Vandetanib-Promomed (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

L01EX04 (Vandetanib)

Active Substance

Vandetanib (Rec.INN registered by WHO)

Dosage Forms

	Vandetanib-Promomed	Film-coated tablets, 100 mg: 10 or 30 pcs.
		Film-coated tablets, 300 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with a white or almost white core on the cross-section.

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, crospovidone, magnesium stearate.

Coating composition: hypromellose 2910, titanium dioxide (E171), macrogol 4000 (polyethylene glycol 4000) or a ready-made film coating of identical composition.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs

.

Film-coated tablets white, oval, biconvex, with a white or almost white core on the cross-section.

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, crospovidone, magnesium stearate.

Coating composition: hypromellose 2910, titanium dioxide (E171), macrogol 4000 (polyethylene glycol 4000) or a ready-made film coating of identical composition.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Protein kinase inhibitor

Pharmacotherapeutic Group

Antineoplastic agents; protein kinase inhibitors; other protein kinase inhibitors

Pharmacological Action

Antitumor agent. It blocks the action of enzymes involved in tumor growth.

Indications

Treatment of unresectable locally advanced or metastatic medullary thyroid cancer.

ICD codes

Dosage Regimen

Take orally once daily at a dose of 300 mg.

Administer with or without food. Swallow the tablet whole with water; do not crush or chew.

For patients with severe toxicity, interrupt therapy until the adverse reaction resolves. Subsequently, resume treatment at a reduced dose.

The first dose reduction is to 200 mg once daily. The second dose reduction is to 100 mg once daily.

Discontinue permanently if unable to tolerate the 100 mg dose. Adjust dosage based on individual safety and tolerability.

Perform ECG monitoring at baseline, at 2-4 weeks and 8-12 weeks after starting treatment, and every 3 months thereafter.

Monitor serum electrolytes, including potassium, calcium, and magnesium, before starting treatment, periodically during treatment, and following dose adjustments.

Correct hypokalemia, hypocalcemia, and hypomagnesemia before administering vandetanib.

Withhold treatment for corrected QT interval (QTc) greater than 500 ms. Resume at a reduced dose only when QTc returns to less than 450 ms.

Discontinue at least 1 month before planned surgical procedures. Suspend for 2 weeks following major surgery and until adequate wound healing is achieved.

Adverse Reactions

Very common nasopharyngitis, bronchitis, upper respiratory tract infections, urinary tract infections, decreased appetite, hypocalcemia, insomnia, headache, paresthesia, dysesthesia, dizziness, increased blood pressure, diarrhea, nausea, vomiting, abdominal pain, dyspepsia, acne, dry skin, dermatitis, skin itching, photosensitivity, fatigue, asthenia, pain, edema.

Common influenza, cystitis, sinusitis, laryngitis, folliculitis, furuncle, fungal infections, pyelonephritis, hypothyroidism, hypokalemia, hypercalcemia, hyperglycemia, dehydration, hyponatremia, depression, anxiety, tremor, lethargy, loss of consciousness, balance disorder, dysgeusia, blurred vision, corneal opacity, conjunctivitis, dry eyes, visual disturbances, photopsia, rainbow halos around light sources, glaucoma, keratopathy, QT interval prolongation on ECG, epistaxis, hemoptysis, stomatitis, dry mouth, colitis, dysphagia, constipation, gastritis, cholelithiasis, palmar-plantar erythrodysesthesia, alopecia, nail disorders, proteinuria, nephrolithiasis, hematuria, dysuria, renal failure, frequent urination, urinary urgency, fever; weight loss, increased ALT and AST activity, increased blood creatinine concentration.

Uncommon bacterial staphylococcal infections, cellulitis, exhaustion, convulsions, myoclonus, cataract, accommodation disorder, heart failure, cardiac arrhythmias, respiratory failure, pancreatitis, intestinal obstruction, fecal incontinence, bullous dermatitis, chromaturia, anuria, impaired wound healing, erythema multiforme; increased hemoglobin concentration, increased plasma amylase activity.

Frequency unknown increased TSH concentration, increased lipase activity.

Contraindications

Hypersensitivity to vandetanib; impaired cardiac conduction, QT interval prolongation, concurrent use of other medicinal products that can prolong the QT_c interval, cause tachycardia, atrial fibrillation, for example, arsenic preparations, cisapride, erythromycin (IV), toremifene, mizolastine, moxifloxacin, antiarrhythmic agents; hepatic insufficiency; pregnancy, breastfeeding period; age under 18 years.

With caution

Suspected brain metastases, arterial hypertension, aneurysm (including in history), impaired renal function, planned surgical operation.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Use in Renal Impairment

Use with caution in impaired renal function.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

Treatment should be conducted under ECG monitoring.

Vandetanib should be discontinued at least 1 month before a surgical operation, and also suspended for 2 weeks after major surgery and until proper wound healing.

If a rash and other skin reactions develop during treatment, including photosensitivity, palmar-plantar erythrodysesthesia syndrome, symptomatic therapy or a dose reduction of vandetanib may be required.
If more severe skin reactions develop – Stevens-Johnson syndrome and toxic epidermal necrolysis – therapy with steroid drugs and possibly discontinuation of vandetanib therapy may be required.

During therapy, the patient should wear clothing that protects from sunlight and/or use sunscreen.

If severe diarrhea develops, treatment should be suspended, and after the condition improves, vandetanib should be resumed at a reduced dose.

During treatment, blood pressure control is required and, if necessary, therapy with antihypertensive drugs should be administered.

Heart failure may develop during vandetanib use, which can be irreversible and life-threatening. If necessary, temporary or permanent discontinuation of vandetanib therapy may be required.

If interstitial lung disease is confirmed, vandetanib should be discontinued and appropriate treatment initiated.

If renal failure develops during treatment, dose adjustment, temporary or permanent discontinuation of this agent may be required.

Effect on ability to drive vehicles and operate machinery

During therapy, increased fatigue and blurred vision may occur. If these adverse reactions occur, the patient should refrain from driving vehicles and operating machinery.

Drug Interactions

Concomitant use of vandetanib with potent inducers of the CYP3A4 isoenzyme, such as rifampicin, St. John’s wort preparations, phenobarbital, should be avoided.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.