Peptide education
Octreotide
Sandostatin · Sandostatin LAR Depot · Mycapssa · SMS 201-995
Octreotide is a prescription medicine that acts like somatostatin, a hormone that suppresses the release of several other hormones. In the United States, it comes as short-acting Sandostatin injection, Sandostatin LAR Depot and oral Mycapssa capsules. Their indications, routes and schedules are not identical.
Octreotide can control hormone-related disease in specific clinical settings. In PROMID, median time to tumor progression was 14.3 months with monthly octreotide LAR and 6.0 months with placebo, but the trial did not establish a survival benefit.
Overview
Quick answer
The Sandostatin labels describe treatment of acromegaly and certain symptoms from hormone-secreting tumors. PROMID separately studied time to progression in metastatic midgut neuroendocrine tumors. Its result is not the same as a US Sandostatin label indication for slowing tumor growth.
What is octreotide used for?
Sandostatin products are used for acromegaly and to reduce severe diarrhea and flushing associated with metastatic carcinoid tumors or watery diarrhea from VIP-secreting tumors. Their acromegaly indications have different treatment prerequisites. Mycapssa has a separate maintenance indication.
What are the acromegaly label criteria?
The short-acting injection label covers patients whose response to surgical resection, pituitary irradiation and bromocriptine at maximally tolerated doses was inadequate, or who cannot receive those treatments. LAR is for long-term maintenance when surgery and/or radiotherapy were inadequate or are not options, after Sandostatin Injection was effective and tolerated. Mycapssa requires a prior response to and tolerability of octreotide or lanreotide.
Are the injection, depot and capsules interchangeable?
No. Short-acting Sandostatin is labeled for subcutaneous or intravenous use, LAR Depot is administered intramuscularly in the buttock, and Mycapssa is an oral delayed-release capsule. Their doses and transition requirements differ; milligram amounts cannot be compared as equivalent doses.
Did a study find an effect on tumor progression?
Yes. PROMID enrolled 85 treatment-naive patients with well-differentiated metastatic midgut neuroendocrine tumors. Monthly intramuscular octreotide LAR delayed time to progression compared with placebo. The study did not establish an overall survival benefit, and its endpoint differs from the US LAR label's tumor-symptom indications.
What are the main safety considerations?
Gallstones and their complications, blood glucose changes, slow heart rate or conduction problems, thyroid changes and fat malabsorption are among the label warnings. Intravenous Sandostatin has a specific warning about serious atrioventricular block.
Evidence
Evidence snapshot
Sandostatin injection and LAR address acromegaly and specified tumor-related symptoms. Mycapssa is for maintenance in patients with acromegaly who have responded to and tolerated octreotide or lanreotide.
Median time to progression favored octreotide LAR over placebo in 85 patients with metastatic midgut neuroendocrine tumors. Overall survival was not established at the interim analysis.
In a 56-person trial, adjusted estimates of biochemical control at the end of 36 weeks were 58.2% with oral octreotide versus 19.4% with placebo. The responder counts were 16 of 28 and 5 of 28, respectively. Participants had previously responded to injectable treatment.
Labels describe gallbladder, glucose, cardiac and thyroid concerns, as well as possible fat malabsorption. They also list drug interactions and formulation-specific precautions.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Octreotide is approved to control certain hormone-related symptoms. | US Sandostatin labels cover severe diarrhea and flushing linked to metastatic carcinoid tumors and profuse watery diarrhea associated with VIP-secreting tumors. Their acromegaly indications and treatment prerequisites are separate. | Octreotide suppresses the release of growth hormone and several gut and pancreatic hormones, including vasoactive intestinal peptide. | Supported within the relevant product label and disease setting. |
| Octreotide LAR delays progression in metastatic midgut tumors. | PROMID found a median time to progression of 14.3 versus 6.0 months in a randomized comparison with placebo. The hazard ratio was 0.34, with a 95% confidence interval of 0.20 to 0.59. | Octreotide has somatostatin-like effects, but the clinical progression result must be interpreted in the trial's own population and formulation. | Supported in this trial, but not a claim of cure or proven longer survival. The US LAR label's carcinoid and VIPoma indications address symptoms, and its limitations state that tumor-growth effects have not been determined. |
| Oral octreotide is suitable for every patient starting treatment. | The oral maintenance study enrolled patients already controlled on injectable somatostatin receptor ligands. Mycapssa's label requires prior response to and tolerance of octreotide or lanreotide. | Not supported. Mycapssa is a formulation-specific maintenance product, not an established starting regimen for everyone with acromegaly. | |
| Approved-drug evidence verifies a compounded or unregulated product. | The cited studies and labels concern specific formulations and populations. FDA states that compounded drugs are not approved and are not checked by FDA for safety, effectiveness or quality before marketing. | No. Product identity, concentration, release characteristics and quality need separate evidence. |
Bottom line
Main takeaway
Octreotide is a medicine used for specific hormone disorders and symptoms from certain tumors. Its different products are not dose-for-dose substitutes.
