Signifor LAR

Cases for consideration

IN YOUR PRACTICE, DO YOU SEE PATIENTS LIKE THESE?

Each story is unique and all have acromegaly uncontrolled with a first-generation somatostatin receptor ligand (SRL). Select a patient to learn more.

Elizabeth S.

Patient Image

Patient portrayal

Persistent symptoms post-surgery

Elizabeth S.

Patient has acromegaly uncontrolled with a first-generation SRL.

AGE: 38 | HEIGHT: 5’5” | WEIGHT: 162 lb
DIAGNOSED: 4 years, 2 months ago (50 months) at age 33
SURGERY: Transsphenoidal (endoscopic); 4 years, 1 month ago

Patient presents with a constellation of symptoms and intolerable side effects with current high-dose therapy:

  • Headache
  • Severe, persistent diarrhea
  • Abdominal pain
  • Fatigue
  • Asthenia
  • Back pain
  • Uncontrolled hypertension
  • Arthralgia, inflamed joints, especially spine, knees, digital joints
  • Menstrual irregularity
  • Uncontrolled hypertension

Moderate difficulty carrying on normal activities of daily living:

  • Enlarged fingers causing poor dexterity
    • Difficulty writing
    • Struggles using kitchen utensils

RELEVANT HISTORY

  • Started intramuscular, long-acting, first-generation SRL 3 years, 10 months ago
    • Symptoms diminished, patient’s acromegaly was in biochemical control
  • 11 months ago, noticeable signs and symptoms reappeared, along with elevated IGF-1 and GH levels
    • Increased dose, and 8 months ago increased again to the maximum dose

BIOCHEMICAL ASSESSMENT

  • GH level: Reached a nadir of 3 μg/L 2 hours post-OGTT (GH level for a normal patient would drop below 1 μg/L)
  • IGF-1 concentration: 464 μg/L (1.8 x ULN for 38-year-old female)

CLINICAL CONSIDERATIONS

  • Persistent signs, symptoms, and comorbidities typical of uncontrolled acromegaly
  • Elizabeth’s physician is adding another medication to help control her acromegaly

GH, growth hormone; IGF-1, insulin-like growth factor 1; OGTT, oral glucose tolerance test; ULN, upper limit of normal.

Questions to consider when developing a treatment plan:

  • Why might Elizabeth’s physician be considering adding another medication to therapy with oral first-generation SRL?
  • What would you recommend as the next course of therapy for a patient on the maximum dose of IM first-generation SRL who remains uncontrolled biochemically?

Maureen C.

Patient Image

Patient portrayal

Recurring symptoms;
evidence of tumor progression

Maureen C.

Patient is on maximum dose of a first-generation SRL, her acromegaly is not biochemically controlled, and there is evidence of tumor progression.

AGE: 58 | HEIGHT: 5’4” | WEIGHT: 146 lb
DIAGNOSED: 4 years ago (48 months) at age 54
SURGERY: Transsphenoidal (endoscopic); 3 years, 11 months ago

Patient is now presenting with complaints of:

  • Persistent headaches
  • GI issues
  • Asthenia
  • Back pain and painful extremities

Occasional need for assistance with activities of daily living:

  • Unable to work in her garden
    • Kneeling is painful
    • Difficulty gripping shears and trowel

RELEVANT HISTORY

  • Initiated deep subcutaneous treatment with a first-generation SRL 3 years, 10 months ago
    • After a year of biochemical control, the patient’s GH and IGF-1 began to rise. New symptoms necessitated an increase to maximum dose
  • Patient was maintained on the maximum dose for 3 years
  • Recently, noticeable signs and symptoms of acromegaly recurred
  • Tumor size is slowly increasing

BIOCHEMICAL ASSESSMENT

  • GH level: Reached a nadir of 3 μg/L 2 hours post-OGTT (GH level for a normal patient would drop below 1 μg/L)
  • IGF-1 concentration: 354 μg/L (1.7 x ULN for 58-year-old female)

CLINICAL CONSIDERATIONS

  • Recurring signs, symptoms, and comorbidities are consistent with progressive acromegaly

Questions to consider when developing a treatment plan:

  • When a previously controlled patient begins to exhibit lack of biochemical control, what would you do next?
  • How do you define ‘control’ in your patients with acromegaly?

