Drugs List

Therapeutic Indications

Uses

HIV infection in adults and adolescents over 12 years: treatment

Administration

Advise patient if they miss a dose and the next dose is not due within 4 hours they should take the missed dose as soon as possible. If the next dose is due within 4 hours, advise the patient not to take the missed dose and simply resume usual dosing.

Contraindications

Children under 12 years
Weight below 40kg
Breastfeeding
Moderate hepatic impairment
Renal impairment - creatinine clearance below 50ml/minute

Precautions and Warnings

Predisposition to hepatic disorder
Hepatitis
Mild hepatic impairment
Pregnancy
Psychiatric disorder

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm negative HLA-B 5701 allele status in all patients
Treatment should be initiated by doctor experienced in HIV management
Women childbearing potential: Discuss potential risk of neural tube defects
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor for signs of osteonecrosis
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk of hepatic disease
Monitor patients with hepatic impairment
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
Autoimmune diseases may occur during treatment
Consider hypersensitivity if any of:rash/fever/G.I/flu-like or resp.dis.
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of neural tube defects
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if hypersensitivity reactions occur
If allergic reaction occurs discontinue and do not re-initiate treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid multivitamins 2 hours after or 6 hours before dose
Advise to avoid iron containing products 2 hrs after or 6 hrs before dose
Avoid antacids/mineral supplements 2 hrs after or 6 hrs before dose
Female: Ensure adequate contraception during treatment
Advise patients that hypersensitivity reactions may be life threatening

Before treatment all patients, irrespective of racial origin, should be screened for the carriage of HLA-B*5701 allele. Dolutegravir with abacavir and lamivudine should not be used in patients carrying the HLA-B*5701 allele unless no other therapeutic option is available based on treatment history and resistance testing. Presence of this allele confers an increased risk of severe hypersensitivity reactions to abacavir. Treatment should also be avoided in patients with a negative HLA-B*5701 status who had a suspected abacavir hypersensitivity reaction on a previous regime.

Hypersensitivity reactions have been reported with the use of dolutegravir and abacavir individually. These reaction can occur at any time during therapy and can potentially be life threatening. Treatment should be discontinued immediately if hypersensitivity reactions occur or are suspected. If treatment has been discontinued as a result of hypersensitivity or suspected hypersensitivity, treatment must never be reinitiated with this fixed dose presentation or with the individual preparations. Hypersensitivity reactions can present themselves as respiratory disease or gastroenteritis.

Patients who have discontinued treatment for reasons other than hypersensitivity could also experience life threatening reaction within hours of reinitiating. Medical assistance should be readily available if restarting therapy.

Dolutegravir with abacavir and lamivudine should not be co-administered with polyvalent cation-containing antacids. Dolutegravir with abacavir and lamivudine is recommended to be administered 2 hours before or 6 hours after these medicinal products. When taken with food, dolutegravir with abacavir and lamivudine and supplements or multivitamins containing calcium, iron or magnesium can be taken at the same time. If administered under fasting conditions, supplements or multivitamins containing calcium, iron or magnesium are recommended to be taken 2 hours after or 6 hours before dolutegravir with abacavir and lamivudine.

Pregnancy and Lactation

Pregnancy

Use dolutegravir with abacavir and lamivudine with caution during pregnancy.

The manufacturer suggests dolutegravir with abacavir and lamivudine should only be used during pregnancy if the expected benefit justifies the potential risk to the foetus.

At the time of writing there are limited data on the use of dolutegravir in pregnant women. The effect of dolutegravir on human pregnancy is unknown. Reproductive toxicity studies in animals have shown dolutegravir to cross the placenta. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

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.

Abacavir crosses the human placenta. The safety of abacavir administration in human pregnancy has not been established, although retrospective studies of exposed pregnancies reported in Briggs (2011) and Schaefer (2007) do not show a marked increase in the number of birth defects nor a discernible pattern. In animals, the placental transfer of abacavir and/or its related metabolites has occurred. In animal studies, embryo toxicity was observed in rats but this was not seen in rabbits at doses up to 8.5 times human exposure based on AUC.