Compare short-acting injection, gluteal IM depot and oral capsules by their own label. Prior response, transition details and monitoring change with the formulation and the condition being treated.
PROMID measured time to progression in metastatic midgut tumors; the oral maintenance study measured biochemical control after prior injectable therapy. These are different populations and endpoints.
Identity
What it is
Octreotide is an eight-residue cyclic analog of somatostatin. Its actions include suppression of growth hormone, insulin, glucagon and a number of gastrointestinal hormones. This broad endocrine activity helps explain both its medical uses and the need to monitor for adverse effects.
Acromegaly involves excess growth hormone and IGF-1. Sandostatin treatment aims to reduce these levels in the patient groups described by its label. Tumor-associated diarrhea and flushing are different problems, with different treatment objectives.
Use context
Routes, doses, and cycle patterns
Short-acting Sandostatin, LAR Depot and Mycapssa have different routes, doses and eligibility requirements. PROMID studied the depot in patients with metastatic midgut neuroendocrine tumors.
Human studies and product labels
Sandostatin injection for acromegaly
- Purpose
- Reduce growth hormone and IGF-1 in the labeled setting
- Context
- US prescribing information
- Route
- Subcutaneous injection for the listed starting regimen
- Amount
- 50 mcg per dose initially
- Frequency
- Three times daily
- Duration
- Adjusted according to response and monitoring
This is the label's starting dose, not a fixed maintenance dose. The product is also labeled for intravenous use, but the cited starting regimen is subcutaneous. The acromegaly label describes patients with an inadequate response to, or unable to receive, surgical resection, pituitary irradiation and maximally tolerated bromocriptine.
Sandostatin LAR Depot for acromegaly
- Purpose
- Long-term maintenance after effective and tolerated injection treatment
- Context
- US prescribing information
- Route
- Gluteal intramuscular depot
- Amount
- 20 mg initially after the short-acting injection phase
- Frequency
- Every 4 weeks
- Duration
- Initial 3 months, followed by response-based adjustment
The acromegaly indication applies when surgery and/or radiotherapy were inadequate or are not options, after Sandostatin Injection was effective and tolerated. The label describes an initial subcutaneous injection phase for patients not already receiving octreotide, and dose adjustments for dialysis and cirrhosis.
Sandostatin LAR for carcinoid symptoms or VIPoma
- Purpose
- Long-term control of the labeled diarrhea and flushing symptoms
- Context
- US prescribing information
- Route
- Gluteal intramuscular depot
- Amount
- 20 mg initially after response to short-acting injection
- Frequency
- Every 4 weeks
- Duration
- Initial 2 months, followed by response-based adjustment
The label calls for continued subcutaneous Sandostatin for at least two weeks after the first depot injection in these patients.
Mycapssa for acromegaly maintenance
- Purpose
- Maintain control after response to and tolerance of octreotide or lanreotide
- Context
- US prescribing information
- Route
- Oral delayed-release capsules
- Amount
- 20 mg twice daily initially, maximum 80 mg daily in the general label
- Frequency
- Twice daily, with adjustments based on IGF-1 and symptoms
- Duration
- Long-term maintenance with monitoring
The label specifies a different initial dose for end-stage renal disease and describes food and interacting medicine precautions.
PROMID trial regimen
- Purpose
- Time to progression in metastatic midgut neuroendocrine tumors
- Context
- Randomized placebo-controlled study
- Route
- Intramuscular long-acting depot
- Amount
- 30 mg octreotide LAR
- Frequency
- Monthly
- Duration
- Until tumor progression or death in the study
PROMID assessed tumor progression. The US LAR label addresses carcinoid and VIPoma symptoms and states that tumor-growth effects in those patients have not been determined.
What varies
- Disease and goal: acromegaly hormone control, carcinoid symptom control and a tumor-progression endpoint are separate questions.
- Formulation and route: short-acting injection, gluteal IM depot and oral capsules are not dose-for-dose substitutes.
- Monitoring: product labels include glucose, gallbladder, thyroid and cardiac precautions, plus relevant drug interactions.
