1.Name of the medicinal product

Artemether and Lumefantrine Tablets BP 80mg+480mg Taj Pharma

2.Qualitative and quantitative composition

Artemether And Lumefantrine Tablets
Each uncoated tablet contains:
Artemether ………….. 80 mg
Lumefantrine …………….. 480 mg

3.Pharmaceutical form

Oral tablet

4.Description

ARTEMETHER AND Lumefantrine tablets are fixed-dose combination (FDC) tablets containing artemether and lumefantrine, indicated for the treatment of Plasmodium falciparum (P. falciparium) malaria cases resistant to both chloroquine and the sulphadoxine-pyrimethamine combination.

5.CLINICAL PHARMACOLOGY

Pharmacodynamics

Both artemether and lumefantrine act as blood schizontocides.

The site of the antiparasitic action of both the components of the combination 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 non- toxic haemozoin malaria pigment.

Parasites in the infected erythrocytes ingest and degrade haemoglobin and concentrate the iron in a food vacuole in the form of toxic haem. Normally, the haem is then made harmless by conversion into haemozoin.

Artemether is concentrated in the food vacuole. It then splits its endoperoxide bridge as it interacts with haem, blocking conversion to haemozoin, destroying the existing haemozoin and releasing haem and a cluster of free radicals into the parasite.

Lumefantrine is thought to interfere with the haem polymerization process, a critical detoxifying pathway for the malaria parasite.

Both artemether and lumefantrine have a secondary action involving the inhibition of nucleic acid and protein synthesis within the malarial parasite.

The artemether and lumefantrine combination is active against the blood stages of Plasmodium vivax (P. vivax), but is not active against hypnozoites. Therefore, an 8-amino-quinoline derivative such as primaquine should be given sequentially after the combination in cases of mixed infections of P. falciparum and P. vivax to achieve hypnozoites eradication. The combination is also associated with rapid gametocyte clearance.

Pharmacokinetics

Absorption
Following administration of artemether-lumefantrine tablets to healthy volunteers and patients with malaria, artemether is absorbed fairly rapidly, with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag-up to 2 hours, with peak plasma concentrations about 6 to 8 hours after administration.

Food enhances the absorption of both artemether and lumefantrine. In healthy volunteers, the relative bioavailability of artemether was increased between 2- to 3-fold, and that of lumefantrine 16-fold when artemether-lumefantrine tablets were taken after a high-fat meal, compared under fasted conditions. Patients should be encouraged to take artemether-lumefantrine tablets with a meal as soon as food can be tolerated.

Distribution
Both artemether and lumefantrine are highly bound to human serum proteins In vitro (95.4% and 99.7%, respectively). The artemether metabolite, dihydroartemisinin (DHA), is also bound to human serum proteins (47 to 76%). Protein binding to human plasma proteins is linear.

Metabolism
In human liver microsomes and recombinant cytochrome (CY) P450 enzymes, the metabolism of artemether was catalysed predominantly by CYP3A4/5. DHA is an active metabolite of artemether. The metabolism of artemether was also catalysed to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. In vitro studies with artemether at therapeutic concentrations revealed no significant inhibition of the metabolic activities of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CY12D6, CYP2E1, CYP3A4/5 and CYP4A9/11.

During repeated administration of artemether-lumefantrine tablets, the systemic exposure of artemether decreased significantly, while concentrations of DHA increased, although not to a statistically significant degree. The artemether/DHA area under the curve (AUC) ratio is 1.2 after a single dose and 0.3 after six doses given over 3 days. This suggests that there was induction of CYP3A4/5, which was responsible for the metabolism of artemether.

In human liver microsomes and in recombinant CYP450 enzymes, lumefantrine was metabolized mainly by CYP3A4 to desbutyl-Iumefantrine. The systemic exposure to the metabolite, desbutyl-Iumefantrine, was less than 1% of the exposure to the parent compound. In vitro, lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations.

Caution is recommended when combining artemether-lumefantrine tablets with substrates, inhibitors or inducers of CYP3A4, especially antiretroviral (ARV) drugs and those that prolong the QT interval (e.g., macrolide antibiotics, pimozide, terfenadine, astemizole, cisapride).

