Available data from case reports with octreotide acetate use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with MYCAPSSA. No adverse developmental effects were observed with intravenous administration of octreotide to pregnant rats and rabbits during organogenesis at doses 7 and 13 times, respectively, the clinical dose based on octreotide injection body surface area. Transient growth retardation, with no impact on postnatal development, was observed in rat offspring from a pre- and post-natal study of octreotide at intravenous doses below the clinical dose based on octreotide injection body surface area (see Data).
The estimated background risk of 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 clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
In embryo-fetal development studies in rats and rabbits, pregnant animals received intravenous doses of octreotide up to 1 mg/kg/day during the period of organogenesis. A slight reduction in body weight gain was noted in pregnant rats at 0.1 and 1 mg/kg/day. There were no maternal effects in rabbits or embryo-fetal effects in either species up to the maximum dose tested. At 1 mg/kg/day in rats and rabbits, the dose multiple was approximately 7 and 13 times, respectively, the clinical dose based on octreotide injection body surface area.
In a pre- and post-natal development rat study at intravenous doses of 0.02-1 mg/kg/day, a transient growth retardation of the offspring was observed at all doses which was possibly a consequence of growth hormone inhibition by octreotide. The doses attributed to the delayed growth are below the clinical dose based on octreotide injection body surface area.
There is no information available on the presence of octreotide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that octreotide administered subcutaneously passes into the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MYCAPSSA and any potential adverse effects on the breastfed child from MYCAPSSA or from the underlying maternal condition.
Following a subcutaneous dose (1 mg/kg) of octreotide to lactating rats, transfer of octreotide into milk was observed at a low concentration compared to plasma (milk/plasma ratio of 0.009).
Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of IGF-1 concentration in acromegalic females treated with octreotide may lead to improved fertility.
Safety and efficacy of MYCAPSSA in pediatric patients have not been established.
In post-marketing reports, serious adverse reactions, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide injection use in pediatric patients, most notably in children under 2 years of age.
Clinical studies of octreotide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In MYCAPSSA clinical studies, 39 patients (21%) were age 65 years or over and 1 patient was age 75 years or over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
In patients with mild, moderate, or severe renal impairment there is no dose adjustment recommended for MYCAPSSA. There is a significant increase in octreotide exposure in patients with end stage renal disease (ESRD). Start patients with ESRD on MYCAPSSA 20 mg orally daily. Adjust the maintenance dose thereafter based on IGF-1 levels, patient’s signs and symptoms, and tolerability [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
Patients with liver cirrhosis and patients with fatty liver disease showed prolonged elimination of octreotide following subcutaneous administration of drug [see Clinical Pharmacology (12.3)].
A limited number of accidental overdoses of injectable octreotide acetate in adults has been reported. The doses ranged from 2.4 mg/day to 6 mg/day administered by continuous infusion or subcutaneously 1.5 mg three times a day. Adverse reactions in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatic steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss.
If overdose occurs, contact Poison Control (1-800-222-1222) for latest recommendations.
MYCAPSSA delayed release capsules contain octreotide acetate, a somatostatin analog. Octreotide is known chemically as L-cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxy-methyl) propyl]-, cyclic (2→7)-disulfide; [R-(R*,R*)].
The molecular weight of octreotide is 1019.3 (free peptide, C49 H66 N10 O10 S2 ) and its amino acid sequence is:
MYCAPSSA (octreotide) delayed-release capsules are enteric-coated capsules for oral use. Each capsule contains 20 mg of octreotide (provided as octreotide acetate). Octreotide is present as a salt with 1.4 to 2.5 molar equivalents of acetate. The capsules contain the following inactive ingredients: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE® (methacrylate). The capsule is printed with “OT 20” in Opacode® black ink.
Octreotide exerts pharmacologic actions similar to the natural hormone somatostatin, but is a more potent inhibitor of GH, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.
In a single-dose PK study conducted in healthy volunteers, inhibition of GH (as measured by Cavg ) was observed in all subjects receiving MYCAPSSA, as compared to their GH levels prior to MYCAPSSA.
In a study designed to assess the duration of MYCAPSSA-induced increased intestinal permeability, an increase in paracellular permeability was observed 2 hours after MYCAPSSA administration and returned to baseline by 5.5 hours after MYCAPSSA administration. MYCAPSSA-induced permeability is completely reversible within this timeframe.
MYCAPSSA maintained GH and IGF-1 levels in patients with acromegaly.
Single doses of octreotide acetate given subcutaneously have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In clinical trials the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions (5.1)].
Octreotide acetate may cause clinically significant suppression of TSH [see Warnings and Precautions (5.3)].
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