Last Updated on eMC 22-12-2015 View medicine  | Roche Products Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:16-12-2015

Legal Category:POM

Black Triangle (CHM): NO

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Current document republished with corrected date:

10.     DATE OF REVISION OF THE TEXT

 

16 December 2015

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:22-10-2015

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Black Triangle (CHM): NO

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4.8     Undesirable effects

 

[ … ]

 

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see section 4.4).

 

As a peptide, enfuvirtide can cause cutaneous amyloidosis at the injection site.

 

Laboratory abnormalities

 

[ … ]

 

 

10.     DATE OF REVISION OF THE TEXT

 

22 October 2015

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:20-03-2014

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4.2       Posology and method of administration

 

Fuzeon should be prescribed by physicians who are experienced in the treatment of HIV infection.

 

Posology

 

Adults and adolescents ³ 16 years: The recommended dose of Fuzeon is 90 mg twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen.

 

In case a Fuzeon dose is missed, patients should be instructed to administer the dose as soon as possible. However, if it is less than 6 hours before the next regular dose, the missed dose should be skipped

[…]

 

4.4          Special warnings and precautions for use

 

Fuzeon must be taken as part of a combination regimen. Please also refer to the respective summary of product characteristics of the other antiretroviral medicinal products used in the combination. As with other antiretrovirals, enfuvirtide should optimally be combined with other antiretrovirals to which the patient’s virus is sensitive. (Ssee section 5.1).

 

Patients must be advised that antiretroviral therapies including enfuvirtide have not been proved to prevent the risk of transmission to of HIV to others through sexual contact or blood contamination. They must continue to use appropriate precautions. Patients should also be informed that Fuzeon is not a cure for HIV-1 infection. While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.

 

[…]

 

4.8       Undesirable effects

 

a. Summary of the safety profile

 

Safety data mainly refer to 48-week data from studies TORO 1 and TORO 2 combined (see section 5.1). Safety results are expressed as the number of patients with an adverse reaction per 100 patient-years of exposure (except for injection site reactions).

 

The most frequently reported events were injection site reactions, diarrhoea and nausea. The addition of Fuzeon to background antiretroviral therapy generally did not increase the frequency or severity of most adverse reactions.

Injection site reactions

 

Injection site reactions (ISRs) were the most frequently reported adverse reaction and occurred in 98% of the patients (Table 2). The vast majority of ISRs occurred within the first week of Fuzeon administration and were associated with mild to moderate pain or discomfort at the injection site without limitation of usual activities. The severity of the pain and discomfort did not increase with treatment duration. The signs and symptoms generally lasted equal to or less than 7 days. Infections at the injection site (including abscess and cellulitis) occurred in 1.5% of patients.

 

Table 2:         Summary of individual signs/symptoms characterising local injection site reactions in studies TORO 1 and TORO 2 combined (% of patients)

 

n=663

Withdrawal Rate due to ISRs

4%

Event Category

Fuzeon +Optimised backgrounda

% of Event comprising Grade 3 reactions

% of Event comprising Grade 4 reactions

Pain / discomfort

96.1%

11.0%b

0%b

Erythema

90.8%

23.8%c

10.5%c

Induration

90.2%

43.5%d

19.4%d

Nodules and cysts

80.4%

29.1%e

0.2%e

Pruritus

65.2%

3.9%f

NA

Ecchymosis

51.9%

8.7%g

4.7%g

aAny severity grade.
bGrade 3= severe pain requiring analgesics (or narcotic analgesics for ≤ 72 hours) and/or limiting usual activities; Grade 4= severe pain requiring hospitalisation or prolongation of hospitalisation, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant.

cGrade 3= ≥ 50 mm but < 85 mm average diameter; Grade 4= ≥ 85 mm average diameter.
dGrade 3= ≥ 25 mm but < 50 mm average diameter; Grade 4= ≥ 50 mm average diameter.
 eGrade 3= ≥ 3 cm; Grade 4= If draining.
fGrade 3= refractory to topical treatment or requiring oral or parenteral treatment; Grade 4= not defined.
gGrade 3= > 3 cm but ≤ 5 cm; Grade 4= > 5 cm.

