Lamzede - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Lamzede 10 mg powder for solution for infusion velmanase alfa

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Lamzede is and what it is used for

• 2. What you need to know before Lamzede is used

• 3. How Lamzede is used

• 4. Possible side effects

• 5. How Lamzede is stored

• 6. Contents of the pack and other information

1. What Lamzede is and what it is used for

Lamzede contains the active substance velmanase alfa which belongs to a group of medicines known as enzyme replacement therapies. It is used to treat patients with mild to moderate alpha-mannosidosis disease. It is given for the treatment of non-neurological symptoms of the disease.

Alpha-mannosidosis disease is a rare genetic disorder caused by a lack of an enzyme named alpha-mannosidase, which is needed to break down certain sugar compounds (called ‘mannose-rich oligosaccharides’) in the body. When this enzyme is missing or does not work properly, these sugar compounds build up inside cells and cause the signs and symptoms of the disease. The typical manifestations of the disease include distinctive facial features, mental retardation, difficulty in controlling movements, difficulties in hearing and speaking, frequent infections, skeletal problems, muscle pain and weakness.

Velmanase alfa is designed to replace the missing enzyme in patients with alpha-mannosidosis disease. This may improve the symptoms of the disease.

2. What you need to know before Lamzede is used

Lamzede must not be used:

• – if you are allergic to velmanase alfa or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor before Lamzede is used.

If you are treated with Lamzede, you may experience a side effect during or immediately following the drip (infusion) used to give the medicine (see section 4). This is known as an infusion-related reaction and can sometimes be severe.

• – Infusion-related reactions include dizziness, headache, nausea, low blood pressure, tiredness and fever. If you experience an infusion-related reaction, you must tell your doctor immediately.

• – If you have an infusion-related reaction you may be given additional medicines to treat or help prevent future reactions. These medicines may include medicines used to treat allergies (antihistamines), medicines used to treat fever (antipyretics) and medicines to control inflammation (corticosteroids).

• – If the infusion-related reaction is severe, your doctor will stop the infusion immediately and start giving you appropriate medical treatment.

• – If the infusion-related reactions are severe and/or there is a loss of effect from this medicine, your doctor will perform a blood test to check for antibodies that might affect the outcome of your treatment.

• – Most of the time you can still be given Lamzede even if you experience an infusion-related reaction.

Other medicines and Lamzede

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before this medicine is used.

Lamzede should be used during pregnancy only when medically necessary. It is not known whether velmanase alfa passes into breast milk. Lamzede can be used during breast-feeding.

Driving and using machines

Lamzede has no or negligible influence on the ability to drive and use machines.

Lamzede contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

• 3. How Lamzede is used

This medicine is only to be used under the supervision of a doctor experienced in the treatment of alpha-mannosidosis or other similar diseases and should only be given by a healthcare professional.

Dosage

The recommended dose of Lamzede is 1 mg/kg of body weight given once every week.

Use in children and adolescents

Lamzede may be given to children and adolescents at the same dose and frequency as in adults. There is no experience with patients younger than 6 years of age.

Administration

Lamzede is supplied in a vial as a powder for infusion which will be made up with water for injections before being given.

Once it has been made up, the medicine will be given by infusion pump (drip) into a vein over a period of at least 50 minutes under your doctor’s super­vision.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects occur during the infusion or shortly after (“infusion-related reaction”, see section 2 Warnings and precautions).

While under treatment with Lamzede, you may experience some of the following reactions:

Serious side effects

Common side effects (may affect up to 1 in 10 people)

• – loss of consciousness (fainting, which may be preceded by feeling dizzy, lightheaded or confused)

• – acute renal insufficiency (kidney problems which can be recognised from fluid retention, swelling in legs, ankles or feet, drowsiness, shortness of breath or fatigue)

• – hypersensitivity and serious allergic reaction (symptoms including localised or diffuse skin itching, dizziness, difficulty breathing, chest pain, gastrointestinal symptoms such as nausea, vomiting, diarrhea or intestinal pain, swelling of the throat, face, lips or tongue)

If you experience any side effect like these, please tell your doctor immediately.

Other side effects

Very common side effects (may affect more than 1 in 10 people)

• – diarrhoea

• – weight increase

• – fever/increased body temperature

Common side effects (may affect up to 1 in 10 people)

• – low heart beat (bradycardia)

• – psychotic behaviour (mental illness with hallucinations, difficulty in thinking clearly and understanding reality, anxiety), initial difficulty in sleeping

• – confused state, fainting, tremor, dizziness, headache

• – intestinal (abdominal) pain, irritation of the stomach caused by digestive acids (reflux gastritis), nausea, vomiting

• – pain at the site the infusion is given, chills, feeling hot, malaise, tiredness (fatigue)

• – skin rashes (urticaria), increased sweating (hyperhidrosis)

• – nosebleed

• – joint pain, back pain, joint stiffness, muscle pain, pain in extremity (hands, feet)

• – eye irritation, eyelid swelling (eyelid oedema), eye redness

• – increased appetite

Reporting of side effects

If you get any side effects, talk to your doctor. 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.

