Lanreotide

H01C - Hypothalamic hormones ATC H01CB03 Protein approved 2007 Parenteral Natural product

JFDA label: Somatuline Autogel PFS

Mechanism of Action

Lanreotide is a synthetic octapeptide analogue of natural somatostatin which is a peptide inhibitor of multiple endocrine, neuroendocrine, and exocrine mechanisms. Lanreotide displays a greater affinity for somatostatin type 2 (SSTR2) and type 5 (SSTR5) receptors found in pituitary gland, pancreas, and growth hormone (GH) secreting neoplasms of pituitary gland and a lesser affinity for somatostatin receptors 1, 3, and 4. Lanreotide reduces GH secretion and also reduces the levels of insulin-like growth factor 1.

Indications

Approved

Acromegaly
Carcinoid syndrome
Gastroenteropancreatic neuroendocrine tumors

Contraindications

Source: Lexicomp

Additional contraindications (not in the US labeling): Hypersensitivity to somatostatin or related peptides Absolute
Hypersensitivity to lanreotide or any component of the formulation Absolute
complicated, untreated bile duct lithiasis Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Very Common Bradycardia · hypertension

Common Sinus bradycardia

Nervous system disorders (3)

Very Common Headache

Common depression · Dizziness

Hepatobiliary disorders (2)

Very Common Cholelithiasis · gallbladder sludge

Blood and lymphatic system disorders (1)

Very Common Anemia

Immune system disorders (1)

Very Common Antibody development

Metabolism and nutrition disorders (2)

Very Common Weight loss

Common Hyperglycemia

Gastrointestinal disorders (7)

Very Common abdominal pain · Diarrhea · flatulence · nausea · vomiting

Common constipation · Loose stools

Musculoskeletal and connective tissue disorders (2)

Very Common Musculoskeletal pain

Common Arthralgia

General disorders and administration site conditions (1)

Very Common Injection site reaction

Dosing

Source: Lexicomp

Acromegaly: SubQ: Initial dose: 90 mg once every 4 weeks for 3 months; after initial 3 months, continue monitoring and adjust dose as necessary based on clinical response of patient, growth hormone (GH) levels, and/or insulin-like growth factor 1 (IGF-1) levels as follows: GH ≤1 ng/mL, IGF-1 normal, symptoms stable: Decrease dose to 60 mg once every 4 weeks; once stabilized on 60 mg once every 4 weeks, may consider regimen of 120 mg once every 6 or 8 weeks (extended-interval dosing) GH >1 to 2.5 ng/mL, IGF-1 normal, symptoms stable: Continue 90 mg once every 4 weeks; once stabilized on 90 mg once every 4 weeks, may consider regimen of 120 mg once every 6 or 8 weeks (extended-interval dosing) GH >2.5 ng/mL, IGF-1 elevated and/or uncontrolled symptoms: Increase dose to 120 mg once every 4 weeks Carcinoid syndrome: SubQ: 120 mg once every 4 weeks (if already receiving lanreotide for treatment of gastroenteropancreatic neuroendocrine tumors [GEP-NETs], do not administer an additional dose for carcinoid syndrome) GEP-NETs: SubQ: 120 mg once every 4 weeks until disease progression or unacceptable toxicity

Refer to adult dosing.

Acromegaly: CrCl ≥60 mL/minute: No dosage adjustment necessary. CrCl Carcinoid syndrome or gastroenteropancreatic neuroendocrine tumors (GEP-NETs): CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling, however, total clearance of lanreotide 120 mg is not affected. CrCl

Acromegaly: Mild impairment (Child-Pugh class A): No dosage adjustment necessary. Moderate to severe impairment (Child-Pugh classes B and C): Initial dose: 60 mg once every 4 weeks for 3 months; adjust dose based on clinical response of patient, growth hormone (GH) levels, and/or insulin-like growth factor 1 (IGF-1) levels; use of an extended-interval dose of 120 mg once every 6 or 8 weeks should be done with caution. Carcinoid syndrome or gastroenteropancreatic neuroendocrine tumors (GEP-NETs): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Cholelithiasis

May reduce gall bladder motility, leading to gall stone formation (may be dose- or duration-related); may require periodic monitoring.

