Details of the Drug

General Information of Drug (ID: DMHN027)

Drug Name
Levothyroxine
Synonyms
Eltroxin; Euthyrox; Forthyron; Laevothyroxinum; Laevoxin; Levolet; Levothroid; Levothyrox; Levothyroxin; Levoxyl; Oroxine; Synthroid; THX; Tetraiodothyronine; Thyratabs; Thyrax; Thyreoideum; Thyroxevan; Thyroxin; Thyroxinal; Levothyroxine sodium; Synthroid sodium; Thyroxine [BAN]; Thyroxine iodine; LT00440967; T4 levothyroxine; DL-Thyroxin; Eltroxin (TN); Euthyrox (TN); Eutirox (TN); Forthyron (TN); L-Thryoxin; L-Thyroxin; L-thyroxine; Laevothyroxinum (acid); Levaxin (TN); Levo-T; Levothyroxine (BAN); Levothyroxinum (acid); Levoxyl (TN); Synthroid (TN); T-3850; T4 (Hormone); Thyrax (TN); Thyrox (TN); Thyroxine (VAN); Thyroxine (l); L-thyroxine (TN); Levothyroxine Sodium (L-thyroxine); Levothroid (*Sodiumsalt*); Synthroid (*Sodium salt*); Thyroxine, L-(8CI); L-3,5,3',5'-Tetraiodothyronine; O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosine; Beta-((3,5-Diiodo-4-hydroxyphenoxy)-3,5-diiodophenyl)alanine; O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine; O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine; (-)-Thyroxine; (125I)T4; (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid; 2-amino-3-[4-(4-hydroxy-3,5-diiodo-phenoxy)-3,5-diiodo-phenyl]-propanoic acid; 3,3',5,5"-Tetraiodo-L-thyronine; 3,3',5,5''-Tetraiodo-L-thyronine; 3,3',5,5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodo-L-thyronine; 3,5,3',5'-Tetraiodothyronine; 3,5,3'5'-Tetraiodo-L-thyronine; 3-(4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)alanine; 3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine; 4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanine
Indication
Disease Entry ICD 11 Status REF
Congenital hypothyroidism N.A. Approved [1]
Edema MG29 Approved [1]
Goiter N.A. Approved [1]
Hashimoto thyroiditis N.A. Approved [1]
Hyperlipidemia 5C80.Z Approved [1]
Hypothyroidism 5A00 Approved [2]
Thyroid cancer 2D10 Approved [1]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Antithyroid Agents
ATC Code
H03AA01: Levothyroxine
H03AA: Thyroid hormones
H03A: THYROID PREPARATIONS
H03: THYROID THERAPY
H: SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
H03AA01: Levothyroxine
H03AA: Thyroid hormones
H03A: THYROID PREPARATIONS
H03: THYROID THERAPY
H: SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 776.87
Logarithm of the Partition Coefficient (xlogp) 2.4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Elimination
Approximately 20% of T<sub>4 is eliminated in the stool []
Half-life
The concentration or amount of drug in body reduced by one-half in 6 - 7 days (T4), and 1 - 2 days (T3) []
Metabolism
The drug is metabolized via sequential deiodination []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00644 micromolar/kg/day [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.000585 mg/mL [3]
Chemical Identifiers
Formula
C15H11I4NO4
IUPAC Name
(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Canonical SMILES
C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@@H](C(=O)O)N
InChI
InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1
InChIKey
XUIIKFGFIJCVMT-LBPRGKRZSA-N
Cross-matching ID
PubChem CID
5819
ChEBI ID
CHEBI:18332
CAS Number
51-48-9
DrugBank ID
DB03978
TTD ID
D06RGG
VARIDT ID
DR00107
INTEDE ID
DR0948
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Thyroid hormone receptor alpha (THRA) TTTSEPU THA_HUMAN Antagonist [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1C1 (SLCO1C1) DTPYCQ4 SO1C1_HUMAN Substrate [6]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [10]
Molecular Interaction Atlas (MIA) 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 Levothyroxine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Glibenclamide DM8JXPZ Moderate Antagonize the effect of Levothyroxine when combined with Glibenclamide. Acute diabete complication [5A2Y] [11]
Methylphenobarbital DMDSWAG Moderate Increased metabolism of Levothyroxine caused by Methylphenobarbital mediated induction of CYP450 enzyme. Anxiety disorder [6B00-6B0Z] [12]
Rabeprazole DMMZXIW Moderate Decreased absorption of Levothyroxine due to altered gastric pH caused by Rabeprazole. Bacterial infection [1A00-1C4Z] [13]
Esterified estrogens DM9KZDO Moderate Decreased plasma concentration of Levothyroxine caused by Esterified estrogens mediated increased concentration of serum thyroid-binding globulin. Breast cancer [2C60-2C6Y] [14]
Quinestrol DMJ6H1Z Moderate Decreased plasma concentration of Levothyroxine caused by Quinestrol mediated increased concentration of serum thyroid-binding globulin. Breast cancer [2C60-2C6Y] [14]
Estradiol DMUNTE3 Moderate Decreased plasma concentration of Levothyroxine caused by Estradiol mediated increased concentration of serum thyroid-binding globulin. Breast cancer [2C60-2C6Y] [14]
Anisindione DM2C48U Moderate Increased risk of bleeding by the combination of Levothyroxine and Anisindione. Coagulation defect [3B10] [15]
Mestranol DMG3F94 Moderate Decreased plasma concentration of Levothyroxine caused by Mestranol mediated increased concentration of serum thyroid-binding globulin. Contraceptive management [QA21] [14]
[3H]estrone-3-sulphate DMGPF0N Moderate Decreased plasma concentration of Levothyroxine caused by [3H]estrone-3-sulphate mediated increased concentration of serum thyroid-binding globulin. Discovery agent [N.A.] [14]
Primidone DM0WX6I Moderate Increased metabolism of Levothyroxine caused by Primidone mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [12]
Phenobarbital DMXZOCG Moderate Increased metabolism of Levothyroxine caused by Phenobarbital mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [12]
Carbamazepine DMZOLBI Moderate Increased metabolism of Levothyroxine caused by Carbamazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [12]
Dexlansoprazole DM1DBV5 Moderate Decreased absorption of Levothyroxine due to altered gastric pH caused by Dexlansoprazole. Gastro-oesophageal reflux disease [DA22] [13]
Rifampin DMA8J1G Moderate Increased metabolism of Levothyroxine caused by Rifampin mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [13]
Rifapentine DMCHV4I Moderate Increased metabolism of Levothyroxine caused by Rifapentine mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [13]
Didanosine DMI2QPE Moderate Decreased absorption of Levothyroxine due to formation of complexes caused by Didanosine. Human immunodeficiency virus disease [1C60-1C62] [16]
Ritonavir DMU764S Moderate Increased metabolism of Levothyroxine caused by Ritonavir mediated induction of UGT. Human immunodeficiency virus disease [1C60-1C62] [17]
Quinapril DMR8H31 Moderate Decreased absorption of Levothyroxine due to formation of complexes caused by Quinapril. Hypertension [BA00-BA04] [12]
Amobarbital DM0GQ8N Moderate Increased metabolism of Levothyroxine caused by Amobarbital mediated induction of CYP450 enzyme. Insomnia [7A00-7A0Z] [12]
Iron DMAP8MV Moderate Decreased absorption of Levothyroxine due to formation of complexes caused by Iron. Iron deficiency anaemia [3A00] [16]
Linaclotide DM4EGV0 Moderate Altered absorption of Levothyroxine caused by Linaclotide. Irritable bowel syndrome [DD91] [12]
Estrone DM5T6US Moderate Decreased plasma concentration of Levothyroxine caused by Estrone mediated increased concentration of serum thyroid-binding globulin. Menopausal disorder [GA30] [14]
Dienestrol DMBSXI0 Moderate Decreased plasma concentration of Levothyroxine caused by Dienestrol mediated increased concentration of serum thyroid-binding globulin. Menopausal disorder [GA30] [14]
Ethinyl estradiol DMODJ40 Moderate Decreased plasma concentration of Levothyroxine caused by Ethinyl estradiol mediated increased concentration of serum thyroid-binding globulin. Menopausal disorder [GA30] [14]
Lanthanum carbonate DMMJQSH Moderate Decreased absorption of Levothyroxine due to formation of complexes caused by Lanthanum carbonate. Mineral absorption/transport disorder [5C64] [12]
Rifabutin DM1YBHK Moderate Increased metabolism of Levothyroxine caused by Rifabutin mediated induction of CYP450 enzyme. Mycobacterium infection [1B10-1B21] [13]
Orlistat DMRJSP8 Moderate Decreased absorption of Levothyroxine caused by Orlistat. Obesity [5B80-5B81] [18]
Esomeprazole DM7BN0X Moderate Decreased absorption of Levothyroxine due to altered gastric pH caused by Esomeprazole. Peptic ulcer [DA61] [13]
Estramustine DMWTAOI Moderate Decreased plasma concentration of Levothyroxine caused by Estramustine mediated increased concentration of serum thyroid-binding globulin. Prostate cancer [2C82] [14]
Warfarin DMJYCVW Moderate Increased risk of bleeding by the combination of Levothyroxine and Warfarin. Supraventricular tachyarrhythmia [BC81] [15]
⏷ Show the Full List of 30 DDI Information of This Drug

