Drugs List

Therapeutic Indications

Uses

HIV where only CCR5-tropic HIV-1 detectable: Combination treatment

Treatment of Human Immunodeficiency Virus (HIV) infection in treatment-experienced patients weighing at least 10kg with only CCR5-tropic HIV-1 detectable.
Maraviroc must be given in combination with other antiretroviral medicines.

Contraindications

Children under 2 years
Children weighing less than 10kg
Breastfeeding

Precautions and Warnings

Patients over 65 years
Hepatic impairment
Hepatitis
Hepatitis B
Hepatitis C
History of postural hypotension
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe cardiovascular disorder

Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
Confirm CCR5-tropic HIV-1 status prior to treatment
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Contains arachis (peanut oil), soya or soya derivative
Autoimmune disorders can occur many months after initiation of treatment
Monitor closely patient with pre-existing hepatic impairment
Start therapy shortly after viral tropism test- changes can occur over time
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider discontinuing treatment if hepatotoxicity occurs
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Advise patient not to take St John's wort concurrently

There are no data regarding the re-use of maraviroc in patients with only CCR5-tropic HIV-1 detectable, but have a history of failure on maraviroc (or other CCR5 antagonists) with a CXCR4 or dual/mixed tropic virus. There are no data on switching to maraviroc from a different antiretroviral class in virologically suppressed patients. Alternative treatment options should be considered.

It is recommended that maraviroc should not be used in treatment naive patients.

Use with caution in patients with a history of postural hypotension and in patients taking concurrent blood pressure lowering medications. Symptomatic cases of postural hypotension have been seen in healthy volunteers at doses above the recommended dose.

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, and 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.

There is an increased risk of postural hypotension in patients with severe renal impairment who also use protease inhibitors which may lead to cardiovascular adverse effects.

Pregnancy and Lactation

Pregnancy

Use maraviroc with caution in pregnancy.

At the time of writing there is limited published information regarding the use of maraviroc during pregnancy. The manufacturer indicates that maraviroc should be only used in pregnancy if the expected benefit outweighs the potential risk to the foetus.

Maraviroc is known to cross the placenta. Animal studies have shown reproductive toxicity at high exposures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Maraviroc is contraindicated in breastfeeding.

It is recommended that mothers infected by HIV do not breast-feed under any circumstances, in order to avoid transmission of HIV. Maraviroc use in breastfeeding is contraindicated by the manufacturer.

It is not known if maraviroc is excreted into human breast milk. The drug's molecular weight and long elimination half life suggest that the drug would be excreted into the breast milk. The effect on a nursing infant is unknown. Animal studies have indicated that maraviroc is extensively secreted in milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Alanine aminotransferase increased
Anaemia
Angina pectoris
Anorexia
Aspartate aminotransferase increased
Asthenia
Autoimmune hepatitis
Back pain
Bile duct cancer
Cirrhosis
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Eosinophilia
Fatigue
Fever
Flatulence
Gamma glutamyl transferase (GGT) increased
Granulocytopenia
Graves' disease
Headache
Hepatic failure
Hodgkin's disease
Hyperbilirubinaemia
Increase in alkaline phosphatase
Insomnia
Lymphoma
Metastatic disease
Muscular atrophy
Myositis
Nausea
Oesophageal candidiasis
Oesophageal carcinoma
Opportunistic infections
Osteonecrosis
Pancytopenia
Pneumonia
Postural hypotension
Proteinuria
Pruritus
Rash
Renal failure
Rhabdomyolysis
Seizures
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Toxic hepatitis

Presentation

Oral formulations of maraviroc.

Drugs List

Therapeutic Indications

Uses

HIV where only CCR5-tropic HIV-1 detectable: Combination treatment

Treatment of Human Immunodeficiency Virus (HIV) infection in treatment-experienced patients weighing at least 10kg with only CCR5-tropic HIV-1 detectable.
Maraviroc must be given in combination with other antiretroviral medicines.

