Dosing & Uses
Dosage Forms & Strengths
capsule, delayed-release (Mycapssa)
- 20mg
injectable solution (Sandostatin)
- 0.05mg/mL
- 0.1mg/mL
- 0.2mg/mL
- 0.5mg/mL
- 1mg/mL
depot injection (Sandostatin LAR Depot)
- 10mg/kit
- 20mg/kit
- 30mg/kit
injectable solution (Bynfezia Pen)
- 2500mcg/mL (single-patient-use pen)
Acromegaly
Reduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) [somatomedin C] in adults with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses
Bynfezia Pen
- 50 mcg SC TID initially
- Usual dose: 100 mcg SC TID; some patients require up to 500 mcg TID
- Doses >300 mcg/day seldom result in additional benefit; if an increase in dose fails to provide additional benefit, reduce dosage
-
Dosing titration
- Measure IGF-I levels q2Weeks after initiation or dosage change
- Alternatively, measuring growth hormone levels at 1-4 hr intervals for 8-12 hr after administration; goal is to achieve growth hormone levels <5 ng/mL or IGF-I levels within normal reference ranges for age and sex
- Once biochemical normalization, or maximal benefit is achieved, re-evaluate IGF-I or growth hormone levels at 6-month intervals
Sandostatin LAR depot
-
Patients not currently receiving octreotide
- Begin therapy with solution as listed above
- Maintain on SC solution for at least 2 weeks as listed above to determine tolerance to octreotide
- Patients who responds to the drug, based on GH and IGF-1 levels and who tolerate the drug, then switch to octreotide suspension
-
Patients currently receiving octreotide
- Switch to octreotide suspension 20 mg IM (gluteal) q4Weeks for 3 months; titrate up or down to 10-30 mg IM q4Weeks, depending on response; not to exceed 40 mg
- After 3 months, dosage may be adjusted as follows:
- GH ≤2.5 ng/mL, IGF-1 normal, and clinical symptoms controlled: Maintain octreotide suspension at 20 mg q4Weeks
- GH >2.5 ng/mL, IGF-1 elevated, and/or clinical symptoms uncontrolled: Increase octreotide suspension to 30 mg q4Weeks
- GH ≤1 ng/mL, IGF-1 normal, and clinical symptoms controlled: Reduce octreotide suspension to 10 mg q4Weeks
- If GH, IGF-1, or symptoms are not adequately controlled at a dose of 30 mg, the dose may be increased to 40 mg q4Weeks; doses >40 mg are not recommended
- In patients who have received pituitary irradiation, withdraw yearly for ~8 weeks to assess disease activity; if GH or IGF-1 levels increase and signs and symptoms recur, resume therapy
Mycapssa
- 20 mg PO BID (40 mg/day) initially
- May titrate up in increments of 20 mg/day, based on IGF-1 levels and signs and symptoms; maximum dosage is 80 mg/day
- Monitor IGF-1levels and signs and symptoms q2Weeks during the dose titration, monthly during maintenance dosage, or as indicated
- For 60 mg/day dose, administer as 40 mg in the AM and 20 mg in the PM
-
Dosage interruptions and modifications
- If IGF-1 levels remain above the UNL after treatment with the maximum recommended dosage of 80 mg/day or the patient cannot tolerate treatment, consider discontinuing treatment and switching patient to another somatostatin analog
- Withdraw therapy periodically to assess disease activity
- If IGF-1 levels increase and signs and symptoms recur, resume therapy
Carcinoid Tumor
Indicated for treatment of adults with severe diarrhea and flushing episodes associated with metastatic carcinoid tumors
Bynfezia Pen
- 100-600 mcg/day SC in 2-4 divided doses for the first 2 weeks
- In clinical studies, median daily maintenance dosage was ~450 mcg, but clinical and biochemical benefits were obtained in some patients ranged from 50-1,500 mcg/day
- Experience with doses >750 mcg/day is limited
- Monitor urinary 5-hydroxyindole acetic acid (5-HIAA), plasma serotonin, and plasma substance
Sandostatin LAR depot
-
Patients not currently receiving octreotide
- Begin therapy with solution as listed above
- Maintain on SC solution for at least 2 weeks as listed above to determine tolerance to octreotide
- Patients who responds to the drug, based on GH and IGF-1 levels and who tolerate the drug, then switch to octreotide suspension
-
Patients currently receiving octreotide
