ASPIRIN AND EXTENDED-RELEASE DIPYRIDAMOLE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ASPIRIN (UNII: R16CO5Y76E) (ASPIRIN - UNII:R16CO5Y76E), DIPYRIDAMOLE (UNII: 64ALC7F90C) (DIPYRIDAMOLE - UNII:64ALC7F90C)

Available from:

Amneal Pharmaceuticals LLC

INN (International Name):

ASPIRIN

Composition:

ASPIRIN 25 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Aspirin and extended-release dipyridamole capsules are indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. Aspirin and extended-release dipyridamole capsules are contraindicated in patients with known hypersensitivity to any of the product components. Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug (NSAID) products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema or bronchospasm. Do not use aspirin in children or teenagers with viral infections because of the risk of Reye syndrome. Risk Summary Available data from published studies and postmarketing experience with aspirin and extended-release dipyridamole use during pregnancy have not identified a clear association between aspirin and extended-release dipyridamole use and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Aspirin and extended-release dipyridamole contains low-dose aspirin which is an NSAID (see Clinical Considerations) . In animal reproduction studies, there were adverse developmental effects with administration of aspirin in rats and rabbits at doses about 66 and 44 times, respectively, the human exposure at the maximum recommended daily dose of aspirin-dipyridamole. Reproduction studies with dipyridamole in mice, rabbits, and rats have revealed no evidence of harm to the fetus up to doses about 25 times the maximum recommended daily human dose of aspirin-dipyridamole. Nonclinical data are suggestive of a possible potentiation of aspirin-related fetal toxicity when combined with dipyridamole (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Labor and Delivery Aspirin and extended-release dipyridamole, which contains dipyridamole and low-dose aspirin, increases the risk for bleeding [see Warnings and Precautions (5.1)] . Maternal use of high-dose aspirin can result in excessive blood loss at delivery, prolonged gestation, prolonged labor, intracranial hemorrhage in premature infants, low birth weight, stillbirth, and neonatal death. Data Human Data Published data from clinical trials, observational studies, case series, and case reports over several decades have not identified a clear association between aspirin-dipyridamole use in pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, these studies cannot definitively establish the absence of any aspirin-dipyridamole associated risks. Methodological limitations of these studies include variability in the timing and dose of drug exposure (e.g., most exposures occurred beyond the first trimester) and the small sample sizes of individual studies. Animal Data Aspirin has been shown to be teratogenic in rats (spina bifida, exencephaly, microphthalmia and coelosomia) and rabbits (congested fetuses, agenesis of skull and upper jaw, generalized edema with malformation of the head, and diaphanous skin) at oral doses of 330 mg/kg/day and 110 mg/kg/day, respectively. These doses, which also resulted in a high resorption rate in rats (63% of implantations versus 5% in controls), are, on a mg/m2 basis, about 66 and 44 times, respectively, the dose of aspirin contained in the maximum recommended daily human dose of aspirin-dipyridamole. Reproduction studies with dipyridamole have been performed in mice, rabbits and rats at oral doses of up to 125 mg/kg, 40 mg/kg, and 1,000 mg/kg, respectively (about 1½, 2, and 25 times the maximum recommended daily human oral dose, respectively, on a mg/m2 basis) and have revealed no evidence of harm to the fetus due to dipyridamole. When 330 mg aspirin/kg/day was combined with 75 mg dipyridamole/kg/day in the rat at doses about 66 and 2 times, respectively, the maximum recommended daily human dose, the resorption rate approached 100%. Risk Summary Based on data from a clinical lactation study in breastfeeding women taking low-dose aspirin, the metabolite salicylic acid is present in human milk in low levels (see Data) . Dipyridamole is also present in human milk. There is no information on the effects of aspirin and extended-release dipyridamole or dipyridamole on the breastfed infant or on milk production. There is insufficient information to determine the effects of aspirin on the breastfed infant and no information on the effects of aspirin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for aspirin and extended-release dipyridamole and any potential adverse effects on the breastfed child from aspirin and extended-release dipyridamole or from the underlying maternal condition. Data A published clinical study involved six exclusively breastfeeding women at 1 to 8 months postpartum who were taking 81 mg aspirin daily. Milk samples were collected at steady-state, at 0, 1, 2, 4, 8, 12, and 24 hours after taking a dose of aspirin. Aspirin was undetectable in human milk. Salicylic acid was present in milk at low levels (average concentration of 24 ng/mL). Based on an average milk consumption of 150 mL/kg/day, the calculated relative infant dose was 0.4%. No adverse effects on the breastfed infants were noted. Safety and effectiveness of aspirin and extended-release dipyridamole in pediatric patients have not been studied. Because of the aspirin component, use of this product in the pediatric population is not recommended [see Contraindications (4.3)] . Of the total number of subjects in ESPS2, 61% were 65 and over, while 27% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)] . Aspirin and extended-release dipyridamole has not been studied in patients with hepatic or renal impairment. Avoid using aspirin containing products, such as aspirin and extended-release dipyridamole, in patients with severe hepatic or severe renal (glomerular filtration rate <10 mL/min) dysfunction [see Warnings and Precautions (5.2, 5.3) and Clinical Pharmacology (12.3)] .

