Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of HIV-1 infection in combination with other antiretroviral medicines in patients who have failed on previous regimens containing at least one product from each of the following antiretroviral classes: protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors, or who have not tolerated previous antiretroviral regimens.

Before treatment, consider carefully the treatment history for each patient and the patterns of mutations associated with different medicinal products. Resistance testing may be appropriate.

Administration

To be administered by subcutaneous injection only into upper arm, anterior thigh or abdomen.

The injection site should be rotated.

Contraindications

Children under 6 years
Breastfeeding

Precautions and Warnings

Elderly
Hepatic impairment
Hepatitis B
Hepatitis C
Moderate renal impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Discard any unused portion
For single use only
Never rechallenge treatment after a hypersensitivity reaction
Warm to room temperature prior to use
Autoimmune disorders can occur many months after initiation of treatment
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Inflammatory symptoms should be evaluated and treated appropriately
May lead to false positive HIV test result in non-infected individuals
Risk of developing opportunistic infections

Patients should be informed that treatment does not prevent the transmission of HIV via blood contamination or sexual contact and appropriate precautions should still be used.

In clinical trials increased incidence of certain bacterial infections especially pneumonia has been seen in patients treated with enfuvirtide. However, it has not been confirmed by subsequent epidemiological data.

Hypersensitivity to enfuvirtide has been seen to manifest as rash, fever, nausea and vomiting, chills, rigors, low blood pressure and elevated serum liver transaminases in various combinations, and possibly primary immune complex reaction, respiratory distress and glomerulonephritis. Patients showing symptoms of a systemic hypersensitivity reaction should discontinue therapy with enfuvirtide immediately and seek medical attention.

Hypersensitivity reactions have recurred on rechallenge so therapy should not be restarted following systemic signs and symptoms of such a reaction.

Treatment in patients suffering from underlying hepatic disorders has not been fully studied.Patients with chronic hepatitis B or C undergoing antiretroviral therapy are at an increased risk of severe and possibly fatal hepatic adverse effects.
Patients in phase III trials suffering from hepatitis B or C did not experience an increase in hepatic related adverse events. If a patient is also receiving antiviral treatment for hepatitis B/C the relevant product literature should be consulted for these products.

Enfuvirtide therapy in non-HIV-1 infected individuals may result in induced anti-enfuvirtide antibodies which react with HIV gp41. This may lead to a false positive HIV test with the anti-HIV ELISA test.

When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis carinii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.

Cases of osteonecrosis have been reported, particularly in patients with advanced HIV disease and/or long term exposure to combination antiretroviral therapy. The aetiology of this condition is thought to be due to several factors including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index. Patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Enfuvirtide should be used with caution during pregnancy.

The manufacturer recommends that enfuvirtide should be used in pregnancy only if the potential benefits justifies the potential risk to the foetus.

Animal studies have not shown teratogenic effects. Reports suggest that enfuvirtide does not cross the placenta due to the high molecular weight and protein binding of enfuvirtide.

Lactation

Enfuvirtide is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking enfuvirtide because of the potential for HIV transmission and any potential undesirable effects in breastfed infants.

The presence of enfuvirtide in human breast milk is unknown but due to its large molecular weight and protein binding, transfer may be inhibited.

The effects of breastfeeding on a nursing infant are unknown.

Side Effects

Abscess formation (injection site)
Acne
Anorexia
Anxiety
Asthenia
Attention disturbances
Autoimmune hepatitis
Cellulitis (injection site)
Chills
Conjunctivitis
Creatine phosphokinase increased
Decrease in haemoglobin
Decreased appetite
Diabetes mellitus
Diarrhoea
Dry skin
Ear infection
Ecchymosis (injection site)
Eczema
Eosinophilia
Erythema
Erythema at injection site
Fever
Gastroesophageal reflux disease
Glomerulonephritis
Graves' disease
Haematuria
Hypersensitivity reactions
Hypertriglyceridaemia
Hypoaesthesia
Hypotension
Immune disorder
Immune Reactivation/Reconstitution Syndrome
Increase in ALT level
Increase in serum transaminases
Induration (injection site)
Influenza
Influenza-like syndrome
Irritability
Local infection at injection site
Local pain (injection site)
Local reaction at injection site
Lymphadenopathy
Myalgia
Nasal congestion
Nausea
Nightmares
Nodules (injection site)
Osteonecrosis
Pancreatitis
Peripheral neuropathy
Pneumonia
Pruritus
Rash
Renal calculus
Respiratory distress syndrome
Rigors
Sinusitis
Skin papilloma
Tremor
Vertigo
Vomiting
Weakness
Weight loss

Presentation

Parenteral formulations of enfuvirtide.

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of HIV-1 infection in combination with other antiretroviral medicines in patients who have failed on previous regimens containing at least one product from each of the following antiretroviral classes: protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors, or who have not tolerated previous antiretroviral regimens.