Louisa M.

Patient Image

Patient portrayal

Surgery not an option; metabolic syndrome

Louisa M.

Patient has acromegaly uncontrolled with a first-generation SRL.

AGE: 51 | HEIGHT: 5’4” | WEIGHT: 165 lb
DIAGNOSED: 1 year, 8 months ago (20 months) at age 49
SURGERY: None; Louisa is a poor candidate for surgery because of a macroadenoma wrapped around the carotid artery

Patient presents with common acromegaly symptoms and concomitant conditions:

  • Acral enlargement
  • Visual field disturbance
  • Intense back pain
  • Hypertension
  • Congestive heart failure
  • Type 2 diabetes
  • Severe obstructive sleep apnea
  • Depression

Difficulty with activities of daily living:

  • Unable to carry laundry
  • Difficulty buttoning shirts
  • Grocery shopping is becoming hard
    • Difficulty reaching for and grasping groceries

RELEVANT HISTORY

  • Started on a first-generation SRL, increased to maximum dose, and was in control until recently
    • Began experiencing headaches and other symptoms recently

BIOCHEMICAL ASSESSMENT

  • GH level: Reached a nadir of 3.5 μg/L 2 hours post-OGTT (GH level for a normal patient would drop below 1 μg/L)
  • IGF-1 concentration: 868 μg/L (4 x ULN for
51-year-old female)

CLINICAL CONSIDERATIONS

Metabolic syndrome

  • Type 2 diabetes (8+ years)
    • HbA1c 7.3, managed with metformin 1000 mg twice daily
  • Hypertension (recent elevations in SBP/DBP noted up to 160/100 mm Hg)
    • Managed with losartan 100 mg once daily and amlodipine besylate 5 mg once daily
  • Hyperlipidemia (LDL = 175,a HDL = 35,a total cholesterol = 210) and hypertriglyceridemia
(TRI = 160a)
    • Recently increased to atorvastatin 80 mg once daily

Macroadenoma

  • Extends beyond the sella turcica, with cavernous sinus invasion and carotid artery involvement
amedlineplus.gov defines LDL of 175 as high, HDL of 35 as a major risk factor for heart attack, and TRI of 160 as borderline high.

Questions to consider when developing a treatment plan:

  • In light of Louisa’s unresected tumor, what options would you consider next after a first-generation SRL?
  • How does the level of glycemic control in a patient with type 2 diabetes mellitus affect your treatment decision for acromegaly?

Gregory D.

Patient Image

Patient portrayal

Stereotactic radiosurgery;
may require further management

Gregory D.

Patient has persistent acromegaly following surgery and radiotherapy.

AGE: 26 | HEIGHT: 6’0” | WEIGHT: 252 lb
DIAGNOSED: 5 months ago at age 25
SURGERY: Transsphenoidal; 5 months ago. Macroadenoma still present. 50% of tumor remains, cavernous sinus involvement. Stereotactic radiosurgery for aggressive tumor performed 1 month ago

Patient presents with worsening symptoms of acromegaly:

  • Visible acral overgrowth
  • New and increasing asthenia
  • New-onset limp due to lumbar spinal stenosis

Significant decline in activities of daily living:

  • Requires assistance from others to unpack groceries, fold laundry, cook, and clean
  • Requires frequent medical care
  • Forced to quit job as delivery driver due to inability to lift and carry packages

RELEVANT HISTORY

  • Patient is naïve to medical therapy for acromegaly
  • Hypertension managed with amlodipine besylate 10 mg/day plus HCTZ 50 mg/day
  • Obstructive sleep apnea managed with CPAP
  • Severe depression managed with paroxetine 50 mg/day
  • Joint and muscle pain partially controlled with acetaminophen every 4-6 hours (maximum 
4 g/day)

