodilators				Interferons

Mechanism of Aminophylline-Peginterferon beta-1a Interaction (Severity Level: Moderate)
CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Aminophylline				Peginterferon beta-1a
Mechanism		CYP450 1A2 substrate				CYP450 1A2 inhibitor
Key Mechanism Factor 1
		Factor Name		Cytochrome P450 1A2				× Structure Sequence MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARLRFSIN
		Gene Name		CYP1A2
		Uniprot ID		CP1A2_HUMAN
		KEGG Pathway		hsa:1544
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable). Click to Show/Hide
Mechanism Description		Decreased metabolism of Aminophylline caused by Peginterferon beta-1a mediated inhibition of CYP450 enzyme

Recommended Action
Management		Caution is advised if theophylline or other methylxanthines are administered with an interferon. Pharmacologic response and serum theophylline levels should be monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of interferon therapy in patients who are stabilized on their methylxanthine regimen. Patients should be advised to contact their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Jonkman JH, Nicholson KG, Farrow PR, et al "Effects of alpha-interferon on theophylline pharmacokinetics and metabolism." Br J Clin Pharmacol 27 (1989): 795-802. [PMID: 2757895]
4	Kramer P, Tsuru M, Cook CE, et al "Effect of influenza vaccine on warfarin anticoagulation." Clin Pharmacol Ther 35 (1984): 416-8. [PMID: 6697649]
5	Okuno H, Takasu M, Kano H, Seki T, Shiozaki Y, Inoue K "Depression of drug-metabolizing activity in the human liver by interferon-beta." Hepatology 17 (1993): 65-9. [PMID: 8423043]
6	Product Information. Intron A (interferon alfa-2b). Schering Laboratories, Kenilworth, NJ.
7	Sakai H, Okamoto T, Kikkawa Y "Suppression of hepatic drug metabolism by the interferon inducer polyriboinosinic acid:polyribocitidylic acid." J Pharmacol Exp Ther 263 (1992): 381-6. [PMID: 1403800]
8	Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part II)." Clin Pharmacokinet 20 (1991): 135-50. [PMID: 1709398]
9	Williams SJ, Baird-Lambert JA, Farrell GC "Inhibition of theophylline metabolism by interferon." Lancet 10/24/87 (1987): 939-41. [PMID: 2444839]