Diazoxide use in specific populations

Diazoxide
PROGLYCEM® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Diazoxide
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Use in Specific Populations

Pregnancy Category C

There are no adequate and well-controlled studies of BRILINTA use in pregnant women. In animal studies, ticagrelor caused structural abnormalities at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. BRILINTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In reproductive toxicology studies, pregnant rats received ticagrelor during organogenesis at doses from 20 to 300 mg/kg/day. The lowest dose was approximately the same as the MRHD of 90 mg twice daily for a 60 kg human on a mg/m2 basis. Adverse outcomes in offspring occurred at doses of 300 mg/kg/day (16.5 times the MRHD on a mg/m2 basis) and included supernumerary liver lobe and ribs, incomplete ossification of sternebrae, displaced articulation of pelvis, and misshapen/misaligned sternebrae. When pregnant rabbits received ticagrelor during organogenesis at doses from 21 to 63 mg/kg/day, fetuses exposed to the highest maternal dose of 63 mg/kg/day (6.8 times the MRHD on a mg/m2 basis) had delayed gall bladder development and incomplete ossification of the hyoid, pubis and sternebrae occurred.

In a prenatal/postnatal study, pregnant rats received ticagrelor at doses of 10 to 180 mg/kg/day during late gestation and lactation. Pup death and effects on pup growth were observed at 180 mg/kg/day (approximately 10 times the MRHD on a mg/m2 basis). Relatively minor effects such as delays in pinna unfolding and eye opening occurred at doses of 10 and 60 mg/kg (approximately one-half and 3.2 times the MRHD on a mg/m2 basis).

8.3 Nursing Mothers

It is not known whether ticagrelor or its active metabolites are excreted in human milk. Ticagrelor is excreted in rat milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from BRILINTA, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

The safety and effectiveness of BRILINTA in pediatric patients have not been established.

8.5 Geriatric Use

In PLATO, 43% of patients were ≥65 years of age and 15% were ≥75 years of age. The relative risk of bleeding was similar in both treatment and age groups.

No overall differences in safety or effectiveness were observed between these patients and younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

8.6 Hepatic Impairment

BRILINTA has not been studied in the patients with moderate or severe hepatic impairment. Ticagrelor is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Hence, BRILINTA is contraindicated for use in patients with severe hepatic impairment and its use should be considered carefully in patients with moderate hepatic impairment. No dosage adjustment is needed in patients with mild hepatic impairment [see Contraindications (4), Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

8.7 Renal Impairment

No dosage adjustment is needed in patients with renal impairment. Patients receiving dialysis have not been studied [see Clinical Pharmacology (12.3)].