Sandostatin Lar Depot (octreotide acetate, microspheres)
Somatostatic Agents Intramuscular Vial (EA)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Octreotide, a somatostatin analog, is a synthetic polypeptide that is pharmacologically related to the natural hormone somatostatin.
Octreotide is a synthetic octapeptide pharmacologically related to the natural hormone somatostatin; it is also known as a somatostatin analog. Octreotide is a more potent inhibitor of growth hormone (GH), glucagon, and insulin than somatostatin. Octreotide 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.
Because of the drug's pharmacologic actions, octreotide has been employed to control gastrointestinal and other manifestations associated with a variety of conditions (e.g., flushing and diarrhea associated with metastatic carcinoid tumors, watery diarrhea associated with VIP-secreting adenomas). Octreotide decreases the concentration of GH and/or insulin-like growth factor 1 (IGF-1) in patients with acromegaly.
Octreotide immediate-release injection (Sandostatin(R) injection and generic equivalents) is absorbed rapidly and completely following subcutaneous injection; peak concentrations are reached in 0.4 hours (0.7 in those with acromegaly). IV and subcutaneous doses were found to be bioequivalent. Octreotide is 65% bound in the plasma (41.2% in those with acromegaly), mainly to lipoprotein and to a lesser extent,to albumin.
The elimination half-life of the drug is 1.7-1.9 hours and approximately 32% of the dose is excreted unchanged in the urine. The duration of action of immediate-release octreotide is variable but extends up to 12 hours depending on the type of tumor, necessitating multiple daily dosing with this dosage form.
Octreotide half-life is longer (2.4-3.1 hours compared to 1.9 hours)in patients with renal impairment (creatinine clearance <= 60 mL/minute); in those requiring dialysis, clearance is reduced by half compared to healthy volunteers. In patients with liver impairment such as cirrhosis and fatty liver, octreotide half-life is increased to 3.7 and 3.4 hours, respectively.
Octreotide long-acting release (LAR) injectable suspension for IM administration (Sandostatin(R) LAR Depot) is a long-acting dosage form consisting of microspheres of the biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer, containing octreotide. All of the clinical and pharmacological characteristics of the immediate-release dosage form (Sandostatin(R) Injection and generic equivalents) are maintained with the added feature of slow release of octreotide from the site of injection, reducing the need for frequent administration. This slow release occurs as the polymer biodegrades, primarily through hydrolysis.
The relative bioavailability of the long-acting suspension compared to the immediate-release solution given subcutaneously was 60-63%. Following a single IM injection in healthy volunteers,serum octreotide concentrations reach a transient initial peak within 1 hour which progressively declines for the next 3-5 days. Following this decline, octreotide concentrations increase slowly, plateau in approximately 2-3 weeks post-injection, and are maintained over a period of nearly 2-3 additional weeks.
Following multiple IM injections given every 4 weeks, steady-state octreotide concentrations are achieved after the third injection. The long-acting suspension has not been studied in patients with renal or hepatic impairment.
Octreotide delayed-release capsules (Mycapssa(R)) are enteric-coated (methacrylate (Acryl-EZE(R))) and utilize Transient Permeability Enhancer (TPE(R)) technology. The capsules are designed to pass through the stomach intact and disintegrate when it reaches the higher pH of the small intestine where the octreotide-TPE formulation is released into the lumen. TPE facilitates paracellular transit across the intestinal wall via transient and reversible opening of the tight junctions between cells, allowing intact octreotide to be absorbed.
The delayed-release preparation does not cause any chemical or physical change in the active compound and once octreotide reaches the systemic circulation, the metabolism and excretion of octreotide is expected to be identical to that of the immediate-release dosage form (Sandostatin Injection and generic equivalents). In a study designed to assess the duration of Mycapssa(R)-induced increased intestinal permeability, an increase in paracellular permeability was observed 2 hours after administration and returned to baseline by 5.5 hours after administration; this permeability is completely reversible within this timeframe. When comparing a single dose of subcutaneous immediate-release octreotide to a single dose of oral octreotide (Mycapssa(R)), absorption time was longer, peak concentrations were reached at a median 1.67-2.5 hours (oral) versus 0.5 hours (subcutaneous), and peak octreotide levels were 33% lower in healthy subjects receiving the oral preparation.
