Details of the Drug

General Information of Drug (ID: DM7RE8P)

Drug Name

Frovatriptan

Synonyms

Allegro; Auradol; Frova; Frovelan; Migard; Miguard; Rilamig; Allergo filmtabletten; SB 209509; Allergo filmtabletten(TN); Frova (TN); Frovatriptan (INN); SB-209509; (3R)-3-(methylamino)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide; (6R)-6-(methylamino)-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide; (R)-5,6,7,8-Tetrahydro-6-(methylamino)carbazole-3-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Migraine	8A80	Approved	[1], [2]

Therapeutic Class

Antimigraine Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

243.3

Topological Polar Surface Area (xlogp)

1.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is rapidly absorbed from the duodenum [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 2.5 mL/min/kg [5]
Elimination: 6% of drug is excreted from urine in the unchanged form [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 26 hours [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.44035 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.85% [5]
Vd: The volume of distribution (Vd) of drug is 4.2 L/kg in males, and 3 L/kg in females [7]

Chemical Identifiers

Formula: C14H17N3O
IUPAC Name: (6R)-6-(methylamino)-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide
Canonical SMILES: CN[C@@H]1CCC2=C(C1)C3=C(N2)C=CC(=C3)C(=O)N
InChI: InChI=1S/C14H17N3O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18)/t9-/m1/s1
InChIKey: XPSQPHWEGNHMSK-SECBINFHSA-N

Cross-matching ID

PubChem CID: 77992
ChEBI ID: CHEBI:134991
CAS Number: 158747-02-5
DrugBank ID: DB00998
TTD ID: D06FPQ
INTEDE ID: DR0755
ACDINA ID: D00294

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1B receptor (HTR1B)	TTK8CXU	5HT1B_HUMAN	Modulator	[8]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Modulator	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2)_{Main DME}	DEJGDUW	CP1A2_HUMAN	Substrate	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Frovatriptan (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Frovatriptan and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[33]
Oliceridine	DM6MDCF	Moderate	Additive CNS depression effects by the combination of Frovatriptan and Oliceridine.	Acute pain [MG31]	[34]
Desipramine	DMT2FDC	Major	Additive serotonergic effects by the combination of Frovatriptan and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[35]
Droxidopa	DM5YF4M	Moderate	Additive hypertensive effects by the combination of Frovatriptan and Droxidopa.	Autonomic nervous system disorder [8D87]	[36]
Dihydrocodeine	DMB0FWL	Moderate	Additive CNS depression effects by the combination of Frovatriptan and Dihydrocodeine.	Chronic pain [MG30]	[34]
Levomilnacipran	DMV26S8	Major	Additive serotonergic effects by the combination of Frovatriptan and Levomilnacipran.	Chronic pain [MG30]	[35]
Sertraline	DM0FB1J	Major	Additive serotonergic effects by the combination of Frovatriptan and Sertraline.	Depression [6A70-6A7Z]	[35]
Vilazodone	DM4LECQ	Major	Additive serotonergic effects by the combination of Frovatriptan and Vilazodone.	Depression [6A70-6A7Z]	[35]
Nefazodone	DM4ZS8M	Major	Additive serotonergic effects by the combination of Frovatriptan and Nefazodone.	Depression [6A70-6A7Z]	[35]
Vortioxetine	DM6F1PU	Major	Additive serotonergic effects by the combination of Frovatriptan and Vortioxetine.	Depression [6A70-6A7Z]	[35]
Isocarboxazid	DMAF1NB	Major	Additive serotonergic effects by the combination of Frovatriptan and Isocarboxazid.	Depression [6A70-6A7Z]	[33]
Milnacipran	DMBFE74	Major	Additive serotonergic effects by the combination of Frovatriptan and Milnacipran.	Depression [6A70-6A7Z]	[35]
Escitalopram	DMFK9HG	Major	Additive serotonergic effects by the combination of Frovatriptan and Escitalopram.	Depression [6A70-6A7Z]	[35]
Desvenlafaxine	DMHD4PE	Major	Additive serotonergic effects by the combination of Frovatriptan and Desvenlafaxine.	Depression [6A70-6A7Z]	[35]
5-hydroxy-L-tryptophan	DMDWZGJ	Major	Additive serotonergic effects by the combination of Frovatriptan and 5-hydroxy-L-tryptophan.	Discovery agent [N.A.]	[37]
Procarbazine	DMIK367	Major	Additive serotonergic effects by the combination of Frovatriptan and Procarbazine.	Hodgkin lymphoma [2B30]	[33]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Frovatriptan caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[38]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Frovatriptan caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[39]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Frovatriptan and Ozanimod.	Multiple sclerosis [8A40]	[40]
Sibutramine	DMFJTDI	Major	Additive serotonergic effects by the combination of Frovatriptan and Sibutramine.	Obesity [5B80-5B81]	[33]
Lorcaserin	DMG6OYJ	Major	Additive serotonergic effects by the combination of Frovatriptan and Lorcaserin.	Obesity [5B80-5B81]	[41]
Dexfenfluramine	DMJ7YDS	Major	Additive serotonergic effects by the combination of Frovatriptan and Dexfenfluramine.	Obesity [5B80-5B81]	[35]
Levomethadyl Acetate	DM06HG5	Moderate	Additive serotonergic effects by the combination of Frovatriptan and Levomethadyl Acetate.	Opioid use disorder [6C43]	[34]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Frovatriptan caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[42]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Frovatriptan caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[43]
Oxymorphone	DM65AGJ	Moderate	Additive CNS depression effects by the combination of Frovatriptan and Oxymorphone.	Pain [MG30-MG3Z]	[34]
Dezocine	DMJDB0Y	Moderate	Additive CNS depression effects by the combination of Frovatriptan and Dezocine.	Pain [MG30-MG3Z]	[34]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Frovatriptan caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[44]
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⏷ Show the Full List of 28 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
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⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Frovatriptan 2.5 mg tablet	2.5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7191).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	BDDCS applied to over 900 drugs
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9	Frovatriptan: a review of drug-drug interactions. Headache. 2002 Apr;42 Suppl 2:S63-73.
10	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
11	Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
12	Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
13	Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
14	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
15	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
16	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
17	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
18	Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
19	Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
20	Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem. 1996 Nov;67(5):2096-103.
21	Triptans in pregnancy. Ther Drug Monit. 2008 Feb;30(1):5-9.
22	Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
23	Company report (NeurAxon)
24	5-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.
25	Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. Br J Pharmacol. 1998 Apr;123(8):1655-65.
26	Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
27	Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
28	An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
29	Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
30	Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
31	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
32	Company report (Fabrekramer)
33	Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5. [PMID: 9861909]
34	Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
35	Achamallah NS "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry 149 (1992): 1406. [PMID: 1530079]
36	Product Information. Northera (droxidopa). Chelsea Therapeutics Inc, Charlotte, NC.
37	Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50. [PMID: 1968472]
38	Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
39	Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
40	Alvine G, Black DW, Tsuang D "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry 51 (1990): 311. [PMID: 2365671]
41	Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ.
42	Cerner Multum, Inc. "Australian Product Information.".
43	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
44	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.