Tobi Podhaler: detailed information

Package leaflet: Information for the user

TOBI Podhaler 28 mg inhalation powder, hard capsules

tobramycin
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What TOBI Podhaler is and what it is used for
What you need to know before you take TOBI Podhaler
How to take TOBI Podhaler
Possible side effects
How to store TOBI Podhaler
Contents of the pack and other information Instructions for use with the Podhaler device ( on the reverse )

1. What TOBI Podhaler is and what it is used for

What TOBI Podhaler is
TOBI Podhaler contains a medicine called tobramycin, which is an antibiotic. This antibiotic belongs to a class known as aminoglycosides.
What TOBI Podhaler is used for
TOBI Podhaler is used in patients aged 6 years and older with cystic fibrosis to treat a long-term infection caused by a bacterium called Pseudomonas aeruginosa.
To get the best results from this medicine, please use it as directed in this leaflet.
How TOBI Podhaler works
TOBI Podhaler is an inhalation powder contained in capsules. When you inhale TOBI Podhaler, the antibiotic can go directly into the lungs to fight the bacteria causing the infection and improve breathing.
What is Pseudomonas aeruginosa
Pseudomonas aeruginosa is a very common bacterium that infects almost all patients with cystic fibrosis at some point in their lives. Some patients do not acquire this infection until later in life, while others become infected at a very young age. This is one of the most harmful bacteria for patients with cystic fibrosis. If the infection is not kept under control, it will continue to damage the lungs, causing further breathing problems.

2. What you need to know before taking TOBI Podhaler

Do not take TOBI Podhaler

if you are allergic to tobramycin, or to any type of aminoglycoside antibiotic, or to any of the other ingredients of this medicine (listed in section 6). If this applies to you, inform your doctor and do not take TOBI Podhaler. If you think you might be allergic, consult your doctor.

Warnings and precautions
Inform your doctor if you have ever had any of the following conditions:

hearing problems (including ringing in the ears and dizziness) or if your mother experienced hearing problems after taking an aminoglycoside
certain genetic variants (changes in the gene) related to inherited hearing disorders passed down from your mother
kidney problems
unusual breathing difficulties with wheezing, coughing, or chest tightness
blood in the sputum (the substance you cough up)
persistent or worsening muscle weakness, a symptom associated with conditions such as myasthenia gravis or Parkinson’s disease. If any of the above conditions apply to you, consult your doctor before taking TOBI Podhaler.

If you are aged 65 years or older, your doctor may carry out additional monitoring to determine whether TOBI Podhaler is an appropriate treatment for you.
Inhaled medicines can cause chest tightness and wheezing, which may occur immediately after inhaling TOBI Podhaler. Your doctor will monitor you when you take the first dose of TOBI Podhaler and will check your lung function before and after taking the dose. Your doctor may ask you to use other appropriate medicines before taking TOBI Podhaler.
Inhaled medicines may cause coughing, and this can occur with TOBI Podhaler. Speak with your doctor if coughing persists or is bothersome.
Over time, strains of Pseudomonas may become resistant to treatment. This means that TOBI Podhaler may become less effective over time. Speak with your doctor if you think this may be happening.
If you are receiving tobramycin or other aminoglycoside antibiotics by injection, this may occasionally cause hearing loss, dizziness, and kidney damage.

Children
TOBI Podhaler must not be given to children under 6 years of age.

Other medicines and TOBI Podhaler
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
You must not take the following medicines while taking TOBI Podhaler:

Furosemide or ethacrynic acid, diuretics
Other medicines with diuretic properties such as urea or mannitol given by intravenous infusion
Other medicines that may damage the kidneys or hearing.

The following medicines may increase the risk of harmful effects when administered at the same time as injections of tobramycin or other aminoglycoside antibiotics:

Amphotericin B, cephalothin, polymyxin (used to treat bacterial infections), cyclosporine, tacrolimus (used to reduce the activity of the immune system). These medicines can damage the kidneys.
Platinum compounds such as carboplatin and cisplatin (used to treat certain types of cancer). These medicines can damage the kidneys or hearing.
Anticholinesterases such as neostigmine and pyridostigmine (used to treat muscle weakness), or botulinum toxin. These medicines may cause the onset or worsening of muscle weakness.
If you are taking one or more of the medicines listed above, speak with your doctor before taking TOBI Podhaler.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
It is not known whether inhaling this medicine causes adverse effects during pregnancy.
When administered by injection, tobramycin and other aminoglycoside antibiotics can cause harm to the fetus, such as deafness.
If you are breastfeeding, you must speak with your doctor before using this medicine.

