Imatinib Mesylate (Page 8 of 8)

14.7 Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia

One open-label, multicenter, phase 2 study was conducted testing Imatinib mesylate tablet in diverse populations of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases. This study included 14 patients with Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia (HES/CEL). HES patients were treated with 100 mg to 1000 mg of Imatinib mesylate tablet daily. The ages of these patients ranged from 16 to 64 years. A further 162 patients with HES/CEL aged 11 to 78 years were reported in 35 published case reports and case series. These patients received Imatinib mesylate tablet at doses of 75 mg to 800 mg daily. Hematologic response rates are summarized in Table 24. Response durations for literature patients ranged from 6+ weeks to 44 months.

Table 24: Response in HES/CEL

Cytogenetic Abnormality	Number of Patients	Complete Hematological Response	Partial Hematological Response
		N (%)	N (%)
Positive FIP1L1-PDGFRα Fusion Kinase	61	61 (100)	0
Negative FIP1L1-PDGFRα Fusion Kinase	56	12 (21)	9 (16)
Unknown Cytogenetic Abnormality	59	34 (58)	7 (12)
Total	176	107 (61)	23 (13)

14.8 Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma Protuberans (DFSP) is a cutaneous soft tissue sarcoma. It is characterized by a translocation of chromosomes 17 and 22 that results in the fusion of the collagen type 1 alpha 1 gene and the PDGF B gene.

An open-label, multicenter, phase 2 study was conducted testing imatinib mesylate tablet in a diverse population of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases. This study included 12 patients with DFSP who were treated with Imatinib mesylate 800 mg daily (age range 23 to 75 years). DFSP was metastatic, locally recurrent following initial surgical resection and not considered amenable to further surgery at the time of study entry. A further 6 DFSP patients treated with Imatinib mesylate tablet are reported in 5 published case reports, their ages ranging from 18 months to 49 years. The total population treated for DFSP therefore comprises 18 patients, 8 of them with metastatic disease. The adult patients reported in the published literature were treated with either 400 mg (4 cases) or 800 mg (1 case) Imatinib mesylate tablet daily. A single pediatric patient received 400 mg/m ² /daily, subsequently increased to 520 mg/m ² /daily. Ten patients had the PDGF B gene rearrangement, 5 had no available cytogenetics and 3 had complex cytogenetic abnormalities. Responses to treatment are described in Table 25.

Table 25: Response in DFSP

	Number of Patients (n = 18)	%
Complete Response	7	39
Partial Response *	8	44
Total Responders	15	83
* 5 patients made disease free by surgery

Twelve of these 18 patients either achieved a complete response (7 patients) or were made disease free by surgery after a partial response (5 patients, including one child) for a total complete response rate of 67%. A further 3 patients achieved a partial response, for an overall response rate of 83%. Of the 8 patients with metastatic disease, five responded (62%), three of them completely (37%). For the 10 study patients with the PDGF B gene rearrangement, there were 4 complete and 6 partial responses. The median duration of response in the phase 2 study was 6.2 months, with a maximum duration of 24.3 months, while in the published literature it ranged between 4 weeks and more than 20 months.

15 REFERENCES

1. OSHA Hazardous Drugs. OSHA. [Accessed on 20-September- 2013, from http://www.osha.gov/SLTC/hazardousdrugs/index.html]

16 HOW SUPPLIED/STORAGE AND HANDLING

Each film-coated tablet contains 100 mg or 400 mg of Imatinib free base.

100 mg film coated tablets

Dark yellow to brownish orange colored, film-coated tablets, round, biconvex with bevelled edges, debossed with ‘S’ and ‘1’ on either side of break line on one side and plain on other side.

Bottles of 90 tablets…………………………… NDC 59923-723-90

400 mg film coated tablets

Dark yellow to brownish orange colored, film-coated tablets, capsule shaped, biconvex with bevelled edges debossed with ‘S’ and ‘2’ on either side of break line on one side and plain on other side.

Bottles of 30 tablets…………………………… NDC 59923-724-30

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15°C — 30°C (59°F-86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container, USP.