 

Other adverse reactions

 

The addition of Fuzeon to background antiretroviral therapy generally did not increase the frequency or severity of most adverse reactions. The most frequently reported events occurring in the TORO 1 and TORO 2 studies were diarrhoea (38 versus 73 patients with event per 100 patient years for Fuzeon + OB versus OB) and nausea (27 versus 50 patients with event per 100 patient years for Fuzeon + OB versus OB).

 

b. Tabulated list of adverse reactions

 

The following listTable 2 presents events seen at a higher rate among patients receiving Fuzeon + OB regimen than among patients on the OB alone regimen with an exposure adjusted increase of at least 2 patients with event per 100 patient-years. These events are then designated frequency estimation (“very common” (≥1/10), or “common” (≥1/100, <1/10)). A statistically significant increase was seen for pneumonia and lymphadenopathy. Most adverse reactions were of mild or moderate intensity.  Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (³1/10); common (³1/100 to <1/10); uncommon (³1/1,000 to <1/100); rare (³1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

 

Table 2:         Adverse reactions attributed to treatment with Fuzeon in studies TORO 1 and TORO 2 combined

 

System organ class

Frequency

Adverse reaction

Infections and infestations

Common

 

 

Sinusitis, skin papilloma, influenza, pneumonia, ear infection

Blood and lymphatic system disorders

Common

 

 

Lymphadenopathy

Metabolism and nutrition disorders

Common

 

 

Appetite decreased, anorexia, hypertriglyceridaemia, blood triglycerides increased, diabetes mellitus

Psychiatric disorders

Common

 

 

Anxiety, nightmare, irritability

Nervous system disorders

Very common

Common

 

 

Peripheral neuropathy

Hypoaesthesia, disturbance in attention, tremor

Eye disorders

Common

 

 

Conjunctivitis

Ear and labyrinth disorders

Common

 

 

Vertigo

Respiratory, thoracic and mediastinal disorders

Common

 

 

Nasal congestion

Gastrointestinal disorders

Common

 

 

Pancreatitis, gastro-oesophageal reflux disease

Skin and subcutaneous tissue disorders

Common

 

Dry skin, eczema seborrhoeic, erythema, acne

 

Musculoskeletal, connective tissue and bone disorders

Common

 

 

 

Myalgia

Renal and Urinary Disorders

Common

 

 

Nephrolithiasis, haematuria

General disorders and administration site conditions

Very common

Common

 

 

 

Weight decreased

Influenza like illness, asthenia

 

Infections and Infestations

Common: - sinusitis, skin papilloma, influenza, pneumonia, ear infection.

 

Blood and Lymphatic System Disorders

Common: - lymphadenopathy.

 

Metabolism and Nutrition Disorders

Common: - appetite decreased, anorexia, hypertriglyceridaemia, diabetes mellitus.

 

Psychiatric Disorders

Common: - anxiety, nightmare, irritability.

 

Nervous System Disorders

Very Common: - peripheral neuropathy.

Common: -hypoaesthesia, disturbance in attention, tremor.

 

Eye Disorders

Common: - conjunctivitis.

 

Ear and Labyrinth disorders

Common: - vertigo.

 

Respiratory, Thoracic and Mediastinal Disorders

Common: - nasal congestion.

 

Gastrointestinal Disorders

Common: - pancreatitis, gastro-oesophageal reflux disease.

 

Skin and Subcutaneous Tissue Disorders

Common: - dry skin, eczema seborrhoeic, erythema, acne.

 

Musculoskeletal, Connective Tissue and Bone Disorders

Common: - myalgia.

 

Renal and Urinary Disorders

Common: - Calculus renal.

 

General Disorders and Administration Site Conditions

Common: - influenza like illness, weakness.

 

Investigations

Very Common: - weight decreased

Common: - blood triglycerides increased, haematuria present.

 

 

c. Description of selected adverse reactions

 

Injection site reactions

 

Injection site reactions (ISRs) were the most frequently reported adverse reaction and occurred in 98% of the patients (Table 3). The vast majority of ISRs occurred within the first week of Fuzeon administration and were associated with mild to moderate pain or discomfort at the injection site without limitation of usual activities. The severity of the pain and discomfort did not increase with treatment duration. The signs and symptoms generally lasted equal to or less than 7 days. Infections at the injection site (including abscess and cellulitis) occurred in 1.5% of patients.

