Drugs List

Therapeutic Indications

Uses

Antiretroviral combination therapy- HIV infected adults & children >14 days

Contraindications

Acute porphyria
Acute renal failure
Breastfeeding
Hereditary fructose intolerance
Long QT syndrome
Pregnancy
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Asian ancestry
Family history of long QT syndrome
Restricted potassium intake
Alcoholism
Brain damage
Cardiac conduction defects
Electrolyte imbalance
Epileptic disorder
Haemophilia
Hepatitis B
Hepatitis C
History of pancreatitis
History of torsade de pointes
Hypertriglyceridaemia
Mild hepatic impairment
Mild renal impairment
Structural cardiac disorder

Correct electrolyte disorders before treatment
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Monitor TSH when starting/stopping treatment if concurrent levothyroxine
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Contains alcohol
Contains fructose
Contains potassium; caution in low potassium diets
Oral liquid contains propylene glycol
Oral solution contains glycerol
Some formulations contain castor oil polyoxyl which may cause diarrhoea
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Consider monitoring ECG in patients at risk of QT prolongation
Monitor patient closely for signs and symptoms of toxicity
Monitor patients with decreased ability to metabolise propylene glycol
Monitor patients with hepatic impairment
Monitor renal function in patients with renal impairment
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum electrolytes
Monitor serum lipase in patients at risk of pancreatitis
Advise patient to report unexplained nausea,vomiting,abdominal pain
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider discontinuation if pancreatitis occurs
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Advise patient not to take St John's wort concurrently
Female: Barrier or non-hormonal contraception advised during treatment
Advise haemophiliac patients of possibility of increased bleeding

Modest asymptomatic prolongation of the PR interval has been observed in some healthy adult subjects. Rare reports of 2nd or 3rd degree atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients also receiving drugs known to prolong the PR interval have been reported. Lopinavir with ritonavir should therefore be used with caution in such patients.

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.

The oral solution contains alcohol (42% v/v), which is potentially harmful to those suffering from hepatic disease, alcoholism, epilepsy, brain injury or brain disease as well as for children and pregnant women. It may modify or increase the effects of other medicines.

Oral solution contains propylene glycol. Patients with hepatic impairment and decreased ability to metabolise propylene glycol (e.g asian ancestry) should be monitored for potential adverse reactions related to propylene glycol toxicity (i.e. seizures, stupor, tachycardia, hyperosmolarity, lactic acidoses, renal toxicity, haemolysis).

Attention should be paid to the total amounts of alcohol and propylene glycol given to infants in order to avoid toxicity from these excipients. Infants should be monitored closely for any signs of toxicity.

Pregnancy and Lactation

Pregnancy

Lopinavir with ritonavir oral solution is contraindicated during pregnancy.

The manufacturer states that the prevalence of birth defects in newborns exposed to lopinavir with ritonavir in any trimester is comparable to the general population and contraindicates the use of the oral solution formulation of lopinavir with ritonavir during pregnancy due to potential risk of toxicity from the excipient propylene glycol. Oral solid formulations are available as an alternative.

Animal studies have shown reproductive toxicity, with Briggs (2015) suggesting a moderate risk in human pregnancy but concluding that the drug should not be withheld because of pregnancy if clinically necessary.

Lactation

Lopinavir with ritonavir is contraindicated in breastfeeding women. It is recommended that HIV infected women do not breast feed their infants in order to avoid transmission of HIV.

It is not known whether this medicinal product is excreted in human milk; little data are available on the use of lopinavir in combination with ritonavir in breastfeeding. Animal studies suggest the drug is excreted in the milk. Use in breastfeeding is contraindicated by the manufacturer.

The molecular weight of lopinavir and ritonavir combined, together with their lipid solubility, suggests that the drugs will be excreted in human breast milk, but that high protein binding should limit this excretion (Briggs 2015).

