Abacavir/ Lamivudine/ Lopinavir/ Ritonavir

Registered South African indications: 

• HIV-1 infection
  - In children aged ≥3 months, who have been stabilised on concomitant use of abacavir, lamivudine, lopinavir, and ritonavir as separate formulations before switching to the fixed-dose combination, provided that similar doses of the active ingredients can be achieved with this combination agent

Hypersensitivity to abacavir Abacavir, contained in this combination product, is associated with a risk for hypersensitivity reactions (HSR) characterised by fever and/or rash with other symptoms indicating multi-organ involvement. HSR can be life-threatening, and may be fatal, when not managed appropriately. The risk for abacavir HSR to occur is significantly increased for patients who test positive for the HLA-B*5701 allele. However, abacavir HSRs have been reported at a lower frequency in patients who do not carry this allele. In clinical studies conducted before the introduction of screening for the HLA-B*5701 allele, approximately 5% of subjects receiving abacavir developed a hypersensitivity reaction. In some cases, this proved fatal. Risk factors Studies have shown that carriage of the HLA B*5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir It is recommended that any HIV-infected patient without prior exposure to abacavir be screened for the HLA-B5701 allele. Screening is recommended prior to re-initiation of abacavir in patients of unknown HLA-B5701 status who have previously tolerated abacavir. Use of abacavir in patients known to carry the HLA-B*5701 allele is not recommended Clinical description The hypersensitivity reaction is characterised by the appearance of symptoms indicating multi-organ/body-system involvement. Most patients have fever and/or rash as part of the syndrome. Some of the other symptoms of hypersensitivity may include fatigue, malaise, gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and abdominal pain, and respiratory signs and symptoms such as dyspnoea, sore throat, cough, and abnormal chest X-ray findings (predominantly infiltrates, which can be localised) The symptoms of this hypersensitivity reaction can occur at any time during treatment with abacavir, but usually occur within the first six weeks of therapy. The symptoms worsen with continued therapy and can be life-threatening. These symptoms usually resolve upon discontinuation of abacavir Clinical management Regardless of their HLA-B*5701 status, any patients developing signs or symptoms of hypersensitivity must contact their healthcare provider immediately for advice If a hypersensitivity reaction is diagnosed, this combination product must be discontinued immediately. This combination product, or any other medicine containing abacavir, must never be restarted following a hypersensitivity reaction, as more severe symptoms may recur within hours and may include life-threatening hypotension and death. To avoid a delay in diagnosis and minimise the risk of a life-threatening hypersensitivity reaction, this combination product should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g. respiratory diseases, flu-like illness, gastro-enteritis, or reactions to other medicines). This combination product, or any other medicine containing abacavir, should not be restarted even if a recurrence of symptoms occurs following rechallenge with alternative medication(s). An Alert Card with information for the patient about the hypersensitivity reaction is included in this combination product pack. Special considerations following an interruption of therapy Regardless of a patient’s HLA-B*5701 status, if therapy with this combination product has been discontinued and restarting therapy is under consideration, the reason for discontinuation should be evaluated to ensure that the patient did not have symptoms of a hypersensitivity reaction. If a hypersensitivity reaction cannot be ruled out, this combination product or any other medicine containing abacavir should not be restarted. There have been infrequent reports of hypersensitivity reactions following re-introduction of abacavir, where the interruption was preceded by a single key symptom of hypersensitivity (rash, fever, malaise/fatigue, gastrointestinal symptoms, or a respiratory symptom). If a decision is made to restart treatment in these patients, this should be done only under direct medical supervision. Hypersensitivity reactions have been reported in patients who have restarted therapy and who had no preceding symptoms of a hypersensitivity reaction. If a decision is made to restart this combination product, this must be done only if medical care can be readily accessed by the patient or others. Screening for carriage of the HLA-B5701 allele is recommended prior to re-initiation of this combination product in patients of unknown HLA-B5701 status who have previously tolerated this combination product. Re-initiation of treatment in such patients who test positive for the HLA-B*5701 allele is not recommended. Essential patient information: Prescribers must ensure that patients are fully informed regarding the following information on the hypersensitivity reaction Patients must be made aware of the possibility of a hypersensitivity reaction to abacavir that may result in a life-threatening reaction or death and that the risk of a hypersensitivity reaction is increased if they are HLA-B*5701-positive Patients must also be informed that HLA-B*5701-negative patients can also experience abacavir hypersensitivity reactions. Therefore, any patient who develops signs or symptoms consistent with a possible hypersensitivity reaction to abacavir must contact their healthcare provider immediately Patients who are hypersensitive to abacavir should be reminded that they must never take this combination product or any other medicine containing abacavir again, regardless of their HLA-B*5701 status To avoid restarting this combination product, patients who have experienced a hypersensitivity reaction to abacavir should be asked to return the remaining product to the pharmacy Patients who have stopped treatment for any reason, and particularly due to possible adverse reactions or illness, must be advised to contact their healthcare provider before restarting Each patient should be reminded to read the professional information included in this combination product pack. They should always be reminded of the importance of removing the Alert Card included in the pack and keeping it with them