Lamivudine appears to cross the placenta by diffusion, with cord levels at term similar to maternal blood levels. More than 3000 outcomes from first trimester exposed to lamivudine did not indicate malformative toxicity. The animal and human data suggest that lamivudine is a low risk to the developing foetus for structural malformations.

Lactation

Dolutegravir with abacavir and lamivudine is contraindicated during breastfeeding.

The manufacturer advises that HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease. HIV is known to be transmitted in milk.

Dolutegravir is excreted in human milk in small amounts. Lamivudine is excreted in human milk at similar concentrations found in serum. Abacavir is also excreted into human milk. The effects to infants are unknown.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Abnormal liver function tests
Adult respiratory distress syndrome
Alopecia
Anaemia
Anaphylaxis
Anorexia
Anxiety
Arthralgia
Asthenia
Autoimmune disorders
Autoimmune hepatitis
Conjunctivitis
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Dyspnoea
Elevated amylase levels
Erythema multiforme
Fatigue
Fever
Flatulence
Gastroesophageal reflux disease
Graves' disease
Headache
Hepatic failure
Hepatitis
Hyperglycaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Lethargy
Lymphadenopathy
Lymphopenia
Malaise
Metabolic changes
Mouth ulcers
Muscle disorders
Myalgia
Myolysis
Nasal symptoms
Nausea
Neutropenia
Nightmares
Oedema
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Rash
Red cell aplasia
Renal failure
Respiratory failure
Rhabdomyolysis
Serum creatinine increased
Severe hepatic reactions
Sleep disorders
Somnolence
Sore throat
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Vomiting
Weight gain

Presentation

Oral formulations containing dolutegravir (as sodium) with abacavir (as sulfate) and lamivudine.

Drugs List

Therapeutic Indications

Uses

HIV infection in adults and adolescents over 12 years: treatment

Dosage

This fixed dose presentation should not be used in patients that require dose adjustments. The individual preparations of dolutegravir, abacavir, and lamivudine are available in cases where discontinuation or dose adjustment of one substance is needed. For further information, refer to the individual monograph of each preparation.

This fixed dose presentation is not recommended in patients with integrase inhibitor resistance as the dose of dolutegravir cannot be achieved.

Adults

Children

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Advise patient if they miss a dose and the next dose is not due within 4 hours they should take the missed dose as soon as possible. If the next dose is due within 4 hours, advise the patient not to take the missed dose and simply resume usual dosing.

Contraindications

Children under 12 years
Weight below 40kg
Breastfeeding
Moderate hepatic impairment
Renal impairment - creatinine clearance below 50ml/minute

Precautions and Warnings

Predisposition to hepatic disorder
Hepatitis
Mild hepatic impairment
Pregnancy
Psychiatric disorder

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm negative HLA-B 5701 allele status in all patients
Treatment should be initiated by doctor experienced in HIV management
Women childbearing potential: Discuss potential risk of neural tube defects
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Exclude pregnancy prior to initiation of treatment
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor for signs of osteonecrosis
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk of hepatic disease
Monitor patients with hepatic impairment
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
Autoimmune diseases may occur during treatment
Consider hypersensitivity if any of:rash/fever/G.I/flu-like or resp.dis.
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of neural tube defects
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if hypersensitivity reactions occur
If allergic reaction occurs discontinue and do not re-initiate treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid multivitamins 2 hours after or 6 hours before dose
Advise to avoid iron containing products 2 hrs after or 6 hrs before dose
Avoid antacids/mineral supplements 2 hrs after or 6 hrs before dose
Female: Ensure adequate contraception during treatment
Advise patients that hypersensitivity reactions may be life threatening

Before treatment all patients, irrespective of racial origin, should be screened for the carriage of HLA-B*5701 allele. Dolutegravir with abacavir and lamivudine should not be used in patients carrying the HLA-B*5701 allele unless no other therapeutic option is available based on treatment history and resistance testing. Presence of this allele confers an increased risk of severe hypersensitivity reactions to abacavir. Treatment should also be avoided in patients with a negative HLA-B*5701 status who had a suspected abacavir hypersensitivity reaction on a previous regime.

