Signifor

Last updated on RxList: 1/24/2020
Signifor Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 1/24/2020

What Is Signifor?

What Are Side Effects of Signifor?

Signifor (pasireotide) Injection is a somatostatin analog drug indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been a cure. Common side effects of Signifor include:

Dosage for Signifor

Signifor is administered as a subcutaneous injection twice a day.

What Drugs, Substances, or Supplements Interact with Signifor?

Signifor can interact with drugs that prolong the QT interval as well as cyclosporine (Sandimmune, Neoral, Restasis, Gengraf) and bromocriptine (Parlodel, Cycloset).

Signifor During Pregnancy and Breastfeeding

There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. As a risk to the breastfed child cannot be excluded, Signifor should not be used by the nursing mother.

Additional Information

Our Signifor (pasireotide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Signifor Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • fast or slow heartbeats;
  • sudden dizziness (like you might pass out);
  • high blood sugar--increased thirst, increased urination, fruity breath odor, tiredness, and weight loss even if you are more hungry than usual;
  • ketoacidosis (too much acid in the blood)--nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing;
  • low cortisol levels--nausea, vomiting, appetite changes, headache, irritability, confusion, slurred speech, or feeling weak, tired, unsteady, anxious, shaky, or light-headed; or
  • gallbladder problems--chalky-colored stools, stomach pain just after eating a meal, heartburn, bloating, and upper stomach pain that may spread to your back.

Common side effects may include:

  • abnormal blood test results;
  • feeling weak or tired;
  • nausea, stomach pain, diarrhea;
  • headache;
  • swelling, rapid weight gain;
  • cold symptoms such as stuffy nose and sneezing;
  • hair loss; or
  • pain, redness, itching, bruising or bleeding where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Signifor (Pasireotide Diaspartate for Injection)

Signifor Professional Information

SIDE EFFECTS

Clinically significant adverse reactions that appear in other sections of the labeling include:

  • Hypocortisolism [see WARNINGS AND PRECAUTIONS]
  • Hyperglycemia and Diabetes [see WARNINGS AND PRECAUTIONS]
  • Bradycardia and QT prolongation [see WARNINGS AND PRECAUTIONS]
  • Liver Test Elevations [see WARNINGS AND PRECAUTIONS]
  • Cholelithiasis and Complications of Cholelithiasis [see WARNINGS AND PRECAUTIONS]
  • Pituitary Hormone Deficiency [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

A total of 162 Cushing's disease patients were exposed to SIGNIFOR in the Phase III study [see Clinical Studies]. At study entry, patients were randomized to receive twice a day doses of either 0.6 mg or 0.9 mg of SIGNIFOR given subcutaneously. The mean age of patients was approximately 40 years old with a predominance of female patients (78%). The majority of the patients had persistent or recurrent Cushing's disease (83%) and few patients (≤ 5%) in either treatment group had received previous pituitary irradiation. The median exposure to the treatment was 10.4 months (0.0337.8) with 68% of patients having at least 6-months exposure.

In the Phase III trial, adverse reactions were reported in 98% of patients. The most common adverse reactions (frequency ≥ 20% in either group) were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes mellitus. There were no deaths during the study. Serious adverse events were reported in 25% of patients. Adverse events leading to study discontinuation were reported in 17% of patients.

Adverse reactions with an overall frequency higher than 5% are presented in Table 1 by randomized dose group and overall. Adverse reactions are ranked by frequency, with the most frequent reactions listed first.

Table 1 : Adverse Reactions [n (%)] With an Overall Frequency of More Than 5% in the Combined Dose Group in the Phase III Study in Cushing's Disease Patients

SIGNIFOR 0.6 mg twice a day
N = 82
SIGNIFOR 0.9 mg twice a day
N = 80
Overall
N = 162
Diarrhea48 (59)46 (58)94 (58)
Nausea38 (46)46 (58)84 (52)
Hyperglycemia31 (38)34 (43)65 (40)
Cholelithiasis25 (30)24 (30)49 (30)
Headache23 (28)23 (29)46 (28)
Abdominal pain19 (23)20 (25)39 (24)
Fatigue12 (15)19(24)31 (19)
Diabetes mellitus13 (16)16 (20)29 (18)
Injection-site reactions14 (17)14 (18)28 (17)
Nasopharyngitis10 (12)11 (14)21 (13)
Alopecia10 (12)10 (13)20 (12)
Asthenia13 (16)5 (6)18 (11)
Glycosylated hemoglobin increased10 (12)8 (10)18 (11)
Alanine aminotransferase increased11 (13)6 (8)17 (10)
Gamma-glutamyl transferase increased10 (12)7 (9)17 (10)
Edema peripheral9 (11)8 (10)17 (10)
Abdominal pain upper10 (12)6 (8)16 (10)
Decreased appetite7 (9)9 (11)16 (10)
Hypercholesterolemia7 (9)9 (11)16 (10)
Hypertension8 (10)8 (10)16 (10)
Dizziness8 (10)7 (9)15 (9)
Hypoglycemia12 (15)3 (4)15 (9)
Type 2 diabetes mellitus10 (12)5 (6)15 (9)
Anxiety5 (6)9 (11)14 (9)
Influenza9 (11)5 (6)14 (9)
Insomnia3 (4)11 (14)14 (9)
Myalgia10 (12)4 (5)14 (9)
Arthralgia5 (6)8 (10)13 (8)
Pruritus6 (7)7 (9)13 (8)
Lipase increased7 (9)5 (6)12 (7)
Constipation7 (9)4 (5)11 (7)
Hypotension5 (6)6 (8)11 (7)
Vomiting3 (4)8 (10)11 (7)
Back pain4 (5)6 (8)10 (6)
Dry skin5 (6)5 (6)10 (6)
Electrocardiogram QT prolonged5 (6)5 (6)10 (6)
Hypokalemia6 (7)4 (5)10 (6)
Pain in extremity6 (7)4 (5)10 (6)
Sinus bradycardia8 (10)2 (3)10 (6)
Vertigo4 (5)6 (8)10 (6)
Abdominal distension4 (5)5 (6)9 (6)
Adrenal insufficiency4 (5)5 (6)9 (6)
Aspartate aminotransferase increased6 (7)3 (4)9 (6)
Blood glucose increased6 (7)3 (4)9 (6)

