lumacaftor, ivacaftor drug combination profile

Orkambi : A two-drug mixture consisting of lumacaftor and ivacaftor, which is used for the treatment of cystic fibrosis. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	71494926
SCHEMBL ID	19410545
MeSH ID	M000607520

Synonym
1815566-23-4
lumacaftor and ivacaftor
lumacaftor, ivacaftor drug combination
lumacaftor and ivacaftor tablet
vx 809-vx 770 combination
lumacaftor / ivacaftor
vx 700-vx 809 combination
orkambi
SCHEMBL19410545
yqcgoszyhrvofw-uhfffaoysa-n

Excerpt	Reference	Relevance
" Most children (236 [99%] of 239 children) had adverse events that were mild (49 [21%] of 239) or moderate (148 [62%] of 239) in severity, and there was a low rate of adverse events leading to treatment discontinuation."	( Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study. Chilvers, MA; Cornell, AG; Davies, JC; Han, Z; Milla, C; Owen, CA; Ratjen, F; Tian, S, 2021)	0.62
"Lumacaftor-ivacaftor therapy in children homozygous for F508del-CFTR who initiated treatment at age 6-11 years was generally safe and well tolerated, and efficacy was sustained for up to 120 weeks."	( Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study. Chilvers, MA; Cornell, AG; Davies, JC; Han, Z; Milla, C; Owen, CA; Ratjen, F; Tian, S, 2021)	0.62

Excerpt	Reference	Relevance
"Cavosonstat (N91115), an orally bioavailable inhibitor of S-nitrosoglutathione reductase, promotes cystic fibrosis transmembrane conductance regulator (CFTR) maturation and plasma membrane stability, with a mechanism of action complementary to CFTR correctors and potentiators."	( Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F508DEL-CFTR. Casey, A; Chmiel, JF; Donaldson, SH; Flume, PA; Mandagere, A; McCoy, K; Shoemaker, SA; Solomon, GM; Taylor-Cousar, JL; Troha, JM; Zeitlin, PL; Zemanick, ET, 2017)	0.46

Excerpt	Relevance	Reference
"Current dosing strategies of CFTR modulators are based on serum pharmacokinetics, but drug concentrations in target tissues such as airway epithelia are not known."	( Accumulation and persistence of ivacaftor in airway epithelia with prolonged treatment. Cholon, DM; Esther, CR; Gentzsch, M; Guhr Lee, TN; Quinney, NL, 2020)	0.56
" Direct measurement of drugs in target tissues may be needed to optimize dosing strategies, and the persistence of CFTR modulators after treatment cessation has implications for personalized medicine approaches."	( Accumulation and persistence of ivacaftor in airway epithelia with prolonged treatment. Cholon, DM; Esther, CR; Gentzsch, M; Guhr Lee, TN; Quinney, NL, 2020)	0.56