Co-administration of artemether and lumefantrine tablets with CYP2D6 substrates may result in increased plasma concentrations of the CYP2D6 substrate and increase the risk of adverse reactions. In addition, many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with artemether-lumefantrine tablets due to the potential additive effect on the QT interval (e.g. flecainide, imipramine, amitriptyline, clomipramine).

Elimination
Artemether and DHA are cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated more slowly, with a terminal half-life of 3 to 6 days in healthy volunteers and in patients with falciparum malaria. Demographic characteristics such as sex and weight appear to have no clinically relevant effects on the pharmacokinetics of artemether and lumefantrine.

In 16 healthy volunteers, neither lumefantrine nor artemether was found in the urine after administration of artemether-lumefantrine, and urinary excretion of DHA amounted to less than 0.01% of the artemether dose.

Hepatic and Renal Impairment
No specific pharmacokinetic studies have been performed in patients with either hepatic or renal impairment. There is no significant renal excretion of lumefantrine, artemether and DHA in healthy volunteers and while clinical experience in this population is limited, no dose adjustment in renal impairment is recommended.

Geriatric Patients
No specific pharmacokinetic studies have been performed in patients older than 65 years of age.

Indications

Artemether and lumefantrine Tablets are indicated for the treatment of P. falciparum malaria cases that are resistant to both chloroquine and the sulphadoxine-pyrimethamine combination. This combination is not recommended for the first-line treatment of malaria.

Limitations of Use

  • Artemether and lumefantrine Tabletsshould not be used to treat patients with severe or complicated  Falciparum malaria.
  • Artemether and lumefantrine Tabletsshould not be used for the prevention of malaria.

Dosage and Administration

Artemether And Lumefantrine Tablets should be taken with food. Patients with acute malaria are frequently averse to food. Patients should be encouraged to resume normal eating as soon as food can be tolerated since this improves the absorption of artemether and lumefantrine.

For patients who are unable to swallow the tablets such as infants and children, artemether and lumefantrine tablets may be crushed and mixed with a small amount of water (one to two teaspoons) in a clean container for administration immediately prior to use. The container can be rinsed with more water and the contents swallowed by the patient. The crushed tablet preparation should be followed whenever possible by food/drink (e.g., milk, formula, pudding, broth, and porridge).

In the event of vomiting within 1 to 2 hours of administration; a repeat dose should be taken. If the repeat dose is vomited, the patient should be given an alternative antimalarial for treatment.

Adult Patients (>16 Years of Age)

A 3-day treatment schedule with a total of six doses is recommended for adult patients with a body weight of 35 kg and above:

  • One tablet as a single initial dose, one tablet again after 8 hours and, then, one tablet twice daily (morning and evening) for the following 2 days (total course of six tablets).

Paediatric Patients (≥35 kg)

A 3-day treatment schedule with a total of six doses as described above is recommended for children weighing 35 kg and above.

Patients with Hepatic or Renal Impairment

No specific pharmacokinetic studies have been carried out in patients with hepatic or renal impairment. Most patients with acute malaria present with some degree of related hepatic and/or renal impairment. In clinical studies, the adverse event profile did not differ in patients with mild or moderate hepatic impairment compared to patients with normal hepatic function. No specific dose adjustments are needed for patients with mild or moderate hepatic impairment.

In clinical studies, the adverse event profile did not differ in patients with mild or moderate renal impairment compared to patients with normal renal function. There were few patients with severe renal impairment in clinical studies. There is no significant renal excretion of lumefantrine, artemether and DHA in healthy volunteers and while clinical experience in this population is limited, no dose adjustment is recommended.

Caution should be exercised when administering artemether-lumefantrine tablets to patients with severe hepatic or renal impairment.

Geriatric Patients

Although no studies have been carried out in the elderly, no special precautions or dosage adjustments are considered necessary in such patients.

