Details of the Drug

General Information of Drug (ID: DMLHESP)

Drug Name

Chlorothiazide

Synonyms

Aldoclor; Alurene; Chloriazid; Chlorosal; Chlorothiazid; Chlorothiazidum; Chlorotiazida; Chlorthiazid; Chlorthiazide; Chlorthiazidum; Chlortiazid; Chlorurit; Chlotride; Chlrosal; Clorotiazida; Clorotiazide; Clotride; Diupres; Diuresal; Diuril; Diurilix; Diurite; Diutrid; Flumen; Minzil; Salisan; Salunil; Saluretil; Saluric; Thiazide; Urinex; Warduzide; Yadalan; Clorotiazide [DCIT]; Component of Aldoclor; Diuril Boluses; C 4911; Chlorothiazidum [INN-Latin]; Clorotiazida [INN-Spanish]; Diuril (TN); Diuril Boluses, Veterinary; Neo-Dema; Sk-chlorothiazide; Chlorothiazide [USAN:INN:BAN]; Diuril, Chlotride, Chlorothiazide; Chlorothiazide (JAN/USP/INN); 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide; 6-Chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-Chloro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; 6-chloro-4H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1], [2], [3]

Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

295.7

Topological Polar Surface Area (xlogp)

-0.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is rapidly absorbed following oral administration [4]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [5]
Elimination: 92% of drug is excreted from urine in the unchanged form [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 45 - 120 minutes [6]
Metabolism: The drug is not metabolised [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 112.60478 micromolar/kg/day [7]
Water Solubility: The ability of drug to dissolve in water is measured as 0.52 mg/mL [5]

Chemical Identifiers

Formula: C7H6ClN3O4S2
IUPAC Name: 6-chloro-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Canonical SMILES: C1=C2C(=CC(=C1Cl)S(=O)(=O)N)S(=O)(=O)N=CN2
InChI: InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)
InChIKey: JBMKAUGHUNFTOL-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 2720
ChEBI ID: CHEBI:3640
CAS Number: 58-94-6
DrugBank ID: DB00880
TTD ID: D0M9WM
VARIDT ID: DR00646
ACDINA ID: D00122

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase II (CA-II)	TTANPDJ	CAH2_HUMAN	Inhibitor	[8]

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

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[10]

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

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Congestive heart failure

ICD Disease Classification

BD10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Carbonic anhydrase II (CA-II)	DTT	CA2	7.95E-08	0.52	0.33
Organic anion transporter 3 (SLC22A8)	DTP	OAT3	9.45E-03	-7.52E-02	-2.76E-01
Breast cancer resistance protein (ABCG2)	DTP	BCRP	1.46E-65	-1.41E+00	-1.41E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Chlorothiazide

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Carvedilol	DMHTEAO	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Carvedilol.	Heart failure [BD10-BD1Z]	[39]
Bumetanide	DMRV7H0	Moderate	Increased risk of fluid/electrolyte loss by the combination of Chlorothiazide and Bumetanide.	Heart failure [BD10-BD1Z]	[40]
-----------