Driving and using machines
TOBI Podhaler does not affect, or has negligible effect on, the ability to drive vehicles or operate machinery.

3. How to take TOBI Podhaler

Take TOBI Podhaler exactly as your doctor has instructed. If you have any doubts, consult your doctor.
Healthcare professionals should assist children at the beginning of treatment with TOBI Podhaler, particularly those aged 10 years and younger, and continue supervision until they are able to use the Podhaler device correctly without help.

How much TOBI Podhaler to take
Inhale the contents of 4 capsules twice daily (4 capsules in the morning and 4 capsules in the evening), using the Podhaler device.
The dose is the same for all patients aged 6 years and older. Do not exceed the recommended dose.

When to take TOBI Podhaler
Take the capsules at the same time each day; this will help you remember when to take them. Inhale the contents of 4 capsules twice daily as follows:

4 capsules in the morning to be inhaled using the Podhaler device.
4 capsules in the evening to be inhaled using the Podhaler device.
It is best to leave at least 12 hours between doses, but the interval must be at least 6 hours.

If you are receiving other inhaled treatments and are following additional therapies for cystic fibrosis, TOBI Podhaler should be taken last. Check with your doctor about the correct order of administration of your medications.

How to take TOBI Podhaler

For inhalation only.
Do not swallow the capsules.
Use the capsules only with the inhaler provided in this package. The capsules must remain in their blister until ready to use.
When starting a new weekly pack of capsules, use the new inhaler provided in the pack. Each inhaler must be used for only 7 days.
Please read the instructions at the end of this leaflet for further information on how to use the inhaler.

How long to take TOBI Podhaler
After taking TOBI Podhaler for 28 days, there must be a 28-day break from treatment, during which you must not inhale TOBI Podhaler. Then begin another cycle.
It is important that you continue using the product twice daily during the 28 days of treatment and that you follow the cycle of 28 days on treatment followed by 28 days off treatment.

YES TOBI Podhaler NO TOBI Podhaler
Take TOBI Podhaler Do not take TOBI
twice daily, every day Podhaler for the next
for 28 days 28 days

Repeat the cycle
Continue taking TOBI Podhaler as prescribed by your doctor.
If you have any questions about the duration of treatment with TOBI Podhaler, consult your doctor or pharmacist.

If you take more TOBI Podhaler than you should
If you inhale too much TOBI Podhaler, consult your doctor as soon as possible. If TOBI Podhaler is swallowed, do not panic, but consult your doctor as soon as possible.

If you forget to take TOBI Podhaler
If you forget to take TOBI Podhaler and there are at least 6 hours before your next dose, take the missed dose as soon as possible. Otherwise, wait until your next scheduled dose. Do not take a double dose to make up for a forgotten dose.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
People with cystic fibrosis have many symptoms of the disease. These may still occur during treatment with TOBI Podhaler, but they should not become more frequent or appear more severe than before.
If your pre-existing lung disease appears to worsen during treatment with TOBI Podhaler, contact your doctor immediately.
Some side effects can be serious

Unusual breathing difficulties with wheezing or coughing and chest tightness (common). If you experience any of these side effects, stop taking TOBI Podhaler and contact your doctor immediately.
Blood in the sputum (very common)
Hearing loss (ringing in the ears may be a warning sign of potential hearing loss), noises (such as ringing) in the ears (common)
Low urine volume, vomiting, confusion, and swelling of the legs, ankles or feet, as these may be signs of a sudden decrease in kidney function (frequency not known). If you experience any of these side effects, contact your doctor immediately.

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

Shortness of breath
Cough, productive cough, voice changes (hoarseness)
Sore throat
Fever

Common (may affect up to 1 in 10 people)

Breathlessness, crackles (rattling sounds)
Chest discomfort, chest pain of muscular or skeletal origin
Nasal congestion
Nosebleeds
Vomiting, nausea
Diarrhoea
Rash
Taste disturbances
Loss of voice

Not known (frequency cannot be estimated from the available data)

Feeling of general discomfort
Change in sputum colour (the substance you cough up)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TOBI Podhaler

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the box or capsule container.
Store in the original packaging to protect the medicine from moisture.

Once a capsule has been removed from the container (blister), it must be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What TOBI Podhaler contains

The active substance is tobramycin. Each capsule contains 28 mg of tobramycin.
The other components are DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), calcium chloride, sulfuric acid (to adjust pH).

