Vandetanib

Oral
Metastatic medullary thyroid carcinoma, Unresectable locally advanced medullary thyroid carcinoma

CrCl (mL/min)	Dosage
<30	Not recommended.
30-49	200 mg once daily.

Not recommended.

May be taken with or without food. Swallow whole, do not chew/crush. For patients w/ difficulty swallowing, disperse tab in ½ glass plain, non-carbonated water & stir for approx 10 min. No other liqd should be used. Swallow immediately after dispersion. Mix remaining residue w/ ½ glass water & swallow. Liqd dispersion may also be administered through nasogastric or gastrotomy tubes.

Patient with QTc interval over 480 milliseconds, congenital long QTc syndrome. Concomitant use with drugs prolonging QTc interval. Pregnancy and lactation.

Patient with brain metastases, history of torsades de pointes, haemoptysis. Hepatic and renal impairment.

Significant: Diarrhoea, hypothyroidism, hypertension, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), rash, photosensitivity reactions, palmar-plantar erythrodysaesthesia, elevated ALT.
Eye disorders: Corneal abnormalities, blurred vision, halo vision, photopsia, glaucoma, conjunctivitis, dry eye, keratopathy.
Gastrointestinal disorders: Colitis, nausea, abdominal pain, vomiting, dyspepsia, dry mouth.
General disorders and admin site conditions: Fatigue, pyrexia, asthenia, pain, oedema.
Hepatobiliary disorders: Cholelithiasis.
Infections and infestations: Sepsis, influenza, furuncle, fungal infection.
Metabolism and nutrition disorders: Decreased appetite, hyperglycaemia, hypocalcaemia, hypokalaemia, dehydration, hyponatremia.
Musculoskeletal and connective tissue disorders: Muscle spasm.
Nervous system disorders: Headache, dysgeusia, paraesthesia, dysaesthesia, dizziness, tremor, lethargy, loss of consciousness, balance disorder.
Psychiatric disorders: Depression, insomnia, anxiety.
Renal and urinary disorders: Proteinuria, UTI, nephrolithiasis, dysuria, haematuria, cystitis, pyelonephritis.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, nasopharyngitis, bronchitis, pneumonia, sinusitis, laryngitis, epistaxis, haemoptysis.
Skin and subcutaneous tissue disorders: Dermatitis acneiform, acne, dry skin, photosensitivity reactions, pruritus, alopecia, nail abnormalities, folliculitis.
Potentially Fatal: Torsades de pointes, QT prolongation, ventricular tachycardia, heart failure, severe skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome), interstitial lung disease, pneumonitis, ischaemic cerebrovascular events, severe haemorrhage.

PO: D

This drug may cause fatigue and blurred vision, if affected, do not drive or operate machinery. Limit exposure to sunlight.

Monitor serum electrolytes (e.g. Ca, Mg, K), TSH, and ECG (QT interval) at baseline, at 2-4 weeks, at 8-12 weeks, and every 3 months thereafter. Monitor renal and hepatic function, blood pressure. Assess for signs and symptoms of heart failure, RPLS, pulmonary and skin toxicities.

Decreased plasma concentration with potent CYP3A4 inducers (e.g. dexamethasone, carbamazepine, phenytoin, phenytoin, phenobarbital, rifabutin, rifampicin). Increased plasma concentration of metformin, digoxin.
Potentially Fatal: Increased risk of torsades de pointes with antiarrhythmic drugs (e.g. amiodarone, disopyramide, dofetilide, procainamide, sotalol) and other drugs prolonging QTc interval (e.g. mizolastine, moxifloxacin, cisapride, arsenic, erythromycin IV, toremifene).

May decrease serum concentration with St John’s wort.

Description: Vandetanib is a tyrosine kinase inhibitor that blocks intracellular signalling, angiogenesis and cellular proliferation through inhibition of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), rearranged during transfection (RET) tyrosine kinase, protein tyrosine kinase 6 (BRK), TIE, EPH kinase receptor and SRC kinase receptors.
Pharmacokinetics:
Absorption: Slowly absorbed. Time to peak plasma concentration: Approx 6 hours (range: 4-10 hours).
Distribution: Volume of distribution: Approx 7,450 L. Plasma protein binding: Approx 90%, mainly to albumin and α₁-acid glycoprotein.
Metabolism: Metabolised in the liver by CYP3A4 enzyme to N-desmethylvandetanib, and by flavin-containing mono-oxygenase enzymes FMO1 and FMO3 to vandetanib-N-oxide.
Excretion: Mainly via faeces (approx 44%); urine (approx 25%). Elimination half-life: Approx 19 days.

Source: National Center for Biotechnology Information. PubChem Database. Vandetanib, CID=3081361, https://pubchem.ncbi.nlm.nih.gov/compound/Vandetanib (accessed on Jan. 23, 2020)

Store at 25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01EX04 - vandetanib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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Anon. Vandetanib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/03/2018.

Buckingham R (ed). Vandetanib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/03/2018.

Caprelsa Tablet (AstraZeneca Pharmaceuticals LP). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/03/2018.

Joint Formulary Committee. Vandetanib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/03/2018.

Preston CL (ed). Interactions of Vandetanib. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/04/2018.