Before treatment, consider carefully the treatment history for each patient and the patterns of mutations associated with different medicinal products. Resistance testing may be appropriate.

Dosage

Advise patients on the correct method of reconstituting and administrating the injection before they begin to self-inject.

Adults

Children

Additional Dosage Information

Administration

To be administered by subcutaneous injection only into upper arm, anterior thigh or abdomen.

The injection site should be rotated.

Contraindications

Children under 6 years
Breastfeeding

Precautions and Warnings

Elderly
Hepatic impairment
Hepatitis B
Hepatitis C
Moderate renal impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Discard any unused portion
For single use only
Never rechallenge treatment after a hypersensitivity reaction
Warm to room temperature prior to use
Autoimmune disorders can occur many months after initiation of treatment
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Inflammatory symptoms should be evaluated and treated appropriately
May lead to false positive HIV test result in non-infected individuals
Risk of developing opportunistic infections

Patients should be informed that treatment does not prevent the transmission of HIV via blood contamination or sexual contact and appropriate precautions should still be used.

In clinical trials increased incidence of certain bacterial infections especially pneumonia has been seen in patients treated with enfuvirtide. However, it has not been confirmed by subsequent epidemiological data.

Hypersensitivity to enfuvirtide has been seen to manifest as rash, fever, nausea and vomiting, chills, rigors, low blood pressure and elevated serum liver transaminases in various combinations, and possibly primary immune complex reaction, respiratory distress and glomerulonephritis. Patients showing symptoms of a systemic hypersensitivity reaction should discontinue therapy with enfuvirtide immediately and seek medical attention.

Hypersensitivity reactions have recurred on rechallenge so therapy should not be restarted following systemic signs and symptoms of such a reaction.

Treatment in patients suffering from underlying hepatic disorders has not been fully studied.Patients with chronic hepatitis B or C undergoing antiretroviral therapy are at an increased risk of severe and possibly fatal hepatic adverse effects.
Patients in phase III trials suffering from hepatitis B or C did not experience an increase in hepatic related adverse events. If a patient is also receiving antiviral treatment for hepatitis B/C the relevant product literature should be consulted for these products.

Enfuvirtide therapy in non-HIV-1 infected individuals may result in induced anti-enfuvirtide antibodies which react with HIV gp41. This may lead to a false positive HIV test with the anti-HIV ELISA test.

When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis carinii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.

Cases of osteonecrosis have been reported, particularly in patients with advanced HIV disease and/or long term exposure to combination antiretroviral therapy. The aetiology of this condition is thought to be due to several factors including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index. Patients should be advised to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

Pregnancy and Lactation

Pregnancy

Enfuvirtide should be used with caution during pregnancy.

The manufacturer recommends that enfuvirtide should be used in pregnancy only if the potential benefits justifies the potential risk to the foetus.

Animal studies have not shown teratogenic effects. Reports suggest that enfuvirtide does not cross the placenta due to the high molecular weight and protein binding of enfuvirtide.

Lactation

Enfuvirtide is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking enfuvirtide because of the potential for HIV transmission and any potential undesirable effects in breastfed infants.

The presence of enfuvirtide in human breast milk is unknown but due to its large molecular weight and protein binding, transfer may be inhibited.

The effects of breastfeeding on a nursing infant are unknown.

Side Effects

Abscess formation (injection site)
Acne
Anorexia
Anxiety
Asthenia
Attention disturbances
Autoimmune hepatitis
Cellulitis (injection site)
Chills
Conjunctivitis
Creatine phosphokinase increased
Decrease in haemoglobin
Decreased appetite
Diabetes mellitus
Diarrhoea
Dry skin
Ear infection
Ecchymosis (injection site)
Eczema
Eosinophilia
Erythema
Erythema at injection site
Fever
Gastroesophageal reflux disease
Glomerulonephritis
Graves' disease
Haematuria
Hypersensitivity reactions
Hypertriglyceridaemia
Hypoaesthesia
Hypotension
Immune disorder
Immune Reactivation/Reconstitution Syndrome
Increase in ALT level
Increase in serum transaminases
Induration (injection site)
Influenza
Influenza-like syndrome
Irritability
Local infection at injection site
Local pain (injection site)
Local reaction at injection site
Lymphadenopathy
Myalgia
Nasal congestion
Nausea
Nightmares
Nodules (injection site)
Osteonecrosis
Pancreatitis
Peripheral neuropathy
Pneumonia
Pruritus
Rash
Renal calculus
Respiratory distress syndrome
Rigors
Sinusitis
Skin papilloma
Tremor
Vertigo
Vomiting
Weakness
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: August 2022

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Fuzeon 90mg/ml powder and solvent for solution for injection. Roche Products Limited. Revised January 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 August 2022