Axishil
Axishil Uses, Dosage, Side Effects, Food Interaction and all others data.
Axishil has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axishil was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.
Axishil prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.
Trade Name | Axishil |
Availability | Prescription only |
Generic | Axitinib |
Axitinib Other Names | Axitinib, Axitinibum |
Related Drugs | Keytruda, pembrolizumab, Avastin, bevacizumab, Opdivo, Afinitor |
Type | Tablet |
Formula | C22H18N4OS |
Weight | Average: 386.47 Monoisotopic: 386.120131908 |
Protein binding | Plasma protein binding for axitinib is high at over 99% with most protein binding to albumin followed by α1-acid glycoprotein. |
Groups | Approved, Investigational |
Therapeutic Class | Targeted Cancer Therapy |
Manufacturer | Shilpa Medicare Limited |
Available Country | India |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
Axishil is used for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.
Axishil is also used to associated treatment for these conditions: Severe Aplastic Anemia (SAA), Advanced Thyroid cancer, Refractory Aplastic anemia
How Axishil works
Axishil selectively blocks the tyrosine kinase receptors VEGFR-1 (vascular endothelial growth factor receptor), VEGFR-2, and VEGFR-3.
Dosage
Axishil dosage
Recommended Dosing: The recommended starting oral dose of Axishil is 5 mg twice daily. Administer Axishil doses approximately 12 hours apart with or without food. Axishil should be swallowed whole with a glass of water.
If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.
Dose Modification Guidelines: Dose increase or reduction is recommended based on individual safety and tolerability.
Over the course of treatment, patients who tolerate Axishil for at least two consecutive weeks with no adverse reactions > Grade 2 (according to the Common Toxicity Criteria for Adverse Events), arenormotensive, and are not receiving anti-hypertensionmedication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, the Axishil dose may be increased to 7 mg twice daily, and further to 10 mg twice daily using the same criteria.
Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of Axishil therapy. If dose reduction from 5 mg twice daily is required, the recommended dose is 3 mg twice daily. If additional dose reduction is required, the recommended dose is 2 mg twice daily.
Side Effects
Selected adverse reactions (all grades) that were reported in < 10% of patients treated with Axishil included dizziness (9%), upper abdominal pain (8%), myalgia (7%), dehydration (6%), epistaxis (6%), anemia (4%), hemorrhoids (4%), hematuria (3%), tinnitus (3%), lipase increased (3%), glossodynia (3%), pulmonary embolism (2%), rectal hemorrhage (2%), hemoptysis (2%), deep vein thrombosis (1%), retinal-veinocclusion/thrombosis (1%), polycythemia (1%), and transient ischemic attack (1%).
Toxicity
Some of the more serious toxic effects seen in patients taking axitinib include, but are not limited to, hypertension, thrombotic events, hemorrhage, and GI perforation.
Precaution
Patient with HTN, cardiac disease, history of or risk for thrombosis. Patients taking strong CYP3A4 inhibitors. Withhold treatment at least 24 hr prior to scheduled surgery. Moderate hepatic impairment (Child-Pugh Class B). Pregnancy.
Interaction
In vitro data indicate that axitinib is metabolized primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.
CYP3A4/5 Inhibitors: Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of Axishil with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor must be co-administered, the Axishil dose should be reduced
CYP3A4/5 Inducers: Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. Co-administration of Axishil with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John's wort) should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 induction potential is recommended. Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitinib and should be avoided if possible.
Food Interaction
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of axitinib.
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of axitinib.
- Take with a full glass of water.
- Take with or without food.
[Moderate] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract.
Axishil may be administered with or without food.
Axishil Hypertension interaction
[Moderate] The use of axitinib may causes hypertension.
Blood pressure should be well-controlled prior to initiating axitinib and treated as needed with standard anti-hypertensive therapy.
It is recommended to reduce the dose in case of persistent hypertension despite use of anti-hypertensive medications and to discontinue therapy if hypertension is severe and persistent despite these measures.
Discontinuation of therapy should be considered if there is evidence of hypertensive crisis.
Close monitoring is recommended.
Axishil Drug Interaction
Minor: esomeprazoleUnknown: aripiprazole, paclitaxel protein-bound, fentanyl, fentanyl, charcoal, doxorubicin, albumin human, aspirin, diphenhydramine, rosuvastatin, hydromorphone, fentanyl, sodium iodide, levetiracetam, fenofibrate, morphine, oxycodone, acetaminophen, cholecalciferol
Axishil Disease Interaction
Major: hemorrhagic eventsModerate: cardiac failure, GI perforation, hepatic impairment, hypertension, proteinuria, renal impairment, RPL syndrome, thromboembolism, thyroid dysfunction, lung toxicity
Volume of Distribution
The volume of distribution is 160 L.
Elimination Route
After one 5 mg dose of axitinib, it takes about 2.5 to 4.1 hours to reach maximum plasma concentration.
Half Life
Axishil has a half life of 2.5 to 6.1 hours.
Clearance
The average clearance of axitinib is 38 L/h.
Elimination Route
Axishil is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. There is also 23% eliminated in the urine, most of which are metabolites.
Pregnancy & Breastfeeding use
Pregnancy Category D. Axishil can cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women using Axishil. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving Axishil. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Nursing Mothers: It is not known whether axitinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Axishil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Special Warning
Hepatic Impairment: The systemic exposure to axitinib was higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with normal hepatic function. A dose decrease is recommended when administering Axishil to patients with moderate hepatic impairment (Child-Pugh class B). Axishil has not been studied in patients with severe hepatic impairment (Child-Pugh class C)
Renal Impairment: No dedicated renal impairment trial for axitinib has been conducted. Based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 mL/min ≤ ClCr < 89 mL/min). No starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. Caution should be used in patients with end-stage renal disease (ClCr< 15 mL/min).
Pediatric Use: The safety and efficacy of axitinib in pediatric patients have not been studied.
Geriatric Use: No dosage adjustment is required in elderly patients
Acute Overdose
There is no specific treatment for Axishil overdose.
In a controlled clinical study with Axishil for the treatment of patients with RCC, 1 patient inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).
In a clinical dose finding study with Axishil, subjects who received starting doses of 10 mg twice daily or 20 mg twice daily experienced adverse reactions which included hypertension, seizures associated with hypertension, and fatal hemoptysis.
In cases of suspected overdose, Axishil should be withheld and supportive care instituted.
Storage Condition
Store at 20°C to 25°C
Innovators Monograph
You find simplified version here Axishil
Axishil contains Axitinib see full prescribing information from innovator Axishil Monograph, Axishil MSDS, Axishil FDA label