Contraindications

Artemether-lumefantrine tablets are contraindicated in the following:

  • In patients hypersensitive to artemether, lumefantrine or to any of the excipients of the tablet.
  • In cases of severe malaria.
  • In the first trimester of pregnancy.
  • In patients with a family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as patients with a history of symptomatic cardiac arrhythmias, patients with clinically relevant bradycardia or with severe cardiac disease, family history of sudden death, disturbance of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia.
  • Concomitant use of drugs that are known to be metabolized by CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
  • Co-administration of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St John’s wort with artemether-lumefantrine tablets can result in decreased concentrations of artemether and/or lumefantrine and loss of anti-malarial efficacy
  • Patients taking drugs that are known to prolong the QTc interval such as anti-arrhythmics of classes IA (quinidine, procainamide, disopyramide) and III (amiodarone, sotalol), neuroleptics, antipsychotics (pimozide, ziprasidone), antidepressant agents and certain antibiotics, including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents.
  • Patients receiving medications that are metabolized by the cytochrome enzyme CYP2D6 which also have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine) (see Warnings and Precautions)

Artemether and lumefantrine tablets are not indicated for prophylaxis or for treating severe malaria, including cerebral malaria, or malaria with pulmonary oedema or renal failure. They are also not indicated for and have not been evaluated in the treatment of malaria due to P. vivax, P. malariae or P. ovale.

Warnings and Precautions

Prolongation of the QT Interval

Some antimalarial (e.g. halofantrine, quinine, quinidine), including artemether-lumefantrine tablets, have been associated with prolongation of the QT interval on the electrocardiogram.

Use of QT-Prolonging Drugs and Other Antimalarials

Halofantrine and artemether-lumefantrine tablets should not be administered within 1 month of each other due to the long elimination half-life of lumefantrine (3 to 6 days) and potential additive effects on the QT interval.

An antimalarial should not be given concomitantly with artemether-lumefantrine tablets unless there is no other treatment option, due to limited safety data.

Drugs that prolong the QT interval, including antimalarials such as quinine and quinidine, should be used cautiously following artemether-lumefantrine tablets, due to the long elimination half-life of lumefantrine (3 to 6 days) and the potential for additive effects on the QT interval. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required (see Drug interactions)

If mefloquine is administered immediately prior to artemether-lumefantrine, there may be a decreased exposure to lumefantrine, possibly due to a mefloquine-induced decrease in bile production. Therefore, patients should be monitored for decreased efficacy and food consumption should be encouraged while taking artemether-lumefantrine tablets (see Drug Interactions).

Drug Interactions with CYP3A4

When artemether-lumefantrine tablets are co-administered with substrates of CYP3A4, it may result in decreased concentrations of the substrate and potential loss of substrate efficacy. When artemether-lumefantrine tablets are co-administered with an inhibitor of CYP3A4, including grapefruit juice, it may result in increased concentrations of artemether and/or lumefantrine and potentiate QT prolongation. When artemether-lumefantrine tablets are co-administered with inducers of CYP3A4, it may result in decreased concentrations of artemether and/or lumefantrine and loss of anti-malarial efficacy (see Drug Interactions).

Drugs that have a mixed effect on CYP3A4, especially ARV drugs such as HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, and those that have an effect on the QT interval should be used with caution in patients taking artemether-lumefantrine tablets (see Drug Interactions).

Artemether-lumefantrine tablets may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral contraceptives, a transdermal patch or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control (see Drug Interactions).

Drug Interactions with CYP2D6

Administration of artemether-lumefantrine tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the co-administered drug and increase the risk of adverse effects. Many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with artemether-lumefantrine tablets due to the potential additive effect on the QT interval (e.g. flecainide, imipramine, amitriptyline, clomipramine) (see Drug Interactions).

Recrudescence

Food enhances the absorption of artemether and lumefantrine following administration of artemether-lumefantrine tablets. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be greater.

In the event of recrudescent P. Falciparum infection after treatment with artemether-lumefantrine tablets, patients should be treated with a different antimalarial drug.