- 20 mg IM q4Weeks for 2 months then modify dose based on response; may increase to 30mg q4Weeks if symptoms are inadequately controlled; decrease to 10 mg IM q4Weeks for trial period if initially responsive to 20 mg dose; dose >30 mg not recommended
- Patients who have periodic exacerbation of symptoms (regardless of whether they are being maintained on Sandostatin injection or Sandostatin LAR Depot)
- During these periods, SC Sandostatin injection may be given for a few days at the dosage they were receiving prior to switching to Sandostatin LAR depot; once symptoms resolve; discontinue SC Sandostatin injection
VIPoma
Indicated for treatment of adults with the profuse watery diarrhea associated with VIP-secreting tumors
Bynfezia Pen
- 200-300 mcg/day SC in 2-4 divided doses for the first 2 weeks
- Adjust dosage to achieve a therapeutic response; daily dosage is 150-750 mcg but usually doses >450 mcg/day are not required
- Monitor plasma vasoactive intestinal peptide (VIP)
Sandostatin LAR depot
-
Patients not currently receiving octreotide
- Begin therapy with solution as listed above
- Maintain on SC solution for at least 2 weeks as listed above to determine tolerance to octreotide
- Patients who responds to the drug, based on GH and IGF-1 levels and who tolerate the drug, then switch to octreotide suspension
-
Patients currently receiving octreotide
- 20 mg IM q4Weeks for 2 months then modify dose based on response; may increase to 30mg q4Weeks if symptoms are inadequately controlled; decrease to 10 mg IM q4Weeks for trial period if initially responsive to 20 mg dose; dose >30 mg not recommended
- Patients who have periodic exacerbation of symptoms (regardless of whether they are being maintained on Sandostatin injection or Sandostatin LAR Depot)
- During these periods, SC Sandostatin injection may be given for a few days at the dosage they were receiving prior to switching to Sandostatin LAR depot; once symptoms resolve; discontinue SC Sandostatin injection
Esophageal Variceal Bleeding (Off-label)
Solution: 25-100 mcg IV bolus (usual bolus dose: 50 mcg); follow by continuous IV infusion of 25-50 mcg/hr for 2-5 days; may repeat bolus in first hr if hemorrhage not controlled
GI or Pancreatic Fistula (Off-label)
Solution: 50-200 mcg SC q8hr for 2-12 days
AIDS-Related Diarrhea (Off-label)
Solution: 100-500 mcg SC q8hr
Ileostomy-Related Diarrhea (Off-label)
Solution: 25 mcg/hr IV or 50 mcg SC q12hr
Chemotherapy-Related Diarrhea (Off-label)
Low-grade or uncomplicated: Solution: 100-150 mcg SC q8hr for 1-30 days
Complicated: Solution: 100-150 mcg SC q8hr or 25-50 mcg/hr IV; may increase to 500 mcg q8hr until controlled
Severe: Solution: 100-150 mcg SC q8hr; may increase to 500-1500 mcg SC/IV q8hr
Dumping Syndrome (Off-label)
Solution: 50-150 mcg/day IV; may adjust to 25-600 mcg/day dose range
Suspension (depot injection): 10-20 mg/month IM
Chylothorax (Off-label)
Solution: 50-100 mcg SC q8hr
Dosage Modifications
Coadministration with proton pump inhibitors, H2-receptor antagonists, or antacids
- Mycapssa only
- Concomitant use of oral octreotide and proton pump inhibitors, H2-receptor antagonists, or antacids may require increased dosages of oral octreotide
Renal impairment
-
Sandostatin or Sandostatin LAR depot
- Mild-to-severe without dialysis: No dosage adjustment necessary
- With dialysis: 10 mg IM q4Weeks initially, then titrate to effect
-
Mycapssa
-
Mild-to-severe: No dosage adjustment necessary
- End-stage renal disease: 20 mg PO qDay initially, then titrate to effect
-
-
Bynfezia Pen
- Patients on dialysis: Half-life of octreotide may increase, may require dosage adjustment on maintenance dose
Hepatic impairment
-
Sandostatin or Sandostatin LAR depot
- Cirrhosis: 10 mg IM q4Weeks initially, then titrate to effect
-
Mycapssa
- Patients with liver cirrhosis and patients with fatty liver disease showed prolonged elimination of octreotide following SC administration
Neuroendocrine Tumors (Orphan)
Orphan indication sponsor
- Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080
Dosage Forms & Strengths
injectable solution (Sandostatin)
- 0.05mg/mL
- 0.1mg/mL
- 0.2mg/mL
- 0.5mg/mL
- 1mg/mL
Safety and efficacy not established
GI Bleeding (Off-label)
