Tygacil 50 mg powder for solution for infusion

Tygacil is an antibiotic of the glycylcycline group that works by stopping the growth of bacteria that cause infections.

Your doctor prescribed Tygacil because you have one of the following types of serious infections:

• Complicated infection of the skin and soft tissues (the tissue below the skin)

Tygacil is not indicated for the treatment of diabetic foot infections.

• Complicated infection in the abdomen

Tygacil should be used only in situations where it is known or suspected that other alternative antibiotics are not suitable.

Do not use Tygacil

• If you are allergic (hypersensitive) to tigecycline, the active substance of Tygacil. If you are allergic to tetracycline class antibiotics (e.g., minocycline, doxycycline, etc.), you may be allergic to tigecycline.

Take special care with Tygacil

• Tell your doctor immediately if you develop symptoms of an allergic reaction.
• Tell your doctor immediately if you develop severe abdominal pain, nausea, and vomiting. These may be symptoms of acute pancreatitis.
• Tell your doctor if you are suffering from diarrhoea before you are given Tygacil. If you develop diarrhoea during or after your treatment, tell your doctor at once. Do not take any diarrhoea medicine without first checking with your doctor.
• Tell your doctor if you have or previously had any side effects due to antibiotics belonging to the tetracycline class (e.g., skin sensitization to sun light, staining on developing teeth, pancreas inflammation, and alteration of certain laboratory values aimed at measuring how well your blood clots).
• In certain serious infections, your doctor may consider to use Tygacil in combination with other antibiotics.
• Tell your doctor if you are taking certain medicines (named anticoagulants) aimed at avoiding an excess of blood clotting (see also Using other medicines in this leaflet).
• Tell your doctor if you are taking the contraceptive pill as you may need an additional method of contraception while receiving Tygacil (see also Using other medicines in this leaflet).
• Tell your doctor if you have, or previously had liver problems. Depending on the condition of your liver, your doctor may reduce the dose to avoid potential side effects.
• While antibiotics including Tygacil fight certain bacteria, other bacteria and fungi may continue to grow. This is called overgrowth. Your doctor will monitor you for any potential infections and treat you if necessary.
• Tygacil is not to be used in children or adolescents (under 18 years of age). In children less than 8 years, tigecycline may induce permanent dental defects such as staining on the developing teeth.
• If you are given Tygacil your doctor will monitor you closely for the development of another infection. If you develop another infection your doctor may prescribe a different antibiotic.

Using other medicines

Always tell your doctor if you are taking or have recently taken any other medicines, including medicines you buy without a prescription.

Tygacil may prolong certain tests that measure how well your blood is clotting. It is important that you tell your doctor if you are taking medicines to avoid an excess of blood clotting. If this were the case, your doctor will monitor you closely.

Tygacil may interfere with the contraceptive pill (birth control pill). Talk to your doctor about the need for an additional method of contraception while receiving Tygacil.

Pregnancy and breast-feeding

Tygacil may cause foetal harm. If you are pregnant, or are planning to become pregnant, talk to your doctor before receiving Tygacil.

It is not known if Tygacil passes into breast milk in humans. Ask your doctor for advice before breast-feeding your baby.

Driving and using machines

Tygacil may cause side effects such as dizziness. This may impair your ability to drive or operate machinery.

Tygacil will be given to you by a doctor or a nurse.

The recommended dose is 100 mg given initially, followed by 50 mg every 12 hours. This dose is given intravenously (directly into your blood stream) over a period of 30 to 60 minutes.

A course of treatment usually lasts for 5 to 14 days. Your doctor will decide how long you should be treated.

If you receive more Tygacil than you should

If you are concerned that you may have been given too much Tygacil, talk to your doctor or nurse immediately.

If you miss a dose of Tygacil

If you are concerned that you may have missed a dose, talk to your doctor or nurse immediately.

Like all medicines, Tygacil may have side effects, although not everybody gets them.

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data)

Very common side effects are:

• Nausea, vomiting, diarrhoea.