Description of the appearance of TOBI Podhaler and contents of the pack
TOBI Podhaler inhalation powder, hard capsules, consists of a white to almost white inhalation powder contained in clear, colourless hard capsules imprinted with "MYL TPH" in blue ink on one side of the capsule and the Mylan logo in blue on the other side.
TOBI Podhaler is supplied in monthly packs containing 4 weekly boxes and one spare Podhaler device in its case.
Each weekly box contains 7 blisters (capsule containers) with 8 capsules each, and one Podhaler device in its case.
The following pack sizes are available:
56 hard capsules, inhalation powder and 1 inhaler (weekly pack)
224 (4 x 56) hard capsules, inhalation powder and 5 inhalers (multiple monthly pack)
448 (8 x 56) hard capsules, inhalation powder and 10 inhalers (2 multiple monthly packs wrapped in a film)
Not all pack sizes may be marketed.

Marketing Authorization Holder
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart
Dublin 15
DUBLIN
Ireland

Manufacturer
McDermott Laboratories Ltd T/A Mylan Dublin Respiratory
Unit 25, Baldoyle Industrial Estate
Grange Road, Baldoyle
Dublin 13, D13 N5X2
Ireland
Mylan Germany GmbH
Zweigniederlassung Bad Homburg v. d. Hoehe
Benzstrasse 1
61352 Bad Homburg v. d. Hoehe
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Viatris Viatris UAB
Tél/Tel: +32 2 658 61 00 Tel: +370 5 205 1288

България Luxembourg/Luxemburg
Майлан ЕООД Viatris
Тел.: +359 2 44 55 400 Tél/Tel: +32 2 658 61 00

Česká republika Magyarország
Viatris CZ s.r.o. Viatris Healthcare Kft.
Tel: +420 222 004 400 Tel.: +36 1 465 2100

Danmark Malta
Viatris ApS V.J. Salomone Pharma Ltd
Tlf.: +45 28 11 69 32 Tel: +356 21 22 01 74

Deutschland Nederland
Viatris Healthcare GmbH Mylan Healthcare B.V.
Tel: +49 800 0700 800 Tel: +31 20 426 3300

Eesti Norge
Viatris OÜ Viatris AS
Tel: +372 6363 052 Tlf: +47 66 75 33 00

Ελλάδα Österreich
Viatris Hellas Ltd Viatris Austria GmbH
Τηλ: +30 210 0100002 Tel: +43 1 86 390

España Polska
Viatris Pharmaceuticals, S.L. Viatris Healthcare Sp. z o.o.
Tel: +34 900 102 712 Tel.: +48 22 546 6400

France Portugal
Viatris Santé Viatris Healthcare, Lda.
Tél: +33 1 40 80 15 55 Tel: ++351 214 127 200

Hrvatska România
Viatris Hrvatska d.o.o. BGP PRODUCTS SRL
Tel: +385 1 23 50 599 Tel: +40 372 579 000

Ireland Slovenija
Viatris Limited Viatris d.o.o.
Tel: +353 1 8711600 Tel: +386 1 23 63 180

Ísland Slovenská republika
Icepharma hf. Viatris Slovakia s.r.o.
Sími: +354 540 8000 Tel: +421 2 32 199 100

Italia Suomi/Finland
Viatris Italia S.r.l. Viatris Oy
Tel: +39 02 612 46921 Puh/Tel: +358 20 720 9555

Κύπρος Sverige
GPA Pharmaceuticals Ltd Viatris AB
Τηλ: +357 22863100 Tel: +46 8 630 19 00

Latvija
Viatris SIA
Tel: +371 676 055 80

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

INSTRUCTIONS FOR USE OF THE PODHALER DEVICE

Please read the following instructions carefully to learn how to use and care for the
Podhaler device.
Contents of the TOBI Podhaler weekly pack
Each TOBI Podhaler weekly pack contains:

1 inhaler (the Podhaler device) and its case.
7 blisters (one blister for each day of the week).
Each blister contains 8 capsules (corresponding to a daily dose: the contents of 4 capsules to be inhaled in the morning and the contents of 4 capsules to be inhaled in the evening).


Blister (capsule container)	Inhaler	Carrying case

How to inhale the medicine using the Podhaler device

Use only the Podhaler device supplied in this package. Do not use TOBI Podhaler capsules with any other device, and do not use the Podhaler device for other medicines.
When starting a new weekly pack of capsules, use the new Podhaler device provided in the pack. Each Podhaler device must be used for only 7 days. Ask your pharmacist how to dispose of medicines and inhalers no longer needed.
Do not swallow the capsules. The powder in the capsules is for inhalation only.
Always keep the capsules in the blister until ready to use. Do not remove the capsules from the blister in advance.
Store the Podhaler device in its closed case when not in use.