1 mcg/kg bolus, then 1 mcg/kg/hr infusion; taper by 50% when no active bleeding for 24 hours
Diarrhea (Off-label)
Chylothorax (Off-label)
0.3-4 mcg/kg/hr SC/IV, depending on nature of chylothorax
Hyperinsulinemia/Hypoglycemia of Infancy (Off-label)
2-10 mcg/kg/day SC/IV divided q12hr; increase on basis of response
Sulfonylurea Overdose (Off-label)
1 mcg/kg SC/IV q12hr OR 25 mcg once; monitor blood glucose concentrations
Acromegaly
Solution: 50 mcg SC q8-12hr initially; titrate up to 500 mcg SC q8hr if necessary; after successful treatment with solution for 2 weeks, initiate treatment with suspension (depot injection)
Suspension (depot injection): 20 mg IM intragluteally every 4 weeks for 3 months; titrate up or down to 10-30 mg IM every 4 weeks, depending on response; not to exceed 40 mg
Dosing Considerations
Dose adjustment may be necessary; clearance may decrease by 26% and half-life by 46%
Monitor IGF-1 levels every 2 weeks to guide titration; goal: GH levels <5 ng/mL or IGF-1 levels <1.9 units/mL (men) and <2.2 units/mL (women)
Monitor IGF-1 or GH levels every 6 months
Withdraw drug yearly for 4 weeks (solution) or 8 weeks (suspension) from patients who have undergone irradiation to assess
Carcinoid Tumor
Solution: 100-600 mcg/day SC divided q6-12hr; may titrate to 1500 mcg/day; after successful treatment with solution for 2 weeks, initiate treatment with suspension (depot injection)
Suspension (depot injection): 20 mg IM every 4 weeks if regular injection well tolerated
VIPoma
Solution: 200-300 mcg/day SC divided q6-12hr; after successful treatment with solution for 2 weeks, initiate treatment with suspension (depot injection)
Suspension (depot injection): 20 mg IM (gluteal) every 4 weeks for 2 months; continue solution for first 2 weeks; titrate suspension up or down to 10-30 mg IM every 4 weeks
Esophageal Variceal Bleeding (Off-label)
Solution: 50 mcg IV bolus, then 25-50 mcg/hr for 1-5 days
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Oral
- Headache (33%)
- Nausea (30%)
- Diarrhea (29%)
- Arthralgia (26%)
- Asthenia (22%)
- Hyperhidrosis (21%)
- Nausea (21%)
- Diarrhea (18%)
- Peripheral swelling (16%)
- Increased blood glucose (14%)
- Vomiting (14%)
- Abdominal discomfort (14%)
- Dyspepsia (11%)
- Sinusitis (11%)
- Osteoarthritis (11%)
Sandostatin
- Diarrhea, loose stools, nausea and abdominal discomfort (34-61%)
- Sinus bradycardia (25%)
- Hyperglycemia (16%)
- Biochemical hypothyroidism (12%)
Sandostatin LAR
- Diarrhea (36.4%)
- Abdominal pain or discomfort (29.1%)
- Hyperglycemia (27%)
- Flatulence (25.7%)
- Sinus bradycardia (<50 bpm) (25%)
- Constipation (18.8%)
- Biochemical hypothyroidism (12%)
- Nausea (10.3%)
1-10%
Oral
- Dyspepsia (8%)
- Urinary tract infection (7%)
- Pain (7%)
- Large intestine polyp (7%)
- Cholelithiasis (7%)
- Blood glucose increased (6%)
- Vomiting (6%)
- Flatulence (6%)
- Back pain (6%)
- Abdominal pain (5%)
- Dizziness (5%)
- Fatigue (5%)
- Upper respiratory tract infection (5%)
- Hypertension (5%)
- Cholelithiasis (4.5%)
- Sandostatin H4
- Conduction abnormalities (10%)
- Arrhythmias (9%)
- Pain on injection (7.7%)
- Headache (6%)
- Goiter (6%)
- Dizziness (5%)
- Hypoglycemia (3%)
- Other adverse events (1-4%) H5
- Fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance and depression
Sandostatin LAR
- Conduction abnormalities (10%)
- Nausea (6-9%)
- Arrhythmia (9%)
- Goiter (8%)
- Abdominal pain (2-8%)
- Fatigue (2-7%)
- Vomiting (4-6.5%)
- Headache (4-6%)
- Back pain (2-6%)
- Dizziness (4-5%)
- Pruritus (4%)
- Hypoglycemia (4%)
- Flatulence (2-4%)
- Upper respiratory tract infection (2-4%)
- Myalgia (1-4%)
- Rash (3%)
- Arthropathy (2-3%)
- Sinusitis (1-3%)
- Generalized pain (1-3%)
- Musculoskeletal pain (1%)
<1%
Sandostatin or Sandostatin LAR
- Gastrointestinal: Hepatitis, jaundice, increase in liver enzymes, GI bleeding, hemorrhoids, appendicitis, gastric/peptic ulcer, gallbladder polyp
- Integumentary: Rash, cellulitis, petechiae, urticaria, basal cell carcinoma
- Musculoskeletal: Arthritis, joint effusion, muscle pain, Raynaud phenomenon
- Cardiovascular: Chest pain, shortness of breath, thrombophlebitis, ischemia, congestive heart failure, hypertension, hypertensive reaction, palpitations, orthostatic BP decrease, tachycardia