Side Effects

Abdominal distension
Abdominal pain
Alopecia
Anaemia
Angioedema
Anxiety
Arteriosclerosis
Arthralgia
Asthenia
Atrioventricular block
Autoimmune hepatitis
Back pain
Cellulitis
Cerebrovascular accident
Cholangitis
Colitis
Constipation
Convulsions
Decrease in creatinine clearance
Deep vein thrombosis (DVT)
Dermatitis
Diabetes mellitus
Diarrhoea
Disturbances of appetite
Dizziness
Dream abnormalities
Dry mouth
Duodenitis
Dyspepsia
Eczema
Erectile dysfunction
Erythema multiforme
Faecal incontinence
Fatigue
Flatulence
Folliculitis
Furunculosis
Gastritis
Gastro-enteritis
Gastro-intestinal ulceration
Gastroesophageal reflux disease
Gastrointestinal bleeding
Graves' disease
Haematuria
Haemorrhoids
Headache
Hepatic steatosis
Hepatitis
Hepatomegaly
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypogonadism
Immune Reactivation/Reconstitution Syndrome
Increase of liver transaminases
Insomnia
Insulin resistance
Jaundice
Leucopenia
Maculopapular rash
Menstrual disturbances
Migraine
Mouth ulcers
Muscle disorders
Muscle spasm
Muscle weakness
Musculoskeletal pain
Myalgia
Myocardial infarction
Nausea
Nephritis
Neuropathy
Neutropenia
Night sweats
Osteonecrosis
Pancreatitis
Prolongation of PR interval
Pruritus
Rash
Rectal haemorrhage
Reduced libido
Respiratory tract infection
Rhabdomyolysis
Skin infection
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Tinnitus
Tremor
Tricuspid valve incompetence
Urticaria
Vasculitis
Vertigo
Visual disturbances
Vomiting
Weight changes

Presentation

Oral solution containing lopinavir and ritonavir.

Drugs List

Therapeutic Indications

Uses

Antiretroviral combination therapy- HIV infected adults & children >14 days

Dosage

The decision to treat protease inhibitor experienced HIV-1 infected patients with lopinavir and ritonavir should be based on individual viral resistance testing and treatment history of patients.

Adults

Children

Additional Dosage Information

Contraindications

Acute porphyria
Acute renal failure
Breastfeeding
Hereditary fructose intolerance
Long QT syndrome
Pregnancy
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Asian ancestry
Family history of long QT syndrome
Restricted potassium intake
Alcoholism
Brain damage
Cardiac conduction defects
Electrolyte imbalance
Epileptic disorder
Haemophilia
Hepatitis B
Hepatitis C
History of pancreatitis
History of torsade de pointes
Hypertriglyceridaemia
Mild hepatic impairment
Mild renal impairment
Structural cardiac disorder

Correct electrolyte disorders before treatment
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Monitor TSH when starting/stopping treatment if concurrent levothyroxine
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Contains alcohol
Contains fructose
Contains potassium; caution in low potassium diets
Oral liquid contains propylene glycol
Oral solution contains glycerol
Some formulations contain castor oil polyoxyl which may cause diarrhoea
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Consider monitoring ECG in patients at risk of QT prolongation
Monitor patient closely for signs and symptoms of toxicity
Monitor patients with decreased ability to metabolise propylene glycol
Monitor patients with hepatic impairment
Monitor renal function in patients with renal impairment
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum electrolytes
Monitor serum lipase in patients at risk of pancreatitis
Advise patient to report unexplained nausea,vomiting,abdominal pain
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider discontinuation if pancreatitis occurs
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Advise patient not to take St John's wort concurrently
Female: Barrier or non-hormonal contraception advised during treatment
Advise haemophiliac patients of possibility of increased bleeding

Modest asymptomatic prolongation of the PR interval has been observed in some healthy adult subjects. Rare reports of 2nd or 3rd degree atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients also receiving drugs known to prolong the PR interval have been reported. Lopinavir with ritonavir should therefore be used with caution in such patients.

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.

