Anagrelide (Page 4 of 4)

13.2 Animal Toxicology and/or Pharmacology

In the 2-year rat study, a significant increase in non-neoplastic lesions was observed in anagrelide treated males and females in the adrenal (medullary hyperplasia), heart (myocardial hypertrophy and chamber distension), kidney (hydronephrosis, tubular dilation and urothelial hyperplasia), and bone (femur enostosis). Vascular effects were observed in tissues of the pancreas (arteritis/periarteritis, intimal proliferation, and medial hypertrophy), kidney (arteritis/periarteritis, intimal proliferation, and medial hypertrophy), sciatic nerve (vascular mineralization), and testes (tubular atrophy and vascular infarct) in anagrelide-treated males.

14 CLINICAL STUDIES

Clinical Studies in Adult Patients:

A total of 942 patients with myeloproliferative neoplasms including 551 patients with Essential Thrombocythemia (ET), 117 patients with Polycythemia Vera (PV), 178 patients with Chronic Myelogenous Leukemia (CML), and 96 patients with other myeloproliferative neoplasms (OMPN), were treated with anagrelide in three clinical trials. Patients with OMPN included 87 patients who had Myeloid Metaplasia with Myelofibrosis (MMM), and 9 patients who had unclassified myeloproliferative neoplasms.

Patients were enrolled in clinical trials if their platelet count was ≥ 900,000/μL on two occasions or ≥ 650,000/μL on two occasions with documentation of symptoms associated with thrombocythemia. The mean duration of anagrelide therapy for ET, PV, CML, and OMPN patients was 65, 67, 40, and 44 weeks, respectively; 23% of patients received treatment for 2 years. Patients were treated with anagrelide starting at doses of 0.5 to 2.0 mg every 6 hours. The dose was increased if the platelet count was still high, but to no more than 12 mg each day. Efficacy was defined as reduction of platelet count to or near physiologic levels (150,000 to 400,000/μL). The criteria for defining subjects as “responders” were reduction in platelets for at least 4 weeks to ≤600,000/μL, or by at least 50% from baseline value. Subjects treated for less than 4 weeks were not considered evaluable. The results are depicted graphically below:

Image
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*x 103 /μL

†Nine hundred and forty-two subjects with myeloproliferative neoplasms were enrolled in three research studies. Of these, 923 had platelet counts measured over the duration of the studies.

Anagrelide was effective in phlebotomized patients as well as in patients treated with other concomitant therapies including hydroxyurea, aspirin, interferon, radioactive phosphorus, and alkylating agents.

Clinical Study in Pediatric Patients:

An open label safety and PK/PD study was conducted in 18 pediatric patients 7 to 16 years of age (8 patients 7 to 11 years of age and 10 patients 12 to 16 years of age, mean age of 12 years; 8 males and 10 females) with thrombocythemia secondary to ET as compared to 17 adult patients (mean age of 66 years, 9 males and 8 females). Prior to entry on to the study, 17 of 18 pediatric patients and 12 of 17 adult patients had received anagrelide treatment for an average of 2 years. The median starting total daily dose, determined by retrospective chart review, for pediatric and adult patients with ET who had received anagrelide prior to study entry was 1 mg for each of the three age groups (7 to 11 and 12 to 16 year old patients and adults). The starting dose for 6 anagrelide-naive patients at study entry was 0.5 mg once daily. At study completion, the median total daily maintenance doses were similar across age groups, median of 1.75 mg for patients of 7 to 11 years of age, 2.25 mg in patients 12 to 16 years of age, and 1.5 mg for adults.

16 HOW SUPPLIED/STORAGE AND HANDLING

Anagrelide capsules, USP 0.5 mg are Size ‘4’, hard gelatin capsule having grey opaque cap and white opaque body, imprinted ‘1453’ on cap and ‘0.5 mg’ on body with black ink containing white to off-white powder.

Bottles of 30 NDC 13668-453-30

Bottles of 100 NDC 13668-453-01

Carton of 100 capsules (10 x 10 unit-dose) NDC 13668-453-74

Anagrelide capsules, USP 1 mg are Size ‘3’, hard gelatin capsule having White opaque cap and White opaque body, imprinted ‘1462’ on cap and ‘1 mg’ on body with black ink containing white to off-white powder.