Other notable adverse reactions which occurred with a frequency less than 5% were: anemia (4%), blood amylase increased (2%), and prothrombin time prolonged (2%).

Gastrointestinal Disorders

Gastrointestinal disorders, predominantly diarrhea, nausea, abdominal pain, and vomiting were reported frequently in the Phase III trial (see Table 1). These events began to develop primarily during the first month of treatment with SIGNIFOR and required no intervention.

Hyperglycemia And Diabetes

Hyperglycemia-related terms were reported frequently in the Phase III trial. For all patients, these terms included: hyperglycemia (40%), diabetes mellitus (18%), increased HbA1c (11%), type 2 diabetes mellitus (9%). In general, increases in FPG and HbA1c were seen soon after initiation of SIGNIFOR and were sustained during the treatment period. In the SIGNIFOR 0.6 mg group, mean FPG levels increased from 98.6 mg/dL at baseline to 125.1 mg/dL at Month 6. In the SIGNIFOR 0.9 mg group, mean fasting FPG levels increased from 97.0 mg/dL at baseline to 128.0 mg/dL at Month 6. In the SIGNIFOR 0.6 mg group, HbA1c increased from 5.8% at baseline to 7.2% at Month 6. In the SIGNIFOR 0.9 mg group, HbA1c increased from 5.8% at baseline to 7.3% at Month 6 [see WARNINGS AND PRECAUTIONS].

At one-month follow-up visits, following discontinuation of SIGNIFOR, mean FPG and HbA1c levels decreased but remained above baseline values. Long-term follow-up data are not available.

Elevated Liver Tests

In the Phase III trial, there were transient mean elevations in aminotransferase values in patients treated with SIGNIFOR. Mean values returned to baseline levels by Month 4 of treatment. The elevations were not associated with clinical symptoms of hepatic disease.

In the clinical development program of SIGNIFOR, there were 4 patients with concurrent elevations in ALT greater than 3 x ULN and bilirubin greater than 2 x ULN: one patient with Cushing's disease and 3 healthy volunteers [see WARNINGS AND PRECAUTIONS]. In all 4 cases, the elevations were noted within the first 10 days of treatment. In all of these cases, total bilirubin elevations were seen either concomitantly or preceding the transaminase elevation. The patient with Cushing's disease developed jaundice. All 4 cases had resolution of the laboratory abnormalities with discontinuation of SIGNIFOR.

Hypocortisolism

Cases of hypocortisolism were reported in the Phase III study in Cushing's disease patients [see ADVERSE REACTIONS, Clinical Studies]. The majority of cases were manageable by reducing the dose of SIGNIFOR and/or adding low-dose, short-term glucocorticoid therapy [see WARNINGS AND PRECAUTIONS].

Injection-Site Reactions

Injection-site reactions were reported in 17% of patients enrolled in the Phase III trial in Cushing's disease. The events were most frequently reported as local pain, erythema, hematoma, hemorrhage, and pruritus. These events resolved spontaneously and required no intervention.

Thyroid Function

Hypothyroidism, with the use of SIGNIFOR, was reported for seven patients participating in the Phase III study in Cushing's disease. All seven patients presented with a TSH close to or below the lower limit at study entry, which precludes establishing a conclusive relationship between the adverse event and the use of SIGNIFOR.

Other Abnormal Laboratory Findings

Asymptomatic and reversible elevations in lipase and amylase were observed in patients receiving SIGNIFOR in clinical studies. Pancreatitis is a potential adverse reaction associated with the use of somatostatin analogs due to the association between cholelithiasis and acute pancreatitis.

For hemoglobin levels, mean decreases that remained within normal range were observed. Also, post-baseline elevations in prothrombin time (PT) and partial thromboplastin time (PTT) were noted in 33% and 47% of patients, respectively. The PT and PTT elevations were minimal.

These laboratory findings are of unclear clinical significance.

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of SIGNIFOR. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Cholelithiasis resulting in complications, including cholecystitis and cholangitis, which have sometimes required cholecystectomy

Read the entire FDA prescribing information for Signifor (Pasireotide Diaspartate for Injection)

© Signifor Patient Information is supplied by Cerner Multum, Inc. and Signifor Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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