Octreotide

The dosage of octreotide is highly individualized and depends on the condition being treated, the patient's clinical response, and laboratory values (such as GH or IGF-1 levels).

• Acromegaly (Immediate Release): Initial dosing often starts at 50 mcg to 100 mcg injected subcutaneously three times daily. Most patients require 100 mcg three times daily, but some may require up to 500 mcg three times daily for maximal suppression of growth hormone.
• Acromegaly (Long-Acting Release - LAR): For patients who have been stabilized on the IR formulation, the switch to LAR typically begins at 20 mg intramuscularly every 4 weeks for three months. Doses may then be adjusted to 10 mg or 30 mg based on GH and IGF-1 levels.
• Carcinoid Tumors: The recommended daily dosage of the IR form ranges from 100 mcg to 600 mcg per day in 2 to 4 divided doses. For the LAR form, the starting dose is usually 20 mg every 4 weeks.
• VIPomas: Daily dosages of 200 mcg to 300 mcg in 2 to 4 divided doses (IR form) are typically used for the first two weeks to manage symptoms, followed by titration to the lowest effective dose.

Octreotide is not FDA-approved for use in pediatric patients for the standard indications of acromegaly or carcinoid syndrome. However, it is occasionally used off-label in specialized pediatric centers for conditions like congenital hyperinsulinism or severe, refractory diarrhea. In these cases, dosing is strictly weight-based (e.g., 1-10 mcg/kg/day) and must be managed by a pediatric endocrinologist or gastroenterologist. Clinical data on the long-term safety and growth effects of octreotide in children are limited.

Renal Impairment

In patients with severe renal failure requiring dialysis, the elimination half-life of octreotide may be increased. Healthcare providers may start at the lower end of the dosing range and titrate slowly. The clearance of octreotide is reduced by approximately 50% in patients with end-stage renal disease.

Hepatic Impairment

In patients with liver cirrhosis, the elimination of the drug may be prolonged. While specific dose adjustment formulas are not standardized, close monitoring of clinical response and side effects is necessary, particularly when using the long-acting formulations.

Elderly Patients

Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects. 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.

• Subcutaneous Injection (IR): This is the most common method for the immediate-release form. Rotate injection sites (thigh, abdomen, upper arm) to reduce the risk of skin irritation. The medication should be at room temperature before injection to minimize local discomfort.
• Intramuscular Injection (LAR): This must be administered by a healthcare professional in a clinical setting. It is given as a deep intragluteal injection. It should never be given intravenously or subcutaneously.
• Oral Capsules: If prescribed the oral form (Mycapssa), it must be taken on an empty stomach with a full glass of water, at least 1 hour before a meal or 2 hours after a meal. This is critical because food significantly reduces the absorption of the drug.
• Storage: Most octreotide injections require refrigeration (36°F to 46°F or 2°C to 8°C). Some formulations may be kept at room temperature for a limited time (e.g., 14 days) if protected from light.

If you miss a dose of the immediate-release injection, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular schedule. Do not double the dose to catch up. For the LAR formulation, if you miss an appointment for your monthly injection, contact your healthcare provider immediately to reschedule.

Signs of an octreotide overdose may include severe nausea, diarrhea, abdominal pain, flushing, dizziness, and an irregular heartbeat (arrhythmia). In clinical trials, doses up to 2000 mcg TID were tolerated but caused significant gastrointestinal distress. If an overdose is suspected, seek emergency medical attention or contact a Poison Control Center immediately. Treatment is primarily supportive, focusing on managing symptoms and maintaining hydration.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as this can lead to a rapid return of symptoms.