  1. vivax Infection
    Artemether-lumefantrine tablets have been shown in limited data (43 patients) to be effective in treating the erythrocytic stage of P. Vivaxinfection. However, relapsing malaria caused by P. Vivaxrequires additional treatment with other antimalarial agents to achieve a radical cure, i.e. eradicate any hypnozoites forms that may remain dormant in the liver.

Drug interactions

Rifampin
Oral administration of rifampin, a strong CYP3A4 inducer, with artemether-lumefantrine tablets resulted in significant decreases in exposure to artemether, DHA (the metabolite of artemether) and lumefantrine by 89%, 85% and 68%, respectively, when compared to exposure values after artemether-lumefantrine tablets alone. Concomitant use of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St John’s wort is contraindicated with artemether-lumefantrine tablets.

Ketoconazole
In a study of 15 healthy subjects, concurrent oral administration of ketoconazole, a potent CYP3A4 inhibitor, with a single dose of artemether-lumefantrine tablets resulted in a moderate increase in exposure to artemether, DHA (the metabolite of artemether), and lumefantrine. No dose adjustment of artemether-lumefantrine tablets is necessary when administered with ketoconazole or other potent CYP3A4 inhibitors. However, due to the potential for increased concentrations of lumefantrine, which could lead to QT prolongation, artemether-lumefantrine tablets should be used cautiously with drugs that inhibit CYP3A4 (e.g. grapefruit juice).

Prior Use of Mefloquine
Administration of three doses of mefloquine, followed 12 hours later by a six-dose regimen of artemether-lumefantrine tablets in 14 healthy volunteers demonstrated no effect of mefloquine on plasma concentrations of artemether or the artemether DHA ratio. However, exposure to lumefantrine was reduced, possibly due to lower absorption secondary to a mefloquine-induced decrease in bile production. Patients should be monitored for decreased efficacy and food consumption should be encouraged with the administration of artemether-lumefantrine tablets.

Antiretroviral Drugs
Both artemether and lumefantrine are metabolized by CYP3A4. Antiretroviral drugs, such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors, are known to have variable patterns of inhibition, induction or competition for CYP3A4. Therefore, the effects of antiretroviral drugs on the exposure to artemether, DHA, and lumefantrine are also variable. Artemether-lumefantrine tablets should be used cautiously in patients on anti-retroviral drugs because decreased artemether, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of artemether-lumefantrine tablets, and increased lumefantrine concentrations may cause QT prolongation

Hormonal Contraceptives
In vitro, the metabolism of ethinyl estradiol and levonorgestrel was not induced by artemether, DHA or lumefantrine. However, artemether has been reported to weakly induce, in humans, the activity of CYP2C19, CYP2B6 and CYP3A. Therefore, artemether-lumefantrine tablets may potentially reduce the effectiveness of hormonal contraceptives. Patients using oral contraceptives, transdermal patch or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control

CYP2D6 Substrates
Lumefantrine inhibits CYP2D6 In vitro. Administration of artemether-lumefantrine tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the co-administered drug and increase the risk of adverse effects. Many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with artemether-lumefantrine tablets due to the potential additive effect on the QT interval (e.g. flecainide, imipramine, amitriptyline, clomipramine).

Sequential Use of Quinine
A single dose of intravenous quinine (10 mg/kg body weight) concurrent with the final dose of a 6-dose regimen of artemether-lumefantrine tablets demonstrated no effect of intravenous quinine on the systemic exposure of DHA or lumefantrine. Quinine exposure was also not altered. Exposure to artemether was decreased. This decrease in artemether exposure is not thought to be clinically significant. However, quinine and other drugs that prolong the QT interval should be used cautiously following treatment with artemether-lumefantrine tablets due to the long elimination half-life of lumefantrine and the potential for additive QT effects; ECG monitoring is advised if use of drugs that prolong the QT interval is medically required .(see Warnings and Precautions)

Pregnancy

Pregnancy Category C Safety data from an observational pregnancy study of approximately 500 pregnant women who were exposed to artemether-lumefantrine tablets (including a third of patients who were exposed in the first trimester), and published data of over 1,000 pregnant patients who were exposed to artemisinin derivatives, did not show an increase in adverse pregnancy outcomes or teratogenic effects over the background rate.

