Drugs List

Therapeutic Indications

Uses

Non-resistant HIV in adults - viral load <100,000 HIV-1 RNA copies/mL

Treatment of Human Immunodeficiency Virus 1 (HIV-1) infected adults without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine, and with a viral load of less than or equal to 100,000 HIV-1 RNA copies/mL.

As with other antiretroviral medicinal products, genotypic resistance testing and/or historical resistance data should guide the use of emtricitabine with rilpivirine and tenofovir disoproxil.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment

Precautions and Warnings

Elderly
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance 50-80ml/minute

Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor renal function in patients with risk factors for renal impairment
Monitor renal function monthly for 1 year, then 3 monthly thereafter
Monitor serum phosphate monthly for 1 year, then 3 monthly thereafter
On discontinuation, may cause recurrence of hepatitis B
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if severe skin reaction occurs
Interrupt treatment if creatinine clearance below 50 ml/minute
Interrupt treatment if serum phosphate decreases to below 1 mg/dL
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level

Creatinine clearance should be calculated in all patients prior to initiating therapy. Renal function tests (including serum creatinine and serum phosphate) should be taken before treatment begins and also monitored after two to four weeks of treatment, after three months of treatment and every three to six months thereafter in patients without renal risk factors. If deemed necessary, this monitoring should be more frequent in patients with a history of renal impairment or those at risk of renal impairment. However, other sources suggest renal function tests (including serum creatinine and serum phosphate) should be taken before treatment begins and at four-weekly intervals during the first year and every three months thereafter.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. Physicians should refer to current HIV treatment guidelines to determine the best treatment for patients co-infected with HIV and hepatitis. Treatment discontinuation is not recommended in patients with advanced liver disease or cirrhosis as post-treatment exacerbation of hepatitis may lead to hepatic decompensation.
The safety and efficacy of emtricitabine with rilpivirine and tenofovir disoproxil has not been established for the treatment of chronic hepatitis B infection. Limited clinical experience suggests that emtricitabine and tenofovir are active against hepatitis B infection when used in antiretroviral combination therapy to control HIV infection.

Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

Pregnancy and Lactation

Pregnancy

Use emtricitabine with rilpivirine and tenofovir disoproxil with caution during pregnancy. It should not be used unless clearly needed.

There are no clinical data regarding emtricitabine with rilpivirine and tenofovir disoproxil in pregnant women. However, a moderate amount of data in pregnant women indicate no malformations or foetal/neonatal toxicity associated with emtricitabine, rilpivirine and tenofovir disoproxil.

Studies in animals have shown no reproductive toxicity with emtricitabine, rilpivirine and tenofovir disoproxil and have shown limited placenta passage of rilpivirine. It is not known whether placental transfer of rilpivirine occurs in pregnant women. There was no teratogenicity with rilpivirine in rats and rabbits.

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

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Emtricitabine with rilpivirine and tenofovir disoproxil is contraindicated in breastfeeding.

Emtricitabine and tenofovir disoproxil are excreted in human breast milk, however it is not known whether rilpivirine is excreted in human milk. There is insufficient information on the effects of emtricitabine, rilpivirine and tenofovir disoproxil in newborn infants, therefore it should not be used during breastfeeding.

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 discomfort
Abdominal distension
Abdominal pain
Abnormal liver function tests
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Alterations in pancreatic enzymes
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Blistering
Bone pain
Conjunctivitis
Creatine kinase increased
Decrease in haemoglobin
Decreased appetite
Depressed mood
Depression
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Dyspepsia
Elevated serum LDL cholesterol
Elevated serum lipase
Eosinophilia
Fanconi syndrome
Fatigue
Fever
Flatulence
Graves' disease
Headache
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hyperpigmentation of skin
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in plasma triglyceride concentration
Increase in serum ALT/AST
Increase in total cholesterol
Increased risk of fractures
Insomnia
Insulin resistance
Lactic acidosis
Maculopapular rash
Muscle weakness
Myopathy
Nausea
Neutropenia
Osteomalacia
Osteonecrosis
Pancreatitis
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Reduced platelet count
Renal failure
Renal impairment
Rhabdomyolysis
Severe skin reactions
Sleep disturbances
Somnolence
Urticaria
Vesiculo-bullous reactions
Vomiting
White blood cell count decreased

Presentation

Oral formulations of emtricitabine with rilpivirine and tenofovir disoproxil

Drugs List

Therapeutic Indications

Uses

Non-resistant HIV in adults - viral load <100,000 HIV-1 RNA copies/mL

Treatment of Human Immunodeficiency Virus 1 (HIV-1) infected adults without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine, and with a viral load of less than or equal to 100,000 HIV-1 RNA copies/mL.

As with other antiretroviral medicinal products, genotypic resistance testing and/or historical resistance data should guide the use of emtricitabine with rilpivirine and tenofovir disoproxil.