 

Table 3:         Summary of individual signs/symptoms characterising local injection site reactions in studies TORO 1 and TORO 2 combined (% of patients)

 

n=663

Withdrawal Rate due to ISRs

4%

Event Category

Fuzeon +Optimised backgrounda

% of Event comprising Grade 3 reactions

% of Event comprising Grade 4 reactions

Pain / discomfort

96.1%

11.0%b

0%b

Erythema

90.8%

23.8%c

10.5%c

Induration

90.2%

43.5%d

19.4%d

Nodules and cysts

80.4%

29.1%e

0.2%e

Pruritus

65.2%

3.9%f

NA

Ecchymosis

51.9%

8.7%g

4.7%g

aAny severity grade.
bGrade 3= severe pain requiring analgesics (or narcotic analgesics for ≤ 72 hours) and/or limiting usual activities; Grade 4= severe pain requiring hospitalisation or prolongation of hospitalisation, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant.

cGrade 3= ≥ 50 mm but < 85 mm average diameter; Grade 4= ≥ 85 mm average diameter.
dGrade 3= ≥ 25 mm but < 50 mm average diameter; Grade 4= ≥ 50 mm average diameter.
 eGrade 3= ≥ 3 cm; Grade 4= If draining.
fGrade 3= refractory to topical treatment or requiring oral or parenteral treatment; Grade 4= not defined.
gGrade 3= > 3 cm but ≤ 5 cm; Grade 4= > 5 cm.

 

In addition there have been a small number of hypersensitivity reactions attributed to enfuvirtide and in some cases recurrence has occurred upon re-challenge. (Ssee section 4.4).

 

Other adverse reactions

 

In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.  Autoimmune disorders (such as Graves’ disease) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

 

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see section 4.4).

 

Laboratory abnormalities

 

The majority of patients had no change in the toxicity grade of any laboratory parameter during the study except for those listed in Table 34. Through week 48, eosinophilia [greater than the Upper Limit of Normal of > 0.7 x 109/l] occurred at a higher rate amongst patients in the Fuzeon containing group (12.4 patients with event per 100 patient-years) compared with OB alone regimen (5.6 patients with event per 100 patient-years). When using a higher threshold for eosinophilia (>1.4 x 109/l), the patient exposure adjusted rate of eosinophilia is equal in both groups (1.8 patients with event per 100 patient-years).

 

Table 34:       Exposure adjusted Grade 3 & 4 laboratory abnormalities among patients on Fuzeon+OB and OB alone regimens, reported at more than 2 patients with event per 100 patient years

Laboratory Parameters

Grading

Fuzeon+OB regimen

Per 100 patient years

OB alone regimen

Per 100 patient years

n

(Total Exposure patient years)

663

(557.0)

334

(162.1)

ALAT

Gr. 3 (>5-10 x ULN)

4.8

4.3

Gr. 4 (>10 x ULN)

1.4

1.2

Haemoglobin

Gr. 3 (6.5-7.9 g/dL)

2.0

1.9

Gr. 4 (<6.5 g/dL)

0.7

1.2

Creatinine phosphokinase

Gr. 3 (>5-10 x ULN)

8.3

8.0

Gr. 4 (>10 x ULN)

3.1

8.6

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.(see details below).

 

Ireland

IMB Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

Malta

ADR Reporting

The Medicines Authority

Post-Licensing Directorate

203 Level 3, Rue D'Argens

GŻR-1368 Gżira

Website: www.medicinesauthority.gov.mt

e-mail: postlicensing.medicinesauthority@gov.mt

 

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

 

10.       DATE OF REVISION OF THE TEXT

 

20 March 2014

 

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC:14-06-2013

Legal Category:POM

Black Triangle (CHM): NO

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Underlined text = new text

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2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each vial contains 108 mg enfuvirtide.

Each ml of reconstituted solution contains 90 mg enfuvirtide.

Excipient with known effect: sodium. Contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

For a the full list of excipients, see section 6.1.

 

 

4.2     Posology and method of administration

 

Fuzeon should be prescribed by physicians who are experienced in the treatment of HIV infection.

 

Posology

Fuzeon is only to be administered by subcutaneous injection.

