Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - apealea

Document Subject

Generated Narrative: MedicinalProductDefinition mp16b17145743fb4005511a462dcbf7da1

identifier: http://ema.europa.eu/identifier/EU/1/18/1292/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Apealea 60 mg powder for solution for infusion

type: Full name

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part: nan

type: Invented name part

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part: nan

type: Scientific name part

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type: Strength part

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type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-16b17145743fb4005511a462dcbf7da1

identifier: http://ema.europa.eu/identifier/EU/1/18/1292/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - apealea

Attesters

What is in this leaflet

1. What Apealea is and what it is used for
2. What you need to know before you are given Apealea
3. How Apealea is given
4. Possible side effects
5. How to store Apealea
6. Contents of the pack and other information

Apealea is a cancer medicine containing the active substance paclitaxel, which belongs to a group of medicines called taxanes. Paclitaxel affects or stops growth of rapidly dividing cells, such as tumour cells.

Apealea is used to treat the following cancers in adults, in combination with another medicine called carboplatin:

• epithelial ovarian cancer a cancer of the ovary, the organ that produces a woman s egg cells
• primary peritoneal cancer a cancer of the cells lining the space between the wall of the belly and the internal organs
• cancer of the fallopian tubes (the connection between the ovaries and the womb) It is used when other therapies have not worked.

Do not use Apealea if you:

• are allergic to paclitaxel or any of the other ingredients of this medicine (listed in section 6)
• are breast-feeding
• have a count of white blood cells called neutrophils below 1.5 109/L before start of the therapy

Talk to your doctor or nurse, if you are not sure if any of the above applies to you.

Warnings and precautions

Talk to your doctor or nurse before you are given Apealea if you have:

• reduced liver, kidney or heart function Apealea is not recommended for patients with severely reduced liver or kidney function.
• previously had nausea, vomiting and diarrhoea during cancer treatment Contact your doctor immediately, if during treatment you develop:
• fever, pain, chills, weakness or other signs of infection
• severe nausea, vomiting or diarrhoea
• severe reactions at the site of infusion
• an allergic reaction
• numbness, tingling, pricking sensation, sensitivity to touch or muscle weakness You may need additional medicines if you develop any of these symptoms. Your doctor may wish to delay further treatment with Apealea or reduce the dose.

Ask your doctor or nurse about hair loss and what can be done to avoid it.

You will be observed closely during treatment:

• regular blood tests to ensure it is safe for you to continue treatment
• symptoms of allergic reaction during the infusion, such as: reddening and swelling at the site of infusion low blood pressure breathing difficulties puffing of the face

Children and adolescents

Apealea is not recommended for children and adolescents under 18 years, because it has not been studied in this age group.

Other medicines and Apealea

Tell your doctor if you are using, have recently used or might use any other medicines.

In particular, tell your doctor or nurse before you are given Apealea if you are using:

• ketoconazole, or other medicines to treat fungal infections
• erythromycin, rifampicin: medicines to treat bacterial infections
• fluoxetine: a medicine to treat depression
• gemfibrozil: a medicine to lower blood fats
• clopidogrel: a medicine that reduces the chances of getting blood clots
• cimetidine: a medicine to reduce stomach acid
• efavirenz, nevirapine, ritonavir, saquinavir, indinavir, nelfinavir: medicines to treat HIV infection
• carbamazepine, phenytoin: medicines to treat epilepsy and certain pain conditions
• cisplatin: a medicine to treat cancer

Pregnancy and breast-feeding

Tell your doctor before treatment if you are pregnant, think you may be pregnant or are breast-feeding.

Apealea is not recommended during pregnancy, as paclitaxel may cause serious birth defects. Patients who can become pregnant should use effective contraception during treatment with Apealea and for six months afterwards.

Stop breast-feeding while being treated, as paclitaxel passes into breast milk and may harm the child.

Driving and using machines

Apealea may cause side effects such as tiredness or dizziness that may reduce your ability to drive or use machines. Do not drive or use machines if you have these symptoms.

Apealea contains sodium

After reconstitution, this medicine contains approximately up to 1.6 g sodium (component of cooking salt) per dose. This is equivalent to 80% of the recommended maximum daily dietary intake of sodium for an adult.

Apealea is given to you by a doctor or nurse by a slow drip (infusion) into a vein. This will take about one hour. The dose is based on your body surface area (worked out from your height and weight) and blood test results. The usual dose is 250 mg/m2 body surface area given every three weeks for up to six treatments.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if you have any of the following:

• Very common (may affect more than 1 in 10 people): nerve disorder in arms and legs which causes tingling, numbness or burning pain, which can persist beyond 6 months of paclitaxel discontinuation.
• Common (may affect up to 1 in 10 people):

fever muscle weakness, cramps or spasms allergic reactions, such as breathing difficulties, fainting, swelling of the face, itching, feeling hot, chills, particularly during your infusion. Uncommonly these can lead to severe allergic shock.