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Dronedarone	DMA8FS5	Major	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Dronedarone.	Angina pectoris [BA40]	[41]
Rabeprazole	DMMZXIW	Moderate	Increased risk of hypomagnesemia by the combination of Chlorothiazide and Rabeprazole.	Bacterial infection [1A00-1C4Z]	[42]
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Cariprazine.	Bipolar disorder [6A60]	[43]
Ketoprofen	DMRKXPT	Moderate	Antagonize the effect of Chlorothiazide when combined with Ketoprofen.	Chronic pain [MG30]	[44]
Levomilnacipran	DMV26S8	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Levomilnacipran.	Chronic pain [MG30]	[45]
Sertraline	DM0FB1J	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Sertraline.	Depression [6A70-6A7Z]	[45]
Vilazodone	DM4LECQ	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Vilazodone.	Depression [6A70-6A7Z]	[45]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Selegiline.	Depression [6A70-6A7Z]	[46]
Vortioxetine	DM6F1PU	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Vortioxetine.	Depression [6A70-6A7Z]	[45]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Isocarboxazid.	Depression [6A70-6A7Z]	[46]
Milnacipran	DMBFE74	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Milnacipran.	Depression [6A70-6A7Z]	[45]
Escitalopram	DMFK9HG	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Escitalopram.	Depression [6A70-6A7Z]	[45]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Desvenlafaxine.	Depression [6A70-6A7Z]	[45]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and OPC-34712.	Depression [6A70-6A7Z]	[43]
Mepenzolate	DM8YU2F	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Mepenzolate.	Digestive system disease [DE2Z]	[47]
Oxybutynine	DMJPBAX	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Oxybutynine.	Discovery agent [N.A.]	[47]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of fluid/electrolyte loss by the combination of Chlorothiazide and Ethacrynic acid.	Essential hypertension [BA00]	[40]
Nadolol	DMW6GVL	Moderate	Increased risk of hypertriglyceridemia by the combination of Chlorothiazide and Nadolol.	Essential hypertension [BA00]	[39]
Solifenacin	DMG592Q	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Solifenacin.	Functional bladder disorder [GC50]	[47]
Tolterodine	DMSHPW8	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Tolterodine.	Functional bladder disorder [GC50]	[47]
Dexlansoprazole	DM1DBV5	Moderate	Increased risk of hypomagnesemia by the combination of Chlorothiazide and Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[42]
Metipranolol	DMJMVKI	Moderate	Increased risk of hypertriglyceridemia by the combination of Chlorothiazide and Metipranolol.	Glaucoma [9C61]	[39]
Levobetaxolol	DMSREPX	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Levobetaxolol.	Glaucoma [9C61]	[39]
Levobunolol	DMTNFCQ	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Levobunolol.	Glaucoma [9C61]	[39]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Procarbazine.	Hodgkin lymphoma [2B30]	[46]
Acebutolol	DM0TI4U	Moderate	Increased risk of hyperglycemia by the combination of Chlorothiazide and Acebutolol.	Hypertension [BA00-BA04]	[39]
Captopril	DM458UM	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Captopril.	Hypertension [BA00-BA04]	[48]
Penbutolol	DM4ES8F	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Penbutolol.	Hypertension [BA00-BA04]	[39]
Nebivolol	DM7F1PA	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Nebivolol.	Hypertension [BA00-BA04]	[39]
Pindolol	DMD2NV7	Moderate	Increased risk of hypertriglyceridemia by the combination of Chlorothiazide and Pindolol.	Hypertension [BA00-BA04]	[39]
Quinapril	DMR8H31	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Quinapril.	Hypertension [BA00-BA04]	[48]
Belladonna	DM2RBWK	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Belladonna.	Infectious gastroenteritis/colitis [1A40]	[47]
Meclofenamic acid	DM05FXR	Moderate	Antagonize the effect of Chlorothiazide when combined with Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[44]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and ITI-007.	Insomnia [7A00-7A0Z]	[43]
Arsenic trioxide	DM61TA4	Major	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Arsenic trioxide.	Mature B-cell lymphoma [2A85]	[49]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Ozanimod.	Multiple sclerosis [8A40]	[46]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Promethazine.	Nausea/vomiting [MD90]	[43]
Sibutramine	DMFJTDI	Moderate	Increased risk of hyponatremia by the combination of Chlorothiazide and Sibutramine.	Obesity [5B80-5B81]	[45]
Levomethadyl Acetate	DM06HG5	Major	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Levomethadyl Acetate.	Opioid use disorder [6C43]	[50]
Ibuprofen	DM8VCBE	Moderate	Antagonize the effect of Chlorothiazide when combined with Ibuprofen.	Pain [MG30-MG3Z]	[44]
Flavoxate	DMKV4NL	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Flavoxate.	Pain [MG30-MG3Z]	[47]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Safinamide.	Parkinsonism [8A00]	[46]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Rasagiline.	Parkinsonism [8A00]	[46]
Methylscopolamine	DM5VWOB	Minor	Altered absorption of Chlorothiazide due to GI dynamics variation caused by Methylscopolamine.	Peptic ulcer [DA61]	[47]
Bromfenac	DMKB79O	Moderate	Antagonize the effect of Chlorothiazide when combined with Bromfenac.	Postoperative inflammation [1A00-CA43]	[44]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Levomepromazine.	Psychotic disorder [6A20-6A25]	[43]
Oxaprozin	DM9UB0P	Moderate	Antagonize the effect of Chlorothiazide when combined with Oxaprozin.	Rheumatoid arthritis [FA20]	[44]
Quetiapine	DM1N62C	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Quetiapine.	Schizophrenia [6A20]	[43]
Mesoridazine	DM2ZGAN	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Mesoridazine.	Schizophrenia [6A20]	[51]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Aripiprazole.	Schizophrenia [6A20]	[43]
Iloperidone	DM6AUFY	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Iloperidone.	Schizophrenia [6A20]	[51]
Paliperidone	DM7NPJS	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Paliperidone.	Schizophrenia [6A20]	[51]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Thiothixene.	Schizophrenia [6A20]	[43]
Amisulpride	DMSJVAM	Moderate	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Amisulpride.	Schizophrenia [6A20]	[51]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Asenapine.	Schizophrenia [6A20]	[43]
Methdilazine	DMAUHQX	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Methdilazine.	Vasomotor/allergic rhinitis [CA08]	[43]
Trimeprazine	DMEMV9D	Moderate	Additive hypotensive effects by the combination of Chlorothiazide and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[52]
Amiodarone	DMUTEX3	Major	Increased risk of ventricular arrhythmias by the combination of Chlorothiazide and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[53]
-----------


⏷ Show the Full List of 58 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
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Magnesium stearate	E00208	11177	lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
--------------------


⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Chlorothiazide 250 mg tablet	250 mg	Oral Tablet	Oral
Chlorothiazide 500 mg tablet	500 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: 4835).
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 084026.
4	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.
5	BDDCS applied to over 900 drugs
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	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
8	Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats. Clin Sci (Lond). 2000 Apr;98(4):481-8.
9	ABCG2 modulates chlorothiazide permeability--in vitro-characterization of its interactions. Drug Metab Pharmacokinet. 2012;27(3):349-53.
10	Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73.
11	Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
12	Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
13	The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
14	Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
15	Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
16	Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
17	The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
18	Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
19	Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
20	Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
21	Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
22	Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
23	Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
24	Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
25	Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
26	Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
27	Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
28	The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
29	Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
30	Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.
31	Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases. J Med Chem. 2010 Apr 8;53(7):2913-26.
32	Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
33	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
34	Selective effect of thiazides on the human osteoblast-like cell line MG-63. Kidney Int. 1996 Nov;50(5):1476-82.
35	Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50.
36	Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4.
37	Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
38	Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
39	Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
40	Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61. [PMID: 6701709]
41	Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
42	FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
43	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
44	Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol 48 (1995): 247-51. [PMID: 7589049]
45	Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
46	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
47	Beermann B, Groschinsky-Grind M "Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline." Eur J Clin Pharmacol 13 (1978): 385-7. [PMID: 668798]
48	Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2. [PMID: 6391404]
49	Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
50	Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25. [PMID: 1678923]
51	Cerner Multum, Inc. "Australian Product Information.".
52	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
53	Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]