COMPOSITION
LONART® TABLETS
Each film coated tablet contains:
| Ingredient | Strength |
|---|---|
| Artemether | 20 mg |
| Lumefantrine | 120 mg |
| Excipients | q.s. |
LONART® FORTE TABLETS
Each film coated tablet contains:
| Ingredient | Strength |
|---|---|
| Artemether | 40 mg |
| Lumefantrine | 240 mg |
| Excipients | q.s. |
LONART®-DS TABLETS
Each film coated tablet contains:
| Ingredient | Strength |
|---|---|
| Artemether | 80 mg |
| Lumefantrine | 480 mg |
| Excipients | q.s. |
PHARMACOLOGY
Pharmacodynamics
Lonart comprises a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively.
The site of antiparasitic action of both components is the food vacuole of the malarial parasite, where they are thought to interfere with the conversion of haem, a toxic intermediate produced during haemoglobin breakdown, to the nontoxic haemozoin, malaria pigment.
Lumefantrine is thought to interfere with the polymerisation process, while artemether generates reactive metabolites as a result of the interaction between its peroxide bridge and haem iron.
Both artemether and lumefantrine have a secondary action involving inhibition of nucleic acid- and protein synthesis within the malarial parasite.
Pharmacokinetics
Artemether is absorbed fairly rapidly and dihydroartemisinin, the active metabolite of artemether, appears rapidly in the systemic circulation with peak plasma concentrations of both compounds reached about 2 hours after dosing.
Food enhances the absorption of both artemether and lumefantrine. In healthy volunteers the relative bioavailability of artemether was increased more than two-fold, and that of lumefantrine sixteen-fold compared with fasted conditions when Lonart was taken after a high-fat meal.
Artemether and lumefantrine are both highly bound to human serum proteins in vitro (95.4% and 99.7%, respectively).
Dihydroartemisinin is also bound to human serum proteins (47–76%).
Artemether is rapidly and extensively metabolised (substantial first-pass metabolism) both in vitro and in humans.
Artemether and dihydroartemisinin are rapidly cleared from plasma with a terminal half-life of about 2 hours.
Lumefantrine is eliminated very slowly with an elimination half-life of 2 to 6 days.
INDICATIONS
For treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum.
DOSAGE AND ADMINISTRATION
Dosage
Refer figure 1 & 2.
Method of administration
Tablets for oral administration.
To increase absorption, Lonart should be taken with food or a milky drink.
If patients are unable to tolerate food, Lonart should be administered with water, but the systemic exposure may be reduced.
Patients who vomit within 1 hour of taking the medication should repeat the dose.
CONTRAINDICATIONS
Patients with known hypersensitivity to the active substances or to any of the excipients of this formulation.
Patients with severe malaria according to WHO definition*.
Patients who are taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (e.g. Metoprolol, Imipramine, Amitriptyline, Clomipramine).
Patients with a family history of sudden death or of congenital prolongation of the QTc interval on electrocardiograms, or with any other clinical condition known to prolong the QTc interval.
Patients taking drugs that are known to prolong the QTc interval (proarrythmic). These drugs include:
Antiarrhythmics of classes IA and III
Neuroleptics
Antidepressive agents
Certain antibiotics including some agents of the following classes:
Macrolides
Fluoroquinolones
Imidazole and triazole antifungal agents
Certain non-sedating antihistamines (terfenadine, astemizole)
Cisapride
Flecainide
Patients with a history of symptomatic cardiac arrythmias or with clinically relevant bradycardia or with congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
Patients with disturbances of electrolyte balance e.g. hypokalemia or hypomagnesemia.
Patients taking drugs that are strong inducers of CYP3A4 such as:
Rifampin
Carbamazepine
Phenytoin
St. John's wort (Hypericum perforatum)
Clinical manifestation
Prostration
Impaired consciousness or unarousable coma
Failure to feed
Deep breathing, respiratory distress (acidotic breathing)
Multiple convulsions
Circulatory collapse or shock
Pulmonary edema (radiological)
Abnormal bleeding
Clinical jaundice
Hemoglobinuria
Laboratory test
Severe normocytic anemia
Hemoglobuniuria
Hypoglycemia
Metabolic acidosis
Renal impairment
Hyperlactatemia
Hyperparasitemia
Pregnancy and Lactation
Lonart treatment must not be used during the first trimester of pregnancy in situations where other suitable and effective antimalarials are available. However, it should not be withheld in life threatening situations, where no other effective antimalarials are available.
During the second and third trimester, treatment should only be considered if the expected benefit to the mother outweighs the risk to the foetus.
Breast-feeding should not resume until at least one week after the last dose of Lonart unless potential benefits to the mother and child outweigh the risks of Lonart treatment.
Warnings and Precautions
Lonart must not be used in the first trimester of pregnancy in situations where other suitable and effective antimalarials are available.
Lonart has not been evaluated for the treatment of severe malaria, including cases of cerebral malaria or other severe manifestations such as pulmonary oedema or renal failure.
Due to limited data on safety and efficacy, Lonart should not be given concurrently with any other antimalarial agent unless there is no other treatment option.
If a patient deteriorates whilst taking Lonart, alternative treatment for malaria should be started without delay. In such cases, monitoring of the ECG is recommended and steps should be taken to correct any electrolyte disturbances.
The long elimination half-life of lumefantrine must be taken into account when administering quinine in patients previously treated with Lonart.
If quinine is given after Lonart, close monitoring of the ECG is advised.
If Lonart is given after mefloquine, close monitoring of food intake is advised.
In patients previously treated with halofantrine, Lonart should not be administered earlier than one month after the last halofantrine dose.
Lonart is not indicated and has not been evaluated for prophylaxis of malaria.
Lonart should be used cautiously in patients on antiretroviral drugs (ARTs) since decreased artemether, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of Lonart.
Like other antimalarials (e.g. halofantrine, quinine and quinidine) Lonart has the potential to cause QT prolongation.
Caution is recommended when combining Lonart with drugs exhibiting variable patterns of inhibition, moderate induction or competition for CYP3A4 as the therapeutic effects of some drugs could be altered.
Caution is recommended when combining Lonart with hormonal contraceptives.
Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be greater.
Renal impairment
No dose adjustment for the use of Lonart in patients with renal impairment is recommended.
Caution is advised when administering Lonart to patients with severe renal impairment.
In these patients, ECG and blood potassium monitoring is advised.
Hepatic impairment
Caution should be exercised in dosing patients with severe hepatic impairment.
In these patients, ECG and blood potassium monitoring is advised.
No dose adjustment is recommended for patients with mild to moderate hepatic impairment.
Older people
There is no information suggesting that the dosage in patients over 65 years of age should be different than in younger adults.
New infections
Data for a limited number of patients in a malaria endemic area show that new infections can be treated with a second course of Lonart.
In the absence of carcinogenicity study data, and due to lack of clinical experience, more than two courses of Lonart cannot be recommended.
Effects on Ability to Drive and Use Machines
Patients receiving Lonart should be warned that dizziness or fatigue/asthenia may occur in which case they should not drive or use machines.
Drug Interactions
If Lonart is given following administration of mefloquine or quinine, close monitoring of food intake (for mefloquine) or of the ECG (for quinine) is advised.
Lonart should be used cautiously with drugs that inhibit CYP3A4 and are contraindicated with drugs which additionally are known to prolong QTc.
Lonart should be used cautiously in patients on ARTs since decreased artemether, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of Lonart, and increased lumefantrine concentrations may cause QT prolongation.
Interaction with drugs metabolized by CYP2D6 e.g. neuroleptics, metoprolol, and tricyclic antidepressants such as imipramine, amitriptyline, clomipramine.
Grapefruit juice should be used cautiously during Lonart treatment.
Adverse Effects
The commonly reported adverse effects with artemether-lumefantrine are:
Decreased appetite
Psychiatric disorders
Sleep disorders
Insomnia
Headache
Dizziness
Paraesthesia
Clonus
Palpitations
Electrocardiogram QT prolonged
Cough
Vomiting
Abdominal pain
Nausea
Diarrhoea
Liver function tests increased
Rash
Pruritus
Arthralgia
Myalgia
Asthenia
Fatigue
Gait disturbance
Overdose
In cases of suspected overdosage symptomatic and supportive therapy should be given as appropriate, which should include ECG and blood potassium monitoring.
Storage
Store in the original package below 30°C.
Keep out of reach and sight of children.
Date of Publication/Review
07/2023
Adverse Reaction Reporting
If you have any questions about this product or would like to report an adverse reaction contact us by:
Phone: 0018888306075
Email: drug.safety@blissgvs.com