Because octreotide affects the gastrointestinal tract and the release of digestive enzymes, GI-related side effects are very common, especially during the first few weeks of treatment. These include:

• Biliary Abnormalities: Up to 50% of patients on long-term octreotide therapy develop gallstones (cholelithiasis) or biliary sludge. This happens because the drug inhibits gallbladder contraction and alters bile composition.
• Gastrointestinal Distress: Diarrhea, loose stools, nausea, and abdominal discomfort are reported by about 10-30% of patients. These symptoms often subside as the body adjusts to the medication.
• Steatorrhea: This is the presence of excess fat in the stools, making them appear oily, foul-smelling, and difficult to flush. It occurs because octreotide inhibits the release of pancreatic enzymes needed to digest fat.
• Injection Site Reactions: Pain, redness, or stinging at the site of subcutaneous injection is common but usually transient.

• Hypothyroidism: Octreotide can suppress the release of Thyroid Stimulating Hormone (TSH) from the pituitary gland. This may lead to low thyroid levels, characterized by fatigue, weight gain, and feeling cold.
• Cardiac Changes: Bradycardia (a slow heart rate) and conduction abnormalities (like a prolonged QT interval) have been observed.
• Glycemic Fluctuations: Because octreotide inhibits both insulin and glucagon, it can cause either hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar). Hyperglycemia is more common in patients with acromegaly.

• Acute Pancreatitis: Sudden inflammation of the pancreas, which causes severe upper abdominal pain radiating to the back.
• Hepatitis: Rare cases of liver inflammation or elevated liver enzymes.
• Hair Loss: Thinning hair or alopecia has been reported in a small number of patients.

> Warning: Stop taking Octreotide and call your doctor immediately if you experience any of these serious symptoms:

1. 1Signs of Gallstones: Severe pain in your upper right abdomen, pain between your shoulder blades, fever, chills, or yellowing of the skin/eyes (jaundice).
2. 2Severe Bradycardia: Feeling like your heart is beating very slowly, fainting, or severe dizziness.
3. 3Anaphylaxis: Sudden rash, hives, swelling of the face or throat, and difficulty breathing.
4. 4Severe Pancreatitis: Intense, persistent abdominal pain that may be accompanied by vomiting and fever.
5. 5Significant Hypoglycemia: Confusion, tremors, sweating, and extreme hunger (more common in Type 1 diabetics).

The most significant long-term concern with octreotide is the development of gallstones. While many of these stones are 'silent' (asymptomatic), some can lead to acute cholecystitis (gallbladder inflammation) or bile duct obstruction. Regular ultrasound monitoring of the gallbladder is often recommended for patients on chronic therapy. Additionally, long-term suppression of TSH may require thyroid hormone replacement therapy in some individuals. There is also a theoretical risk of vitamin B12 deficiency over many years due to altered gastric acid secretion and intrinsic factor release, though this is clinically rare.

No FDA black box warnings for Octreotide. Unlike some other medications, the FDA has not mandated a boxed warning for octreotide. However, the warnings regarding biliary tract abnormalities and cardiac conduction are considered major safety precautions that require diligent clinical monitoring.

Report any unusual symptoms or persistent side effects to your healthcare provider. Many GI side effects can be managed by reducing the fat content in your diet or by taking the injection between meals or at bedtime.

Octreotide is a potent hormonal regulator that affects multiple organ systems. Patients must be aware that while it is highly effective for its intended uses, it requires regular medical follow-up to monitor for complications, particularly those involving the gallbladder and the endocrine system. It is not a cure for acromegaly or neuroendocrine tumors but a management tool to control hormone levels and symptoms.

No FDA black box warnings for Octreotide. The safety profile is well-established, provided that patients undergo the recommended monitoring for biliary and cardiac health.