	1. Wash and completely dry your hands.
	2. • Immediately before use, remove the inhaler from its case by holding the base and turning the top part of the case counterclockwise. • Set the top part of the case aside. • Check the inhaler to make sure it is not damaged or dirty. • Hold the inhaler upright on the base of the case.
	3. • Hold the body of the inhaler and unscrew the mouthpiece counterclockwise. • Set the mouthpiece aside on a clean, dry surface.
	4. Tear along the perforations of the blister strip lengthwise, then widthwise, as shown in figures (1) and (2).
	5. • Peel back the foil covering the blister to release a single capsule. • Remove the capsule from the blister.
	6. • Immediately insert the capsule into the chamber of the inhaler (1). • Replace the mouthpiece. • Screw the mouthpiece back on firmly until it stops. Do not overtighten (2).
	7. • Hold the inhaler with the mouthpiece pointing downward. • Pierce the capsule by pressing firmly on the blue button with your thumb until it stops, then release the button. • The device is now ready for you to inhale the capsule in two separate breaths (Steps 8 and 9).
	8. Inhale the capsule – 1st breath: Before placing the mouthpiece in your mouth, breathe out fully, away from the inhaler. Place your mouth over the mouthpiece – to achieve a good seal. Breathe in deeply and steadily through the mouth in a single breath to inhale the powder. Remove the inhaler from your mouth and hold your breath for about 5 seconds. Then breathe out normally, away from the inhaler.
	9. Inhale the capsule – 2nd breath: • Take a few normal breaths away from the inhaler. • When ready, repeat Step 8 using the same capsule for the second inhalation.
	10. Unscrew the mouthpiece (1) and remove the capsule from the chamber (2).
	11. Examine the used capsule. It should appear pierced and empty. If it is empty, discard the capsule.
	If the capsule is pierced but still contains some powder: • Reinsert the capsule into the inhaler chamber (Step 6). Place the pierced end of the capsule in first. • Replace the mouthpiece and repeat Steps 8, 9, and 10.
	If the capsule does not appear to be pierced: • Reinsert the capsule into the inhaler chamber (Step 6). • Replace the mouthpiece and repeat Steps 7, 8, and 9. • After this, if the capsule is still full and appears unperforated, replace the inhaler with the backup inhaler and repeat Steps 2, 3, 6, 7, 8, 9, and 10.
	12. Take the other 3 capsules in the same way. • For each remaining capsule, repeat Steps 5, 6, 7, 8, 9, 10, and 11. • Discard empty capsules.
	13. • Replace the mouthpiece and screw it on firmly until it stops. After the full dose (4 capsules) has been inhaled, clean the mouthpiece with a clean, dry cloth. • Do not wash the inhaler with water.
	14. • Place the inhaler back into its case. • Screw the top part of the case on clockwise until it is securely closed.

PLEASE REMEMBER:

For inhalation use only.
Do not swallow TOBI Podhaler capsules.
Use only the inhaler provided in this package.
Always keep TOBI Podhaler capsules in their blister. Remove a capsule only immediately before use. Do not store the capsules in the inhaler.
Always keep TOBI Podhaler capsules and the device in a dry place.
Never place a TOBI Podhaler capsule directly into the mouthpiece of the device.
Always hold the inhaler with the mouthpiece pointing downwards when piercing the capsule.
Never press the piercing button more than once at the same time.
Never blow into the mouthpiece of the device.
Never wash the Podhaler device with water. Avoid getting it wet and store it in its protective case.

Additional information
Sometimes, small pieces of the capsule may pass beyond the ring and reach the mouth.

If this happens, you should be able to feel these pieces on your tongue.
It is not harmful if these pieces are swallowed or inhaled.
The likelihood of the capsule breaking into pieces increases if the capsule is accidentally pierced more than once or if the inhaler is not held with the mouthpiece pointing downwards during step 7.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATIONS
Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for tobramycin (inhalation powder, capsules), the PRAC's scientific conclusions are as follows:
In view of the available data on nephrotoxicity from the literature, including in some cases a close temporal relationship and a positive response upon treatment withdrawal (positive de-challenge), the PRAC considers that there is at least a reasonable possibility of a causal relationship between tobramycin (inhalation powder, capsules) and acute renal failure (ARF). The PRAC concluded that the product information for medicinal products containing tobramycin (inhalation powder, capsules) should be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the reasoning of the recommendation.
Grounds for the variation of the terms of the marketing authorisations
Based on the scientific conclusions for tobramycin (inhalation powder, capsules), the CHMP considers that the benefit-risk balance of medicinal products containing tobramycin (inhalation powder, capsules) remains favourable, subject to the proposed amendments to the product information.
The CHMP recommends the variation of the terms of the marketing authorisations.