 

[ … ]

 

Method of Administration

 

Fuzeon is only to be administered by subcutaneous injection.  For instructions on reconstitution before administration, see section 6.6.

 

 

4.3     Contraindications

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

 

 

4.6     Fertility, pregnancy and lactation

 

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Animal studies do not indicate harmful effects with respect to foetal development. Enfuvirtide should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

 

Breast-feeding:  It is not known whether enfuvirtide is secreted in human milk. Mothers should be instructed not to breast-feed if they are receiving enfuvirtide because of the potential for HIV transmission and any possible undesirable effects in breast-fed infants.

 

 

 

5.2     Pharmacokinetic properties

 

[ … ]

 

MetabolismBiotransformation: As a peptide, enfuvirtide is expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool. In vitro human microsomal studies and in in vivo studies indicate that enfuvirtide is not an inhibitor of CYP450 enzymes. In in vitro human microsomal and hepatocyte studies, hydrolysis of the amide group of the C-terminus amino acid, phenylalanine results in a deamidated metabolite and the formation of this metabolite is not NADPH dependent. This metabolite is detected in human plasma following administration of enfuvirtide, with an AUC ranging from 2.4 to 15% of the enfuvirtide AUC.

 

[ … ]

 

Hepatic Insufficiencyimpairment: The pharmacokinetics of enfuvirtide have not been studied in patients with hepatic impairment.

 

Renal Insufficiencyimpairment: Analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide is not affected to any clinically relevant extent in patients with mild to moderate renal impairment. In a renal impairment study AUC of enfuvirtide was increased on average by 43-62% in patients with severe or end stage renal disease compared to patients with normal renal function. Hemodialysis did not significantly alter enfuvirtide clearance. Less than 13% of the dose was removed during hemodialysis. No dose adjustment is required for patients with impaired renal function.

 

[ … ]

 

Paediatric Patientspopulation: The pharmacokinetics of enfuvirtide have been studied in 37 paediatric patients. A dose of 2 mg/kg bid (maximum 90 mg bid) provided enfuvirtide plasma concentrations similar to those obtained in adult patients receiving 90 mg bid dosage. In 25 paediatric patients ranging in age from 5 to 16 years and receiving the 2 mg/kg bid dose into the upper arm, anterior thigh or abdomen, the mean steady-state AUC was 54.3 ± 23.5 mg*h/ml, Cmax was 6.14 ± 2.48 mg/ml, and Ctrough was 2.93 ± 1.55 mg/ml.

 

 

6.4     Special precautions for storage

 

Powder

Keep the vial in the outer carton in order to protect from light. For storage conditions after reconstitution of the reconstituted medicinal product, see section 6.3.

 

Solvent

This medicinal product does not require any special storage conditions.

 

6.5     Nature and contents of container

 

Powder

Vial:              3 ml vial, colourless glass type 1

Closure:        lyophilisate stopper, rubber (latex free)

Seal:              aluminumaluminium seal with flip-off cap

 

Solvent

Vial:              2 ml vial, colourless glass type 1

Closure:        rubber stopper (latex free)

Seal:              aluminumaluminium seal with flip-off cap

 

Pack sizes

 

Pack 1

60 vials powder for solution for injection

60 vials solvent

60 3 ml syringes

60 1 ml syringes

180 alcohol swabs

 

Pack 2

60 vials powder for solution for injection

60 vials solvent

 

6.6       Special precautions for disposal and reconstitution

 

Any unused medicinal product should be disposed of in accordance with local requirements.

 

[ … ]

 

8.       MARKETING AUTHORISATION NUMBER(S)

 

EU/1/03/252/001-002

 

 

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation:                   27 May 2003

Date of lastlatest renewal:                    27 May 2008

 

 

10.     DATE OF REVISION OF THE TEXT

 

27 April 201014 June 2013

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:28-05-2013

Legal Category:POM

Black Triangle (CHM): NO

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Underlined text = new text

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4.4       Special warnings and precautions for use

 

[ … ]

 

Autoimmune disorders (such as Graves’ disease), have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and can occur many months after initiation of treatment.