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	73 (61.86)	24.3611
2020's	45 (38.14)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	8 (6.50%)	5.53%
Reviews	27 (21.95%)	6.00%
Case Studies	10 (8.13%)	4.05%
Observational	12 (9.76%)	0.25%
Other	66 (53.66%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
chlorine chloride : A halide anion formed when chlorine picks up an electron to form an an anion.	3.23	4	0	halide anion; monoatomic chlorine	cofactor; Escherichia coli metabolite; human metabolite
glycine [no description available]	2.17	1	0	alpha-amino acid; amino acid zwitterion; proteinogenic amino acid; serine family amino acid	EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor; fundamental metabolite; hepatoprotective agent; micronutrient; neurotransmitter; NMDA receptor agonist; nutraceutical
ibuprofen Midol: combination of cinnamedrine, phenacetin, aspirin & caffeine	2.17	1	0	monocarboxylic acid	antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; radical scavenger; xenobiotic
4-phenylbutyric acid 4-phenylbutyric acid: RN refers to the parent cpd. 4-phenylbutyric acid : A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the gamma-globin gene and affects hPPARgamma activation.	3.27	1	0	monocarboxylic acid	antineoplastic agent; apoptosis inducer; EC 3.5.1.98 (histone deacetylase) inhibitor; prodrug
carbostyril Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.	17.04	121	12	monohydroxyquinoline; quinolone	bacterial xenobiotic metabolite
phenylalanine Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.. L-phenylalanine : The L-enantiomer of phenylalanine.. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group.	2.61	2	0	amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid	algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite
arginine Arginine: An essential amino acid that is physiologically active in the L-form.. arginine : An alpha-amino acid that is glycine in which the alpha-is substituted by a 3-guanidinopropyl group.	2.21	1	0	arginine; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid	biomarker; Escherichia coli metabolite; micronutrient; mouse metabolite; nutraceutical
pyrazines Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.	2.25	1	0	diazine; pyrazines	Daphnia magna metabolite
hydrazine diamine : Any polyamine that contains two amino groups.	2.17	1	0	azane; hydrazines	EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor
alpha-aminopyridine alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.	17.04	121	12
dronabinol Dronabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.. Delta(9)-tetrahydrocannabinol : A diterpenoid that is 6a,7,8,10a-tetrahydro-6H-benzo[c]chromene substituted at position 1 by a hydroxy group, positions 6, 6 and 9 by methyl groups and at position 3 by a pentyl group. The principal psychoactive constituent of the cannabis plant, it is used for treatment of anorexia associated with AIDS as well as nausea and vomiting associated with cancer chemotherapy.	2.31	1	0	benzochromene; diterpenoid; phytocannabinoid; polyketide	cannabinoid receptor agonist; epitope; hallucinogen; metabolite; non-narcotic analgesic
ursodeoxycholic acid Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.. ursodeoxycholic acid : A bile acid found in the bile of bears (Ursidae) as a conjugate with taurine. Used therapeutically, it prevents the synthesis and absorption of cholesterol and can lead to the dissolution of gallstones.. ursodeoxycholate : A bile acid anion that is the conjugate base of ursodeoxycholic acid, obtained by deprotonation of the carboxy group; major species at pH 7.3.	4.19	2	0	bile acid; C24-steroid; dihydroxy-5beta-cholanic acid	human metabolite; mouse metabolite
tobramycin Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.. tobramycin : A amino cyclitol glycoside that is kanamycin B lacking the 3-hydroxy substituent from the 2,6-diaminoglucose ring.	2.25	1	0	amino cyclitol glycoside	antibacterial agent; antimicrobial agent; toxin
colforsin Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	2.59	2	0	acetate ester; cyclic ketone; labdane diterpenoid; organic heterotricyclic compound; tertiary alpha-hydroxy ketone; triol	adenylate cyclase agonist; anti-HIV agent; antihypertensive agent; plant metabolite; platelet aggregation inhibitor; protein kinase A agonist
zithromax Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.. azithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.	4.27	2	0	macrolide antibiotic	antibacterial drug; environmental contaminant; xenobiotic
leuprolide Leuprolide: A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.. leuprolide : An oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, D-leucyl, leucyl, arginyl, and N-ethylprolinamide residues joined in sequence. It is a synthetic nonapeptide analogue of gonadotropin-releasing hormone, and is used as a subcutaneous hydrogel implant (particularly as the acetate salt) for the treatment of prostate cancer and for the suppression of gonadal sex hormone production in children with central precocious puberty.	2.25	1	0	oligopeptide	anti-estrogen; antineoplastic agent; gonadotropin releasing hormone agonist
lenabasum lenabasum: a CB2 cannabinoid receptor agonist; structure in first source	2.31	1	0
oxadiazoles Oxadiazoles: Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.	3.27	1	0
ptc 124 [no description available]	3.27	1	0	oxadiazole; ring assembly
oligonucleotides [no description available]	2.25	1	0
vx-770 ivacaftor: a CFTR potentiator; structure in first source. ivacaftor : An aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis.	10.84	36	1	aromatic amide; monocarboxylic acid amide; phenols; quinolone	CFTR potentiator; orphan drug
lumacaftor lumacaftor: a corrector of CF transmembrane conductance regulator (CTFR); structure in first source. lumacaftor : An aromatic amide obtained by formal condensation of the carboxy group of 1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxylic acid with the aromatic amino group of 3-(6-amino-3-methylpyridin-2-yl)benzoic acid. Used for the treatment of cystic fibrosis.	9.2	16	1	aromatic amide; benzodioxoles; benzoic acids; cyclopropanes; organofluorine compound; pyridines	CFTR potentiator; orphan drug
rifampin Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)	6.85	3	3	cyclic ketal; hydrazone; N-iminopiperazine; N-methylpiperazine; rifamycins; semisynthetic derivative; zwitterion	angiogenesis inhibitor; antiamoebic agent; antineoplastic agent; antitubercular agent; DNA synthesis inhibitor; EC 2.7.7.6 (RNA polymerase) inhibitor; Escherichia coli metabolite; geroprotector; leprostatic drug; neuroprotective agent; pregnane X receptor agonist; protein synthesis inhibitor