The efficacy of artemether-lumefantrine tablets in the treatment of acute, uncomplicated malaria in pregnant women has not been established. However, it is contraindicated during the first trimester of pregnancy.

In the second trimester, treatment with artemether-lumefantrine tablets should only be considered if the potential benefit justifies the potential risk to the foetus.

Lactation

It is not known whether artemether or lumefantrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when artemether-lumefantrine tablets are administered to a nursing mother. Animal data suggest that both artemether-lumefantrine are excreted into breast milk. The benefits of breastfeeding to the mother and the infant should be weighed against the potential risks from exposure of the infant to artemether-lumefantrine through breast milk.

Paediatric Use

Artemether and lumefantrine Tablets can be used in children weighing 35 kg and above.

Geriatric Use

Clinical studies of artemether-lumefantrine tablets did not include sufficient numbers of subjects aged 65 years and over to determine if they respond differently from younger subjects. In general, the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing artemether-lumefantrine tablets.

Hepatic and Renal Impairment

Artemether-lumefantrine tablets have not been studied for efficacy and safety in patients with severe hepatic and/or renal impairment (see DOSAGE AND ADMINISTRATION).

Undesirable Effects

Hypersensitivity reactions have been reported during post marketing surveillance.

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice.

The data described below reflect exposure to a 6-dose regimen of artemether-lumefantrine tablets in 1,979 patients, including 647 adults (older than 16 years) and 1,332 children (16 years and younger). For the 6-dose regimen, artemether-lumefantrine tablets were studied in active-controlled (366 patients) and non-controlled, open-label trials (1,613 patients). The 6-dose artemether-lumefantrine tablets population was patients with malaria between the ages of 2 months and 71 years; 67% (1,332) were 16 years and younger and 33% (647) were older than 16 years. Males represented 73% and 53% of the adult and paediatric populations, respectively. The majority of adult patients were enrolled in studies in Thailand, while the majority of paediatric patients were enrolled in Africa.

Tables 1 and 2 show the most frequently reported adverse reactions (≥3%) in adults and children, respectively, who received the 6-dose regimen of artemether-lumefantrine tablets. Adverse reactions collected in clinical trials included signs and symptoms at baseline, but only treatment-emergent adverse events, defined as events that appeared or worsened after the start of treatment, are presented below. In adults, the most frequently reported adverse reactions were headache, anorexia, dizziness and asthenia. In children, the adverse reactions were pyrexia, cough, vomiting, anorexia and headache. Most adverse reactions were mild, did not lead to discontinuation of study medication, and resolved.

In limited comparative studies, the adverse reaction profile of artemether-lumefantrine tablets appeared similar to that of another antimalarial regimen.

Discontinuation of artemether-lumefantrine tablets due to adverse drug reactions occurred in 1.1% of patients treated with the 6-dose regimen overall: 0.2% (1/647) in adults and 1.6% (21/1,332) in children.

The adverse reactions occurring in 3% or more of adult patients treated in clinical trials with the 6-dose regimen of artemether-lumefantrine tablets are as follows:

Table 1: Adverse Reactions Occurring in 3% or More of Adult Patients Treated in Clinical Trials with the 6-Dose Regimen of Artemether-Lumefantrine Tablets

System Organ Class Preferred term Adults*
N=647 (%)
Nervous system disoracrs Headache 360(56)
Dizziness 253(39)
Metabolism and nutrition disorders Anorexia 260(40)
General disorders and administration site conditions Aslneina 243(38)
Pyrexia 159(25)
Chills 147(23)
Fatigue 111(17)
Malaise 20(3)
Musculoskeletal and connective tissue disorders Arthralgia 219(34)
Myalgia 206(32)
Gastrointestinal disorders Nausea 169(26)
Vomiting 113(17)
Abdominal pain 112(17)
Diarrhea 46(7)
Psychiatric disorders Sleep disorder 144(22)
Insomnia 32(5)
Cardiac disorders Palpitations 115(18)
Hepatobiliary disorders Hepatomegaly 59(9)
Blood and lymphatic system disorders Splenomegaly 57(9)
Anemia 23(4)
Respiratory, thoracic and mediastinal disorders cough 37(6)
Skin and subcutaneous tissue disorders Pruriius 24(4)
Rash 21(3)
Ear and labyrinth disorders Vertigo 21(3)
Infections and infestations Malaria 18(3)
Nasopharyngitis 17(3)

* Adult patients defined as >16 years of age.