 

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• History of severe hypersensitivity reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any component
• Pregnancy
• Breastfeeding
• Moderate (Child-Pugh class B) or severe hepatic impairment (Child-Pugh class C)
• Coadministration with medicines highly dependent on CYP3A for clearance and associated with serious/life-threatening reactions
  • Alfuzosin (alpha 1-adrenoreceptor antagonist)
  • Ranolazine (antianginal)
  • Dronedarone (antidysrhythmic)
  • Fusidic acid (antibiotic)
  • Neratinib (anticancer)
  • Colchicine in renal and/or hepatic impairment (anti-gout)
  • Astemizole (antihistamine)
  • Blonanserin, lurasidone, pimozide (antipsychotics)
  • Ergot derivatives (ergotamine, dihydroergotamine, ergonovine, methylergonovine)
  • Cisapride (GI motility medicine)
  • Elbasvir/grazoprevir (Hepatitis C direct-acting antiviral)
  • Lovastatin, simvastatin (HMG-CoA reductase inhibitors)
  • Salmeterol (long-acting beta-adrenoceptor agonist)
  • Lomitapide (microsomal triglyceride transfer protein (MTTP) inhibitor)
  • Sildenafil for pulmonary arterial hypertension (PDE5 inhibitor)
  • Triazolam, midazolam (sedative/hypnotics)
• Coadministration with potent CYP3A inducers, which may cause significant reduction in lopinavir plasma concentrations
  • Rifampicin (antimycobacterial)
  • St. John's Wort (Hypericum perforatum) (herbal product)

South African recommendations

Caution in the following patient groups

• Moderate to severe renal impairment
• Mild hepatic impairment (Child-Pugh class A)
• Elderly

Hypersensitivity to abacavir

• Some patients with the HLA-B*5701 allele developed abacavir-associated hypersensitivity reactions, which were fatal in some cases (see Boxed Warning)
• Hypersensitivity is characterised by the appearance of symptoms indicating multi-organ/body-system involvement
• Patients who develop a hypersensitivity reaction must discontinue abacavir/lamivudine/lopinavir/ritonavir and must not be rechallenged with Abacavir/lamivudine/lopinavir/ritonavir, or any other product containing abacavir

Lactic acidosis / hyperlactataemia

• Long-term use of abacavir/lamivudine/lopinavir/ritonavir can result in potentially fatal lactic acidosis due to mitochondrial dysfunction
• Clinical features include nausea, vomiting, abdominal pain, dyspnoea, tachypnoea, fatigue, and weight loss
• Suspicious biochemical features include raised transaminases, lactate dehydrogenase (LDH), and/or creatine kinase
• If lactate >10mmol/L, stop all therapy immediately (80% mortality)
• Diagnosis of lactic acidosis is confirmed by demonstrating metabolic acidosis with an increased anion gap and raised serum lactate level

Mitochondrial dysfunction

• Nucleoside and nucleotide analogues cause mitochondrial damage, and have been associated with haematological disorders (anaemia, neutropenia) and peripheral neuropathy
• Any foetus exposed to nucleoside and nucleotide analogues in utero should be followed up for possible mitochondrial dysfunction if relevant signs or symptoms appear

Pancreatitis

• Pancreatitis has been observed in patients receiving lopinavir/ritonavir, including those with marked triglyceride elevations
• Patients with advanced HIV disease may be at increased risk for elevated triglycerides and pancreatitis
• Patients with a history of pancreatitis may be at increased risk for recurrence during abacavir/lamivudine/lopinavir/ritonavir therapy