Hypersensitivity reactions have been reported with the use of dolutegravir and abacavir individually. These reaction can occur at any time during therapy and can potentially be life threatening. Treatment should be discontinued immediately if hypersensitivity reactions occur or are suspected. If treatment has been discontinued as a result of hypersensitivity or suspected hypersensitivity, treatment must never be reinitiated with this fixed dose presentation or with the individual preparations. Hypersensitivity reactions can present themselves as respiratory disease or gastroenteritis.

Patients who have discontinued treatment for reasons other than hypersensitivity could also experience life threatening reaction within hours of reinitiating. Medical assistance should be readily available if restarting therapy.

Dolutegravir with abacavir and lamivudine should not be co-administered with polyvalent cation-containing antacids. Dolutegravir with abacavir and lamivudine is recommended to be administered 2 hours before or 6 hours after these medicinal products. When taken with food, dolutegravir with abacavir and lamivudine and supplements or multivitamins containing calcium, iron or magnesium can be taken at the same time. If administered under fasting conditions, supplements or multivitamins containing calcium, iron or magnesium are recommended to be taken 2 hours after or 6 hours before dolutegravir with abacavir and lamivudine.

Pregnancy and Lactation

Pregnancy

Use dolutegravir with abacavir and lamivudine with caution during pregnancy.

The manufacturer suggests dolutegravir with abacavir and lamivudine should only be used during pregnancy if the expected benefit justifies the potential risk to the foetus.

At the time of writing there are limited data on the use of dolutegravir in pregnant women. The effect of dolutegravir on human pregnancy is unknown. Reproductive toxicity studies in animals have shown dolutegravir to cross the placenta. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

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.

Abacavir crosses the human placenta. The safety of abacavir administration in human pregnancy has not been established, although retrospective studies of exposed pregnancies reported in Briggs (2011) and Schaefer (2007) do not show a marked increase in the number of birth defects nor a discernible pattern. In animals, the placental transfer of abacavir and/or its related metabolites has occurred. In animal studies, embryo toxicity was observed in rats but this was not seen in rabbits at doses up to 8.5 times human exposure based on AUC.

Lamivudine appears to cross the placenta by diffusion, with cord levels at term similar to maternal blood levels. More than 3000 outcomes from first trimester exposed to lamivudine did not indicate malformative toxicity. The animal and human data suggest that lamivudine is a low risk to the developing foetus for structural malformations.

Lactation

Dolutegravir with abacavir and lamivudine is contraindicated during breastfeeding.

The manufacturer advises that HIV infected mothers should avoid breastfeeding in order to prevent transmission of the disease. HIV is known to be transmitted in milk.

Dolutegravir is excreted in human milk in small amounts. Lamivudine is excreted in human milk at similar concentrations found in serum. Abacavir is also excreted into human milk. The effects to infants are unknown.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Abnormal liver function tests
Adult respiratory distress syndrome
Alopecia
Anaemia
Anaphylaxis
Anorexia
Anxiety
Arthralgia
Asthenia
Autoimmune disorders
Autoimmune hepatitis
Conjunctivitis
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dyspepsia
Dyspnoea
Elevated amylase levels
Erythema multiforme
Fatigue
Fever
Flatulence
Gastroesophageal reflux disease
Graves' disease
Headache
Hepatic failure
Hepatitis
Hyperglycaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Lethargy
Lymphadenopathy
Lymphopenia
Malaise
Metabolic changes
Mouth ulcers
Muscle disorders
Myalgia
Myolysis
Nasal symptoms
Nausea
Neutropenia
Nightmares
Oedema
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pruritus
Rash
Red cell aplasia
Renal failure
Respiratory failure
Rhabdomyolysis
Serum creatinine increased
Severe hepatic reactions
Sleep disorders
Somnolence
Sore throat
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Vomiting
Weight gain

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: December 2018

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: Triumeq 50mg, 300mg, 600mg tablets. Viiv Healthcare. Revised August 2021.