• Biliary Tract Abnormalities: As noted, the risk of gallstones is high. Healthcare providers typically perform a baseline gallbladder ultrasound and periodic follow-up scans. If gallstones are discovered and become symptomatic, the drug may need to be discontinued or the gallbladder removed.
• Cardiac Function: Octreotide can slow the heart rate (bradycardia). This is particularly important for patients with pre-existing heart conditions, such as congestive heart failure or arrhythmias. In rare cases, it can lead to more serious heart rhythm issues like AV block.
• Glucose Metabolism: Because octreotide suppresses the release of insulin, glucagon, and growth hormone, it can disrupt blood sugar control. Patients with diabetes may need to adjust their insulin or oral medication doses frequently when starting or stopping octreotide.
• Thyroid Function: Suppression of TSH can lead to clinical or subclinical hypothyroidism. Thyroid function tests (T4 and TSH) should be monitored periodically.
• Nutritional Deficiencies: By slowing the gut and inhibiting pancreatic enzymes, octreotide can interfere with the absorption of dietary fats and fat-soluble vitamins (A, D, E, and K). In rare cases, vitamin B12 levels may also be affected.

To ensure the safe use of octreotide, your doctor will likely order the following tests:

• Gallbladder Ultrasound: At baseline and every 6 to 12 months during long-term therapy.
• Thyroid Function Tests: TSH and Free T4 levels periodically.
• Blood Glucose: Regular monitoring, especially for patients with diabetes or pre-diabetes.
• Hormone Levels: For acromegaly, GH and IGF-1 levels are checked to ensure the dose is effective. For carcinoid/VIPomas, specific tumor markers or 5-HIAA (a serotonin metabolite) levels may be tracked.
• Liver and Kidney Function: Periodic CMP (Comprehensive Metabolic Panel) to check for organ health.

Octreotide generally does not cause significant impairment of motor skills or cognitive function. However, some patients may experience dizziness or fatigue, especially when first starting the medication or during a dosage increase. It is advisable to see how the drug affects you before driving or operating heavy machinery.

There is no direct chemical interaction between alcohol and octreotide. However, alcohol can worsen some of the gastrointestinal side effects of octreotide, such as nausea and diarrhea. Furthermore, alcohol can affect blood sugar levels, which may complicate the glycemic management already being influenced by octreotide. Moderation is advised, and you should discuss your alcohol consumption with your doctor.

Octreotide should not be stopped abruptly without medical supervision. In patients with acromegaly, stopping the drug will lead to a rapid rise in growth hormone levels and a return of symptoms (headache, joint pain, swelling). In patients with carcinoid tumors, discontinuation can lead to a 'rebound' of severe diarrhea and flushing. If the drug must be stopped, it is usually done under close observation.

> Important: Discuss all your medical conditions, especially heart disease, diabetes, and history of gallstones, with your healthcare provider before starting Octreotide.

There are no drugs that are strictly 'contraindicated' for use with octreotide in the sense of causing immediate fatality, but certain combinations are avoided because they negate the effects of the treatment or cause severe toxicity. For example, using octreotide with other somatostatin analogs (like lanreotide) is generally redundant and not recommended.

• Cyclosporine: Octreotide can significantly decrease the intestinal absorption of cyclosporine (an immunosuppressant). This can lead to low blood levels of cyclosporine, increasing the risk of organ transplant rejection. Patients on both drugs require frequent monitoring of cyclosporine blood levels and likely dosage increases.
• Insulin and Oral Hypoglycemics: Octreotide can either increase or decrease the need for these medications. Because it suppresses both insulin (which lowers blood sugar) and glucagon/growth hormone (which raise blood sugar), the net effect is unpredictable. Close monitoring of blood glucose is mandatory.
• Bromocriptine: Octreotide increases the bioavailability of bromocriptine (used for Parkinson's or prolactinomas). This may require a reduction in the bromocriptine dose to avoid side effects like nausea or low blood pressure.
• Drugs Metabolized by CYP3A4: While octreotide doesn't directly inhibit CYP enzymes, the suppression of growth hormone can indirectly alter the activity of these enzymes in the liver. Drugs with a narrow therapeutic index, such as quinidine or certain anticonvulsants, should be used with caution.