Patients with moderate to severe renal impairment

• In patients with moderate to severe renal impairment, the terminal half-life of abacavir/lamivudine/lopinavir/ritonavir is increased, and dosage adjustment is required

Liver disease

• Use of abacavir/lamivudine/lopinavir/ritonavir can result in hepatomegaly due to non-alcoholic fatty liver disease (hepatic steatosis)
• The safety and efficacy of abacavir/lamivudine/lopinavir/ritonavir have not been established in patients with significant underlying liver disorders/diseases

Patients with HIV and hepatitis B or C virus co-infection

• Patients with chronic hepatitis B or C and treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions
• Patients co-infected with HIV and HBV who discontinue abacavir/lamivudine/lopinavir/ritonavir should be closely monitored after stopping treatment

Lipodystrophy and metabolic abnormalities

• Combination antiretroviral therapy has been associated with fat redistribution/accumulation, central obesity, peripheral wasting, and elevated serum lipid and glucose levels

Immune Reconstitution Inflammatory Syndrome (IRIS)

• In HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunistic infections may occur, causing aggravation of symptoms

Diabetes mellitus / hyperglycaemia

• New onset diabetes mellitus and exacerbation of pre-existing diabetes mellitus have been reported with protease inhibitor therapy

Opportunistic infections

• Patients receiving abacavir/lamivudine/lopinavir/ritonavir may still develop opportunistic infections and should remain under close clinical observation

Risk of transmission to others

• Abacavir/lamivudine/lopinavir/ritonavir has not been proven to prevent the risk of HIV transmission through sexual contact or blood contamination

Myocardial infarction

• Use of abacavir in combination with other antiretroviral therapies has been associated with an increased risk of myocardial infarction

Osteonecrosis

• Osteonecrosis has been reported, particularly in patients with advanced HIV disease or long-term exposure to combination antiretroviral therapy

Resistance / cross-resistance

• Various degrees of cross-resistance among protease inhibitors have been observed

Haemophilia

• There have been reports of increased bleeding in patients with haemophilia type A and B treated with protease inhibitors

PR interval prolongation

• Protease inhibitors have been shown to cause modest asymptomatic prolongation of the PR interval
• Use abacavir/lamivudine/lopinavir/ritonavir with caution in patients with underlying structural heart disease or conduction system abnormalities

Lipid elevations

• Protease inhibitors, including abacavir/lamivudine/lopinavir/ritonavir, have resulted in increases in total cholesterol and triglycerides

Carcinogenicity

• An increased incidence of malignant and non-malignant tumours occurred in rats and mice administered abacavir. The carcinogenic potential is not known in humans. However, it is thought that the potential clinical benefit outweighs the clinical carcinogenic risk in humans

Excipients

• Abacavir/lamivudine/lopinavir/ritonavir contains sucrose, which should be avoided in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency
• Abacavir/lamivudine/lopinavir/ritonavir contains aspartame, which is not suitable for patients with phenylketonuria

Effect on ability to drive and use machines

• There are less frequent reports of visual impairment due to use of abacavir/lamivudine/lopinavir/ritonavir. Patients need to be aware of how this treatment affects them before engaging in potentially dangerous activities such as driving or operating machinery

Not indicated for use in adults

Paed. forms avail. in SA and covered in this monograph: cap

South African registered indications and dosages

Patients should be screened for the HLA-B*5701 allele prior to initiating therapy with this combination agent (see boxed warning)

HIV-1 infection
- In children aged ≥3 months, weighing ≥3 to ≤19.9kg (WHO weight band 1 ( WB 1), WB 2, WB 3 and WB 4), who have been stabilised on concomitant use of abacavir, lamivudine, lopinavir, and ritonavir as separate formulations before switching to the fixed-dose combination, provided that similar doses of the active ingredients can be achieved with this combination agent

Abacavir/ Lamivudine/ Lopinavir/ Ritonavir
30/15/40/10 (mg)

• Oral (cap): Admin. contents of the cap twice dly with age-appropriate soft food/liquid according to weight band as per the below table

Weight (in kg)	Number of capsules to be administered
	In the morning	In the evening
3.0 to 5.9	2	2
6.0 to 9.9	3	3
10.0 to 13.9	4	4
14.0 to 19.9	5	5

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Abacavir/lamivudine/lopinavir/ritonavir should not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days has been attained