In patients with acromegaly, octreotide concentrations are dose proportional following chronic administration of the oral preparation (40, 60, or 80 mg total daily dose); mean peak plasma concentrations were lower compared to single-dose peak concentrations in healthy subjects. Administration of the oral preparation with food decreases the rate and extent of absorption by 90% in healthy subjects. In patients with acromegaly, elimination after chronic dosing of the oral preparation was slightly slower than that seen in healthy subjects, with a mean apparent half-life at steady state ranging from 3.2-4.5 hours across all doses (20 mg, 40 mg, 60 mg, and 80 mg).
Elimination is complete approximately 48 hours after the last dose in patients who have achieved steady-state plasma levels; minimal accumulation (approximately 10%) was observed in patients after repeat administration of the oral preparation. In patients with severe renal impairment (estimated glomerular filtration rate 15-19 mL/minute per 1.73 m2), octreotide AUC and half-life are increased, but not to the same extent as matched-controls requiring dialysis. In patients with end stage renal disease requiring dialysis, clearance is reduced 46%, AUC is increased 87%, and the half-life increased 85% compared to healthy subjects.
USES: This medication is a long-acting form of octreotide. Octreotide is used to treat severe watery diarrhea and sudden reddening of the face and neck caused by certain types of tumors (such as carcinoid tumors, vasoactive intestinal peptide tumors) that are found usually in the intestines and pancreas. The symptoms occur when these tumors make too much of certain natural substances (hormones).
This medication works by blocking the production of these hormones. By decreasing watery diarrhea, octreotide helps to reduce the loss of body fluids and minerals. Octreotide is also used to treat a certain condition (acromegaly) that occurs when the body makes too much of a certain natural substance called growth hormone.
Treating acromegaly helps reduce the risk of serious problems such as diabetes and heart disease. Octreotide works by decreasing how much growth hormone your body makes. This drug is not a cure for these conditions.
This medication is usually used with other treatment (such as surgery, radiation, other drugs).
Generic name: octreotide acetate, microspheres
Pronunciation: (ok-TREE-oh-tide)
Drug class: Somatostatic Agents
Therapeutic class: Endocrine
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Sandostatin Lar Depot
Indications
The following indications are listed for Sandostatin Lar Depot:
- Acromegaly
- Carcinoid Syndrome
- Diarrhea Associated With Vasoactive Intestinal Peptide (VIP)-Secreting Tumor
Also known as: Acromegalia, Diarrhea Associated With Vasoactive Intestinal Peptide (VIP)-Producing Tumor, Diarrhea Associated With Vasoactive Intestinal Peptide Tumor, Diarrhea Associated With Vipoma, Malignant Carcinoid Syndrome, Marie's Disease, Marie's Syndrome, Metastatic Carcinoid Syndrome.
Dosing
Dosage of octreotide acetate is expressed in terms of octreotide.
Octreotide acetate is administered by the subcutaneous, IV, IM, or oral route depending on the specific use.
Octreotide immediate-release injection is administered by subcutaneous injection orby IV injection or infusion for symptom control in patients with acromegaly, carcinoid tumors, or vasoactive intestinal peptide (VIP) tumors. Subcutaneous injection is the usual route of administration; IV administration generally is reserved for emergency situations (e.g., acute management of carcinoid crisis) that require rapid injection.
Octreotide is also available as a long-acting release (LAR) suspensionfor IM administration in patients with acromegaly, carcinoid tumors, or VIP-secreting tumors who have responded to and tolerated the immediate-release injection. Octreotide LAR suspension shouldnot be administered subcutaneously or IV. The LARinjectablesuspension may be used after tolerance has been established with at least 2 weeks of subcutaneous therapy with immediate-release octreotide.
Octreotide is also available as delayed-release capsules for the long-term maintenance treatment of acromegaly in patients who have responded to and tolerated treatment with octreotide or lanreotide.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Sandostatin Lar Depot 10 Mg Vl | Maintenance | Inject 10 mg by intramuscular route every 4 weeks. |
| Sandostatin Lar Depot 20 Mg Vl | Maintenance | Inject 20 mg by intramuscular route every 4 weeks. |
| Sandostatin Lar Depot 30 Mg Vl | Maintenance | Inject 30 mg by intramuscular route every 4 weeks. |
| Sandostatin Lar Depot 10 Mg Kt | Maintenance | Inject 10 mg by intramuscular route every 4 weeks. |
| Sandostatin Lar Depot 20 Mg Kt | Maintenance | Inject 20 mg by intramuscular route every 4 weeks. |
| Sandostatin Lar Depot 30 Mg Kt | Maintenance | Inject 30 mg by intramuscular route every 4 weeks. |
| Drug label | Dosing type | Instructions |
|---|---|---|
| Octreotide Acet Er 10 Mg Im Vl | Maintenance | Inject 10 mg by intramuscular route every 4 weeks. |
| Octreotide Acet Er 20 Mg Im Vl | Maintenance | Inject 20 mg by intramuscular route every 4 weeks. |
| Octreotide Acet Er 30 Mg Im Vl | Maintenance | Inject 30 mg by intramuscular route every 4 weeks. |
Drug interactions
Octreotide is not known to be metabolized by cytochrome P-450 (CYP) isoenzymes or other drugmetabolizing enzymes.