Other side effects and their frequencies include: Very common (may affect more than 1 in 10 people):

• low level of white blood cells called neutrophils
• lack of appetite
• diarrhoea, nausea, vomiting
• hair loss
• joint or muscle pain or discomfort
• weakness, tiredness
• reactions at the infusion site such as pain, inflammation, discolouration, redness, swelling, tingling, rash, bleeding

Common (may affect up to 1 in 10 people):

• low level of white blood cells called leukocytes and granulocytes
• low level of blood platelets or red blood cells
• reduced sense of touch or sensation
• abnormal sensation such as tingling, burning, pricking or numbness of the skin or in the mouth
• dizziness or feeling of spinning
• taste disturbance
• headache
• rapid heartbeat
• chest pain or discomfort
• low blood pressure, flushing, vein inflammation, vein pain, increased blood flow to some parts of the body
• breathing difficulties, nasal congestion
• abdominal pain, constipation, wind
• dry mouth, inflammation of the inner lining of the mouth
• skin reddening, rash, itching, nettle-rash
• pain for instance in arms, legs, breast or at site of tumour
• back pain, bone pain
• swelling of ankles, feet, face or fingers

Uncommon (may affect up to 1 in 100 people):

• blood poisoning
• pus in body tissue
• lung inflammation, influenza, tonsil inflammation
• herpes simplex (a viral infection), viral airways infections
• urinary tract infection, inflammation of the bladder
• skin infections, including infections at the infusion site
• disturbed blood clotting mechanisms in the body
• lack of white and red blood cells, and blood platelets
• low blood levels of potassium, magnesium or sodium
• excessive water loss (dehydration)
• allergic reactions to other medicines, such as penicillin
• depression, sleeplessness, anxiety
• epileptic fit lasting longer than five minutes or more than one fit within five minutes
• coma, feeling very sleepy, drowsy and/or being deeply unresponsive
• low muscle tone, facial palsy
• toxicity to the nervous system
• cognitive disorder (difficulty thinking or processing thoughts, difficulty remembering)
• brain damage, abnormal fluid accumulation within the brain
• stroke
• blurred vision, eye discomfort or irritation, watery eyes
• deafness, inner ear disorder, ringing in the ears
• blood vessel disorders, such as:

formation of blood clots

blood vessel inflammation

build-up of water in tissue because of blocked lymph vessel

hot flushes

bleeding

• cardiac arrest, heart failure
• blue tinged lips or skin
• a heart rhythm disorder causing irregular rapid activity in the upper heart chambers
• feeling your heartbeat (palpitations), slow heartbeat
• blood circulation failure
• high blood pressure, blood pressure changes, paleness
• lung failure, narrowing of airways
• severe lack of oxygen, arising from abnormal breathing
• difficulty producing voice sounds
• nosebleed, allergic inflammation inside the nose, runny nose
• cough
• mouth and throat pain or discomfort, throat disorder, bleeding gums
• inflammation of the stomach lining, abdominal discomfort or bloating, lower abdominal pain
• indigestion, disorder of bowel function, very hard stools, bloody stool
• liver inflammation or disorder, raised liver enzyme in your blood
• painful severe swelling of deep skin layers, mainly in the face
• skin discolouration, pigmentation disorder
• skin inflammation with blisters
• increased sweating, cold sweat
• dry skin, nail disorder
• bleeding into a joint
• sensation of heaviness in the legs
• multi-organ failure which can lead to death
• tissue swelling caused by excess fluid
• hernia
• feeling hot
• low body temperature
• vaginal bleeding
• abnormally high levels of nitrogen-containing compounds in the blood

Frequency not known (cannot be estimated from the available data):

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to peel

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. The expiry date refers to the last day of that month.

Unopened vial: Store in a refrigerator (2 C 8 C). Keep the vial in the outer carton in order to protect from light.

Once opened, Apealea is recommended to be used immediately.

Any unused medicine or waste material should be disposed of in accordance with local requirements. Do not throw away any medicines via wastewater or household waste. These measures will help protect the environment.

What Apealea contains

• The active substance is paclitaxel. One vial contains 60 mg of paclitaxel. After preparation, each millilitre of solution contains 1 mg of paclitaxel (micellar).
• The other ingredients are:

N-(all-trans-retinoyl)-L-cysteic acid methyl ester sodium salt

N-(13-cis-retinoyl)-L-cysteic acid methyl ester sodium salt

sodium hydroxide (for pH adjustment)

See section 2 Apealea contains sodium .

