Fluvoxamine Maleate (Page 7 of 12)

7.3 Other Drugs

Alosetron: See Contraindications (4), Warnings and Precautions (5.7), and Lotronex^® (alosetron) package insert.

Digoxin: Administration of immediate-release fluvoxamine maleate tablets 100 mg daily for 18 days (N=8) did not significantly affect the pharmacokinetics of a 1.25 mg single intravenous dose of digoxin.

Diltiazem: Bradycardia has been reported with the coadministration of immediate-release fluvoxamine maleate tablets and diltiazem.

Mexiletine: See Warnings and Precautions (5.9).

Propranolol and Other Beta-Blockers: Coadministration of immediate-release fluvoxamine maleate tablets 100 mg per day and propranolol 160 mg per day in normal volunteers resulted in a mean five-fold increase (range 2 to 17) in minimum propranolol plasma concentrations. In this study, there was a slight potentiation of the propranolol-induced reduction in heart rate and reduction in the exercise diastolic pressure.

One case of bradycardia and hypotension and a second case of orthostatic hypotension have been reported with the coadministration of immediate-release fluvoxamine maleate tablets and metoprolol.

If propranolol or metoprolol is coadministered with fluvoxamine maleate extended-release capsules, a reduction in the initial beta-blocker dose and more cautious dose titration are recommended. No dosage adjustment is required for fluvoxamine maleate extended-release capsules.

Coadministration of immediate-release fluvoxamine maleate tablets 100 mg per day with atenolol 100 mg per day (N=6) did not affect the plasma concentrations of atenolol. Unlike propranolol and metoprolol, which undergo hepatic metabolism, atenolol is eliminated primarily by renal excretion.

Theophylline: See Warnings and Precautions (5.9).

Warfarin and Other Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, etc.): See Warnings and Precautions (5.9, 5.11).

7.4 Effects of Smoking on Fluvoxamine Metabolism

Smokers had a 25% increase in the metabolism of fluvoxamine compared to nonsmokers.

7.5 Electroconvulsive Therapy (ECT)

There are no clinical studies establishing the benefits or risks of combined use of ECT and fluvoxamine maleate.

7.6 Monoamine Oxidase Inhibitors (MAOIs)

See Dosage and Administration (2.6, 2.7), Contraindications (4.1), Warnings and Precautions (5.2).

7.7 Serotonergic Drugs

See Dosage and Administration (2.6, 2.7), Contraindications (4.1), Warnings and Precautions (5.2).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects: When pregnant rats were given daily doses of fluvoxamine (60 mg/kg, 120 mg/kg, or 240 mg/kg) orally throughout the period of organogenesis, developmental toxicity in the form of increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses of 120 mg/kg or greater. Decreased fetal body weight was seen at the high dose. The no effect dose for developmental toxicity in this study was 60 mg/kg (approximately 2 times the maximum recommended human dose [MRHD] on a mg/m² basis).

In a study in which pregnant rabbits were administered doses of up to 40 mg/kg (approximately 2 times the MRHD on a mg/m² basis) orally during organogenesis, no adverse effects on embryofetal development were observed.

In other reproduction studies in which female rats were dosed orally during pregnancy and lactation (5 mg/kg, 20 mg/kg, 80 mg/kg, or 160 mg/kg), increased pup mortality at birth was seen at doses of 80 mg/kg or greater and decreases in pup body weight and survival were observed at all doses (low effect dose approximately 0.1 times the MRHD on a mg/m² basis).

Nonteratogenic Effects: Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.11) and Clinical Considerations]. Neonates exposed to fluvoxamine maleate tablets and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs) late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability and constant crying. These features are consistent with either a direct toxic effect of SSRIs or SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see Warnings and Precautions-Serotonin Syndrome [5.2]).

Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (fluvoxamine maleate and fluvoxamine maleate extended-release are SSRIs) in pregnancy and PPHN. Other studies do not show a significant statistical association.

Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy.

When treating a pregnant woman with fluvoxamine, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis (see Dosage and Administration [2.7]).

Maternal Adverse Reactions : Use of fluvoxamine maleate extended-release capsules in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.11)].