Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Females of childbearing potential
Patients over 65 years
Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Moderate hepatic impairment
Severe renal impairment
Torsade de pointes

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Avoid H2 antagonists 12hrs before or 4hrs after dose
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Women childbearing potential: Discuss potential risk of neural tube defects
Contains lactose
Indigestion remedies should not be taken at the same time
Non-significant increase in QT interval at therapeutic doses
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Monitor for signs of osteonecrosis
Monitor hepatic function in patients with hepatic impairment
Monitor levels of hepatic enzymes and bilirubin
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Autoimmune diseases may occur during treatment
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of neural tube defects
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
Advise to avoid calcium and antacids 6hrs before & 4hrs after dose
Advise to avoid iron and multivitamins 6hrs before & 4hrs after dose
Female: Ensure adequate contraception during treatment
Advise patients that hypersensitivity reactions may be life threatening

Use with caution when co-administered with products with a known risk of Torsade de Pointes.

Hypersensitivity reactions have been reported with use of dolutegravir. These were characterised by rash, constitutional findings, organ dysfunction, including severe liver reactions. Dolutegravir should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop. These hypersensitivity reactions can include, severe rash or rash accompanied by raised liver enzymes, fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, eosinophilia, angioedema. Delay in stopping treatment may result in a life-threatening allergic reaction.

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 and can cause serious clinical conditions or aggravation of symptoms. Reactions are usually observed within the first few weeks or months after treatment initiation. Examples are cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treated appropriately.

Pregnancy and Lactation

Pregnancy

Dolutegravir with rilpivirine is contraindicated during pregnancy.

The manufacturer does not recommend using dolutegravir with rilpivirine during pregnancy. If pregnancy is detected in the first trimester during therapy, it is advised to switch to an alternative treatment unless there is no suitable alternative. Animal reproductive toxicity studies have shown dolutegravir to cross the placenta but have not shown dolutegravir to be teratogenic.

The MHRA states that due to results from an observational study there is evidence of an increased risk of neural tube defects in babies born to mothers who became pregnant while taking dolutegravir. They advise that dolutegravir should not be prescribed to women seeking to become pregnant and that pregnancy should be excluded in women of child bearing potential before starting dolutegravir. Women of childbearing potential are advised to use effective contraception throughout treatment with dolutegravir.

Lactation

Dolutegravir with rilpivirine is contraindicated during breastfeeding.

The manufacturer recommends that infants are not breastfed by HIV infected women in order to avoid HIV transmission. Animal studies have demonstrated that dolutegravir and rilpivirine are excreted in milk. Lactating rats dosed with a single 50mg/kg oral dose 10 days postpartum, dolutegravir was measured in milk concentrations typically higher than blood. The presence of dolutegravir and rilpivirine in human breast milk is unknown.

Side Effects

Abdominal discomfort
Abdominal pain
Acute hepatic failure
Anxiety
Arthralgia
Creatine phosphokinase increased
Decrease in haemoglobin
Decreased appetite
Depressed mood
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Elevated amylase levels
Elevated serum LDL cholesterol
Elevated serum lipase
Elevated triglyceride levels
Fatigue
Flatulence
Headache
Hepatitis
Hypersensitivity reactions
Immune Reactivation/Reconstitution Syndrome
Increase in serum transaminases
Increase in total cholesterol
Insomnia
Myalgia
Nausea
Pruritus
Rash
Reduced platelet count
Serum bilirubin increased
Sleep disorders
Somnolence
Suicidal tendencies
Vomiting
White blood cell count decreased

Presentation

Oral formulations containing dolutegravir (as sodium) with rilpivirine (as hydrochloride).

Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Dosage

Adults

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Females of childbearing potential
Patients over 65 years
Glucose-galactose malabsorption syndrome
Hepatitis B
Hepatitis C
Lactose intolerance
Moderate hepatic impairment
Severe renal impairment
Torsade de pointes

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Avoid H2 antagonists 12hrs before or 4hrs after dose
Perform viral resistance testing before initiating therapy
Treatment should be initiated by doctor experienced in HIV management
Women childbearing potential: Discuss potential risk of neural tube defects
Contains lactose
Indigestion remedies should not be taken at the same time
Non-significant increase in QT interval at therapeutic doses
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Monitor for signs of osteonecrosis
Monitor hepatic function in patients with hepatic impairment
Monitor levels of hepatic enzymes and bilirubin
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Autoimmune diseases may occur during treatment
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of neural tube defects
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
Advise to avoid calcium and antacids 6hrs before & 4hrs after dose
Advise to avoid iron and multivitamins 6hrs before & 4hrs after dose
Female: Ensure adequate contraception during treatment
Advise patients that hypersensitivity reactions may be life threatening

Use with caution when co-administered with products with a known risk of Torsade de Pointes.