BIOCHEMICAL ASSESSMENT

  • Persistently elevated since stereotactic radiosurgery 1 month ago
  • GH level: Reached a nadir of 3 μg/L 2 hours post-OGTT (GH level for a normal patient would drop below 1 μg/L)
  • IGF-1 concentration: 1645 μg/L (5 x ULN for 26-year-old male)

CLINICAL CONSIDERATIONS

  • Despite intensive treatment for hypertension, depression, and joint pain, signs and symptoms of each have worsened since stereotactic radiosurgery
  • GH and IGF-1 test results show inadequate biochemical improvements
  • MRI shows persistent tumor post-surgery with invasion into the cavernous sinus
  • Medication needed to control acromegaly while waiting for radiotherapy to work

Questions to consider when developing a treatment plan:

  • What would you recommend next for a patient like Gregory who has failed transsphenoidal surgery?
  • Does the presence of an aggressive macroadenoma affect your recommendation for Gregory?
  • What are the factors you consider when initiating medical therapy for a patient with a large, inoperable residual tumor?
See more patient cases

INDICATIONS AND USAGE

SIGNIFOR LAR® (pasireotide) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

Hyperglycemia, Diabetes, and Ketoacidosis: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Monitor glucose levels as clinically appropriate during therapy. There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with or without history of diabetes. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic treatment or adjustment in their current anti-diabetic treatment. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, reduce the dose or discontinue SIGNIFOR LAR. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. If ketoacidosis is suspected, discontinue SIGNIFOR LAR and promptly evaluate and treat the patient.

Bradycardia and QT Prolongation: Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factors for bradycardia, such as history of clinically significant bradycardia, high grade heart block, or concomitant use of drugs associated with bradycardia, should be monitored. Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances may be necessary when initiating or during the course of SIGNIFOR LAR treatment. In cardiac electrophysiology studies with pasireotide via subcutaneous route, QT prolongation occurred at therapeutic and supra-therapeutic doses. Use with caution in patients at significant risk; evaluate ECG and electrolytes prior to dosing and periodically while on treatment. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy.

Liver Test Elevations: Increases in liver enzymes have been observed with SIGNIFOR LAR. Evaluate liver enzyme tests prior to and during treatment.

Cholelithiasis and Complications of Cholelithiasis: There have been reports of cholelithiasis resulting in complications including cholecystitis or cholangitis and requiring cholecystectomy in patients taking SIGNIFOR LAR. Monitor periodically. Discontinue SIGNIFOR LAR if complications of cholelithiasis are suspected and treat appropriately.

Pituitary Hormone Deficiency(ies): Suppression of anterior pituitary hormones may occur on SIGNIFOR LAR. Monitor for occurrence periodically and treat if clinically indicated.

Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency.

The most common adverse reactions occurring in ≥ 20% of patients with acromegaly were diarrhea, hyperglycemia, cholelithiasis, and diabetes mellitus.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

  • Drugs that Prolong QT: Co-administration of drugs that prolong the QT interval with SIGNIFOR LAR may have additive effects on the prolongation of the QT interval. Monitoring effects on the QT interval at 21 days is recommended.
  • Cyclosporine: Concomitant administration of cyclosporine with SIGNIFOR LAR may decrease the relative bioavailability of cyclosporine and, therefore, dose adjustment of cyclosporine to maintain therapeutic levels may be necessary.
  • Bromocriptine: Co-administration of SIGNIFOR LAR with bromocriptine may increase the blood levels of bromocriptine. Dose reduction of bromocriptine may be necessary.

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy.

SIGNIFOR LAR® (pasireotide) for injectable suspension, for intramuscular use, is available as 10 mg, 20 mg, 30 mg, 40 mg, and 60 mg powder in a vial to be reconstituted with the provided 2 mL diluent.

Please see full Prescribing Information and Patient Information.