Abeclib Tablet 200 mg
Abeclib Tablet 200 mg Uses, Dosage, Side Effects, Food Interaction and all others data.
Abeclib Tablet 200 mg is an antitumor agent and dual inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6) that are involved in the cell cycle and promotion of cancer cell growth in case of unregulated activity. On September 28, 2017, FDA granted approval of abemaciclib treatment under the market name Verzenio for the treatment of HR-positive and HER2-negative advanced or metastatic breast cancer that has progressed after unsuccessful endocrine therapy. It is either given alone in patients who has undergone endocrine therapy and chemotherapy after the metastasis of cancer, or in combination with Fulvestrant. Following oral treatment in patients with HR-positive, HER2-negative breast cancer, abemaciclib demonstrated increased progression-free survival rates and objective response rates. Abeclib Tablet 200 mg has been used in trials studying the treatment of melanoma, lymphoma, neoplasm, solid tumor, and glioblastoma.
In combination with fulvestrant, the progression-free survival for patients with HR-positive, HER2-negative breast cancer was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant. As a monotherapy, 19.7% of patients taking abemaciclib achieved complete or partial shrinkage of their tumors for a median 8.6 months after treatment . Abeclib Tablet 200 mg induces cell cycle arrest and exerts an antitumor activity in human tumor xenograft models .
In patient investigations and a healthy volunteer study, abemaciclib is not shown to induce any clinically significant changes in the QTc interval .
| Trade Name | Abeclib Tablet 200 mg |
| Availability | Prescription only |
| Generic | Abemaciclib |
| Abemaciclib Other Names | Abemaciclib |
| Related Drugs | Arimidex, Ibrance, Femara, Aromasin, Faslodex, Verzenio, Afinitor, Xeloda, Herceptin, Lynparza |
| Weight | 200 mg |
| Type | Tablet |
| Formula | C27H32F2N8 |
| Weight | Average: 506.606 Monoisotopic: 506.271799388 |
| Protein binding | According to in vitro models using animal brain tissues, the protein binding of abemaciclib is approximately 95-98% . While abemaciclib demonstrated in vitro binding to serum albumin, alpha-1-acid glycoprotein and other human plasma proteins in a concentration-depedent manner, its major metabolites are also shown to bind to plasms proteins as well. The approximate bound fractions of M2, M18 and M20 are 93.4%, 96.8% and 97.8%, respectively . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Eskayef Pharmaceuticals Ltd. |
| Available Country | Bangladesh |
| Last Updated: | October 19, 2023 at 6:27 am |
Uses
Abeclib Tablet 200 mg is a medication used to treat HR+ HER2- advanced or metastatic breast cancer.
Indicated in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
Inidicated as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
Abeclib Tablet 200 mg is also used to associated treatment for these conditions: Advanced Breast Cancer, Metastatic Breast Cancer
How Abeclib Tablet 200 mg works
Regulation of cell cycle is crucial in maintaining proper cell growth; dysregulated cell cycle signalling pathway is a key component in inducing hyperproliferation of cells and tumor formation in various cancers. G1 to S phase cell cycle progression, or transition through the G1 restriction point (R), is promoted by the retinoblastoma tumor suppressor protein (Rb)-mediated pathway. Activation of Rb-mediated pathway requires the interaction of Cyclin-dependent kinases (CDK) 4 and 6 with D-type cyclins, which drives the formation of active CDK4/CDK6 and subsequent phosphorylation of Rb .
Rb is a tumor suppressant protein that inhibits proliferation through binding to and suppressing the activity of the E2F family of transcription factors . However, phosphorylation of Rb relieves suppression of E2F to allow expression of genes required for passage through the restriction point . This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. Phosphorylation of Rb and other proteins by CDK4/6 additionally leads to transcription of genes involved in cell cycle-independent activities including signal transduction, DNA repair transcriptional control, and mRNA processing .
Abeclib Tablet 200 mg selectively inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells . Unlike other CDK inhibitors such as Palbociclib and Ribociclib, abemaciclib exhibits greater selectivity for CDK4 compared to CDK6 .
