Symdeko
Symdeko Uses, Dosage, Side Effects, Food Interaction and all others data.
Tezacaftor is a drug of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator class. It was developed by Vertex Pharmaceuticals and FDA approved in combination with ivacaftor to manage cystic fibrosis. This drug was approved by the FDA on February 12, 2018.
Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.
Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy. Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation. When given with ivacaftor, tezacaftor can lead to liver transaminase elevations. Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.
| Trade Name | Symdeko |
| Generic | tezacaftor + ivacaftor, ivacaftor |
| Weight | 150mg + 100mgivacaftor150mg, 75mg + 50mgivacaftor75mg, |
| Type | Oral tablet |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Australia, Canada, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Tezacaftor is a medication used to treat homozygous or heterozygous F508del mutation cystic fibrosis.
Tezacaftor is combined with ivacaftor in one product for the treatment of cystic fibrosis (CF) in patients aged 12 years or older with two copies of the F508del gene mutation or at least one mutation in the CFTR gene that is responsive to this drug.
Tezacaftor, when used in combination with ivacaftor and elexacaftor in the product Trikafta, is also indicated for the treatment of CF in patients 12 years of age and older that have at least one F508del mutation in the CFTR gene.
Symdeko is also used to associated treatment for these conditions: Cystic Fibrosis (CF)
How Symdeko works
The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues and impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the F508del mutation of the CFTR gene, one amino acid is deleted at the position 508, therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions. CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing. This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased in water and salt movement through the cell membrane. The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride, reducing thick mucus production.
Toxicity
The LD50 of an oral dose in rats is >2000 mg/kg.
Overdose symptoms may include dizziness and diarrhea. There have been no reports to this date of tezacaftor overdose, but the highest dose of 450 mg every 12 hours commonly resulted in reports of dizziness and diarrhea. No antidote exists for treating an overdose with this drug. General supportive measures should be undertaken along with monitoring of vital signs and close monitoring of clinical status.
Volume of Distribution
The apparent volume of distribution of tezacaftor was 271 L in a study of patients in the fed state who received 100 mg of tezacaftor every 12 hours.
Elimination Route
The Cmax, Tmax and AUC of tezacaftor, when administered with ivacaftor, are 5.95 mcg/ml, 2-6 h, and 84.5 mcg.h/ml respectively. Exposure of tezacaftor/ivacaftor increases 3-fold when it is administered with a high-fat meal.
Half Life
The apparent half-life of tezacaftor is approximately 57.2 hours.
Clearance
The apparent clearance of tezacaftor has been measured at 1.31 L/h for patients in the fed state during a clinical trial.
Elimination Route
After oral administration, the majority of tezacaftor dose (72%) is found excreted in the feces either unchanged or as its metabolite, M2. About 14% of the administered dose is found excreted in the urine as the metabolite, M2. It was noted that less than 1% of the administered dose is excreted unchanged in the urine and thus, renal excretion is not the major elimination pathway.
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