Hypersensitivity reactions have been reported with use of dolutegravir. These were characterised by rash, constitutional findings, organ dysfunction, including severe liver reactions. Dolutegravir should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop. These hypersensitivity reactions can include, severe rash or rash accompanied by raised liver enzymes, fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, eosinophilia, angioedema. Delay in stopping treatment may result in a life-threatening allergic reaction.

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 and can cause serious clinical conditions or aggravation of symptoms. Reactions are usually observed within the first few weeks or months after treatment initiation. Examples are cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treated appropriately.

Pregnancy and Lactation

Pregnancy

Dolutegravir with rilpivirine is contraindicated during pregnancy.

The manufacturer does not recommend using dolutegravir with rilpivirine during pregnancy. If pregnancy is detected in the first trimester during therapy, it is advised to switch to an alternative treatment unless there is no suitable alternative. Animal reproductive toxicity studies have shown dolutegravir to cross the placenta but have not shown dolutegravir to be teratogenic.

The MHRA states that due to results from an observational study there is evidence of an increased risk of neural tube defects in babies born to mothers who became pregnant while taking dolutegravir. They advise that dolutegravir should not be prescribed to women seeking to become pregnant and that pregnancy should be excluded in women of child bearing potential before starting dolutegravir. Women of childbearing potential are advised to use effective contraception throughout treatment with dolutegravir.

Lactation

Dolutegravir with rilpivirine is contraindicated during breastfeeding.

The manufacturer recommends that infants are not breastfed by HIV infected women in order to avoid HIV transmission. Animal studies have demonstrated that dolutegravir and rilpivirine are excreted in milk. Lactating rats dosed with a single 50mg/kg oral dose 10 days postpartum, dolutegravir was measured in milk concentrations typically higher than blood. The presence of dolutegravir and rilpivirine in human breast milk is unknown.

Counselling

Advise patients treatment with dolutegravir does not prevent the risk of transmission of HIV.

Advise patient if they miss a dose and the next dose is not due within 12 hours they should take the missed dose as soon as possible. If the next dose is due within 12 hours, advise the patient not to take the missed dose and simply resume usual dosing.

Advise patient if they vomit within 4 hours of a dose, another dose should be taken with a meal as soon as possible. If the patient vomits more than 4 hours after the dose, they do not need to take another dose until the next regularly scheduled dose.

Advise patient to avoid taking St John's wort concurrently.

Advise patients to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Advise patient to discontinue treatment and contact to contact a medical profession if hypersensitivity reactions occur. Hypersensitivity reactions may be life threatening.

Advise patient to use adequate contraception during treatment.

Advise patients their ability to drive or operate machinery may be affected by side effects.

Side Effects

Abdominal discomfort
Abdominal pain
Acute hepatic failure
Anxiety
Arthralgia
Creatine phosphokinase increased
Decrease in haemoglobin
Decreased appetite
Depressed mood
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dry mouth
Elevated amylase levels
Elevated serum LDL cholesterol
Elevated serum lipase
Elevated triglyceride levels
Fatigue
Flatulence
Headache
Hepatitis
Hypersensitivity reactions
Immune Reactivation/Reconstitution Syndrome
Increase in serum transaminases
Increase in total cholesterol
Insomnia
Myalgia
Nausea
Pruritus
Rash
Reduced platelet count
Serum bilirubin increased
Sleep disorders
Somnolence
Suicidal tendencies
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: February 2020

Reference Sources

Summary of Product Characteristics: Juluca 50mg/25mg film-coated tablets. ViiV Healthcare UK Ltd. Revised January 2019.

MHRA Drug Safety Update June 2018
Available at: https://www.mhra.gov.uk
Last accessed: 16 July 2018

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 February 2020.