Common side effects are:

• Abscess (collection of pus), infections
• Laboratory measurements of decreased ability to form blood clots
• Dizziness
• Vein irritations from the injection, including pain, inflammation, swelling and clotting
• Abdominal pain, dyspepsia (stomach ache and indigestion), anorexia (loss of appetite)
• Increases in liver enzymes, hyperbilirubinaemia (excess of bile pigment in the blood)
• Pruritus (itching), rash
• Headache
• Increase in amylase, which is an enzyme found in the salivary glands and pancreas, increased blood urea nitrogen (BUN).

Uncommon side effects are:

• Sepsis (severe infection in the body and blood stream)/septic shock (serious medical condition which can lead to multiple organ failure and death as a result of sepsis)
• Low protein levels in the blood
• Acute pancreatitis (inflamed pancreas which may result in severe abdominal pain, nausea, and vomiting)
• Jaundice, inflammation of the liver
• Injection site reaction (pain, redness, inflammation).

Not known side effects are:

• Anaphylaxis/anaphylactoid reactions (that may range from mild to severe, including a sudden, generalised allergic reaction that may lead to a life-threatening shock [e.g. difficulty in breathing, drop of blood pressure, fast pulse]).
• Low platelet levels in the blood (which may lead to an increased bleeding tendency and bruising/haematoma)
• Liver failure

Pseudomembranous colitis may occur with most antibiotics including Tygacil. This consists of severe, persistent or bloody diarrhoea associated with abdominal pain or fever, which can be a sign of serious bowel inflammation, which may occur during or after your treatment.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Store below 25°C.Do not use Tygacil after the expiry date which is stated on the vial.

Storage after preparation

Once the powder has been made into a solution and diluted ready for use, it should be given to you almost immediately.

What Tygacil contains

The active substance is tigecycline. Each vial contains 50 mg of tigecycline.

The other ingredients are lactose monohydrate, hydrochloric acid, and sodium hydroxide.

What Tygacil looks like and contents of the pack

Tygacil is supplied as a powder for solution for infusion in a vial and looks like an orange powder or cake before it is diluted. These vials are distributed to the hospital in a ten tray pack. The powder should be mixed in the vial with a small amount of solution. The vial should be gently swirled until the medicine is dissolved. Thereafter, the solution should be immediately withdrawn from the vial and added to a 100 ml intravenous bag or other suitable infusion container in the hospital.

The Tygacil solution should be yellow to orange in colour after dissolving; if it is not, the solution should be discarded.

Marketing Authorisation Holder Wyeth Europa Ltd. Huntercombe Lane South Taplow, Maidenhead Berkshire, SL6 0PH United Kingdom Manufacturer Wyeth Pharmaceuticals New Lane Havant Hampshire PO9 2NG United Kingdom

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

Magyarország Pfizer Kft. Tel 36 1 488 3700 Malta Vivian Corporation Ltd. Tel 35621 344610 BelgiëBelgiqueBelgien LuxembourgLuxemburg Pfizer S.A. N.V. TélTel 32 02 554 62 11 EestiLatvijaLietuva Slovenija Wyeth Whitehall Export GmbH TeTelTãlr43 1 89 1140 eská Republika Pfizer s.r.o. Tel 420-283-004-111 Nederland Wyeth Pharmaceuticals B.V. Tel 31 23 567 2567

Danmark Pfizer ApS Tlf 45 44 201 100 Norge Pfizer AS Tlf 47 67 526 100

Deutschland Pfizer Pharma GmbH Tel 49 030 550055-51000 Pfizer Hellas A.E. . 30 210 6785 800 España Pfizer, S.A. Télf34914909900 France Pfizer Tél 33 1 58 07 34 40 Ireland Wyeth Pharmaceuticals Tel 353 1 449 3500 Ísland Icepharma hf Tel 354 540 8000 Österreich Pfizer Corporation Austria Ges.m.b.H. Tel 43 01 521 15-0 Polska Pfizer Polska Sp. z o.o., Tel. 48 22 335 61 00 Portugal Laboratórios Pfizer, Lda. Tel 351 21 423 55 00 România Pfizer Romania S.R.L Tel 40 0 21 207 28 00 Slovenská Republika Pfizer Luxembourg SARL, organizaná zloka Tel 421 2 3355 5500 SuomiFinland Pfizer Oy PuhTel 358 09 430 040