Condition	Relationship Strength	Studies	Trials
Cystic Fibrosis of Pancreas [description not available]	17.92	130	22
Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.	17.92	130	22
Acute Symptom Flare [description not available]	2.61	2	0
Adverse Drug Event [description not available]	2.25	1	0
Infections, Respiratory [description not available]	2.25	1	0
Respiratory Tract Infections Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases.	2.25	1	0
Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.	2.25	1	0
Endometrioma An enlarged area of ENDOMETRIOSIS that resembles a tumor. It is usually found in the OVARY. When it is filled with old blood, it is known as a chocolate cyst.	2.25	1	0
Thoracic Diseases Disorders affecting the organs of the thorax.	2.25	1	0
Endometriosis A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.	2.25	1	0
Hemoptysis Expectoration or spitting of blood originating from any part of the RESPIRATORY TRACT, usually from hemorrhage in the lung parenchyma (PULMONARY ALVEOLI) and the BRONCHIAL ARTERIES.	2.25	1	0
Infections, Pseudomonas [description not available]	5.29	7	0
Pseudomonas Infections Infections with bacteria of the genus PSEUDOMONAS.	5.29	7	0
Impaired Glucose Tolerance [description not available]	2.25	1	0
Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.	2.25	1	0
Glucose Intolerance A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.	2.25	1	0
Innate Inflammatory Response [description not available]	3.17	1	0
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	3.17	1	0
Allergy, Drug [description not available]	2.31	1	0
Drug Hypersensitivity Immunologically mediated adverse reactions to medicinal substances used legally or illegally.	2.31	1	0
Pancreatic Cyst A true cyst of the PANCREAS, distinguished from the much more common PANCREATIC PSEUDOCYST by possessing a lining of mucous EPITHELIUM. Pancreatic cysts are categorized as congenital, retention, neoplastic, parasitic, enterogenous, or dermoid. Congenital cysts occur more frequently as solitary cysts but may be multiple. Retention cysts are gross enlargements of PANCREATIC DUCTS secondary to ductal obstruction. (From Bockus Gastroenterology, 4th ed, p4145)	2.25	1	0
Disease Exacerbation [description not available]	11.88	17	9
Airflow Obstruction, Chronic [description not available]	2.25	1	0
Airway Remodeling The structural changes in the number, mass, size and/or composition of the airway tissues.	2.25	1	0
Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.	2.25	1	0
Catarrh Inflammation of a mucous membrane with increased flow of mucous in humans or animals. Catarrh is used mostly in a historical context.	2.31	1	0
Common Cold A catarrhal disorder of the upper respiratory tract, which may be viral or a mixed infection. It generally involves a runny nose, nasal congestion, and sneezing.	2.31	1	0
Anasarca [description not available]	2.25	1	0
Edema Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.	2.25	1	0
Acute Myelogenous Leukemia [description not available]	2.25	1	0
Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.	2.25	1	0
Kidney Diseases Pathological processes of the KIDNEY or its component tissues.	2.25	1	0
Channelopathies A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.	2.25	1	0
Electrocardiogram QT Prolonged [description not available]	2.63	2	0
Long QT Syndrome A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.	2.63	2	0
Breathlessness [description not available]	2.15	1	0
Dyspnea Difficult or labored breathing.	2.15	1	0
Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.	2.15	1	0
Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.	2.15	1	0
Suicidal Ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm.	2.15	1	0
Esophageal Reflux [description not available]	3.06	1	0
Liver Dysfunction [description not available]	3.94	2	0
Gastroesophageal Reflux Retrograde flow of gastric juice (GASTRIC ACID) and/or duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the distal ESOPHAGUS, commonly due to incompetence of the LOWER ESOPHAGEAL SPHINCTER.	3.06	1	0
Intestinal Diseases Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM.	3.06	1	0
Liver Diseases Pathological processes of the LIVER.	3.94	2	0
Weight Gain Increase in BODY WEIGHT over existing weight.	3.06	1	0
Complications, Pregnancy [description not available]	2.17	1	0
Delayed Effects, Prenatal Exposure [description not available]	2.17	1	0
Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	2.17	1	0
Stunted Growth [description not available]	2.21	1	0
Growth Disorders Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth.	2.21	1	0
Infections, Staphylococcal [description not available]	2.21	1	0
Staphylococcal Infections Infections with bacteria of the genus STAPHYLOCOCCUS.	2.21	1	0
Health Care Associated Infection [description not available]	3.17	1	0
Atypical Mycobacterial Infection, Disseminated [description not available]	3.17	1	0
Pulmonary Consumption [description not available]	3.17	1	0
Cough A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs.	5.81	2	1
Cross Infection Any infection which a patient contracts in a health-care institution.	3.17	1	0
Tuberculosis, Pulmonary MYCOBACTERIUM infections of the lung.	3.17	1	0
Cirrhosis, Liver [description not available]	3.12	1	0
Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.	3.12	1	0
Genetic Predisposition [description not available]	3.91	2	0
Apoplexy [description not available]	2.11	1	0
Cerebral Ischemia [description not available]	2.11	1	0
Cancer of Rectum [description not available]	2.11	1	0
Acute Disease Disease having a short and relatively severe course.	2.11	1	0
Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.	2.11	1	0
Rectal Neoplasms Tumors or cancer of the RECTUM.	2.11	1	0
Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)	2.11	1	0

lumacaftor, ivacaftor drug combination

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Synonyms (10)

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Toxicity

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Dosage Studied

Research

Studies (118)

Market Indicators

Research Demand Index: 40.89

Study Types