Dosage

When one active substance needs to be discontinued or when dosage modification is needed, separate preparations of emtricitabine, rilpivirine hydrochloride and tenofovir disoproxil are available. For further information, refer to the individual summary of products characteristics of these medicinal products.

As with other antiretroviral medicinal products, genotypic resistance testing should guide the use of this product combination.

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment

Precautions and Warnings

Elderly
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis B
Hepatitis C
Lactose intolerance
Osteoporosis
Pregnancy
Renal impairment - creatinine clearance 50-80ml/minute

Therapy cessation not recommended in decompensated liver disease/cirrhosis
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Contains lactose
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor renal function in patients with risk factors for renal impairment
Monitor renal function monthly for 1 year, then 3 monthly thereafter
Monitor serum phosphate monthly for 1 year, then 3 monthly thereafter
On discontinuation, may cause recurrence of hepatitis B
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May cause loss of bone mineral density
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if severe skin reaction occurs
Interrupt treatment if creatinine clearance below 50 ml/minute
Interrupt treatment if serum phosphate decreases to below 1 mg/dL
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level

Creatinine clearance should be calculated in all patients prior to initiating therapy. Renal function tests (including serum creatinine and serum phosphate) should be taken before treatment begins and also monitored after two to four weeks of treatment, after three months of treatment and every three to six months thereafter in patients without renal risk factors. If deemed necessary, this monitoring should be more frequent in patients with a history of renal impairment or those at risk of renal impairment. However, other sources suggest renal function tests (including serum creatinine and serum phosphate) should be taken before treatment begins and at four-weekly intervals during the first year and every three months thereafter.

Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. Physicians should refer to current HIV treatment guidelines to determine the best treatment for patients co-infected with HIV and hepatitis. Treatment discontinuation is not recommended in patients with advanced liver disease or cirrhosis as post-treatment exacerbation of hepatitis may lead to hepatic decompensation.
The safety and efficacy of emtricitabine with rilpivirine and tenofovir disoproxil has not been established for the treatment of chronic hepatitis B infection. Limited clinical experience suggests that emtricitabine and tenofovir are active against hepatitis B infection when used in antiretroviral combination therapy to control HIV infection.

Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

Pregnancy and Lactation

Pregnancy

Use emtricitabine with rilpivirine and tenofovir disoproxil with caution during pregnancy. It should not be used unless clearly needed.

There are no clinical data regarding emtricitabine with rilpivirine and tenofovir disoproxil in pregnant women. However, a moderate amount of data in pregnant women indicate no malformations or foetal/neonatal toxicity associated with emtricitabine, rilpivirine and tenofovir disoproxil.

Studies in animals have shown no reproductive toxicity with emtricitabine, rilpivirine and tenofovir disoproxil and have shown limited placenta passage of rilpivirine. It is not known whether placental transfer of rilpivirine occurs in pregnant women. There was no teratogenicity with rilpivirine in rats and rabbits.

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

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Emtricitabine with rilpivirine and tenofovir disoproxil is contraindicated in breastfeeding.

Emtricitabine and tenofovir disoproxil are excreted in human breast milk, however it is not known whether rilpivirine is excreted in human milk. There is insufficient information on the effects of emtricitabine, rilpivirine and tenofovir disoproxil in newborn infants, therefore it should not be used during breastfeeding.

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 discomfort
Abdominal distension
Abdominal pain
Abnormal liver function tests
Acute interstitial nephritis
Acute tubular necrosis
Allergic reaction
Alterations in pancreatic enzymes
Anaemia
Angioedema
Asthenia
Autoimmune hepatitis
Blistering
Bone pain
Conjunctivitis
Creatine kinase increased
Decrease in haemoglobin
Decreased appetite
Depressed mood
Depression
Diabetes insipidus
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Dyspepsia
Elevated serum LDL cholesterol
Elevated serum lipase
Eosinophilia
Fanconi syndrome
Fatigue
Fever
Flatulence
Graves' disease
Headache
Hepatic steatosis
Hepatitis
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hyperpigmentation of skin
Hypertriglyceridaemia
Hypokalaemia
Hypophosphataemia
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in plasma triglyceride concentration
Increase in serum ALT/AST
Increase in total cholesterol
Increased risk of fractures
Insomnia
Insulin resistance
Lactic acidosis
Maculopapular rash
Muscle weakness
Myopathy
Nausea
Neutropenia
Osteomalacia
Osteonecrosis
Pancreatitis
Proximal tubulopathy
Pruritus
Pustular rash
Rash
Reduced platelet count
Renal failure
Renal impairment
Rhabdomyolysis
Severe skin reactions
Sleep disturbances
Somnolence
Urticaria
Vesiculo-bullous reactions
Vomiting
White blood cell count decreased

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: June 2015

Reference Sources

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 4 June 2015.

Summary of Product Characteristics: Eviplera 200mg/25mg/245mg film-coated tablets. Gilead Sciences Ltd. Revised October 2018.