 

 

4.8     Undesirable effects

 

[ … ]

 

In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4). Autoimmune disorders (such as Graves’disease) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

 

[ … ]

 

 

10.     DATE OF REVISION OF THE TEXT

 

28 May 2013

 

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:27-04-2010

Legal Category:POM

Black Triangle (CHM): NO

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4.4       Special warnings and precautions for use

Animal studies have shown that enfuvirtide may impair some immune functions (see section 5.3). In clinical trials, an increased rate of some bacterial infections, most notably a higher rate of pneumonia, was seen in patients treated with Fuzeon; however, an increased risk of bacterial pneumonia related to the use of Fuzeon has not been confirmed by subsequent epidemiological data.

An increased rate of some bacterial infections, most notably a higher rate of pneumonia, has been seen in patients treated with Fuzeon. Patients should be monitored closely for signs and symptoms of pneumonia. (See section 4.8)

 

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life

Date of revision of text on the SPC:22-12-2009

Legal Category:POM

Black Triangle (CHM): NO

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shelf life increased to 4 years

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties

Date of revision of text on the SPC:08-07-2008

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The following text has been removed:

5.1     Pharmacodynamic properties

This medicinal product has been authorised under “Exceptional Circumstances”. This means that  for scientific reasons it has not been possible to obtain complete information on this medicinal product. The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.

Reasons for adding or updating:

  • Removal of Black Triangle

Date of revision of text on the SPC:05-09-2008

Legal Category:POM

Black Triangle (CHM): NO

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Removal of Black Triangle

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 4 - Special Precautions for Storage

Date of revision of text on the SPC:08-07-2008

Legal Category:POM

Black Triangle (CHM): YES

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Underlined text has been added, text with strike through deleted:

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each vial contains 108 mg enfuvirtide.

Each1 ml of reconstituted solution contains 90 mg enfuvirtide.

 

Excipient(s):

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium- free'. For a full list of excipients, see section 6.1.

 

4.8     Undesirable effects

Infections and Infestations

Common (1/100, <1/10): - sinusitis, skin papilloma, influenza, pneumonia, ear infection.

 

Blood and Lymphatic System Disorders

Common (1/100, <1/10): - lymphadenopathy.

 

Metabolism and Nutrition Disorders

Common (1/100, <1/10): - appetite decreased, anorexia, hypertriglyceridaemia, diabetes mellitus.

 

Psychiatric Disorders

Common ((1/100, <1/10): - anxiety, nightmare, irritability.

 

Nervous System Disorders

Very Common (1/10): - peripheral neuropathy.

Common (1/100, <1/10): -hypoaesthesia, disturbance in attention, tremor.

 

Eye Disorders

Common (1/100, <1/10): - conjunctivitis.

 

Ear and Labyrinth disorders

Common (1/100, <1/10): - vertigo.

 

Respiratory, Thoracic and Mediastinal Disorders

Common (1/100, <1/10): - nasal congestion.

 

Gastrointestinal Disorders

Common (1/100, <1/10): - pancreatitis, gastro-oesophageal reflux disease.

 

Skin and Subcutaneous Tissue Disorders

Common (1/100, <1/10): - dry skin, eczema seborrhoeic, erythema, acne.

 

Musculoskeletal, Connective Tissue and Bone Disorders

Common (1/100, <1/10): - myalgia.

 

Renal and Urinary Disorders

Common (1/100, <1/10): - Calculus renal.

 

General Disorders and Administration Site Conditions

Common (1/100, <1/10): - influenza like illness, weakness.

 

Investigations

Very Common (1/10): - weight decreased

Common (1/100, <1/10): - blood triglycerides increased, haematuria present.

 

6.3     Shelf life

After reconstitution: Store in a refrigerator (2°C – 8°C).

 

6.4     Special precautions for storage

This medicinal product does not require any special storage conditions.After reconstitution: Store in a refrigerator (2°C – 8°C). Keep the vial in the outer carton in order to protect from light. For storage conditions of the reconstituted medicinal product, see section 6.3.

 

Reasons for adding or updating:

  • Change to section 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:01-10-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined text has been added:
 
Pharmacokinetic properties
 
In HIV patients, enfuvirtide levels in the cerebrospinal fluid have been reported to be negligible

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:01-10-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined text has been added, text with strike through deleted

 

4.2     Posology and method of administration

Renal impairment: No dose adjustment is required for patients with renal impairment including creatinine clearance above 35 ml/min. and  No data are available to establish a dose recommendation for patients with creatinine clearance below 35 ml/min or those receiving dialysis. (See sections 4.4 and 5.2).

