Adult: In patients with whom surgery is not an option or has not been curative: As pasireotide pamoate or pasireotide embonate: Initially, 40 mg every 4 weeks, may increase to max 60 mg every 4 weeks after 3 months, if necessary. Dose titration, reduction, interruption or discontinuation may be required according to individual response, safety and tolerability.
Intramuscular Cushing's disease
Adult: In patients with whom surgery is not an option or has not been curative: As pasireotide pamoate: Initially, 10 mg every 4 weeks, titrate every 2-4 months up to max: 40 mg every 4 weeks. Dose titration, reduction, interruption or discontinuation may be required according to individual response, safety and tolerability.
Subcutaneous Cushing's disease
Adult: In patients with unsuccessful surgery or unsuitable for surgery: As pasireotide diaspartate: Initially, 0.6 mg bid, may increase to 0.9 mg bid. Dose titration, reduction, or discontinuation may be required according to individual response and tolerability.
Hepatic Impairment
IM: Acromegaly: Moderate (Child-Pugh B): Initially, 20 mg every 4 weeks. Max: 40 mg every 4 weeks. Severe (Child-Pugh C): Contraindicated. Cushing's disease: Moderate (Child-Pugh B): Initially, 10 mg every 4 weeks. Max: 20 mg every 4 weeks. Severe (Child-Pugh C): Contraindicated.
IM: Add 2 mL diluent to a vial labelled as containing 20, 40, 60 mg to provide a solution containing 10, 20, 30 mg/mL respectively. Shake moderately for a minimum of 30 seconds until the powder is completely suspended.
Contraindications
Severe hepatic impairment (Child-Pugh C).
Special Precautions
Patient with diabetes mellitus, pre-existing cardiac disease, risk factors for bradycardia and QT prolongation (e.g. high-grade heart block, acute MI, CHF, congenital long QT, heart failure, unstable angina). Mild to moderate hepatic and severe renal impairment or ESRD. Pregnancy and lactation.
Adverse Reactions
Significant: Bradycardia, QT prolongation, cholelithiasis, hyper/hypoglycaemia, diabetes mellitus, hypocortisolism, hypothyroidism, elevated liver enzyme. Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Atrioventricular block. Gastrointestinal disorders: Diarrhoea, nausea, constipation, vomiting, abdominal pain, abdominal distention. General disorders and administration site conditions: Fatigue, weakness, injection site reactions (e.g. pain, erythema, haematoma, haemorrhage, pruritus). Infections and infestations: Influenza. Investigations: Increased gamma-glutamyl transferase, increased serum lipase and amylase, prolonged prothrombin time, elevated glycosylated Hb, increased creatinine phosphokinase, weight loss. Metabolism and nutrition disorders: Peripheral oedema, decreased appetite, hypercholesterolaemia, hypokalaemia, adrenal insufficiency, impaired glucose tolerance. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, back pain, limb pain. Nervous system disorders: Headache, dizziness, vertigo. Psychiatric disorders: Anxiety, insomnia. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, upper respiratory tract infection, cough. Skin and subcutaneous tissue disorders: Alopecia, pruritus, xeroderma. Vascular disorders: Hypo/hypertension.
This drug may cause fatigue, dizziness or headache, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor glycaemic status (e.g. fasting plasma glucose, HbA1c) prior to initiation and after discontinuation of therapy. Monitor plasma glucose weekly for 3 months during therapy; ECG, serum K and Mg levels, thyroid, gonadal and adrenal function at baseline and periodically during therapy; LFT prior to initiation, then monthly for 3 months, and periodically thereafter; gallbladder ultrasound at baseline and every 6-12 months during therapy. Monitor for signs and symptoms of cholelithiasis; pituitary functions, adrenal insufficiency, cardiac events during therapy.
Drug Interactions
Increased risk of bradycardia with beta blockers (e.g. metoprolol); Ca channel blockers (e.g. verapamil); acetylcholinesterase inhibitors (e.g. physostigmine). May increase the risk QT prolongation with anti-arrhythmics (e.g. quinidine, amiodarone); antibacterials (e.g. clarithromycin, moxifloxacin); antipsychotics (e.g. chlorpromazine, haloperidol); antihistamines (e.g. terfenadine, astemizole); antimalarials (e.g. chloroquine, lumefantrine); antifungals (e.g. ketoconazole). May diminish therapeutic effects of ciclosporin. May increase serum concentration with bromocriptine.
Action
Description: Mechanism of Action: Pasireotide is a cyclohexapeptide somatostatin analogue. It binds to somatostatin receptors thereby inhibiting ACTH secretion. This results in decreased circulating levels of cortisol, corticotropin and growth hormone. Pharmacokinetics: Absorption: Rapidly absorbed. Time to peak plasma concentration: Within 15-30 minutes. Distribution: Mostly distributed in the plasma. Volume of distribution: >100 L. Plasma protein binding: Approx 88%. Excretion: Mainly via faeces (approx 40-56%, as unchanged drug); urine (approx 6-10%, as unchanged drug). Elimination half-life: Approx 12 hours.
Chemical Structure
Pasireotide Source: National Center for Biotechnology Information. PubChem Database. Pasireotide, CID=9941444, https://pubchem.ncbi.nlm.nih.gov/compound/Pasireotide (accessed on Jan. 22, 2020)
Storage
Powder for inj: Store between 2-8°C. Do not freeze. Solution for inj: Store at 25°C. Protect from light.
H01CB05 - pasireotide ; Belongs to the class of antigrowth hormone. Used in hypothalamic hormone preparations.
References
Anon. Pasireotide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 27/03/2018 .Anon. Pasireotide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/03/2018.Buckingham R (ed). Pasireotide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/04/2018.Signifor Injection (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/03/2018.Signifor LAR for Injectable Suspension (Novartis Pharmaceuticals Corportation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/03/2018.
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