LIVE
COURSES
2016
October 21–22
October 21–22
November 18–20
November 19
Grand Traverse Resort
Traverse City, MI
Chase Park Plaza Hotel
St. Louis, MO
The Ritz-Carlton at Reynolds Plantation
Greensboro, GA
Heart House
Washington, DC
Michigan Chapter Annual
Meeting 2016
Missouri Chapter Annual
Meeting 2016
Georgia Chapter Annual
Meeting 2016
Mid Atlantic Capital
Cardiology Symposium 2016
S:7 in
Corlanor® (ivabradine)
Ivabradine
N=3260
Placebo
N=3278
Bradycardia
10%
2.2%
Hypertension, blood
pressure increased
8.9%
7.8%
Atrial fibrillation
8.3%
6.6%
Phosphenes, visual
brightness
2.8%
0.5%
Monitor pregnant women with chronic heart failure in 3rd
trimester of pregnancy for preterm birth.
Data
Animal Data
In pregnant rats, oral administration of ivabradine during
the period of organogenesis (gestation day 6-15) at doses of
2.3, 4.6, 9.3, or 19 mg/kg/day resulted in fetal toxicity and
teratogenic effects. Increased intrauterine and post-natal
mortality and cardiac malformations were observed at doses
≥ 2.3 mg/kg/day (equivalent to the human exposure at the MRHD
based on AUC0-24hr). Teratogenic effects including interventricular
septal defect and complex anomalies of major arteries were
observed at doses ≥ 4.6 mg/kg/day (approximately 3 times the
human exposure at the MRHD based on AUC0-24hr).
In pregnant rabbits, oral administration of ivabradine during the
period of organogenesis (gestation day 6-18) at doses of 7, 14,
or 28 mg/kg/day resulted in fetal toxicity and teratogenicity.
Treatment with all doses ≥ 7 mg/kg/day (equivalent to the
human exposure at the MRHD based on AUC0-24hr) caused an
increase in post-implantation loss. At the high dose of 28 mg/kg/
day (approximately 15 times the human exposure at the MRHD
based on AUC0-24hr), reduced fetal and placental weights were
observed, and evidence of teratogenicity (ectrodactylia observed
in 2 of 148 fetuses from 2 of 18 litters) was demonstrated.
In the pre- and postnatal study, pregnant rats received
oral administration of ivabradine at doses of 2.5, 7, or
20 mg/kg/day from gestation day 6 to lactation day 20. Increased
postnatal mortality associated with cardiac teratogenic findings
was observed in the F1 pups delivered by dams treated at the
high dose (approximately 15 times the human exposure at the
MRHD based on AUC0-24hr).
8.2 Lactation
Risk Summary
There is no information regarding the presence of ivabradine in
human milk, the effects of ivabradine on the breastfed infant, or
the effects of the drug on milk production. Animal studies have
shown, however, that ivabradine is present in rat milk [see Data].
Because of the potential risk to breastfed infants from exposure
to Corlanor, breastfeeding is not recommended.
Data
Lactating rats received daily oral doses of [14C]-ivabradine
(7 mg/kg) on post-parturition days 10 to 14; milk and maternal
plasma were collected at 0.5 and 2.5 hours post-dose on
day 14. The ratios of total radioactivity associated with [14C]ivabradine or its metabolites in milk vs. plasma were 1.5 and
1.8, respectively, indicating that ivabradine is transferred to milk
after oral administration.
8.3 Females and Males of Reproductive Potential
Contraception
Females
Corlanor may cause fetal harm, based on animal data. Advise
females of reproductive potential to use effective contraception
during Corlanor treatment [see Use in Specific Populations (8.1)].
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been
established.
8.5 Geriatric Use
No pharmacokinetic differences have been observed in elderly
(≥ 65 years) or very elderly (≥ 75 years) patients compared to
the overall population. However, Corlanor has only been studied
in a limited number of patients ≥ 75 years of age.
8.6 Hepatic Impairment
No dose adjustment is required in patients with mild or moderate
hepatic impairment. Corlanor is contraindicated in patients with
severe hepatic impairment (Child-Pugh C) as it has not been studied
in this population and an increase in systemic exposure is anticipated
[see Contraindications (4) and Clinical Pharmacology (12.3)].
8.7 Renal Impairment
No dosage adjustment is required for patients with creatinine
clearance 15 to 60 mL/min. No data are available for patients
with creatinine clearance below 15 mL/min [see Clinical
Pharmacology (12.3)].
10. OVERDOSAGE
Overdose may lead to severe and prolonged bradycardia. In
the event of bradycardia with poor hemodynamic tolerance,
temporary cardiac pacing may be required. Supportive treatment,
including intravenous (IV) fluids, atropine, and intravenous betastimulating agents such as isoproterenol, may be considered.
This Brief Summary is based on the Corlanor® Prescribing
Information v1, 04/15
C