Dosage

Before taking maraviroc, it must be established that only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or dual/mixed tropic virus not detected). An adequately validated and sensitive detection method on a newly drawn sample of blood should be used. The viral tropism cannot be safely predicted based on treatment history and assessment of stored blood samples.

Therapy should be started shortly after a tropism test as changes in viral tropism occur over time in patients with HIV.

The dose will depend on the interactions with concurrent antiretroviral therapy and other medicinal products.

Adults

Children

Patients with Renal Impairment

Contraindications

Children under 2 years
Children weighing less than 10kg
Breastfeeding

Precautions and Warnings

Patients over 65 years
Hepatic impairment
Hepatitis
Hepatitis B
Hepatitis C
History of postural hypotension
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe cardiovascular disorder

Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
Confirm CCR5-tropic HIV-1 status prior to treatment
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Contains arachis (peanut oil), soya or soya derivative
Autoimmune disorders can occur many months after initiation of treatment
Monitor closely patient with pre-existing hepatic impairment
Start therapy shortly after viral tropism test- changes can occur over time
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider discontinuing treatment if hepatotoxicity occurs
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if drug-related rash or other hypersensitivity reactions occur
Advise patient not to take St John's wort concurrently

There are no data regarding the re-use of maraviroc in patients with only CCR5-tropic HIV-1 detectable, but have a history of failure on maraviroc (or other CCR5 antagonists) with a CXCR4 or dual/mixed tropic virus. There are no data on switching to maraviroc from a different antiretroviral class in virologically suppressed patients. Alternative treatment options should be considered.

It is recommended that maraviroc should not be used in treatment naive patients.

Use with caution in patients with a history of postural hypotension and in patients taking concurrent blood pressure lowering medications. Symptomatic cases of postural hypotension have been seen in healthy volunteers at doses above the recommended dose.

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, and 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.

There is an increased risk of postural hypotension in patients with severe renal impairment who also use protease inhibitors which may lead to cardiovascular adverse effects.

Pregnancy and Lactation

Pregnancy

Use maraviroc with caution in pregnancy.

At the time of writing there is limited published information regarding the use of maraviroc during pregnancy. The manufacturer indicates that maraviroc should be only used in pregnancy if the expected benefit outweighs the potential risk to the foetus.

Maraviroc is known to cross the placenta. Animal studies have shown reproductive toxicity at high exposures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Maraviroc is contraindicated in breastfeeding.

It is recommended that mothers infected by HIV do not breast-feed under any circumstances, in order to avoid transmission of HIV. Maraviroc use in breastfeeding is contraindicated by the manufacturer.

It is not known if maraviroc is excreted into human breast milk. The drug's molecular weight and long elimination half life suggest that the drug would be excreted into the breast milk. The effect on a nursing infant is unknown. Animal studies have indicated that maraviroc is extensively secreted in milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Alanine aminotransferase increased
Anaemia
Angina pectoris
Anorexia
Aspartate aminotransferase increased
Asthenia
Autoimmune hepatitis
Back pain
Bile duct cancer
Cirrhosis
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Eosinophilia
Fatigue
Fever
Flatulence
Gamma glutamyl transferase (GGT) increased
Granulocytopenia
Graves' disease
Headache
Hepatic failure
Hodgkin's disease
Hyperbilirubinaemia
Increase in alkaline phosphatase
Insomnia
Lymphoma
Metastatic disease
Muscular atrophy
Myositis
Nausea
Oesophageal candidiasis
Oesophageal carcinoma
Opportunistic infections
Osteonecrosis
Pancytopenia
Pneumonia
Postural hypotension
Proteinuria
Pruritus
Rash
Renal failure
Rhabdomyolysis
Seizures
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Toxic hepatitis

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: April 2018.

Reference Sources

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: Celsentri 25mg, 75mg, 150mg and 300mg film-coated tablets. ViiV Healthcare UK Ltd. Revised September 2018.
Summary of Product Characteristics: Celsentri 20mg/ml oral solution. ViiV Healthcare UK Ltd. Revised September 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: Aprl 2018.