• Beta-Blockers and Calcium Channel Blockers: Since octreotide can cause bradycardia, using it with other heart-rate-slowing drugs (like atenolol, metoprolol, or diltiazem) can lead to excessively slow heart rates.
• Diuretics: Octreotide can affect fluid and electrolyte balance. When used with diuretics (like furosemide), there is an increased risk of electrolyte imbalances, particularly hypokalemia (low potassium).

• High-Fat Meals: For the oral formulation (Mycapssa), food—especially high-fat food—significantly reduces the amount of drug that reaches the bloodstream. It must be taken on an empty stomach.
• Nutrient Absorption: Octreotide may reduce the absorption of dietary fats and fat-soluble vitamins. Your doctor may recommend a low-fat diet to minimize GI side effects like steatorrhea.

• St. John's Wort: This herb can induce liver enzymes and potentially reduce the effectiveness of many medications, although its specific effect on octreotide is not well-documented. It is best avoided.
• Vitamin B12: Long-term use of octreotide may theoretically impair B12 absorption. Patients on chronic therapy should have their B12 levels checked periodically.

• Thyroid Function Tests: Octreotide can suppress TSH, leading to lower-than-expected TSH and T4 results that may be misinterpreted as primary hypothyroidism.
• Glucose Tolerance Tests: Octreotide will interfere with the results of an oral glucose tolerance test (OGTT) by altering the insulin response.
• 5-HIAA: In patients with carcinoid syndrome, octreotide will lower urinary 5-HIAA levels, which is a therapeutic goal but must be considered when using the test for diagnosis.

For each major interaction, the management strategy usually involves more frequent monitoring of the patient's clinical status and laboratory values, rather than avoiding the drug entirely.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter drugs.

• Hypersensitivity: The only absolute contraindication to octreotide is a known hypersensitivity or severe allergic reaction to octreotide acetate or any of the inactive ingredients in the formulation (such as mannitol, lactic acid, or phenol). An allergic reaction may manifest as anaphylaxis, angioedema (swelling of the face/throat), or severe urticaria (hives).

These are conditions where the benefit of octreotide must be carefully weighed against the risks, and the patient must be monitored closely:

• Pre-existing Gallstones: Since octreotide is known to cause or worsen cholelithiasis, patients who already have gallstones are at a higher risk for acute gallbladder complications. Alternative therapies may be considered, or the patient may be monitored with more frequent ultrasounds.
• Severe Cardiac Disease: Patients with a history of bradycardia, heart block, or significant arrhythmias should use octreotide with extreme caution due to its potential to slow the heart rate further.
• Type 1 Diabetes: These patients are at a higher risk for severe hypoglycemia because octreotide's suppression of glucagon can remove the body's natural defense against low blood sugar.
• Severe Renal Failure: While not a contraindication, the significantly reduced clearance of the drug means that standard doses may lead to toxicity. Dosing must be conservative.

There is a potential for cross-sensitivity between octreotide and other somatostatin analogs, such as lanreotide or pasireotide. If a patient has had a severe reaction to one drug in this class, they should generally not be prescribed another unless under the strict supervision of an allergist and endocrinologist.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous drug allergies or gallbladder issues, before prescribing Octreotide.

Octreotide is classified as Pregnancy Category B. This means that animal reproduction studies (in rats and rabbits) have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

• Trimester-Specific Risks: There is no evidence of teratogenicity (birth defects) in animal models. However, because octreotide can cross the placenta and is a potent hormone inhibitor, it could theoretically affect fetal growth or the development of the fetal endocrine system.
• Fertility: In women with acromegaly, octreotide may actually improve fertility by normalizing hormone levels. Women of childbearing age should use effective contraception while on octreotide unless they are specifically trying to conceive.
• Recommendation: Octreotide should be used during pregnancy only if clearly needed. Many specialists recommend pausing octreotide therapy during pregnancy unless the mother's condition (e.g., a large pituitary tumor) poses a significant risk.