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Long-Acting Somatostatin Analogs/Copper Cu 64 Dotatate
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Both somatostatin analogs and copper Cu 64 dotatate bind to the same somatostatin receptors (SSTR2), resulting in competitive inhibition.(1)
CLINICAL EFFECTS: Concurrent use of copper Cu 64 dotatate and somatostatin analogs may affect the results of the scan.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: In patients receiving somatostatin analogs, perform the image just prior to dosing with long-acting somatostatin analogs. For patients on long-acting somatostatin analogs, a washout period of 28 days is recommended prior to imaging. For patients on short-acting somatostatin analogs, a washout period of 2 days is recommended prior to imaging.(1)
DISCUSSION: Both somatostatin analogs and copper Cu 64 dotatate bind to the same somatostatin receptors (SSTR2), resulting in competitive inhibition, which can affect the results of the scan.(1)
Long-Acting Somatostatin Analogs/Lutetium Lu 177 Dotatate
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Somatostatin and somatostatin analogs bind to somatostatin receptors and may interfere with the efficacy of lutetium lu 177 dotatate.(1)
CLINICAL EFFECTS: Concurrent administration of lutetium lu 177 dotatate and somatostatin analogs may decrease the efficacy of lutetium lu 177 dotatate.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of lutetium lu 177 dotatate recommends the following: - Before initiating lutetium lu 177 dotatate, discontinue long-acting somatostatin analogs for at least 4 weeks prior to initiation. Administer short-acting somatostatin analogs as needed; discontinue at least 24 hours prior to initiation of lutetium lu 177 dotatate. - During lutetium lu 177 dotatate treatment, administer long-acting octreotide 30 mg intramuscularly between 4 and 24 hours after each lutetium lu 177 dotatate dose. Do not administer long-acting octreotide within 4 weeks of each subsequent lutetium lu 177 dotatate dose. Short-acting octreotide may be given for symptomatic management during lutetium lu 177 dotatate treatment, but must be withheld for at least 24 hours before each lutetium lu 177 dotatate dose. - Following lutetium lu 177 dotatate treatment, continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing lutetium lu 177 dotatate until disease progression or for up to 18 months following treatment initiation.(1)
DISCUSSION: Somatostatin and somatostatin analogs bind to somatostatin receptors and may interfere with the efficacy of lutetium lu 177 dotatate.(1)
Somatostatin Analogs/Gallium Ga 68 Dotatate; Ga 68 Dotatoc
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Both somatostatin analogs and gallium Ga 68 dotatate/ gallium Ga 68 dotatoc bind to the same somatostatin receptors, resulting in competitive inhibition.(1)
CLINICAL EFFECTS: Concurrent use of gallium Ga 68 dotatate/ gallium Ga 68 dotatoc and somatostatin analogs may affect the results of the scan.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: In patients receiving somatostatin analogs, perform the image just prior to dosing with long-acting somatostatin analogs. Short acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatate or gallium Ga 68 dotatoc. (1)
DISCUSSION: Both somatostatin analogs and gallium Ga 68 dotatate/ gallium Ga 68 dotatoc bind to the same somatostatin receptors, resulting in competitive inhibition, which can affect the results of the scan.(1)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Octreotide/Cyclosporine
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Octreotide may interfere with the enterohepatic circulation of cyclosporine or may delay or inhibit the absorption of cyclosporine.(2)
CLINICAL EFFECTS: The concurrent administration of octreotide and cyclosporine may result in a decrease in cyclosporine levels.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Cyclosporine levels should be monitored in patients receiving concurrent therapy with cyclosporine and octreotide. The dosage of cyclosporine may need to be adjusted if octreotide is added to or discontinued from cyclosporine therapy. Octreotide may need to be discontinued.
