Toprol XL

[Metoprolol]

Cardiovascular

2 nd and 3 rd degree heart block.

Gastrointestinal

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hepatitis, vomiting.

Hematologic

thrombocytopenia.

Musculoskeletal

arthralgia.

Nervous System/ Psychiatric

anxiety/ nervousness, hallucinations, paresthesia.

Reproductive, male

impotence.

Skin

increased sweating, photosensitivity.

Special Sense Organs

taste disturbances.

Drug Interactions

Catecholamine-depleting drugs (eg, reserpine, mono amine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents. Patients treated with TOPROL-XL plus a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.

Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone are likely to increase metoprolol concentration. In healthy subjects with CYP2D6 exten-sive metabolizer phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with cardiovascular disease, coadmin-istration of propafenone 150 mg t. i. d. with immediate release metoprolol 50 mg t. i. d. resulted in two-to five-fold increases in the steady-state concentration of metoprolol.

These increases in plasma concentration would decrease the cardioselectivity of metoprolol. Beta-blockers may exacerbate the rebound hypertension which can follow the with-drawal of clonidine. If the two drugs are coadministered, the beta blocker should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have been conducted to evaluate the carcinogenic poten-tial of metoprolol tartrate. In 2-year studies in rats at three oral dosage levels of up to 800 mg/ kg/ day (41 times, on a mg/ m 2 basis, the daily dose of 200 mg for a 60-kg patient), there was no increase in the development of spontaneously occurring benign or malignant neoplasms of any type. The only histologic changes that appeared to be drug related were an increased incidence of generally mild focal accumulation of foamy macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia.

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