Toprol XL use in specific populations

Metoprolol

Clinical data
Trade names	Lopressor, Toprol-xl
AHFS/Drugs.com	Monograph
MedlinePlus	a682864
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Metoprolol
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral, IV
ATC code	C07AB02 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	12%
Metabolism	Hepatic via CYP2D6, CYP3A4
Elimination half-life	3-7 hours
Excretion	Renal
Identifiers
IUPAC name (RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
CAS Number	51384-51-1 Y
PubChem CID	4171
IUPHAR/BPS	553
DrugBank	DB00264 Y
ChemSpider	4027 Y
UNII	GEB06NHM23
KEGG	D02358 Y
ChEBI	CHEBI:6904 Y
ChEMBL	ChEMBL13 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H25NO3
Molar mass	267.364 g/mol
3D model (JSmol)	Interactive image
Melting point	120 °C (248 °F)
SMILES O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
InChI InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3 Y Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N Y
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Use In Specific Populations

8.1 Pregnancy

Pregnancy Category: C

Metoprolol tartrate has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 22 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. Distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug during pregnancy only if clearly needed.

8.3 Nursing Mothers

Metoprolol is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. Consider possible infant exposure when TOPROL-XL is administered to a nursing woman.

8.4 Pediatric Use

One hundred forty-four hypertensive pediatric patients aged 6 to 16 years were randomized to placebo or to one of three dose levels of TOPROL-XL (0.2, 1.0 or 2.0 mg/kg once daily) and followed for 4 weeks. The study did not meet its primary endpoint (dose response for reduction in SBP). Some pre-specified secondary endpoints demonstrated effectiveness including:

Dose-response for reduction in DBP,

mg/kg vs. placebo for change in SBP, and

mg/kg vs. placebo for change in SBP and DBP.

The mean placebo corrected reductions in SBP ranged from 3 to 6 mmHg, and DBP from 1 to 5 mmHg. Mean reduction in heart rate ranged from 5 to 7 bpm but considerably greater reductions were seen in some individuals [see Dosage and Administration (2.1)].

No clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients.

Safety and effectiveness of TOPROL-XL have not been established in patients < 6 years of age.

8.5 Geriatric Use

Clinical studies of TOPROL-XL in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients.

Of the 1,990 patients with heart failure randomized to TOPROL-XL in the MERIT-HF trial, 50% (990) were 65 years of age and older and 12% (238) were 75 years of age and older. There were no notable differences in efficacy or the rate of adverse reactions between older and younger patients.

In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Hepatic Impairment

No studies have been performed with TOPROL-XL in patients with hepatic impairment. Because TOPROL-XL is metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. Therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function.

8.7 Renal Impairment

The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. No reduction in dosage is needed in patients with chronic renal failure [see Clinical Pharmacology (12.3)].

References

Adapted from the FDA Package Insert.