Product summary:

Aspirin and extended-release dipyridamole capsules, 25 mg/200 mg , are available as two piece hard gelatin capsules, with a red opaque cap and a yellow opaque body, filled with light yellow to yellow extended-release dipyridamole pellets and a white to off-white, round, film-coated, biconvex, unscored, plain aspirin tablet. The capsule is imprinted axially with “AN” in yellow ink on the cap and “596” in red ink on the body. Aspirin and extended-release dipyridamole capsules are supplied as follows: Bottles of 60:                          NDC 65162-596-06 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from excessive moisture.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

ASPIRIN AND EXTENDED-RELEASE DIPYRIDAMOLE- ASPIRIN AND EXTENDED-
RELEASE DIPYRIDAMOLE CAPSULE
AMNEAL PHARMACEUTICALS LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ASPIRIN AND EXTENDED-
RELEASE DIPYRIDAMOLE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION
FOR ASPIRIN AND EXTENDED-RELEASE DIPYRIDAMOLE CAPSULES.
ASPIRIN AND EXTENDED-RELEASE DIPYRIDAMOLE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 1999
INDICATIONS AND USAGE
Aspirin and extended-release dipyridamole capsules are a combination
of aspirin and dipyridamole,
antiplatelet agents, indicated to reduce the risk of stroke in
patients who have had transient ischemia
of the brain or completed ischemic stroke due to thrombosis. (1)
DOSAGE AND ADMINISTRATION
One capsule twice daily (morning and evening) with or without food.
(2)
In case of intolerable headaches during initial treatment, switch to
one capsule at bedtime and low-
dose aspirin in the morning; resume BID dosing within one week. (2.1)
Do not chew capsule. (2)
Not interchangeable with the individual components of aspirin and
dipyridamole tablets. (2)
Dispense in this unit-of-use container. (16)
DOSAGE FORMS AND STRENGTHS
Capsule: 25 mg aspirin/200 mg extended-release dipyridamole. (3)
CONTRAINDICATIONS
Hypersensitivity to any product ingredients. (4.1)
Patients with known allergy to NSAIDs. (4.2)
Patients with the syndrome of asthma, rhinitis, and nasal polyps.
(4.2)
WARNINGS AND PRECAUTIONS
Aspirin and extended-release dipyridamole capsules increases the risk
of bleeding. (5.1)
Avoid use in patients with severe hepatic or renal insufficiency.
(5.2, 5.3)
Interrupt aspirin and extended-release dipyridamole capsules 48 hours
before using intravenous
dipyridamole or other adenosinergic agents for stress testing. (5.6,
7.1)
ADVERSE REACTIONS
The most frequently reported adverse reactions (>10% and greater than
placebo) were headache,
dyspepsia, abdominal pain, nausea, and diarrhea. (6.1)
TO REPORT SUSPECTED ADVERSE R