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Dose adjustment
In case of concomitant therapy with efavirenz or nevirapine, a dose increase of lopinavir and ritonavir may be required. However, precise dose titration will not be possible with this combination agent. Thus, it is recommended that other formulation of individual components be used in this situation

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Method of administration
Capsules should not be swallowed whole
Contents of the capsules should be administered with age-appropriate soft food/liquid (See Additional Prescribing Points)

Pregnancy 

South African recommendations

• Contraindicated
• Abacavir/lamivudine/lopinavir/ritonavir is contraindicated during pregnancy
• Abacavir: Safety in human pregnancy has not been established. Abacavir should not be used during pregnancy and lactation since teratogenicity and/ or foetal toxicity cannot be excluded
• Lamivudine: Lamivudine has not been studied in pregnant women. However, use of NRTIs in pregnancy has been associated with mild and transient elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum. The clinical relevance of elevations in serum lactate is unknown. There have also been reports of developmental delay, seizures and other neurological disease

Breastfeeding

South African recommendations

• Contraindicated
• Studies have indicated that components of this combination product (abacavir, lamivudine and lopinavir) are excreted in breast milk. Therefore, nursing mothers should not breastfeed their children while on abacavir/lamivudine/lopinavir/ritonavir therapy

Fertility

South African recommendations

• There are no data on fertility

South African recommendations

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended
  In patients with moderate to severe renal impairment, the terminal half-life of this combination product is increased due to decreased clearance. The dose of abacavir/lamivudine/lopinavir/ritonavir should therefore be adjusted
  Lamivudine concentrations are increased in patients with moderate to severe renal impairment due to decreased clearance

South African recommendations

• Mild (Child-Pugh class A): Caution; no dose adjustment recommended
• Moderate (Child-Pugh class B) or severe (Child-Pugh class C): Contraindicated

South African recommendations

• Caution; no information available

Infections and Infestations

Lopinavir/ritonavir component

Frequent

• Upper respiratory tract infection
• Lower respiratory tract infection
• Skin infections including cellulitis, folliculitis, and furuncle

Less frequent

• Otitis media
• Bronchitis
• Sinusitis
• Furunculosis
• Bacterial infection
• Viral infection
• Pharyngitis
• Flu syndrome
• Gastroenteritis
• Sialadenitis

Neoplasms Benign, Malignant and Unspecified (including cysts and polyps)

Lopinavir/ritonavir component

Less frequent

• Skin benign neoplasm
• Cyst
• Neoplasm

Blood and Lymphatic System Disorders

Lamivudine component

Less frequent

• Neutropenia
• Anaemia
• Thrombocytopenia
• Pure red cell aplasia

Lopinavir/ritonavir component

Frequent

• Anaemia
• Leucopenia
• Lymphadenopathy
• Neutropenia

Immune System Disorders

Lopinavir/ritonavir component

Frequent

• Hypersensitivity including urticaria and angioedema

Less frequent

• Immune reactivation syndrome

Endocrine Disorders

Lopinavir/ritonavir component

Less frequent

• Hypogonadism
• Cushing syndrome
• Hypothyroidism

Metabolism and Nutrition Disorders

Abacavir component

Frequent

• Anorexia

Lamivudine component

Frequent

• Hyperlactataemia

Less frequent

• Lactic acidosis
• Lipodystrophy (redistribution/ accumulation of body fat)

Lopinavir/ritonavir component

Frequent

• Hypercholesterolemia
• Hypertriglyceridemia
• Lactic acidosis
• Blood glucose disorders including diabetes mellitus, hyperglycaemia, decreased appetite

Less frequent

• Avitaminosis
• Dehydration
• Increased appetite
• Obesity
• Anorexia
• Weight gain
• Weight loss

Psychiatric Disorders

Lopinavir/ritonavir component

Frequent

• Anxiety

Less frequent

• Abnormal dreams
• Agitation
• Anxiety
• Confusion
• Depression
• Emotional lability
• Decreased libido
• Nervousness
• Abnormal thinking
• Apathy

Nervous System Disorders

Abacavir component

Frequent

• Headache

Lamivudine component

Frequent

• Headache

Less frequent

• Paraesthesia
• Peripheral neuropathy

Lopinavir/ritonavir component

Frequent

• Headache (including migraine)
• Neuropathy including (peripheral neuropathy)
• Dizziness
• Insomnia