Table 2: Adverse Reactions Occurring in 3% or More of Paediatric Patients Treated in Clinical Trials with the 6-dose Regimen of Artemether-Lumefantrine Tablets

System Organ Class Preferred term Children*
N=1,332 (%)
General disorders and administration site conditions Pyrexia
Chills
Asthenia
Fatisue
381 (29)
72 (5)
63 (5)
46 (3)
Respiratory, thoracic and mediastinal disorders Cough 302 (3)
Gastrointestinal disorders Vomiting
Abdominal pam
Diarrhea
Nausea
242 (18)
112 (8)
100 (8)
61 (5)
Infections and infestations Plasmodium falciparum infection
Rhinitis
224 (17)
51 (4)
Metabolism and nutrition disorders Anorexia 175 (13)
Nervous system disorders Headache
Dizziness
168 (13)
56 (4)
Blood and lymphatic system disorders Splenomegaly
Anemia
124 (9)
115 (9)
Hepatobiliary disorders Hepatomesaly 75 (6)
Investisations Aspartate aminotransferase increased 51 (4)
Musculoskeletal and connective tissue disorders Arthralgia
Myalgia
39 (3)
39 (3)
Skin and subcutaneous tissue disorders Rash 38 (3)

* Children defined as patients less than or equal to 16 years of age

Clinically significant adverse reactions reported in adults and/or children treated with the 6-dose regimen of artemether-lumefantrine tablets, which occurred in clinical studies at

  • Blood and Lymphatic System Disorders: Eosinophilia
  • Ear and Labyrinth Disorders:Tinnitus
  • Eye Disorders:Conjunctivitis
  • Gastrointestinal Disorders:Constipation, dyspepsia, dysphagia, peptic ulcer
  • General Disorders:Gait disturbance
  • Infections and Infestations:Abscess, acrodermatitis, bronchitis, ear infection, gastroenteritis, helminthic infection, hookworm infection, impetigo, influenza, lower respiratory tract infection, malaria, nasopharyngitis, oral herpes, pneumonia, respiratory tract infection, subcutaneous abscess, upper respiratory tract infection, urinary tract infection
  • Investigations:Alanine aminotransferase increased, aspartate aminotransferase increased, haematocrit decreased, lymphocyte morphology abnormal, platelet count decreased, platelet count increased, white blood cell count decreased, white blood cell count increased
  • Metabolism and Nutrition Disorders:Hypokalaemia
  • Musculoskeletal and Connective Tissue Disorders:Back Pain
  • Nervous System disorders:Ataxia, clonus, fine motor delay, hyper-reflexia, hypoaesthesia, nystagmus, tremor
  • Psychiatric Disorders:Agitation, mood swings
  • Renal and Urinary Disorders:Haematuria, proteinuria
  • Respiratory, Thoracic and Mediastinal Disorders:Asthma, pharyngo-laryngeal pain
  • Skin and Subcutaneous Tissue Disorders:Urticaria

Post marketing Experience

The following adverse reactions have been identified during post-approval use of artemether-lumefantrine tablets. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

  • Hypersensitivity, including urticaria and angio-oedema. Serious skin reactions (bullous eruption) have been rarely reported.

Overdosage

There is no information on overdoses of artemether-lumefantrine tablets higher than the doses recommended for treatment.

In cases of suspected overdosage, symptomatic and supportive therapy, which would include electrocardiographic and blood electrolyte monitoring, should be given as appropriate.

Storage and Handling Instructions

Store in a cool, dry, dark place.

Packaging Information

Artemether And Lumefantrine Tablets: Blister pack of 6 tablets

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com