Toxicity
According to the bacterial reverse mutation (Ames) assay, abemaciclib and its active metbolites M2 and M20 did not display mutagenic properties. Abeclib Tablet 200 mg was not clastogenic in vitro rat bone marrow micronucleus assay. Repeat-dose toxicity studies were performed to assess the effects of abemaciclib in testis, epididymis, prostate, and seminal vesicle at doses ≥10 mg/kg/day in rats and ≥0.3 mg/kg/day in dogs which exceed the recommeded therapeutic doses in humans. The findings included decreased organ weights, intratubular cellular debris, hypospermia, tubular distillation, atrophy and degeneration or necrosis .
Food Interaction
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of abemaciclib.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of abemaciclib.
- Take at the same time every day.
- Take with or without food.
[Moderate] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of abemaciclib.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
Inhibition of hepatic CYP450 3A4 may also contribute.
The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors.
According to the product labeling, abemaciclib systemic exposure (AUC) is predicted to increase by up to 16-fold when administered with the potent CYP450 3A4 inhibitor ketoconazole.
Itraconazole, another potent inhibitor, is predicted to increase the relative potency-adjusted unbound AUC of abemaciclib plus its active metabolites by 2.2-fold.
In cancer patients, administration of a single 50 mg dose of abemaciclib (one-third the approved recommended dose of 150 mg) with clarithromycin 500 mg twice daily increased the relative potency-adjusted unbound AUC of abemaciclib plus its active metabolites by 2.5-fold relative to abemaciclib administered alone.
The moderate CYP450 3A4 inhibitors, diltiazem and verapamil, are predicted to increase the relative potency-adjusted unbound AUC of abemaciclib plus its active metabolites by 2.4-fold and 1.6-fold, respectively.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Increased exposure to abemaciclib may increase adverse effects such as nausea, vomiting, diarrhea, stomatitis, venous thromboembolism, hepatotoxicity, anemia, neutropenia, and thrombocytopenia.
Food has modest effects on the pharmacokinetics of abemaciclib.
A high-fat, high-calorie meal (800 to 1000 calories; 150 calories from protein, 250 calories from carbohydrate, and 500 to 600 calories from fat) administered to healthy subjects increased the Cmax and AUC of abemaciclib plus its active metabolites by 26% and 9%, respectively.
MANAGEMENT: Abeclib Tablet 200 mg may be administered with or without food.
Patients should avoid consumption of grapefruit and grapefruit juice during treatment with abemaciclib.
Abeclib Tablet 200 mg Drug Interaction
Moderate: palbociclibUnknown: paclitaxel protein-bound, charcoal, diphenhydramine, multivitamin with minerals, multivitamin with minerals, tadalafil, methylcellulose, sulfamethoxazole / trimethoprim, ubiquinone, prochlorperazine, copper gluconate, fulvestrant, sodium iodide, metoprolol, acetaminophen, bioflavonoids, levothyroxine, ascorbic acid, cholecalciferol
Abeclib Tablet 200 mg Disease Interaction
Major: hepatic dysfunctionModerate: diarrhea, ILD, neutropenia, VTE, lung toxicity
Volume of Distribution
The geometric mean systemic volume of distribution is approximately 690.3 L (49% CV) .
Elimination Route
The plasma concentration of the drug increases in a dose-proportional manner. Following a single oral dose administration of 200 mg abemaciclib, the mean peak plasma concentration (Cmax) of 158 ng/mL is reached after 6 hours. The median time to reach maximum plasma concentration (Tmax) ranges from 4-6 hours following an oral administration of abemaciclib over a range of 50–275 mg , but may range up to 24 hours . The absolute bioavailability of the drug is reported to be 45% .
Half Life
The mean plasma elimination half-life for abemaciclib in patients was 18.3 hours (72% CV) .
Clearance
The geometric mean hepatic clearance (CL) of abemaciclib in patients was 26.0 L/h (51% CV) .
Elimination Route
Following a single oral dose of 150mg radiolabeled abemaciclib, approximately 81% of the total dose was recovered in feces while 3% of the dose was detected in urine. The majority of the drug is exceted as metabolites .
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