Less frequent

• Amnesia
• Ataxia
• Encephalopathy
• Facial paralysis
• Hypertonia
• Neuropathy
• Paraesthesia
• Peripheral neuritis
• Somnolence
• Tremor
• Taste loss
• Taste perversion
• Migraine
• Dyskinesia
• Cerebral infarct
• Convulsion
• Extrapyramidal syndrome

Eye Disorders

Lopinavir/ritonavir component

Less frequent

• Abnormal vision
• Eye disorders

Ear and Labyrinth Disorders

Lopinavir/ritonavir component

Less frequent

• Tinnitus
• Vertigo

Cardiac Disorders

Lopinavir/ritonavir component

Less frequent

• Atherosclerosis
• Myocardial infarction
• Angina pectoris
• Atrioventricular block
• Tricuspid valve incompetence

Vascular Disorders

Lopinavir/ritonavir component

Less frequent

• Hypertension
• Thrombophlebitis
• Vasculitis
• Varicose vein
• Deep thrombophlebitis
• Vascular disorder
• Postural hypotension

Respiratory, Thoracic and Mediastinal Disorders

Lopinavir/ritonavir component

Less frequent

• Dyspnoea
• Rhinitis
• Asthma
• Lung oedema
• Increased coughing

Gastrointestinal Disorders

Abacavir component

Frequent

• Nausea
• Vomiting
• Diarrhoea

Lamivudine component

Frequent

• Nausea
• Vomiting
• Upper abdominal pain
• Diarrhoea

Less frequent

• Pancreatitis
• Rises in serum amylase

Lopinavir/ritonavir component

Frequent

• Diarrhoea
• Nausea
• Pancreatitis
• Vomiting
• Gastro oesophageal reflux disease
• Gastroenteritis and colitis abdominal pain (upper and lower)
• Abdominal distension
• Dyspepsia
• Haemorrhoids
• Flatulence

Less frequent

• Gastrointestinal haemorrhage including gastrointestinal ulcer
• Duodenitis
• Gastric ulcer
• Gastritis
• Mouth ulcerations
• Rectal haemorrhage
• Stomatitis
• Faecal incontinence
• Constipation
• Dry mouth

Hepato-biliary Disorders

Lamivudine component

Less frequent

• Transient rises in liver enzymes (AST, ALT)

Lopinavir/ritonavir component

Frequent

• Hepatitis including AST, ALT and GGT increases

Less frequent

• Cholecystitis
• Cholangitis
• Jaundice
• Hepatomegaly
• Liver fatty deposit
• Liver tenderness

Skin and Subcutaneous Tissue Disorders

Lamivudine component

Frequent

• Rash
• Alopecia

Lopinavir/ritonavir component

Frequent

• Rash including maculo papular rash
• Dermatitis/ rash including eczema and seborrheic dermatitis
• Night sweats
• Pruritus
• Alopecia
• Capillaritis
• Vasculitis

Less frequent

• Dry skin
• Exfoliative dermatitis
• Stevens-Johnson syndrome
• Erythema multiforme
• Alopecia
• Eczema
• Exfoliative dermatitis
• Maculopapular rash
• Nail disorder
• Pruritis
• Seborrhoea
• Skin discolouration
• Skin ulcer
• Face oedema
• Acne
• Sweating
• Skin striae

Musculoskeletal and Connective Tissue Disorders

Lamivudine component

Frequent

• Arthralgia
• Muscle disorders

Less frequent

• Rhabdomyolysis

Lopinavir/ritonavir component

Frequent

• Myalgia
• Musculoskeletal pain including arthralgia and back pain
• Muscle disorders such as weakness and spasms

Less frequent

• Rhabdomyolysis
• Osteonecrosis

Renal and Urinary Disorders

Lopinavir/ritonavir component

Less frequent

• Creatinine clearance decreased
• Nephritis
• Haematuria

Reproductive System and Breast Disorders

Lopinavir/ritonavir component

Frequent

• Erectile dysfunction
• Menstrual disorders
• Amenorrhoea and menorrhagia

Less frequent

• Ejaculation disorder
• Breast enlargement
• Gynaecomastia

General Disorders and Administration Site Conditions

Abacavir component

Frequent

• Fever
• Lethargy
• Fatigue

Lamivudine component

Frequent

• Fatigue
• Malaise
• Fever

Lopinavir/ritonavir component

Frequent

• Fatigue including asthenia

Less frequent

• Chest pain
• Chest pain substernal
• Chills
• Fever
• Malaise
• Pain
• Peripheral oedema
• Medicine interaction
• Oedema
• Hypertrophy