• 5. How Lamzede is stored

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 label and the carton after ‘EXP’.

The expiry date refers to the last day of that month.

Store and transport refrigerated (2°C – 8°C).

Store in the original package in order to protect from light.

After reconstitution, the medicine should be used immediately. If not used immediately, the reconstituted solution may be stored up to 24 hours at 2°C to 8°C.

This medicine must not be used if the reconstituted solution contains opaque particles or is discoloured.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Lamzede contains

• – The active substance is velmanase alfa.

One vial contains 10 mg of velmanase alfa.

After reconstitution, one mL of the solution contains 2 mg of velmanase alfa (10 mg / 5 mL).

• – The other ingredients are: disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, mannitol and glycine.

What Lamzede looks like and contents of the pack

Lamzede is a white to off-white powder for solution for infusion, supplied in a glass vial.

Each carton contains 1, 5 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Chiesi Farmaceutici S.p.A.

Via Palermo 26/A

43122 Parma

Italy

Manufacturer

Chiesi Farmaceutici S.p.A.

Via San Leonardo, 96

43122 Parma

Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien Chiesi sa/nv Tél/Tel: + 32 (0)2 788 42 00 Efcnrapua Chiesi Bulgaria EOOD Ten.: + 359 29201205 Česká republika Chiesi CZ s.r.o. Tel: + 420 261221745 Danmark Chiesi Pharma AB Tlf: + 46 8 753 35 20

Lietuva Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 Luxembourg/Lu­xemburg Chiesi sa/nv Tel/Tel: + 32 (0)2 788 42 00 Magyarorszag Chiesi Hungary Kft. Tel.: + 36–1–429 1060 Malta Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791

Deutschland Chiesi GmbH Tel: + 49 40 89724–0	Nederland Chiesi Pharmaceuticals B.V. Tel: + 31 88 501 64 00
Eesti Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919	Norge Chiesi Pharma AB Tlf: + 46 8 753 35 20
EÀÀàôa Chiesi Hellas AEBE Tql: + 30 210 6179763	Österreich Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919
España Chiesi España, S.A.U. Tel: + 34 93 494 8000	Polska Chiesi Poland Sp. z.o.o. Tel.: + 48 22 620 1421
France Chiesi S.A.S. Tél: + 33 1 47688899	Portugal Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791
Hrvatska Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919	Romania Chiesi Romania S.R.L. Tel: + 40 212023642
Ireland Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791	Slovenija Chiesi Slovenija d.o.o. Tel: + 386–1–43 00 901
Ísland Chiesi Pharma AB Sími: +46 8 753 35 20	Slovenská republika Chiesi Slovakia s.r.o. Tel: + 421 259300060
Italia Chiesi Italia S.p.A. Tel: + 39 0521 2791	Suomi/Finland Chiesi Pharma AB Puh/Tel: +46 8 753 35 20
Kùnpoç Chiesi Farmaceutici S.p.A. Tql: + 39 0521 2791	Sverige Chiesi Pharma AB Tel: +46 8 753 35 20
Latvija Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919	United Kingdom Chiesi Ltd Tel: + 44 (0)161 488 5555

This leaflet was last revised in {MM/YYYY}.

This medicine has been authorised under ‘exceptional circumstances’. This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.

The European Medicines Agency will review any new information on this medicine every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:. There are also links to other websites about rare diseases and treatments. The following information is intended for healthcare professionals only.

Lamzede requires reconstitution and is intended for intravenous infusion only.

Each vial is for single use only.

Instructions for reconstitution and administration

Lamzede should be reconstituted and administrated by a healthcare professional.

Aseptic technique is to be used during preparation. Filter needles must not be used during preparation.

• a) The number of vials to be used should be calculated based on the individual patient’s weight. The recommended dose of 1 mg/kg is determined using the following calculation: – Patient’s weight (kg) x dose (mg/kg) = Patient dose (in mg)

• – Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to reconstitute. If the number of calculated vials includes a fraction, it should be rounded up to the next whole number.

• – Approximately 30 minutes prior to reconstitution, the required number of vials should be

removed from the refrigerator. The vials should reach ambient temperature (between 15°C and 25°C) prior to reconstitution.

Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the wall of each vial. Each mL of reconstituted solution contains 2 mg of velmanase alfa. Only the volume corresponding to the recommended dose should be administered.