Research
Research evidence
The evidence has several distinct endpoints. Product labels describe control of growth hormone and IGF-1 or of tumor-related symptoms. PROMID measured tumor progression in a selected metastatic midgut population. A separate randomized trial measured oral maintenance of biochemical control in patients who had already responded to injectable treatment.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Sandostatin injection and LAR prescribing information | Patients with the specified acromegaly or tumor-related symptom indications | US prescribing information and clinical-study summaries | Short-acting injection or intramuscular depot | The labels define treatment goals, formulation-specific dosing, transition and monitoring, and symptom indications for carcinoid tumors and VIPomas. | The LAR label says effects on tumor size, growth and metastases in carcinoid syndrome and VIPoma have not been determined. | Strong for labeled indications |
| PROMID | 85 treatment-naive patients with well-differentiated metastatic midgut tumors | Randomized double-blind placebo-controlled trial | 30 mg intramuscular octreotide LAR monthly | Median time to progression was 14.3 months with octreotide versus 6.0 months with placebo, with a hazard ratio of 0.34. | The planned interim analysis had few deaths and did not establish a survival benefit. Findings do not cover every neuroendocrine tumor or formulation. | Randomized, population-specific |
| CHIASMA OPTIMAL | 56 patients with acromegaly controlled on injectable treatment | Randomized double-blind placebo-controlled trial over 36 weeks | Oral octreotide capsules versus placebo | The adjusted proportions maintaining normal IGF-1 at the end of treatment were 58.2% with oral octreotide versus 19.4% with placebo. The responder counts were 16 of 28 and 5 of 28, respectively. | Participants had already demonstrated control on injectable treatment; this does not establish effectiveness as initial therapy or for tumor symptoms. | Randomized, maintenance population |
Use context
Reported use context
PROMID evaluated monthly octreotide LAR in patients with well-differentiated metastatic midgut neuroendocrine tumors.
Study and label context
30 mg monthly until progression or death, compared with placebo.
The participants had not received prior treatment for their metastatic tumors.Cautions
Safety and unknowns
- Gallstones can occur and may cause complications, including inflammation of the gallbladder or pancreas. Labels describe periodic monitoring and clinical assessment when complications are suspected.
- Both low and high blood glucose can occur. Thyroid function and heart rate or rhythm may also be affected, and diabetes or heart medicines may need review.
- Intravenous Sandostatin has a warning for serious atrioventricular block; risk and monitoring depend on the setting and coexisting conditions.
- New or worsening loose, oily stools, bloating or weight loss may reflect fat malabsorption or pancreatic exocrine insufficiency and warrant clinical review.
- In acromegaly, hormone control can improve fertility and create a possibility of unintended pregnancy. The LAR and Mycapssa labels say pediatric safety and effectiveness have not been established.
- Mycapssa can reduce levonorgestrel exposure, which may reduce the effectiveness of combined oral contraceptives. Its label calls for counseling about an alternative non-hormonal or backup method when they are used together.
Product quality
Product identity and quality
Approved injection, depot and oral products use different formulations and routes. Their labeled amounts and release characteristics should not be assumed equivalent.
FDA states that compounded drugs are not FDA-approved and are not assessed by FDA for safety, effectiveness or quality before marketing.
Formulation and route
The approved products have different routes, release profiles and dosing schedules.
Identity and quality
A product name alone does not establish its concentration, sterility or quality.
Mechanism
How it is proposed to work
Octreotide mimics somatostatin's inhibitory effects. It can lower growth hormone and suppress release of several gastrointestinal and pancreatic hormones, which helps explain its uses and its effects on glucose and digestion.
In acromegaly, the treatment goal includes reducing growth hormone and IGF-1; measured hormone levels help guide treatment assessment.
Reduced gallbladder contractility and altered insulin and glucagon secretion help explain why biliary and glucose monitoring appear in the labels.
Details
Technical details
Sources
References
- 1.
DailyMed: Sandostatin injection. Sandostatin injection prescribing information
US prescribing information for short-acting octreotide injection, including indications, routes, dosing and precautions.
- 2.
DailyMed: Sandostatin LAR. Sandostatin LAR Depot prescribing information
US prescribing information for gluteal intramuscular depot treatment, transition requirements and limitations of use.
- 3.
DailyMed: Mycapssa. Mycapssa prescribing information
US prescribing information for delayed-release oral octreotide maintenance treatment in previously responsive acromegaly patients.
- 4.
doi:10.1200/JCO.2009.22.8510 PMID:19704057 NCT00171873
Randomized trial reporting time to tumor progression with monthly intramuscular octreotide LAR versus placebo.
- 5.
doi:10.1210/clinem/dgaa526 PMID:32882036 NCT03252353
Randomized placebo-controlled study of oral octreotide in patients with acromegaly previously controlled on injectable treatment.
- 6.
FDA. Compounding and the FDA: Questions and Answers
FDA explains that compounded drugs are not approved and are not evaluated by FDA before marketing for safety, effectiveness or quality.