References

1 Levothyroxine FDA Label
2 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: 4627).
3 BDDCS applied to over 900 drugs
4 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
5 Thyroid hormone resistance and pituitary enlargement after thyroid ablation in a woman on levothyroxine treatment. Thyroid. 2008 Oct;18(10):1119-23.
6 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96.
7 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
8 Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
9 [Metabolic interaction between psychopharmaceuticals. Probable cause of exacerbation of hypothyroidism according to a case report]. Lakartidningen. 2002 Jun 20;99(25):2854-6.
10 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
11 Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70. [PMID: 1838051]
12 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13 Cerner Multum, Inc. "Australian Product Information.".
14 Arafah BM "Increased need for thyroxine in women with hypothyroidism during estrogen therapy." N Engl J Med 344 (2001): 1743-9. [PMID: 11396440]
15 Costigan DC, Freedman MH, Ehrlich RM "Potentiation of oral anticoagulant effect by l-thyroxine." Clin Pediatr (Phila) 23 (1984): 172-4. [PMID: 6697623]
16 Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC "Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism." Ann Intern Med 117 (1992): 1010-3. [PMID: 1443969]
17 Berger JL, Nguyen Y, et. al "Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine." Antivir Ther 22 (2017): 271-2. [PMID: 27834772]
18 Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS "Orlistat-associated adverse effects and drug interactions: a critical review." Drug Saf 31 (2008): 53-65. [PMID: 18095746]