Octreotide

Uses

Acromegaly: Octreotide acetate injection is used to reduce blood levels of growth hormone and IGF-I (somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. The goal is to achieve normalization of growth hormone and IGF-I (somatomedin C) levels. In patients with acromegaly, Octreotide acetate injection reduces growth hormone to within normal ranges in 50% of patients and reduces IGF-I (somatomedin C) to within normal ranges in 50% to 60% of patients. Since the effects of pituitary irradiation may not become maximal for several years, adjunctive therapy with Octreotide acetate injection to reduce blood levels of growth hormone and IGF-I (somatomedin C) offers potential benefit before the effects of irradiation are manifested.

Improvement in clinical signs and symptoms or reduction in tumor size or rate of growth were not shown in clinical trials performed with Octreotide acetate injection; these trials were not optimally designed to detect such effects.

Carcinoid Tumors: Octreotide acetate injection is used for the symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease.

Octreotide acetate injection studies were not designed to show an effect on the size, rate of growth or development of metastases.

Vasoactive Intestinal Peptide Tumors (VIPomas): Octreotide acetate injection is used for the treatment of the profuse watery diarrhea associated with VIP-secreting tumors. Octreotide acetate injection studies were not designed to show an effect on the size, rate of growth or development of metastases.

Octreotide is also used to associated treatment for these conditions: Acromegaly, Diarrhoea, Metastatic Carcinoid Tumors, Long-term maintenance therapy

How Octreotide works

Octreotide binds to somatostatin receptors coupled to phospholipase C through G proteins and leads to smooth muscle contraction in the blood vessels. Downstream effects that stimulate phospholipase C, the production of 1, 4,5-inositol triphosphate, and action on the L-type calcium channels lead to the inhibition of growth hormone, treating the various growth-hormone and metabolic effects of acromegaly.

Octreotide's suppression of luteinizing hormone (LH), reduction in splanchnic blood flow, and inhibition of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide provide relief for the gastrointestinal and flushing symptoms of carcinoid and/or VIPoma tumors.

Dosage

Octreotide dosage

Intramuscular-Acromegaly:

• Adult: Following initial control with SC therapy: As a depot preparation, initially 20 mg every 4 wk. Adjust if required after 3 mth to 10-30 mg every 4 wk. Max: 40 mg every 4 wk.

Intravenous-

Variceal haemorrhage in patients with cirrhosis:

• Adult: As continuous IV infusion: 25 mcg/hr for 48 hr (up to 5 days in patients at high risk of re-bleeding).
• Child: ≥1 mth: 1 mcg/kg/hr (up to 50 mcg/hr); given as continuous IV infusion. Higher doses may be needed initially, reduce dose gradually over 24 hr until bleeding has stopped.

Subcutaneous-

Prophylaxis of complications following pancreatic surgery:

• Adult: 100 mcg tid of a rapid-acting preparation given for 7 consecutive days, starting at least 1 hr before operation.

Subcutaneous-

Acromegaly:

• Adult: Initially 50 mcg tid, increased as necessary to usual dose 100-200 mcg tid. Max: 500 mcg tid.

Subcutaneous-

Secretory neoplasms:

• Adult: Initially, 50 mcg 1-2 times daily, increased gradually to up to 600 mcg daily in 2-4 divided doses according to response. Continued treatment is not recommended if there is no benefit within a wk of starting treatment for carcinoid tumour. Initial dose may be given via IV admin of a rapid response is required.

Subcutaneous-

HIV-associated diarrhoea:

• Adult: Initial dose 100 mcg tid. If symptoms are not controlled after 1 wk, increase dose to 250 mcg tid, if still not effective after 1 wk stop therapy.

Side Effects

Local pain, stinging, tingling at site of inj; anorexia, nausea, vomiting, abdominal pain, bloating, flatulence, loose stools, steatorrhoea; biliary tract abnormalities. Hypoglycaemia and hyperglycaemia, hypothyroidism, cardiac conduction abnormalitles, pancreatitis.