- Central nervous system (CNS): Anxiety, libido decrease, syncope, tremor, seizure, vertigo, Bell’s Palsy, paranoia, pituitary apoplexy, increased intraocular pressure, amnesia, hearing loss, neuritis
- Respiratory: Pneumonia, pulmonary nodule, status asthmaticus
- Endocrine: Galactorrhea, hypoadrenalism, diabetes insipidus, gynecomastia, amenorrhea, polymenorrhea, oligomenorrhea, vaginitis
- Urogenital: Nephrolithiasis, hematuria
- Hematologic: Anemia, iron deficiency, epistaxis
- Miscellaneous: Otitis, allergic reaction, increased CK, weight loss
- Anaphylactoid reactions, including anaphylactic shock
Postmarketing experience
Sandostatin
- Hepatobiliary: Cholelithiasis, cholecystitis, cholangitis and pancreatitis, which have sometimes required cholecystectomy
- Gastrointestinal: Intestinal obstruction
- Hematologic: Thrombocytopenia
Warnings
Contraindications
Hypersensitivity
Cautions
Use caution in patients with hepatic impairment; patients with established cirrhosis may necessitate dosage adjustment
Use caution in patients with renal impairment; patients receiving dialysis may necessitate dosage adjustment
May alter fat absorption in some patients (monitor for pancreatitis)
Monitor for cholelithiasis; may impair gallbladder function; incidence of gallbladder stone or biliary sludge increases with duration of therapy exceeding 12 months; prophylactic cholecystectomy recommended if octreotide treatment is planned in in patients with gastrointestinal or pancreatic neuroendocrine tumors
May decrease vitamin B12 levels (monitor)
Monitor for hypothyroidism (octreotide suppresses secretion of TSH)
Use caution when giving drug to patients with cardiovascular disease
May enhance toxicity of QTc-prolonging agents
Use caution in patients with heart failure or concomitant medications that may alter heart rate or rhythm; arrhythmia, conduction abnormalities, and bradycardia reported in acromegalic and carcinoid syndrome patients; cardiovascular medications requirements may change
Depot formulation, not for treatment of sulfonylurea-induced hypoglycemia
Somatostatin analogs may affect glucose regulation; severe hypoglycemia may occur in type 1 diabetes patients; hyperglycemia may occur in type 2 diabetes or patients without diabetes; therapy may worsen hypoglycemia in patients with insulinomas; use with caution
Dosage adjustments may be necessary in the elderly
Females of childbearing age should use adequate contraception because the treatment may restore fertility
In patients maintained on total parenteral nutrition (TPN), monitoring for elevations in zinc levels recommended
May reduce excessive fluid loss in patients with conditions that cause fluid losses
Drug interaction overview
- Coadministration with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection
- Octreotide inhibits the secretion of insulin and glucagon; monitor blood glucose levels upon initiation or dose adjustment; patients with diabetes mellitus may require dose adjustments of insulin or other antidiabetic agents
- Coadministration with bromocriptine increases the availability of bromocriptine
- Patients receiving beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may require dose adjustments of these therapeutic agents
- 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 might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormones
Pregnancy & Lactation
Pregnancy
Limited data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage
Reproductive potential
- Discuss potential for unintended pregnancy with premenopausal women as therapeutic benefits of a reduction in growth hormone (GH) levels and normalization of insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with drug may lead to improved fertility
Animal data
- In animal reproduction studies, no-adverse- developmental-effects were observed with intravenous administration of drug to pregnant rats and rabbits during organogenesis at doses 7 and 13-times, respectively the maximum recommended human dose (MRHD) of 1500 mcg/day based on 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 MRHD based on body surface area
Lactation