The oral solution contains alcohol (42% v/v), which is potentially harmful to those suffering from hepatic disease, alcoholism, epilepsy, brain injury or brain disease as well as for children and pregnant women. It may modify or increase the effects of other medicines.

Oral solution contains propylene glycol. Patients with hepatic impairment and decreased ability to metabolise propylene glycol (e.g asian ancestry) should be monitored for potential adverse reactions related to propylene glycol toxicity (i.e. seizures, stupor, tachycardia, hyperosmolarity, lactic acidoses, renal toxicity, haemolysis).

Attention should be paid to the total amounts of alcohol and propylene glycol given to infants in order to avoid toxicity from these excipients. Infants should be monitored closely for any signs of toxicity.

Pregnancy and Lactation

Pregnancy

Lopinavir with ritonavir oral solution is contraindicated during pregnancy.

The manufacturer states that the prevalence of birth defects in newborns exposed to lopinavir with ritonavir in any trimester is comparable to the general population and contraindicates the use of the oral solution formulation of lopinavir with ritonavir during pregnancy due to potential risk of toxicity from the excipient propylene glycol. Oral solid formulations are available as an alternative.

Animal studies have shown reproductive toxicity, with Briggs (2015) suggesting a moderate risk in human pregnancy but concluding that the drug should not be withheld because of pregnancy if clinically necessary.

Lactation

Lopinavir with ritonavir is contraindicated in breastfeeding women. It is recommended that HIV infected women do not breast feed their infants in order to avoid transmission of HIV.

It is not known whether this medicinal product is excreted in human milk; little data are available on the use of lopinavir in combination with ritonavir in breastfeeding. Animal studies suggest the drug is excreted in the milk. Use in breastfeeding is contraindicated by the manufacturer.

The molecular weight of lopinavir and ritonavir combined, together with their lipid solubility, suggests that the drugs will be excreted in human breast milk, but that high protein binding should limit this excretion (Briggs 2015).

Side Effects

Abdominal distension
Abdominal pain
Alopecia
Anaemia
Angioedema
Anxiety
Arteriosclerosis
Arthralgia
Asthenia
Atrioventricular block
Autoimmune hepatitis
Back pain
Cellulitis
Cerebrovascular accident
Cholangitis
Colitis
Constipation
Convulsions
Decrease in creatinine clearance
Deep vein thrombosis (DVT)
Dermatitis
Diabetes mellitus
Diarrhoea
Disturbances of appetite
Dizziness
Dream abnormalities
Dry mouth
Duodenitis
Dyspepsia
Eczema
Erectile dysfunction
Erythema multiforme
Faecal incontinence
Fatigue
Flatulence
Folliculitis
Furunculosis
Gastritis
Gastro-enteritis
Gastro-intestinal ulceration
Gastroesophageal reflux disease
Gastrointestinal bleeding
Graves' disease
Haematuria
Haemorrhoids
Headache
Hepatic steatosis
Hepatitis
Hepatomegaly
Hyperbilirubinaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypogonadism
Immune Reactivation/Reconstitution Syndrome
Increase of liver transaminases
Insomnia
Insulin resistance
Jaundice
Leucopenia
Maculopapular rash
Menstrual disturbances
Migraine
Mouth ulcers
Muscle disorders
Muscle spasm
Muscle weakness
Musculoskeletal pain
Myalgia
Myocardial infarction
Nausea
Nephritis
Neuropathy
Neutropenia
Night sweats
Osteonecrosis
Pancreatitis
Prolongation of PR interval
Pruritus
Rash
Rectal haemorrhage
Reduced libido
Respiratory tract infection
Rhabdomyolysis
Skin infection
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Tinnitus
Tremor
Tricuspid valve incompetence
Urticaria
Vasculitis
Vertigo
Visual disturbances
Vomiting
Weight changes

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 2020

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.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 April 2018

MHRA Drug Safety Update October 2018
Available at: https://www.mhra.gov.uk
Last accessed: 11/02/2019

Summary of Product Characteristics: Kaletra 80mg/20mg oral solution. AbbVie Limited. Revised October 2019.