 

4.4       Special warnings and precautions for use

There is no experience in patients with reduced hepatic function. Data is limited  Enfuvirtide clearance is not significantly altered or in patients with moderate to severe renal impairment and only limited data, in patients with moderate renal impairment and in patients maintained on dialysis. Fuzeon should be used with caution in these populations. (See sections 4.2 and 5.2)

 

5.2     Pharmacokinetic properties

Renal Insufficiency: AA specific pharmacokinetic study has not been conducted in patients with renal impairment or those receiving dialysis. However analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide is not affected to any clinically relevant extent in patients with mild to moderate renal impairmentcreatinine clearance above 35 ml/min. The results ofIn a renal impairment study indicate clearanceAUC of enfuvirtide was increased on average reduced by 3843-62% in patients with severe renal impairment and by 14-28% in patients withor end stage renal disease maintained on dialysis compared to patients with normal renal function. Haemodialysis did not significantly alter enfuvirtide clearance. Less than 13% of the dose was removed during haemodialysis. No dose adjustment is required for patients with impaired renal function.

 

Paediatric Patients: The pharmacokinetics of enfuvirtide have been studied in 9037 paediatric patients.

 

 

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-01-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined text has been added, text with strike through deleted:

 

4.4       Special warnings and precautions for use

 

Osteonecrosis:

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

 

4.8       Undesirable effects

 

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see section 4.4).

 

10.       DATE OF REVISION OF THE TEX

 

Updated to: 24 January 2007

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 6 - Instructions for use, handling and disposal
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-10-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined text has been added, text with strike through deleted

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Excipient(s):

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially "sodium-free". For a full list of excipients, see section 6.1.

 

 

3.         PHARMACEUTICAL FORM

 

Fuzeon is a whiteWhite to off-white lyophilised powder.

 

 

4.2       Posology and method of administration

 

Children ³ 6 years and adolescents: The experience in children is based on a very limited number of children. (See section 5.2). In ongoing clinical trials the dosage regimen in table 1 below is being used.

 

No data are available to establish dose recommendations of Fuzeon in children below the age of 6 years.

Fuzeon is not recommended for use in children below age 6 due to insufficient data on safety and efficacy (see section 5.2).

 

 

4.4       Special warnings and precautions for use

 

Animal studies have shown that enfuvirtide may impair some immune functions (See section 5.3).

 

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Interactions studies have only been performed in adults.

 

 

4.8       Undesirable effects

 

These events are then designated frequency estimation ("very common" (³ 1/10), or "common" (³ 1/100, < 1/10)).

 

 

5.1       Pharmacodynamic properties

 

This medicinal product has been authorised under "Exceptional Circumstances". This means that for scientific reasons it has not been possible to obtain complete information on this medicinal product. The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.

 

 

5.3       Preclinical safety data

 

Studies in guinea pigs indicated a potential for enfuvirtide to produce delayed contact hypersensitivity.  In a rat model on the resistance to influenza infection, an impairment of IFN-g production was observed. The resistance to influenza and streptococcal infection in rats was only weakly compromised. In vitro studies have shown that enfuvirtide may act as an agonist on the formyl peptide receptor, a receptor on leucocytes believed to be important for the early defense against infection.

 

 

6.4       Special precautions for storage

 

For storage conditions of the reconstituted medicinal product, see section 6.3.

 

 

6.6       Special precautions for disposal

 

Any unused product should be disposed of in accordance with local requirements.

 

 

10.       DATE OF REVISION OF THE TEXT

 

Updated to: 24 October 2006

 

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 (date of (partial) revision of the text
  • Addition of Legal Category

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 (date of (partial) revision of the text
  • Addition of Legal Category

Reasons for adding or updating:

  • Change to section 4.3 - Contra-indications
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 6.2 - Incompatibilities
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 6. 6 - Instruction for Use/Handling
  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 3 - Shelf Life
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 4.3 - Contra-indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 8 - MA number
  • Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

  • New SPC for new product