There is no information available on presence of drug in human milk, effects on breastfed infant, or on milk production; studies show that drug administered subcutaneously passes into milk of lactating rats
Consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Somatostatin analog; decreases GH secretion, secretion of gastrin, VIP, glucagon, secretin, serotonin release and pancreatic polypeptide; in acromegaly, octreotide decreases growth hormone and IGF-1 secretion; suppresses LH response to GnRH secretion and decreases splanchnic blood flow
Absorption
Absorption rapid and complete (SC)
Bioavailability: SC, 100%; IM, 60%
Peak plasma time: IV, immediately after injection; SC, 15-30 min; PO, 90-120 min; IM, 60 min
Distribution
Protein bound: 65% binds to lipoprotein
Vd: 13.6 L
Metabolism
Metabolized by liver
Elimination
Half-life: 1.7 hr
Total body clearance: 10 L/hr
Excretion: Urine (32%)
Administration
IV Incompatibilities
Total parenteral nutrition solutions because of the formation of a glycosyl octreotide conjugate which may decrease the efficacy of the product
IV Compatibilities
Dextrose 5%
IV Administration (Sandostatin)
Diluted volumes of 50-200 mL: Infuse over 15-30 min
Undiluted volumes
- Administer IV push over 3 min
- In emergency situation (eg, carcinoid crisis), it may be given by rapid bolus
IM Administration (Sandostatin LAR Depot)
IM administration only; should not be administer IV or SC
Administer immediately after mixing; do not directly inject diluent without preparing suspension
Recommended needle size for administration is the 1.5 inch 19 gauge safety injection needle (supplied in the kit)
For patients with a greater skin to muscle depth, a size 2 inch 19 gauge needle (not supplied) may be used
Rotate injection sites in a systematic manner to avoid irritation; deltoid injections should be avoided due to significant discomfort at the injection site when given in that area
Oral Administration (Mycapssa)
Take with a glass of water on an empty stomach, at least 1 hr before a meal or at least 2 hr after a meal
Swallow capsules whole; do not crush or chew
SC Administration (Bynfezia Pen or Sandostatin)
Visually inspect for particulate matter and discoloration; solution should appear colorless with no visible particles
Sandostatin
- Use of smaller volumes to deliver desired dose will reduce pain with administration
- Avoid multiple SC injections at the same site within short periods of time
- Rotate sites in a systematic manner
Bynfezia Pen
- Pen should be at room temperature before injecting to reduce potential injection site reactions
- Administer by SC into the abdomen, the front of the middle thighs, or the back/outer area of the upper arms
- Rotate injection sites so that the same site is not used repeatedly; injection sites should be at least 2 inches away from last injection site
- Provide proper training to patients and/or caregivers on administration; and refer to “Instruction for Use”
Storage
Bynfezia Pen
Unopened pen
- Refrigerate at 2-8ºC (36-46ºF)
- Protect from light
- Do not freeze
Opened pen
- Store at room temperature (20-25ºC [68-77ºF]) for up to 28 days
- Store pen with the pen cap on; do not store pen with needle attached
- Protect from light
- Do not freeze
Mycapssa
- Unopened wallet: Refrigerate at 2-8ºC (36-46ºF); do not freeze
- After first use, opened wallets may be stored at 20-25ºC (68-77ºF) for up to 1 month
Sandostatin
-
Unopened ampules and multidose vials
- Refrigerate at 2-8ºC (36-46ºF) and store in ºouter carton in order to protect from light
- Store at room temperature (20-25ºC [68-77F]) for up to14 days if protected from light
- Allow solution to come to room temperature before administration; do not warm artificially
- After initial use, discard multidose vials within 14 days
- Open ampules just prior to administration and discard any unused portion discarded
Sandostatin LAR Depot
- Refrigerate at 2-8ºC (36-46ºF)
- Kit should remain at room temperature for 30-60 min prior to preparation of the drug suspension
- Protect from light
- After preparation, administer suspension immediately
Images
Patient Handout
Formulary
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