Schedule H

Subcutaneous (SC), Intramuscular (IM – long-acting release)

Solution for injection (prefilled syringe) 0.3 mg/mL SC

Solution for injection (prefilled syringe) 0.6 mg/mL SC

Solution for injection (prefilled syringe) 0.9 mg/mL SC

Powder for suspension (LAR vial) 20 mg IM

Powder for suspension (LAR vial) 40 mg IM

Powder for suspension (LAR vial) 60 mg IM

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Cushing's Disease

(Adults — when pituitary surgery has failed or is not an option)

Parameter Recommendation

Starting dose 0.6 mg SC twice daily

Titration May increase to 0.9 mg SC twice daily after 2 months if urinary free cortisol (UFC) not normalised and drug is tolerated

Usual maintenance dose 0.3–0.9 mg SC twice daily

Maximum dose 0.9 mg SC twice daily

Clinical Notes:

• Reassess therapeutic benefit at 2–4 months; discontinue if no biochemical improvement

• Monitor for hyperglycaemia closely during initiation

• Adjust timing of doses to morning and evening, approximately 12 hours apart

1. Acromegaly

(Adults — when inadequate response to surgery and/or other somatostatin analogues such as octreotide/lanreotide)

Parameter Recommendation

Starting dose 40 mg IM (LAR) once every 28 days

Titration Assess GH/IGF-1 at 3 months; adjust to 60 mg (if inadequate control) or reduce to 20 mg (if well-controlled or adverse effects)

Usual maintenance dose 20–60 mg IM every 4 weeks

Maximum dose 60 mg IM every 4 weeks

Clinical Notes:

• Evaluate biochemical and clinical response at 3 months

• Discontinue if no meaningful GH/IGF-1 reduction or symptom improvement

• LAR formulation preferred for long-term therapy due to improved adherence

Secondary Indications — Adults Only (Off-label, if any)

Not applicable.

No documented off-label indications established in Indian sources.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable.

• Not approved for use in patients below 18 years of age

• Safety and efficacy not established in paediatric population

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

Safety Statement:

• Not recommended below 18 years except under specialist endocrine supervision in clinical trial or compassionate use setting

• No paediatric formulations available in India

Mild impairment 60–89 No dose adjustment required

Moderate impairment 30–59 No dose adjustment required

Severe impairment <30 Use with caution; limited data; increased monitoring recommended

Dialysis (Haemodialysis/Peritoneal) — No data available; avoid or use under specialist supervision only

• Known hypersensitivity to pasireotide or any excipient in formulation

• Severe uncontrolled hyperglycaemia or diabetic ketoacidosis (until stabilised)

• Pre-existing diabetes mellitus or impaired glucose tolerance — high risk of worsening hyperglycaemia

• Cardiac conduction abnormalities — risk of bradycardia and QT interval prolongation

• History of cholelithiasis or gallbladder sludge — increased risk of gallstone formation

• Hepatic impairment — requires dose modification and LFT monitoring

• Pituitary macroadenoma — monitor for tumour expansion and visual field defects

• Hypokalaemia or hypomagnesaemia — correct electrolyte abnormalities before initiation

• Concurrent use with drugs causing bradycardia or QT prolongation

Parameter Recommendation

Risk category Not recommended; limited human data; animal studies indicate fetal risk

Preferred alternatives Octreotide is preferred if somatostatin analogue therapy required during pregnancy

When to use Only if potential benefit clearly outweighs risk; specialist input mandatory

Monitoring Maternal blood glucose, fetal growth (serial ultrasound), signs of adrenal insufficiency

Parameter Recommendation

Compatibility Not recommended; excretion in human milk unknown but expected (peptide-based)

Preferred alternatives Octreotide preferred if somatostatin analogue required during breastfeeding

Drug levels in milk Unknown; likely low to moderate

Infant monitoring Feeding difficulties, hypoglycaemia, poor weight gain, gastrointestinal disturbances

Parameter Recommendation

Starting dose Lower end of dosing range (0.3 mg SC twice daily for Cushing's; 20 mg IM for acromegaly)

Titration Slower, more cautious titration recommended

Special risks Increased susceptibility to bradycardia, hyperglycaemia, electrolyte imbalances; reduced renal reserve

Monitoring More frequent ECG, fasting glucose, renal function, and electrolyte monitoring

Interacting Drug/Class Effect Management

QT-prolonging agents (amiodarone, fluoroquinolones, haloperidol, ondansetron, methadone) Additive QT prolongation risk; potential for torsades de pointes Avoid combination or ensure baseline and periodic ECG monitoring

