The following adverse reactions have been identified during the postapproval use of SANDOSTATIN LAR DEPOT. 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.
Blood and lymphatic: pancytopenia, thrombocytopenia
Cardiac: myocardial infarction, cardiac arrest, atrial fibrillation
Ear and labyrinth: deafness
Endocrine: diabetes insipidus, adrenal insufficiency in patients 18 months of age and under, pituitary apoplexy
Eye: glaucoma, visual field defect, scotoma, retinal vein thrombosis
Gastrointestinal: intestinal obstruction, peptic/gastric ulcer, abdomen enlarged
General and administration site: generalized edema, facial edema
Hepatobiliary: gallbladder polyp, fatty liver, hepatitis
Immune: anaphylactoid reactions including anaphylactic shock
Infections and infestations: appendicitis
Laboratory abnormalities: increased liver enzymes, CK increased, creatinine increased
Metabolism and nutrition: diabetes mellitus
Musculoskeletal: arthritis, joint effusion, Raynaud’s syndrome
Nervous system: convulsions, aneurysm, intracranial hemorrhage, hemiparesis, paresis, suicide attempt, paranoia, migraines, Bell’s palsy, aphasia
Renal and urinary: renal failure, renal insufficiency
Reproductive and breast: gynecomastia, galactorrhea, libido decrease, breast carcinoma
Respiratory: status asthmaticus, pulmonary hypertension, pulmonary nodule, pneumothorax aggravated
Skin and subcutaneous tissue: urticaria, cellulitis, petechiae
Vascular: orthostatic hypotension, hematuria, gastrointestinal hemorrhage, arterial thrombosis of the arm
Concomitant administration of octreotide injection with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.
Octreotide inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when SANDOSTATIN LAR DEPOT treatment is initiated or when the dose is altered and anti-diabetic treatment should be adjusted accordingly.
Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine.
Concomitant administration of bradycardia-inducing drugs (e.g., beta-blockers) may have an additive effect on the reduction of heart rate associated with octreotide. Dose adjustments of concomitant medication may be necessary.
Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.
Limited published data indicate that somatostatin analogs may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.
Octreotide competitively binds to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate. Discontinue SANDOSTATIN LAR DEPOT at least 4 weeks prior to each lutetium Lu 177 dotatate dose.
The limited data with SANDOSTATIN LAR DEPOT in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, no-adverse-developmental-effects were observed with intravenous administration of octeotride to pregnant rats and rabbits during organogenesis at doses 7- and 13-times, respectively the maximum recommended human dose (MRHD) of 1.5 mg/day based on body surface area (BSA). 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 MRHD based on BSA (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% to 4% and 15% to 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, at the highest recommended human dose of 1.5 mg/day based on BSA.
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 human dose of 1.5 mg/day, based on BSA.
There is no information available on the presence of SANDOSTATIN LAR DEPOT 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; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SANDOSTATIN LAR DEPOT, and any potential adverse effects on the breastfed child from SANDOSTATIN LAR DEPOT 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 insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with octeotride may lead to improved fertility.
Safety and efficacy of SANDOSTATIN LAR DEPOT in the pediatric population have not been demonstrated.
No formal controlled clinical trials have been performed to evaluate the safety and effectiveness of SANDOSTATIN LAR DEPOT in pediatric patients under 6 years of age. In postmarketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with Sandostatin use in children, most notably in children under 2 years of age. The relationship of these events to octreotide has not been established as the majority of these pediatric patients had serious underlying comorbid conditions.
The efficacy and safety of SANDOSTATIN LAR DEPOT was examined in a single randomized, double-blind, placebo-controlled, 6-month pharmacokinetics study in 60 pediatric patients age 6 to 17 years with hypothalamic obesity resulting from cranial insult. The mean octreotide concentration after 6 doses of 40 mg SANDOSTATIN LAR DEPOT administered by IM injection every four weeks was approximately 3 ng/mL. Steady-state concentrations were achieved after 3 injections of a 40-mg dose. Mean BMI increased 0.1 kg/m2 in SANDOSTATIN LAR DEPOT-treated subjects compared to 0.0 kg/m2 in saline control-treated subjects. Efficacy was not demonstrated. Diarrhea occurred in 11 of 30 (37%) patients treated with SANDOSTATIN LAR DEPOT. No unexpected adverse events were observed. However, with SANDOSTATIN LAR DEPOT 40 mg once a month, the incidence of new cholelithiasis in this pediatric population (33%) was higher than that seen in other adult indications, such as acromegaly (22%) or malignant carcinoid syndrome (24%), where SANDOSTATIN LAR DEPOT was dosed at 10 mg to 30 mg once a month.
Clinical studies of Sandostatin did not include sufficient numbers of subjects age 65 years 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 be cautious, usually starting 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.
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