Gastrointestinal effects

Diarrhea and loose stools may occur (may affect intestinal absorption of concurrently-administered medication); abdominal pain may also occur.

Hyper-/hypoglycemia

Inhibition of insulin and glucagon secretion may affect glucose regulation, leading to hyper-/hypoglycemia. Carefully monitor blood glucose levels with the initiation of therapy and with dosage alterations. Use with caution in patients with diabetes; may require dosage adjustments in antidiabetic therapy.

Hypersensitivity

Allergic reactions, including angioedema and anaphylaxis, have been reported.

Thyroid disorders

Decreases (slight) in thyroid function have been observed during treatment for acromegaly; monitor thyroid function tests if clinically indicated. The incidence of clinical hypothyroidism is rare. Disease-related concerns:

Cardiac disorders

Bradycardia, sinus bradycardia, and hypertension have been observed with therapy. Use with caution in patients with preexisting cardiac disease; monitor heart rate. Patients without preexisting cardiac disease may experience a decrease in heart rate though not to the level of bradycardia. Appropriate medical therapy should be initiated if patients develop symptomatic bradycardia.

Hepatic impairment

Use with caution in patients with acromegaly with moderate to severe hepatic impairment (systemic exposure may be increased); lower doses are recommended at therapy initiation. Lanreotide has not been studied in patients with neuroendocrine tumors with hepatic impairment.

Renal impairment

Use with caution in patients with acromegaly with moderate to severe renal impairment; lower initial doses are recommended. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

Adverse events were observed in animal reproduction studies. Information related to the use of lanreotide in pregnancy is limited (deMenis 1999) and it is recommended to discontinue therapy during pregnancy (Chandraharan 2003; Melmed 2012).

Lactation

Avoid

It is not known if lanreotide is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant (including possible effects on glucose metabolism and bradycardia), breastfeeding is not recommended by the manufacturer during treatment and for 6 months after the last lanreotide dose.

Monitoring

Clinical pearl	Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) at 3 months and as clinically indicated in acromegaly patients (obtain levels 6 weeks after dose adjustment when switching to extended-interval dosing), glucose levels, thyroid function (where clinically indicated); heart rate, consider periodic gall bladder monitoring

Chemistry & Properties

Formula	C54H69N11O10S2
Molecular weight	1096.35 g/mol
IUPAC name	(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2R)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
CAS	108736-35-2
PubChem CID	6918011
InChIKey	`PUDHBTGHUJUUFI-SCTWWAJVSA-N`

SMILES

CC(C)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](NC(=O)[C@H](N)Cc2ccc3ccccc3c2)CSSC[C@@H](C(=O)N[C@H](C(N)=O)[C@@H](C)O)NC1=O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.656 h
Volume of distribution	0.512 L/kg
Protein binding	46.3%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Copper oxodotreotide Cu-64	major
Lonafarnib	major
Pexidartinib	major
Acalabrutinib	moderate
Acarbose	moderate
Acebutolol	moderate
Acetohexamide	moderate
Adenosine	moderate
Albiglutide	moderate
Alogliptin	moderate
Amiodarone	moderate
Amlodipine	moderate
Atenolol	moderate
Avapritinib	moderate
Bepridil	moderate
Betaxolol	moderate
Betaxolol (ophthalmic)	moderate
Bisoprolol	moderate
Bromocriptine	moderate
Canagliflozin	moderate
Carteolol	moderate
Carteolol (ophthalmic)	moderate
Carvedilol	moderate
Chlorpropamide	moderate
Cyclosporine	moderate
Dapagliflozin	moderate
Digitoxin	moderate
Digoxin	moderate
Dihydroergotamine	moderate
Diltiazem	moderate
Disopyramide	moderate
Dofetilide	moderate
Dotatate	moderate
Dronedarone	moderate
Dulaglutide	moderate
Duvelisib	moderate
Empagliflozin	moderate
Entrectinib	moderate
Ergometrine	moderate
Ergotamine	moderate

Showing 40 of 100+.

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Somatuline Autogel PFS	Pre-filled Syringe 120 mg	1 PFS	Petra Drug Store	—
Somatuline Autogel PFS	Pre-filled Syringe 60 mg	1 PFS	Petra Drug Store	—
Somatuline Autogel PFS	Pre-filled Syringe 90 mg	1 PFS	Petra Drug Store	—