Sincalide

The recommended dosage and administration of Sincalide for Injection by indication is shown in Table 1. For preparation instructions see Dosage and Administration (2.2).

Table 1:  Recommended Adult Dosage and Administration of Sincalide for Injection by Treatment Indication

For Intravenous Injection

• Reconstitute Sincalide for Injection aseptically by adding 5 mL of Sterile Water for Injection USP to the vial.
• Inspect the reconstituted solution visually for particulate matter and discoloration after reconstitution and prior to administration.
• Withdraw the prescribed dose of the reconstituted solution from the vial and administer as an intravenous injection over 30 to 60 seconds, as shown in Table 1. Discard the unused portion.
• Store the reconstituted solution at room temperature. Discard after 8 hours.
• For single use only; discard unused portion.

For Intravenous Infusion 

• Reconstitute Sincalide for Injection aseptically by adding 5 mL of Sterile Water for Injection USP to the vial.
• After reconstitution, withdraw the prescribed dose of the solution from the vial. Discard unused portion.
• Dilute the reconstituted solution in 30 mL or 100 mL of 0.9% Sodium Chloride Injection USP, depending on the indication, as described in Table 1.
• Inspect the Sincalide solutions visually for particulate matter and discoloration after reconstitution, dilution and prior to administration.
• Store the diluted solution at room temperature. Discard after 1 hour.

Contains sodium metabisulfite ​[see Description (11)],​ 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 nonasthmatic people.

In postmarketing experience, anaphylaxis, anaphylactic shock and other serious hypersensitivity reactions have been reported during and within one hour following administration of sincalide [see Adverse Reactions (6)].

Sincalide for Injection is contraindicated in patients with a history of hypersensitivity to sulfites. Due to the potential for anaphylaxis, appropriate medical support should be readily available when Sincalide for Injection is administered.  If anaphylaxis or other hypersensitivity reactions occur, immediately discontinue the infusion and initiate appropriate medical treatment.  Observe patients closely during and after the infusion.  Do not reinitiate Sincalide for Injection in patients who have experienced symptoms of hypersensitivity [see Contraindications (4)].

Stimulation of gallbladder contraction in patients with small gallbladder stones could lead to the evacuation of the stones from the gallbladder, resulting in their lodging in the cystic duct or in the common bile duct.

Administration of Sincalide for Injection as an intravenous injection may cause adverse reactions such as nausea, vomiting, abdominal pain or cramping, dizziness, and flushing [see Adverse Reactions (6)]. These reactions are generally transient. To reduce the risk of adverse reactions with intravenous injection when used to simulate contraction of the gallbladder or accelerate transit of a barium meal through the small intestine, administer Sincalide for Injection as an intravenous infusion over 50 or 30 minutes, respectively [see Dosage and Administration (2.1)].

Based on limited human data and mechanism of action, advise pregnant patients that Sincalide for Injection may cause preterm labor or spontaneous abortion [see Use in Specific Populations (8.1)].

Drugs that may stimulate or inhibit gallbladder motility or contractile response, may interfere with the response to sincalide.  Consider discontinuing these drugs prior to administration of Sincalide for Injection, when used to simulate contraction of the gallbladder.

Risk Summary

Based on limited human data and mechanism of action, Sincalide for Injection may cause preterm labor or spontaneous abortion [see Warnings and Precautions (5.4)]. Limited available data with Sincalide for Injection are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal embryo-fetal development studies in which sincalide was administered to hamsters and rats during the period of organogenesis, no effects were seen at doses comparable to the maximum recommended clinical dose on a mg/kg basis. However, in a prenatal development study in which rats were administered sincalide during organogenesis through parturition, decreased weight gain and developmental delays were observed at a dose 122 times higher than the maximum recommended human dose based on body surface area.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

There were no effects on embryo-fetal development in hamsters when sincalide was administered subcutaneously at 250 or 750 ng/kg during organogenesis (Gestation Days 7 to 13) at doses up to 0.8 times the maximum recommended dose of 120 ng/kg on a body surface area basis. No effects on embryo-fetal development were observed in Sprague-Dawley rats at subcutaneous doses of 250, 450, or 750 ng/kg from Gestation Days 6 to16, representing 1.0 time the maximum recommended human dose on a body surface area basis. In a separate study at a higher dose of 90 mcg/kg administered subcutaneously to CFY rats from Gestation Day 10 through parturition (representing 122 times the maximum recommended human dose on a body surface area basis), offspring showed decreased growth, behavioral changes, and developmental delays.

Risk Summary

There are no data regarding the presence of sincalide in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sincalide for Injection and any potential adverse effect on the breastfed infant from Sincalide for Injection or from the underlying condition.

The safety and effectiveness in pediatric patients have not been established.

Animal Data

Direct injection of sincalide in neonatal rats reduced milk consumption with the youngest rats exhibiting the greatest sensitivity to this effect. Although safety margins relative to maternal doses cannot be calculated since rat pups were injected directly, the safety margin in the youngest rat pups was less than 0.1 on a body surface area bases compared to the maximum adult clinical dose. At higher doses administered subcutaneously in neonatal rats, transient behavioral changes and small effects on physical developmental milestones such as ear opening, eye opening, and incisor appearance were observed (at doses 10 to 200-fold higher than the maximum recommended human dose on a body surface area basis).

Clinical studies of sincalide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

When injected intravenously, Sincalide stimulates gallbladder contraction and reduction in size. The evacuation of bile that results is similar to that which occurs physiologically in response to endogenous cholecystokinin. Sincalide also stimulates pancreatic secretion and intestinal motility causing pyloric contraction and slows gastric emptying.

Concurrent administration of sincalide with secretin increases both the volume of pancreatic secretion and the output of bicarbonate and enzymes. This combined effect of secretin and sincalide permits the assessment of specific pancreatic function through measurement and analysis of the duodenal aspirate.

Following an intravenous (bolus) injection of 0.02 mcg/kg sincalide, maximal contraction of the gallbladder occurred in 5 to 15 minutes. Sincalide reduced gallbladder radiographic size by at least 40%, which is generally considered satisfactory contraction.

Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential, or possible impairment of fertility in males or females.