Toxicity

There is limited information regarding cases of octreotide overdose aside from case reports of an overdose with injectable octreotide. The dose ranged from 2.4 mg/day to 6 mg/day administered by continuous infusion or subcutaneous administration of 1.5 mg three times daily. Effects of an overdose with octreotide may include hypotension, brain hypoxia, arrhythmia, cardiac arrest, lactic acidosis, pancreatitis, hepatomegaly, diarrhea, flushing, lethargy, and weakness.

Precaution

Renal disease; risk of gall bladder disease; DM; hypothyroidism. Pregnancy, lactation, children, elderly. Monitor levels of vitamin B12 during long term therapy.

Interaction

Dosage adjustment of concurrent therapy may be necessary with calcium channel blockers, oral hypoglycaemics, β-blockers, diuretics. May increase concentration of bromocriptine.

Food Interaction

• Take on an empty stomach. The oral capsules should be taken on an empty stomach. Food reduces oral octreotide absorption by 90%.
• Take with or without food. Octreotide injections may be taken with or without food.

[Moderate] MONITOR: Due to their gastrointestinal pharmacologic effects, somatostatin analogs (e.g., octreotide, lanreotide) may variously affect the absorption of dietary nutrients and concomitantly administered oral medications.

Somatostatin analogs have been shown to prolong gastrointestinal transit time and inhibit intestinal absorption of some nutrients such as fat.

Clinical data are limited, however.

In case reports, octreotide has been reported to reduce the relative bioavailability of cyclosporine.

Transplant rejection and significant reductions in cyclosporine levels, sometimes to undetectable levels, have been reported in association with the interaction.

Vitamin K absorption was not affected when concomitantly administered with lanreotide according to the manufacturer.

MANAGEMENT: Clinicians should be aware of the potential for altered absorption of concomitantly administered oral medications during treatment with somatostatin analogs.

Blood levels and clinical response should be monitored, particularly for drugs that have a narrow therapeutic index, and the dosages adjusted as necessary.

Octreotide Drug Interaction

Unknown: lorazepam, ciprofloxacin, pancrelipase, duloxetine, hydromorphone, levetiracetam, furosemide, acetaminophen, clopidogrel, pantoprazole, levothyroxine, acetaminophen, valproic acid, cyanocobalamin, ascorbic acid, cholecalciferol, phytonadione, phytonadione, ondansetron, cetirizine

Octreotide Disease Interaction

Major: renal dysfunctionModerate: gallbladder/biliary dysfunction, glucose intolerance, heart disease, hepatic impairment, thyroid dysfunction, vitamin B12 deficiency

Volume of Distribution

In a pharmacokinetic study, the volume of distribution was 13.6 L in healthy volunteers. One pharmacokinetic study revealed a volume of distribution ranging from 18.1-30.4L after intravenous administration in healthy volunteers.

Elimination Route

After a subcutaneous dose, octreotide is absorbed completely upon administration. After the administration of an oral delayed-release capsule, peak concentrations were found to be 33% lower than after subcutaneous administration. The Cmax was attained at 1.67–2.5 hours after oral administration versus 30 minutes for the subcutaneous route. At 20 mg twice a day in patients with acromegaly, peak concentration was 2.5 mg/nL versus 5.30 ng/mL at 40 mg twice a day. AUC increases in proportion with the dose, regardless of the route.

Half Life

After a subcutaneous dose, the plasma half-life is estimated to be 0.2 hours. The average elimination half-lives for subcutaneous and oral administration ranged from 2.3 - 2.7 hours and did not differ significantly. One pharmacokinetic study revealed a plasma half-life ranging from 72-113 minutes.

Clearance

The total body clearance of octreotide is 7-10 L/h. One pharmacokinetic study revealed a total body clearance of 11.4 L/h.

Elimination Route

About 32% of an oral octreotide dose is excreted into the urine and 30-40% is excreted by the liver into the feces.. About 11% of the unchanged parent drug is found in the urine, and 2% of the unchanged parent drug can be recovered in the feces.

Pregnancy & Breastfeeding use

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Hypersensitivity

Special Warning

Renal Impairment: Dosage may need to be reduced in severe renal impairment requiring dialysis.

Storage Condition

Store at 2-8° C. Stable at room temperature for up to 14 days.

Innovators Monograph

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