Antidiabetic agents (insulin, sulfonylureas, metformin) Pasireotide induces hyperglycaemia; may reduce efficacy of antidiabetics Increase antidiabetic dose as needed; intensify glucose monitoring

Cyclosporine Pasireotide may decrease cyclosporine absorption and bioavailability Monitor cyclosporine trough levels; adjust dose accordingly

Beta-blockers, non-dihydropyridine CCBs (verapamil, diltiazem) Additive bradycardia; risk of symptomatic heart rate reduction Monitor heart rate closely; consider alternative antihypertensives

Interacting Drug/Class Effect Management

CYP3A4 substrates (simvastatin, atorvastatin, midazolam) Pasireotide mildly inhibits CYP3A4; may increase substrate exposure Monitor for toxicity of co-administered CYP3A4 substrates

Diuretics (thiazides, loop diuretics) Enhanced risk of electrolyte disturbances (hypokalaemia, hypomagnesaemia) Correct electrolytes before initiation; monitor periodically

Bromocriptine, cabergoline May be used concurrently in pituitary disorders; additive hormonal suppression possible Monitor for efficacy and adverse effects

Proton pump inhibitors No direct interaction; may mask GI side effects Clinical awareness only

• Hyperglycaemia (up to 70% incidence)

• Diarrhoea

• Nausea

• Abdominal pain

• Cholelithiasis / biliary sludge

• Headache

• Fatigue

• Injection site reactions (pain, erythema, pruritus)

• Alopecia

Adverse Effect Action

New-onset diabetes mellitus or diabetic ketoacidosis Discontinue or reduce dose; initiate/intensify antidiabetic therapy

QT prolongation / torsades de pointes Discontinue immediately; obtain ECG; correct electrolytes

Severe bradycardia (symptomatic) Discontinue; cardiology consultation

Acute cholecystitis Discontinue; surgical evaluation

Hepatotoxicity (elevated ALT/AST >3× ULN) Hold therapy; monitor LFTs; consider permanent discontinuation

Hypocortisolism (in Cushing's disease treatment) Reduce dose; glucocorticoid replacement if symptomatic

Phase Parameters

Baseline Fasting plasma glucose, HbA1c; ECG (QTc interval); LFTs (ALT, AST, bilirubin); renal function (creatinine, eGFR); serum electrolytes (K⁺, Mg²⁺); gallbladder ultrasound (if risk factors); GH/IGF-1 (acromegaly); UFC/serum cortisol (Cushing's)

After initiation / dose change Blood glucose: weekly for first 2–3 months; ECG: within 1 week in high-risk patients; hormonal markers: every 1–3 months initially

Long-term HbA1c: every 3 months; LFTs: every 6 months; gallbladder ultrasound: annually; GH/IGF-1 or UFC: as clinically indicated; periodic ECG if on QT-prolonging co-medications

Brand Name Manufacturer Formulation

Signifor Novartis SC solution (0.3, 0.6, 0.9 mg/mL)

Signifor LAR Novartis IM powder for suspension (20, 40, 60 mg)

Notes:

• Not included in NLEM (National List of Essential Medicines)

• Not under NPPA price control

• Available in private sector only; not in government supply

1. Hyperglycaemia is frequent and often severe — anticipate need for insulin initiation or intensification; involve endocrinology early for glucose management

1. Pasireotide binds sst5 with higher affinity than octreotide/lanreotide, making it more effective in Cushing's disease and octreotide-resistant acromegaly

1. LAR formulation improves adherence — preferred for long-term acromegaly management once response confirmed with SC formulation

1. Avoid in poorly controlled diabetics unless no alternative exists; if used, mandate intensive glucose monitoring

1. Assess response at 2–4 months — discontinue promptly if no biochemical improvement to minimise unnecessary metabolic and cardiac risks

1. Gallbladder imaging recommended at baseline if patient has risk factors (obesity, rapid weight loss, family history)

pasireotide; Cushing's disease; acromegaly; somatostatin analogue; pituitary tumour; hyperglycaemia risk; QT prolongation; Schedule H; specialist only; endocrinology

RxIndia v0.2 — 10 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia / National Formulary of India (IP/NFI)

• NLEM 2022 (for exclusion note)

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine, 21st Edition

• AIIMS Endocrine Drug Protocols

• Indian Endocrine Society Clinical Practice Recommendations

• Product Insert: Signifor® / Signifor LAR® (Novartis India)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics