Each film coated tab contains Lopinavir 200 mg and ritonavir 50 mg.
Each ml of oral solution contains Lopinavir 80 mg and ritonavir 20 mg.
Excipients/Inactive Ingredients: Oral solution: Alcohol 42.2 % v/v.
Pharmacology: Pharmacodynamics: Mechanism of Action: Lopinavir and Ritonavir are protease inhibitors. A coformulation of lopinavir and ritonavir. The lopinavir component is the active inhibitor of HIV protease. Lopinavir inhibits HIV protease and renders the enzyme incapable of processing polyprotein precursor which leads to production of noninfectious immature HIV particles. The ritonavir component inhibits the CYP3A metabolism of lopinavir, allowing increased plasma levels of lopinavir.
Pharmacokinetics: Lopinavir and Ritonavir is 98-99% bound to plasma proteins. The plasma half-life in adults averages 5-6 hours for Lopinavir and 3-5 hours for Ritonavir. Lopinavir and Ritonavir are metabolized in the liver and excreted principally in the feces, both as unchanged drug and metabolites. Lopinavir is excreted in urine (2%) and feces (83%, 20% as unchanged drug) and Ritonavir is excreted in urine (11%) and feces (86%, 34% as unchanged drug). Ritonavir is well absorbed following oral administration, and peak plasma concentrations of the drug are attained within 2-4 hours. Oral administration of ritonavir 600 mg every 12 hours in adults with HIV infection results in peak plasma concentrations averaging 11 mcg/mL.
Lopinavir/Ritonavir are indicated for the treatment of HIV-1 infected adults and children above the age of 6 months, in combination with other antiretroviral agents.
Lopinavir/Ritonavir can be taken with or without food.
Lopinavir/Ritonavir should be prescribed by physicians who are experienced in the treatment of HIV infection.
Adults and adolescents:
The tablets should be swallowed whole and not chewed, broken or crushed.
Adults and adolescent use: Oral, 4 tablets (800/200 mg) once daily or 2 tablets (400/100 mg) twice daily.
Children 12 years of age and above: The adult dose of Lopinavir/Ritonavir tablets: 2 tablets (400/100 mg) twice daily. May be used to children 40 kg or greater.
Children 6 months to 12 years of age: Lopinavir/Ritonavir Oral Solution:
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To date, there is limited human experience of acute overdose with Lopinavir/Ritonavir. There is no specific antidote for overdose with Lopinavir/Ritonavir. Treatment of overdose with Lopinavir/Ritonavir consists of general supportive measures including monitoring of vital signs and observation of clinical status of the patient. If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage.
Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since Lopinavir/Ritonavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Note: The solution contains 42.4% alcohol by volume. Overdosage in a child may cause alcohol-related toxicity and may be potentially lethal.
Hypersensitivity to lopinavir, ritonavir or any ingredient in the formulation.
Should not co administer Lopinavir/Ritonavir with drugs that are highly dependent on the cytochrome P-450 (CYP) 3A and for which elevated plasma concentrations are associated with serious and/or life threatening events (e.g., astemizole, terfenadine, cisapride, ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, triazolam).
Concomitant use with certain drugs such as lovastatin, rifampicin, simvastatin, St. John's wort (Hypericum perforatum), fluticasone propionate is not recommended due to the risk of decreased plasma concentrations and reduced clinical effects of Lopinavir/Ritonavir.
Pancreatitis receiving Lopinavir/Ritonavir, including those who developed hypertriglyceridemia. In most of these cases patients have had a prior history of pancreatitis and/or concurrent therapy with other medicinal products associated with pancreatitis. Marked triglycerides elevation is a risk factor for development of pancreatitis. Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis.
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis. Patients who exhibit those signs or symptoms should be evaluated and Lopinavir/Ritonavir should be suspended if pancreatitis is diagnosed.
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors.
There have been reports of increased bleeding, including spontaneous skin haematomas and haemathrosis in patients with haemophilia type A and B treated with protease inhibitors. Haemophilic patients should therefore be made aware of the possibility of increased bleeding.
Lopinavir/Ritonavir has resulted in increase, sometimes marked, in the concentration of total cholesterol and triglycerides. Triglyceride and cholesterol testing is to be performed prior to initiating Lopinavir/Ritonavir therapy and at periodic intervals during therapy. Particular caution should be paid to patients with high values at baseline and with history of lipid disorders.
Use with caution since lopinavir plasma concentration may be increased. Risk of further transaminase elevations in patients with underlying hepatitis B or C or preexisting elevations in transaminases prior to initiation of lopinavir and ritonavir.
Lopinavir/Ritonavir Oral Solution: It contains 42.4% alcohol by volume.
Category C: There are no data from the use of Lopinavir/Ritonavir in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Lopinavir/Ritonavir should not be used during pregnancy unless clearly necessary.
Studies in rats revealed that lopinavir is excreted in the milk. It is not known whether this medicinal product is excreted in human milk. HIV infected women must not breast-feed their infants under any circumstances to avoid transmission of HIV.
The most frequent side-effects associated with lopinavir and ritonavir therapy involve diarrhea, nausea, vomiting, headache, abdominal pain, asthenia, anorexia, dyspepsia, flatulence, weight loss, myalgia, decreased libido, paresthesia, bronchitis, rash, hypogonadism (male), insomnia.
Lopinavir/Ritonavir are inhibitors of the P450 isoform CYP3A. Coadministration of Lopinavir/Ritonavir and drugs primarily metabolised by CYP3A may result in increased plasma concentration of the other drugs, which could increase or prolong its therapeutic and adverse effects. Lopinavir/Ritonavir does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2.
The HMG-CoA reductase inhibitors: simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of Lopinavir/Ritonavir with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis. Caution must also exercised and reduced doses should be considered if Lopinavir/Ritonavir are used concurrently with atorvastatin, which is metabolised to a lesser extent by CYP3A4. If treatment with a HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.
Others: Antiarrhythmics: (bepridil, systemic lidocaine and quinidine): Concentrations may be increased when coadministered with Lopinavir/Ritonavir. Caution is warranted and therapeutic concentration monitoring is recommended when available.
Anticonvulsants: (phenobarbital, phenytoin, carbamazepine): Will induce CYP3A4 and may decrease lopinavir concentrations.
Trazodone: Adverse events of nausea, dizziness, hypotension and syncope were observed following coadministration of trazodone and ritonavir in a clinical study. However, it is unknown whether the combination of Lopinavir/Ritonavir cause a similar increase in trazodone exposure. The combination should be used with caution and a lower dose of trazodone should be considered.
Calcium channel blockers: (e.g. felodipine, nifedipine, nicardipine): Serum concentrations may be increased by Lopinavir/Ritonavir.
Phosphodiesterase inhibitors: Lopinavir/Ritonavir may result in an increase PDE5 inhibitor associated adverse reactions including hypotension, syncope, visual changes and prolonged erection. Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Lopinavir/Ritonavir. Increase monitoring for adverse events.
Ketoconazole and Itraconazole: Serum concentrations may be increased be Lopinavir/Ritonavir. High doses of ketoconazole and itraconzole (> 200 mg/day) are not recommended.
Voriconazole: Due to the potential for reduced voriconazole concentrations, co-administration of voriconazole and low dose ritonavir (100 mg twice daily) as contained in Lopinavir/Ritonavir should be avoided unless an assessment of the benefit/risk to patient justifies the use of voriconazole.
Methadone: Lopinavir/Ritonavir was demonstrated to lower plasma concentrations of methadone. Monitoring plasma concentrations of methadone is recommended.
Special precautions for storage: Lopinavir/Ritonavir Tablets: Store below 30°C.
Lopinavir/Ritonavir Oral Solution: Store between 2 to 8°C for 24 months, if store below 25°C must use in 2 months.
Shelf-life: Lopinavir/Ritonavir tablets: 24 months.
Lopinavir/Ritonavir Oral Solution: 24 months (2-8°C). 2 months (below 25° C).
J05AR10 - lopinavir and ritonavir ; Belongs to the class of antivirals for treatment of HIV infections, combinations.
FC tab (light yellow to yellow, oval shaped, with "GLR" marked on one side and plain on the other side) x 120's. Oral soln (clear light yellow to orange) 60 mL x 1's.