Do not crush Imatinib mesylate tablets. Avoid direct contact of crushed tablets with the skin or mucous membranes. If such contact occurs, wash thoroughly as outlined in the references. Avoid exposure to crushed tablets .

17 PATIENT COUNSELING INFORMATION

Dosing and Administration

Advise patients to take imatinib mesylate tablets exactly as prescribed, not to change their dose or to stop taking imatinib mesylates tablet unless they are told to do so by their doctor. If the patient missed a dose of imatinib mesylate tablets, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time. Advise patients to take imatinib mesylate tablets with a meal and a large glass of water. [ See Dosage and

Administration (2.1) ].

Fluid Retention and Edema

Inform patients of the possibility of developing edema and fluid retention. Advise patients to contact their health care provider if unexpected rapid weight gain occurs [see Warnings and Precautions (5.1)].

Hepatotoxicity

Inform patients of the possibility of developing liver function abnormalities and serious hepatic toxicity. Advise patients to immediately contact their health care provider if signs of liver failure occur, including jaundice, anorexia, bleeding or bruising [see Warnings and Precautions (5.4)].

Pregnancy and Breast-Feeding

Advise patients to inform their doctor if they are or think they may be pregnant. Advise women of reproductive potential to avoid becoming pregnant while taking imatinib mesylate tablets. Female patients of reproductive potential taking imatinib mesylate tablets should use highly effective contraception during treatment and for fourteen days after stopping treatment with imatinib mesylate tablets [see Use in Specific Populations (8.3)]. Avoid breastfeeding during treatment and for 1 month after the last dose [see Use in Specific Populations (8.2)].

Drug Interactions

Imatinib mesylate tablet and certain other medicines such as warfarin, erythromycin, and phenytoin, including over-the-counter medications such as herbal products, can interact with each other. Advise patients to tell their doctor if they are taking or plan to take iron supplements. Avoid grapefruit juice and other foods known to inhibit CYP3A4 while taking imatinib mesylate tablets. [See Drug Interactions (7)].

Pediatric

Advise patients that growth retardation has been reported in children and pre-adolescents receiving imatinib mesylate tablets. The long term effects of prolonged treatment with imatinib mesylate tablets on growth in children are unknown. Therefore, closely monitoring of growth in children under imatinib mesylate tablets treatment. [See Warnings and Precautions (5.11)].

Driving and Using Machines

Advise patients that they may experience side effects such as dizziness, blurred vision or somnolence during treatment with imatinib mesylate tablets. Therefore, caution patients about driving a car or operating machinery. [See Warnings and Precautions (5.13)].

Distributed by:

Areva Pharmaceuticals, Inc.

Georgetown, IN 47122

Made in India

Imatinib Mesylate Tablets

100 mg

Imatinib Mesylate Tablets

400 mg

IMATINIB MESYLATE imatinib mesylate tablet, coated

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59923-723 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength IMATINIB MESYLATE (IMATINIB) IMATINIB 100 mg

Inactive Ingredients Ingredient Name Strength POVIDONE MAGNESIUM STEARATE FERRIC OXIDE YELLOW POLYETHYLENE GLYCOL, UNSPECIFIED FERRIC OXIDE RED TITANIUM DIOXIDE HYPROMELLOSES TALC

Product Characteristics Color yellow Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code S;1 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:59923-723-90 90 TABLET, COATED in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA208302 03/01/2020

IMATINIB MESYLATE imatinib mesylate tablet, coated

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59923-724 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength IMATINIB MESYLATE (IMATINIB) IMATINIB 400 mg

Inactive Ingredients Ingredient Name Strength HYPROMELLOSES FERRIC OXIDE RED POVIDONE TALC MAGNESIUM STEARATE FERRIC OXIDE YELLOW TITANIUM DIOXIDE POLYETHYLENE GLYCOL, UNSPECIFIED

Product Characteristics Color yellow Score 2 pieces Shape CAPSULE Size 16mm Flavor Imprint Code S;2 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:59923-724-30 30 TABLET, COATED in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA208302 03/01/2020

Labeler — Areva Pharmaceuticals (833189835)

Revised: 01/2021 Areva Pharmaceuticals