DISCUSSION: In a study, 23 of 65 pancreas transplant patients were treated octreotide. During octreotide therapy, the dosage of oral cyclosporine required to maintain therapeutic levels increased. In addition 15 patients required supplemental intravenous cyclosporine to maintain cyclosporine levels.(2) In a case report, a cadaver renal and whole-pancreas transplant recipient was treated for a fistula with octreotide. Cyclosporine blood levels slowly decreased despite an increase in cyclosporine dosage (from 180 mg to 300 mg daily). When the cyclosporine level decreased below 100 ng/ml, intravenous cyclosporine was administered. Octreotide was discontinued when the patient developed graft rejection. Cyclosporine levels returned to baseline and the rejection was reversed.(1) In another case report, cyclosporine levels dropped below detection when octreotide was added to his therapy. The patient was successfully treated for graft rejection and octreotide was discontinued.(3) These authors reported a total of nine patients in whom cyclosporine levels decreased following the addition of octreotide to cyclosporine.(4) In a study of 10 patients with severe diarrhea following bone marrow transplantation, cyclosporine dosage requirements increased by 50% in two subjects following the addition of octreotide.(5)
Somatostatin Analogues/Pegvisomant
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: The exact mechanism is unknown.
CLINICAL EFFECTS: Concurrent use may result in an increased risk of hepatotoxicity.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The Canadian manufacturer of pegvisomant states that the concurrent use of pegvisomant and somatostatin analogues may lead to markedly increase hepatic enzymes in patients treated with this combination.(1)
DISCUSSION: Based on post marketing studies, there was marked hepatic elevations (greater than 10 times the upper limit of normal (ULN) which was reported in 3 out of 26 patients treated with the combination of pegvisomant and octreotide. The ranges for the elevations for ALT and AST ranged from 13 to 45 times the ULN within three months of treatment. All three patients recovered after discontinuation of treatment.(1)
Contraindications
*Hypersensitivity to octreotide or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
- Biliary calculus
- Bradycardia
- Cardiac arrhythmia
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
- Gallbladder disease
- Hepatic cirrhosis
- Untreated hypothyroidism
- Diabetes mellitus
- Exocrine pancreatic insufficiency
- Hypoglycemic disorder
- Vitamin b12 deficiency
Adverse reactions
Adverse effects reported in at least 20% of patients receiving octreotideLAR for carcinoid syndrome include back pain, fatigue, headache, abdominal pain, nausea, and dizziness.
Adverse effects reported in greater than 10% of patients receiving immediate-release octreotide for acromegaly include biliary tract abnormalities (gallstones, biliary sludge, duct dilatation), diarrhea, loose stools, nausea, abdominal discomfort, sinus bradycardia, hyperglycemia, and biochemical hypothryroidism.
Adverse effects reported in at least 20% of patients receiving octreotideLAR for acromegaly include diarrhea, cholelithiasis, abdominal pain, and flatulence.
Adverse effects reported in greater than 10% of patients receiving oral octreotide (Mycapssa(R)) include nausea, diarrhea, headache, arthralgia, asthenia, hyperhidrosis, peripheral swelling, blood glucose increased, vomiting, abdominal discomfort, dyspepsia, sinusitis, and osteoarthritis.
More Frequent
- Bradycardia
- Cardiac arrhythmia
Less Frequent
- Biliary calculus
- Hypothyroidism
- Steatorrhea
Rare or Very Rare
- Abnormal hepatic function tests
- Acute myocardial infarction
- Acute pancreatitis
- Anaphylaxis
- Anemia
- Aphasia
- Appendicitis
- Atrial fibrillation
- Atrioventricular block
- Cellulitis
- Cholestasis
- Diabetes insipidus
- Diabetes mellitus
- Gastrointestinal hemorrhage
- Gastrointestinal obstruction
- Hearing loss
- Hemiparesis
- Hepatitis
- Hyperbilirubinemia
- Hyperglycemia
- Hypoglycemic disorder
- Intracranial bleeding
- Kidney disease with reduction in glomerular filtration rate (GFr)
- Kidney stone
- Ocular hypertension
- Pancytopenia
- Paranoid disorder
- Pituitary apoplexy
- Pulmonary hypertension
- Renal failure
- Seizure disorder
- Suicidal
- Thrombocytopenic disorder
- Thrombosis of retinal vein
- Thrombotic disorder
- Visual field defect
More Frequent
- Acute abdominal pain
- Back pain
- Constipation
- Diarrhea
- Disorder of the digestive system
- Fatigue
- Flatulence
- Hyperhidrosis
- Injection site sequelae
- Loose stools
- Nausea
- Peripheral edema
- Sinusitis
- Vomiting
Less Frequent
- Depression
- Discolored feces
- Dizziness
- Dyspepsia
- Flushing
- General weakness
- Headache disorder
- Pruritus of skin
- Tenesmus
- Visual changes
Rare or Very Rare
- Abdominal distension
- Alopecia
- Arthralgia
- Arthritis
- Bell's palsy
- Edema
- Fever
- Flu-like symptoms
- Galactorrhea not associated with childbirth
- Gynecomastia
- Hematuria
- Libido changes
- Memory impairment
- Migraine
- Oligomenorrhea
- Orthostatic hypotension
- Paresthesia
- Peripheral sensory neuropathy
- Petechiae
- Polyp of gallbladder
- Raynaud's phenomenon
- Scotomata
- Urticaria
- Vitamin b12 deficiency
- Weight loss
Precautions
No enhanced messaging available.