What Apealea looks like and contents of the pack

Apealea is supplied as a greenish-yellow to yellow powder in a glass vial with a rubber stopper and aluminium seal.

Each carton contains 1 glass vial with powder equivalent to 60 mg of paclitaxel.

Marketing Authorisation Holder and Manufacturer Inceptua AB Gustavslundsv. 16751 Bromma Sweden

For any information about this medicine, please contact the Marketing Authorisation Holder.

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

Administration precautions Paclitaxel is an antineoplastic medicinal product and as with other potentially toxic compounds, caution should be exercised in handling Apealea. The use of gloves, goggles and protective clothing is recommended. If the solution contacts the skin, the skin should be washed immediately and thoroughly with soap and water. If it contacts mucous membranes, the membranes should be flushed thoroughly with water. Apealea should only be prepared and administered by personnel appropriately trained in the handling of cytotoxic agents. Pregnant and breast-feeding staff should not handle Apealea. The reconstituted product should not be diluted.

Reconstitution of the medicinal product Apealea is supplied as a sterile powder for reconstitution before use. After reconstitution, the solution contains 1 mg/mL of paclitaxel formulated as micellar nanoparticles. The reconstituted solution for infusion is a clear, greenish-yellow solution.

Protect from direct and/or bright light throughout the preparation process. The (reconstituted) product can only withstand short-term handling in absence of light protection.

Only reconstitute Apealea using one of the following commercially available solutions for reconstitution:

• sodium chloride 9 mg/mL (0.9%) solution suitable for infusion;
• lactated Ringer s solution suitable for infusion;
• acetated Ringer s solution suitable for infusion.

The pH of lactated or acetated Ringer s solution must be in the range of 5.0 to 7.5 and acceptable ion concentrations of calcium and magnesium are listed below (Table 1).

Table 1. Acceptable ion concentrations for calcium and magnesium in lactated and acetated Ringer s solutions suitable for reconstitution Ion Range (mmol/L) Ca2+ 1.0 3.5* Mg2+ 0.0 2.5*

• Solutions containing both Ca2+ and Mg2+ should have a total (combined) concentration of Ca2+ and Mg2+ within the range of 1.0 to 3.5 mmol/L.

Apealea should be reconstituted using either one of the three suitable solutions for reconstitution and according to the following steps:

1. Take the desired number of vials from the refrigerator. The powder should be greenish-yellow to yellow. In case of discolouration (orange), discard the vial. To reach room temperature, let the vials stand protected from light for approximately 15 to 20 minutes not above 25 C.
2. Due to negative pressure in the vial, pressure must be equilibrated by a needle before and during injection of the solution for reconstitution. Using a sterile syringe, inject 60 mL of solution for reconstitution per vial. The solution should be injected during approximately one minute towards the inner wall of the vial and not directly onto the powder as this will result in foaming.
3. Swirl the vial in an upright position for approximately for 20 seconds. To keep the generation of foam to a minimum, do not shake the vial.
4. Protect from light and allow the vial to stand for three to five minutes.
5. Swirl the vial again in upright position for approximately 20 seconds, then gently invert it five times. Do not shake.
6. Continue to swirl the vial until the powder is completely dissolved. Alternatively, the vial may be placed on a shaker and rotated for up to 20 minutes, while being protected from light (orbital shake pattern; 200 250 rpm). Steps 3 to 6 should not be more than 30 minutes.
7. The solution should be clear and greenish-yellow without visible particles or precipitates. If particles, precipitates, discolouration (orange) or opalescence are observed, the solution should be discarded.
8. Inject the required amount of reconstituted Apealea into an empty, sterile ethylene-vinyl acetate (EVA) bag. Ensure that the solution is clear and place a light protective-bag over the EVA infusion bag.

Shelf life after reconstitution Chemical and physical in-use stability has been demonstrated for 24 hours at 2 C to 8 C in lactated and acetated Ringer s solution and for 4 hours at 2 C to 8 C in sodium chloride 9 mg/mL (0.9%) solution when protected from light. From a microbiological point of view, unless the method of opening and reconstituting precludes the risks of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Intravenous administration
Compatibility with administration sets made of DEHP-free PVC (i.e. polyvinyl chloride without the plasticizer di-(2-ethylhexyl) phthalate) has been demonstrated. However, compatibility with DEHP-containing administration sets has not been demonstrated. Administration sets containing a 15 m polyamide fluid filter should be used. It is important to flush the infusion set and catheter/cannula before and after the administration using the solution for reconstitution in order to avoid accidental administration into the surrounding tissue and to ensure administration of the complete dose.

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.