It is not known whether octreotide is excreted in human milk. Many drugs are excreted in milk, and because of the potential for serious adverse reactions in nursing infants (such as growth suppression), a decision should be made whether to discontinue nursing or discontinue the drug. Most clinicians advise against breastfeeding while using octreotide, or they monitor the infant's growth very closely if breastfeeding is continued.

As previously mentioned, octreotide is not FDA-approved for children. The safety and effectiveness in the pediatric population have not been established. There are concerns that long-term use could lead to growth retardation due to the suppression of growth hormone. If used off-label for conditions like hyperinsulinism, it must be under the care of a specialist.

In clinical trials, elderly patients did not show significantly different safety profiles compared to younger patients. However, the elderly are more likely to have decreased renal function and a higher prevalence of cardiovascular disease. This increases the risk of drug accumulation and bradycardia. Dosage titration in the elderly should be slow and cautious.

In patients with severe renal impairment (Creatinine Clearance < 30 mL/min), the half-life of octreotide is prolonged. For the immediate-release form, starting doses should be reduced. For the LAR formulation, the 10 mg or 20 mg dose is often preferred over the 30 mg dose to start. Octreotide is not significantly removed by hemodialysis.

In patients with liver cirrhosis, the half-life of the drug is increased to approximately 3 hours (compared to 1.5 hours in healthy subjects). This may lead to higher steady-state levels. While specific dose adjustments are not always required for mild impairment, those with moderate to severe hepatic impairment (Child-Pugh Class B or C) require careful monitoring for increased side effects.

> Important: Special populations require individualized medical assessment and more frequent laboratory monitoring.

Octreotide is a synthetic octapeptide analog of somatostatin. It exerts its effects by binding with high affinity to somatostatin receptors (SSTRs), specifically subtypes 2 and 5. These receptors are coupled to inhibitory G-proteins (Gi). Binding leads to:

1. 1Inhibition of Adenylyl Cyclase: This reduces intracellular cyclic AMP (cAMP), a key messenger for hormone secretion.
2. 2Activation of Potassium Channels: This hyperpolarizes the cell, making it less likely to fire and release hormones.
3. 3Inhibition of Calcium Entry: It closes voltage-gated calcium channels, which is the final trigger for the exocytosis of hormone vesicles.

Through these mechanisms, octreotide suppresses the secretion of growth hormone, insulin, glucagon, gastrin, vasoactive intestinal peptide (VIP), and serotonin.

• Onset of Action: For the IR form, the onset of hormone suppression is rapid, usually within 30 minutes.
• Duration of Effect: The IR form lasts for 6 to 12 hours. The LAR form provides continuous therapeutic levels for approximately 4 weeks.
• Tolerance: While some 'escape' from symptom control can occur over years of treatment, true pharmacological tolerance is rare. Most cases of reduced efficacy are due to tumor growth rather than drug desensitization.

| Parameter | Value |

|---|---|

| Bioavailability | ~100% (Subcutaneous) |

| Protein Binding | ~65% (primarily to lipoproteins) |

| Half-life | 1.5 to 1.7 hours (IR); ~2-3 weeks (LAR) |

| Tmax | 0.4 to 1.0 hours (Subcutaneous) |

| Metabolism | Hepatic and tissue peptidases |

| Excretion | Renal 32%, Fecal <2% |

• Molecular Formula: C49H66N10O10S2 (as acetate)
• Molecular Weight: 1019.2 g/mol
• Solubility: Highly soluble in water and glacial acetic acid.
• Structure: A cyclic octapeptide containing a disulfide bridge, which provides the stability needed for its longer half-life compared to natural somatostatin.

Octreotide is the prototypical Somatostatin Analog [EPC]. Related medications include Lanreotide (Somatuline) and Pasireotide (Signifor). It is categorized therapeutically as an Antigrowth Hormone Agent and an Antidiarrheal Agent for specific tumor-related conditions.