Safety and efficacy of octreotide immediate-release injection, long-acting release (LAR) injectable suspension, and the oral preparation have not been established in pediatric patients. Controlled clinical trials to evaluate the safety and effectiveness of octreotide injection in pediatric patientsyounger than 6 years of age have not been performed. In postmarketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide use in children, most notably in children under 2 years of age. The majority of these pediatric patients had serious underlying co-morbid conditions and the relationship of such adverse events to octreotide has not been established.
Octreotide LARinjectable suspension (40 mg once monthly) has been investigated in a randomized, placebo-controlled study in pediatric patients 6-17 years of age withhypothalamic obesity secondary to cranial insult+. Efficacy was not demonstrated and treatment with octreotide was not associated with unexpected adverse events; however, new cholelithiasis was reported in 33% of children receiving octreotide.
There are no adequate and controlled studies of octreotide in pregnant women, and the drug should be used during pregnancy only when clearly needed. In cases with a known outcome, no congenital malformations have been reported among patients with acromegaly exposed to octreotide during the first trimester, including women electing to continue the drug throughout pregnancy. The women were exposed to 100-300 mcg/day of octreotide immediate-release or 20-30 mg once a month of octreotide LAR suspension.
Animal reproduction studies conducted with octreotide at doses up to 16 times the highest recommended human dose based on body surface area (BSA) have not revealed evidence of harm to the fetus. Transient growth retardation of rat offspring was observed atIV octreotide doses of 0.02-1 mg/kg per day which are below the maximum recommended human dose of 1.5mg/day, based on body surface area; this is possibly a consequence of growth hormone inhibition by octreotide.
There are insufficient data with octreotide LAR suspension in pregnant womento inform drug-associated-risk for major birth defects and miscarriage.
Octreotide is present in rat milk following subcutaneous injection;however, there is no information regarding the presence of octreotide in human milk. Consider the benefits of breast-feeding and the importance of octreotide to the woman along with potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Geriatric patients may be more sensitive to octreotide due to the greater frequency of decreased hepatic, renal, or cardiacfunction, and of concomitant disease or other drug therapy; initiate dosage cautiously at the low end of the dosage range.
Clinical trials of octreotide did not include sufficient numbers of patients 65 years of age or older to determine whether such patients respond differently than younger patients. In a small number of patients 65 years of age or older treated with the oral preparation (Mycapssa(R)), no overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in response between geriatric patients and younger adults, but greater sensitivity of some older individuals cannot be ruled out. Half-life increased by 46% andclearance decreasedby 26% following administration of immediate-release octreotide injection in an elderly population. Dosage of octreotide should be selected with caution and generally initiated at the lower end of the dosing range because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
ICD codes
| Code | Type | Description |
|---|---|---|
| Acromegaly | ||
| E22.0 | ICD10CM | Acromegaly and pituitary gigantism |
| Carcinoid syndrome | ||
| E34.0 | ICD10CM | Carcinoid syndrome |
| E34.00 | ICD10CM | Carcinoid syndrome, unspecified |
| E34.01 | ICD10CM | Carcinoid heart syndrome |
| E34.09 | ICD10CM | Other carcinoid syndrome |
| Diarrhea associated with vasoactive intestinal peptide (VIp)-secreting tumor | ||
| C25.4 | ICD10CM | Malignant neoplasm of endocrine pancreas |
| R19.7 | ICD10CM | Diarrhea, unspecified |
ICD code information from First Databank (FDB).
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.