Example:

• – Patient’s weight (44 kg) x dose (1 mg/kg) = Patient dose (44 mg)

• – 44 mg divided by 10 mg/vial = 4.4 vials, therefore, 5 vials should be reconstituted.

• – From the total reconstituted volume, only 22 mL (corresponding to 44 mg) should be administered.

• b) The powder should be reconstituted in the vial by a slow drop-wise addition of the water for injections down the inside of the vial and not directly onto the lyophilised powder. Forcefully ejecting the water for injections from the syringe onto the powder should be avoided to minimise foaming. The reconstituted vials should stand on the table for about 5–10 minutes. Thereafter each vial should be tilted and rolled gently for 15–20 seconds to enhance the dissolution process. The vial should not be inverted, swirled, or shaken.

• c) An immediate visual inspection of the solution for particulate matter and discoloration should be performed after reconstitution. The solution should be clear and not used if opaque particles are observed or if the solution is discoloured. Due to the nature of the medicinal product, the reconstituted solution may occasionally contain some proteinaceous particles in form of thin white strands or translucent fibers which will be removed by the in-line filter during infusion (see point e).

• d) The reconstituted solution is to be slowly withdrawn from each vial with caution to avoid foaming in the syringe. If the volume of the solution exceeds one syringe capacity, the required number of syringes should be prepared in order to replace the syringe quickly during the infusion.

• e) The reconstituted solution should be administered using an infusion set equipped with a pump and an in-line low protein-binding 0.22 jam filter.

The total volume of infusion is determined by the patient’s weight and should be administrated over a minimum of 50 minutes. For patients weighing less than 18 kg, and receiving less than 9 mL reconstituted solution, the infusion rate should be calculated so that the infusion time is >50 minutes. The maximum infusion rate is 25 mL/hour. The infusion time can be calculated from the following table:

Patient weight (kg)	Dose (mL)	Maximum infusion rate (mL/h)	Minimum infusion time (min)
5	2.5	3	50
6	3	3.6	50
7	3.5	4.2	50
8	4	4.8	50
9	4.5	5.4	50
10	5	6	50
11	5.5	6.6	50
12	6	7.2	50
13	6.5	7.8	50
14	7	8.4	50
15	7.5	9	50
16	8	9.6	50
17	8.5	10.2	50
18	9	10.8	50
19	9.5	11.4	50
20	10	12	50
21	10.5	12.6	50
22	11	13.2	50
23	11.5	13.8	50
24	12	14.4	50
25	12.5	15	50
26	13	15.6	50
27	13.5	16.2	50
28	14	16.8	50
29	14.5	17.4	50
30	15	18	50
31	15.5	18.6	50
32	16	19.2	50
33	16.5	19.8	50
34	17	20.4	50
35	17.5	21	50
36	18	21.6	50
37	18.5	22.2	50
38	19	22.8	50
39	19.5	23.4	50
40	20	24	50
41	20.5	24.6	50
42	21	25	50
43	21.5	25	52
44	22	25	53
45	22.5	25	54
46	23	25	55
47	23.5	25	56
48	24	25	58
49	24.5	25	59
50	25	25	60

Patient weight (kg)	Dose (mL)	Maximum infusion rate (mL/h)	Minimum infusion time (min)
53	26.5	25	64
54	27	25	65
55	27.5	25	67
56	28	25	67
57	28.5	25	68
58	29	25	70
59	29.5	25	71
60	30	25	72
61	30.5	25	73
62	31	25	74
63	31.5	25	76
64	32	25	77
65	32.5	25	78
66	33	25	79
67	33.5	25	80
68	34	25	82
69	34.5	25	83
70	35	25	84
71	35.5	25	85
72	36	25	86
73	36.5	25	88
74	37	25	89
75	37.5	25	90
76	38	25	91
77	38.5	25	92
78	39	25	94
79	39.5	25	95
80	40	25	96
81	40.5	25	97
82	41	25	98
83	41.5	25	100
84	42	25	101
85	42.5	25	102
86	43	25	103
87	43.5	25	104
88	44	25	106
89	44.5	25	107
90	45	25	108
91	45.5	25	109
92	46	25	110
93	46.5	25	112
94	47	25	113
95	47.5	25	114
96	48	25	115
97	48.5	25	116
98	49	25	118

Patient weight (kg)	Dose (mL)	Maximum infusion rate (mL/h)	Minimum infusion time (min)
51	25.5	25	61
52	26	25	62

Patient weight (kg)	Dose (mL)	Maximum infusion rate (mL/h)	Minimum infusion time (min)
99	49.5	25	119

• f) When the last syringe is empty, the dosage syringe is replaced with a 20 mL syringe filled with sodium chloride 9 mg/mL (0.9%) solution for injection. A volume of 10 mL sodium chloride solution should be administered through the infusion system to infuse the remaining fraction of Lamzede in the line to the patient.