Italia Wyeth Lederle S.p.A. Tel 39 06 927151 Sverige Pfizer AB Tel 46 08 550 520 00

K Wyeth Hellas Cyprus Branch AEBE T 357 22 817690 United Kingdom Wyeth Pharmaceuticals Tel 44 1628 415330

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

The following information is intended for medical or healthcare professionals only:

Instructions for use and handling (see also 3. HOW TYGACIL IS GIVEN in this leaflet )

The lyophilised powder should be reconstituted with 5.3 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection, dextrose 50 mg/ml (5 %) solution for injection, or Lactated Ringer?s solution for injection to achieve a concentration of 10 mg/ml of tigecycline. The vial should be gently swirled until the active substance is dissolved. Thereafter, 5 ml of the reconstituted solution should be immediately withdrawn from the vial and added to a 100 ml intravenous bag for infusion or other suitable infusion container (e.g. glass bottle).

For a 100 mg dose, reconstitute using two vials into a 100 ml intravenous bag for infusion or other suitable infusion container (e.g. glass bottle).

Note: The vial contains a 6 % overage. Thus, 5 ml of reconstituted solution is equivalent to 50 mg of the active substance. The reconstituted solution should be yellow to orange in colour; if not, the solution should be discarded. Parenteral products should be inspected visually for particulate matter and discolouration (e.g. green or black) prior to administration.

Tygacil may be administered intravenously through a dedicated line or through a Y-site. If the same intravenous line is used for sequential infusion of several active substances, the line should be flushed before and after infusion of Tygacil with either sodium chloride 9 mg/ml (0.9 %) solution for injection or dextrose 50 mg/ml (5 %) solution for injection. Injection should be made with an infusion solution compatible with tigecycline and any other medicinal product(s) via this common line.

Compatible intravenous solutions include: sodium chloride 9 mg/ml (0.9 %) solution for injection, dextrose 50 mg/ml (5 %) solution for injection, and Lactated Ringer?s solution for injection.

When administered through a Y-site, compatibility of Tygacil diluted in sodium chloride 0.9 % for injection is demonstrated with the following medicinal products or diluents: amikacin, dobutamine, dopamine HCl, gentamicin, haloperidol, Lactated Ringer?s, lidocaine HCl, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, propofol, ranitidine HCl, theophylline, and tobramycin.

Tygacil must not be mixed with other medicinal products for which compatibility data are not available.

Once reconstituted and diluted in the bag or other suitable infusion container (e.g. glass bottle) tigecycline should be used immediately.

For single use only, any unused solution should be discarded.

Annex IV

Grounds for one additional renewal

Based upon the data that have become available since the granting of the initial Marketing Authorisation, the CHMP considers that the benefit-risk balance of Tygacil remains positive, but considers that its safety and efficacy profile is to be closely monitored for the following reasons:

• In an analysis of clinical studies conducted with Tygacil a higher mortality rate has been observed in Tygacil versus comparator groups. The higher mortality trend is consistently observed throughout the product clinical program in approved and non approved indications, and is maintained in recent post marketing trials.
• The causes of these findings have not been identified but a lower efficacy of Tygacil cannot be ruled out; furthermore the development of superinfection seems to be associated with a worse patient outcome.

The CHMP has recommended that measures aimed to secure a safe use of Tygacil and minimise the risk of fatal outcome in susceptible or severely ill patients be implemented by the MAH. These measures include:

• SmPC amendment to indicate that Tygacil should only be used in the approved indications when there are no suitable therapeutic alternatives, and to warn about the mortality findings, the need to closely monitor patients and institute alternative antibacterial therapy if superinfection occurs.
• Implementation of risk minimisation plan to address the identified risks, in particular superinfections and treatment failures, and a post-authorisation safety study expected to provide relevant data and monitor these risks.

The CHMP concluded that the MAH should continue to submit yearly PSURs.

Therefore, based upon the above Tygacil safety profile, the CHMP also concluded that the MAH should submit one additional renewal application in 5 years time