CORLOPAM Solution for injection Ref.[10053] Active ingredients: Fenoldopam

5.1 Tachycardia

Fenoldopam causes a dose-related tachycardia, particularly with infusion rates above 0.1 mcg/kg/min in adults and >0.8 mcg/kg/min in pediatric patients. Tachycardia in adults may diminish with continued therapy at doses of fenoldopam of <0.1 mcg/kg/min.

5.2 Hypokalemia

Hypokalemia has been observed after less than 6 hours of fenoldopam infusion. Hypokalemia reflects a pressure natriuresis with enhanced potassium-sodium exchange or a direct drug effect. Monitor serum potassium levels.

5.3 Increased Intraocular Pressure

In a clinical study of 12 patients with open-angle glaucoma or ocular hypertension (mean baseline intraocular pressure was 29.2 mm Hg with a range of 22 to 33 mm Hg), infusion of fenoldopam at escalating doses ranging from 0.05 to 0.5 mcg/kg/min over a 3.5 hour period caused a dose-dependent increase in intraocular pressure (IOP). At the peak effect, the intraocular pressure was raised by a mean of 6.5 mm Hg (range -2 to +8.5 mm Hg, corrected for placebo effect). Upon discontinuation of the fenoldopam infusion, the IOP returned to baseline values within 2 hours.

5.4 Allergic Reactions Associated with Sulfite

Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common reactions associated with fenoldopam use are headache, cutaneous dilation (flushing), nausea, and hypotension, each reported in more than 5% of patients.

Adverse reactions occurring more than once in any dosing group (once if potentially important or plausibly drug-related) in the fixed-dose constant-infusion studies are presented in Table 3. There was no clear dose relationship, except possibly for headache, nausea, flushing.

Table 3. Adverse reactions in fixed-dose studies occurring in >5% of subjects on fenoldopam:

The following additional adverse reactions were observed more frequently in patients treated with fenoldopam.

Incidence 0.5% to 5%:

Metabolism and Nutrition Disorders: Hypokalemia

Psychiatric Disorders: Nervousness/Anxiety, insomnia

Nervous System Disorders: Dizziness

Cardiac Disorders: Extrasystoles, palpitations, cardiac failure, ischemic heart disease, myocardial infarction, angina pectoris, tachycardia

Gastrointestinal Disorders: Abdominal pain

Skin and Subcutaneous Tissue Disorders: Hyperhidrosis

Musculoskeletal and Connective Tissue Disorders: Muscle spasms

Renal and Urinary Disorders: Oliguria

General Disorders and Administration Site Conditions: Chest pain, pyrexia

Investigations: Blood urea increased, blood creatinine increased, blood glucose increased, transaminases increased, blood lactate dehydrogenase increased

The following adverse reactions have been identified during post approval use of CORLOPAM. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Voluntary reports of adverse reactions temporally associated with CORLOPAM that have been received since market introduction include the following:

Cardiac Disorders: Cardiogenic shock

Vascular Disorders: Hypotension

Gastrointestinal Disorders: Abdominal distension

Investigations: Electrocardiogram ST segment depression, oxygen saturation decreased

7.1 Beta-Blockers

Avoid concomitant use of fenoldopam with beta-blockers. If the drugs are used together, blood pressure should be monitored frequently because hypotension could result from beta-blocker inhibition of the sympathetic reflex response to fenoldopam.

Risk Summary

There are insufficient data regarding CORLOPAM use in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

In animal studies, there was no evidence of teratogenicity or fetotoxicity when fenoldopam was orally administered to rats and rabbits during organogenesis (see Data). There are adverse effects on maternal and fetal outcomes associated with severe hypertension (see Clinical Considerations).

The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Severe hypertension can result in maternal stroke, pulmonary edema, myocardial ischemia or death of the mother or fetus.

Data

Animal Data

Oral reproduction studies have been performed in rats and rabbits at doses of 12.5 to 200 mg/kg/day and 6.25 to 25 mg/kg/day, respectively, administered during the period of organogenesis. Studies have revealed maternal toxicity at the highest doses tested but no evidence of harm to the fetus due to fenoldopam.

Risk Summary

There are no data on the presence of fenoldopam in human milk, the effects on the breastfed child, or the effects on milk production. Fenoldopam is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk.

Because of the potential for severe adverse reactions in the breastfed infant, advise women not to breastfeed during treatment with CORLOPAM.

Safety and effectiveness of fenoldopam have been established in the age groups age <1 month (at least 2 kg or full term) to 12 years old requiring blood pressure reduction [see Clinical Pharmacology (12.2)]. The adverse event profile in pediatric patients is similar to that seen in adults.

The pharmacokinetics of fenoldopam are independent of age when corrected for body weight.

The long-term effects of fenoldopam on growth and development have not been studied.

Clinical studies of fenoldopam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.