Post-marketing Data
(Post-marketing side effects reported from individual formulations of abacavir/lamivudine/lopinavir/ritonavir)

Blood and Lymphatic System Disorders

Abacavir component

• Lymphopenia

Metabolism and Nutrition Disorders

Abacavir component

• Hyperlactataemia
• Lactic acidosis

Nervous System Disorders

Abacavir component

• Headache
• Paraesthesia

Cardiac Disorders

Lopinavir/ritonavir component

• Bradydysrhythmia

Respiratory, Thoracic and Mediastinal Disorders

Abacavir component

• Dyspnoea
• Cough
• Sore throat
• Adult respiratory distress syndrome
• Respiratory failure

Gastrointestinal Disorders

Abacavir component

• Pancreatitis
• Nausea
• Vomiting
• Diarrhoea
• Abdominal pain
• Mouth ulceration

Hepato-biliary Disorders

Abacavir component

• Elevated liver function tests
• Hepatic failure

Lopinavir/ritonavir component

• Hepatitis

Skin and Subcutaneous Tissue Disorders

Abacavir component

• Rash (maculopapular or urticarial)
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Lopinavir/ritonavir component

• Stevens-Johnson Syndrome
• Erythema multiforme

Musculoskeletal and Connective Tissue Disorders

Abacavir component

• Myalgia
• Myolysis
• Arthralgia
• Elevated creatine phosphokinase

Renal and Urinary Disorders

Abacavir component

• Elevated creatinine
• Renal failure

General Disorders and Administrative Site Conditions

Abacavir component

• Fever
• Fatigue
• Malaise
• Oedema
• Lymphadenopathy
• Hypotension
• Conjunctivitis
• Anaphylaxis

Clinical Trials Experience in Paediatric Subjects

Abacavir and Lamivudine

• No additional safety issues identified in paediatric subjects compared to adults

Lopinavir and Ritonavir

• In paediatric patients aged six months to 12 years, the adverse event profile was similar to that observed in adults

Abacavir/ Lamivudine/ Lopinavir/ Ritonavir

• Alfuzosin
• Ranolazine
• Fusidic acid
• Astemizole
• Blonanserin
• Lurasidone
• Pimozide
• Ergot derivatives
• Ergotamine
• Dihydroergotamine
• Ergonovine
• Methylergonovine
• Cisapride
• Elbasvir/grazoprevir
• Salmeterol
• Triazolam
• Midazolam
• Tenofovir
• Nevirapine
• Efavirenz
• Delavirdine
• Etravirine
• Rilpivirine
• Boceprevir
• Glecaprevir/pibrentasvir
• Ombitasvir/paritaprevir/ritonavir and dasabuvir
• Simeprevir
• Sofosbuvir/velpatasvir/voxilaprevir
• Telaprevir
• Fentanyl
• Methadone
• Rifampicin
• Bedaquiline
• Delamanid
• Atovaquone
• St. John's Wort (Hypericum perforatum)
• Ethinyl estradiol

Abacavir

• Retinoids
• Isotretinoin

Lamivudine

• Trimethoprim
• Trimethoprim/sulphamethoxazole (Co-trimoxazole)
• Zalcitabine
• Emtricitabine

Lopinavir/Ritonavir

• Medicines primarily metabolised by CYP3A
• Dihydropyridine calcium channel blockers
• HMG-CoA reductase inhibitors
• Immunosuppressants
• PDE5 inhibitors
• Amprenavir
• Fosamprenavir
• Indinavir
• Nelfinavir
• Ritonavir
• Saquinavir
• Maraviroc
• Amiodarone
• Bepridil
• Dronedarone
• Lidocaine (Lignocaine)
• Quinidine
• Digoxin
• Abemaciclib
• Dasatinib
• Ibrutinib
• Neratinib
• Nilotinib
• Venetoclax
• Vincristine
• Vinblastine
• Warfarin
• Rivaroxaban
• Bupropion
• Trazodone
• Phenobarbital
• Phenytoin
• Carbamazepine
• Lamotrigine
• Valproate
• Colchicine
• Ketoconazole
• Itraconazole
• Voriconazole
• Clarithromycin
• Rifabutin
• Quetiapine
• Dexamethasone
• Fluticasone
• Budesonide
• Triamcinolone (Injectable)
• Felodipine
• Nifedipine
• Nicardipine
• Avanafil
• Sildenafil
• Tadalafil
• Vardenafil
• Lovastatin
• Simvastatin
• Atorvastatin
• Pravastatin
• Fluvastatin
• Lomitapide
• Cyclosporin
• Tacrolimus
• Sirolimus (Rapamycin)
• Bosentan