Bottles of 30 NDC 13668-462-30

Bottles of 100 NDC 13668-462-01

Carton of 100 capsules (10 x 10 unit-dose) NDC 13668-462-74

Store at 20° to 25° C (68° to 77° F); excursions permitted between 15° C and 30° C (59° F and 86° F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container with a child-resistant closure.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

17 PATIENT COUNSELING INFORMATION

  • Dose: Tell the patient that their dose will be adjusted on a weekly basis until they are on a dose that lowers their platelets to an appropriate level. This will also help the patient to adjust to common side effects. Tell the patient to contact their doctor if they experience tolerability issues, so the dose or dosing frequency can be adjusted [see Dosage and Administration (2)].
  • Cardiovascular effects: Tell the patient to contact a doctor immediately if they experience chest pain, palpitations, or feel their heartbeat is irregular [see Warnings and Precautions (5.1)].
  • Risk of Pulmonary Hypertension: Tell the patient to contact a doctor immediately if they experience shortness of breath, swelling in legs or ankles, or lips and skin turn a bluish color [see Warnings and Precautions (5.2)].
  • Risk of bleeding: Warn the patient that concomitant aspirin (or other medicines that affect blood clotting) may increase the risk of bleeding. Tell the patient to contact a doctor immediately if they experience signs or symptoms of bleeding (e.g. vomit blood, pass bloody or black stools) or experience unexplained bruising/bruise more easily than usual [see Warnings and Precautions (5.3), Drug Interactions (7.1)].
  • Lactation: Advise patients not to breastfeed during treatment with anagrelide, and for one week following the last dose [see Use in Specific Populations (8.2)].
  • Infertility: Advise females of reproductive potential treatment with anagrelide may impair fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].
Image

Manufactured by:

TORRENT PHARMACEUTICALS LTD., INDIA.

Manufactured for:

TORRENT PHARMA INC., Basking Ridge, NJ 07920.

8078374 Revised March 2020

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Anagrelide capsules 0.5 mg

05 labels
(click image for full-size original)

Anagrelide capsules 1 mg

1 mg lab
(click image for full-size original)
ANAGRELIDE
anagrelide capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:13668-453
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ANAGRELIDE HYDROCHLORIDE (ANAGRELIDE) ANAGRELIDE 0.5 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
CROSCARMELLOSE SODIUM
FERROSOFERRIC OXIDE
GELATIN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POTASSIUM HYDROXIDE
PROPYLENE GLYCOL
SHELLAC
TITANIUM DIOXIDE
Product Characteristics
Color GRAY (grey opaque cap and white opaque body) Score no score
Shape CAPSULE Size 4mm
Flavor Imprint Code 1453;05
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:13668-453-30 30 CAPSULE in 1 BOTTLE None
2 NDC:13668-453-01 100 CAPSULE in 1 BOTTLE None
3 NDC:13668-453-74 100 CAPSULE in 1 CARTON None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA209151 06/30/2017
ANAGRELIDE
anagrelide capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:13668-462
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ANAGRELIDE HYDROCHLORIDE (ANAGRELIDE) ANAGRELIDE 1 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
CROSCARMELLOSE SODIUM
FERROSOFERRIC OXIDE
GELATIN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POTASSIUM HYDROXIDE
PROPYLENE GLYCOL
SHELLAC
TITANIUM DIOXIDE
Product Characteristics
Color WHITE (White opaque cap and White opaque body) Score no score
Shape CAPSULE Size 3mm
Flavor Imprint Code 1462;1
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:13668-462-30 30 CAPSULE in 1 BOTTLE None
2 NDC:13668-462-74 100 CAPSULE in 1 CARTON None
3 NDC:13668-462-01 100 CAPSULE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA209151 06/30/2017
Labeler — Torrent Pharmaceuticals Limited (916488547)
Registrant — Torrent Pharma, Inc. (790033935)
Establishment
Name Address ID/FEI Operations
Torrent Pharmaceuticals Limited 916488547 ANALYSIS (13668-453), ANALYSIS (13668-462), PACK (13668-453), PACK (13668-462), MANUFACTURE (13668-453), MANUFACTURE (13668-462), API MANUFACTURE (13668-453), API MANUFACTURE (13668-462)

Revised: 03/2020 Torrent Pharmaceuticals Limited

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