• Screening for the HLA-B*5701 allele
• CD4 count and viral load
• Lipid profile
  • Triglyceride and cholesterol

Specific cases may require

• Hepatic function
• Blood glucose
• Electrocardiogram (ECG)
• Cardiovascular risk assessment
• Venous lactate level and serum bicarbonate in suspected lactic acidosis

Additional observations

• Signs and symptoms of mitochondrial dysfunction
• Evaluation for physical signs of fat redistribution
• Signs and symptoms of hypersensitivity

Method of administration with milk/drinking water

• Obtain the prescribed number of capsules needed for a dose
• Dose the required number of capsules one by one
• Hold one capsule vertically with the brown cap at the top and white body at the bottom and then gently tap on top of the capsule. Open the capsule by gently twisting and pulling up the cap
• Pour the contents of capsule into a spoon
• Add milk/drinking water to the spoon till the spoon fills and feed to the child immediately
• Repeat this step for the prescribed number of capsules. Additional milk/drinking water can be taken after each dose if required
• Refer to product specific information for diagrammatic guidance

Method of administration with soft food (e.g. porridge or mashed fruit)

• Prepare porridge/ fruit and cool to room temperature
• Obtain the prescribed number of capsules needed for a dose
• Dose the required number of capsules one by one
• Take a small amount of porridge or fruit on the spoon
• Hold one capsule vertically with the brown cap at the top and white body at the bottom and then gently tap on top of the capsule. Open the capsule by gently twisting and pulling up the cap
• Pour the contents of capsule on the spoon containing porridge / fruit and feed to the child immediately. The porridge/ fruit with the drug sprinkled on top should be swallowed immediately and should not be stored for future use
• Repeat this step for the prescribed number of capsules
• Administration of the required dose should be followed by more food or drinking water/ milk, to ensure that no granules remain in the mouth
• Refer to product specific information for diagrammatic guidance

Abacavir
Abacavir is a nucleoside analogue reverse transcriptase inhibitor that is metabolised intracellularly to the active moiety, carbovir 5’-triphosphate (TP), which inhibits the HIV reverse transcriptase enzyme, resulting in chain termination and interruption of the viral replication cycle. Abacavir is a selective inhibitor of HIV-1 and HIV-2, including HIV-1 isolates with reduced susceptibility to zidovudine, lamivudine, zalcitabine, didanosine, or nevirapine. It showed synergy in vitro in combination with nevirapine and zidovudine and was shown to be additive in combination with didanosine, zalcitabine, lamivudine, and stavudine.

Lamivudine
Lamivudine is a selective inhibitor of HIV-1 and HIV-2 replication in vitro. It is also active against zidovudine-resistant clinical isolates of HIV. Lamivudine is metabolised intracellularly to the 5'-triphosphate, which has an intracellular half-life of 16-19 hours. Lamivudine 5'-triphosphate is a weak inhibitor of the RNA- and DNA-dependent activities of HIV reverse transcriptase, its mode of action being chain termination of HIV reverse transcription. Lamivudine does not interfere with cellular deoxynucleotide metabolism and has little effect on mammalian cell and mitochondrial DNA content. In vitro, lamivudine demonstrates low cytotoxicity to peripheral blood lymphocytes, established lymphocyte and monocyte-macrophage cell lines, and a variety of bone marrow progenitor cells.

Lopinavir
Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases.

Ritonavir
Ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir. Inhibition of HIV protease prevents cleavage of the gag-pol polyprotein, resulting in the production of immature, non-infectious virus.

Combination Abacavir/ Lamivudine/ Lopinavir/ Ritonavir 

Capsule (30 mg/15 mg/40 mg/10 mg)

• Quadrimune (Cipla Medpro) originator