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Coartem

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Coartem uses


1 INDICATIONS AND USAGE

Coartem (artemether/lumefantrine) Tablets are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above. Coartem Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported [see Clinical Studies (14.1)].

Limitations of Use :

2 DOSAGE AND ADMINISTRATION

5 to <15 kg 1 tablet
15 to <25 kg 2 tablets
25 to <35 kg 3 tablets
35 kg and over 4 tablets

2.1 Administration Instructions

Coartem 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 absorption of Coartem and lumefantrine.

For patients who are unable to swallow the tablets such as infants and children, Coartem Tablets may be crushed and mixed with a small amount of water (1 to 2 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.

2.2 Dosage in Adult Patients

A 3-day treatment schedule with a total of 6 doses is recommended for adult patients with a bodyweight of 35 kg and above:

Four tablets as a single initial dose, 4 tablets again after 8 hours and then 4 tablets twice-daily (morning and evening) for the following 2 days (total course of 24 tablets).

For patients weighing less than 35 kg, see Dosage in Pediatric Patients (2.3).

2.3 Dosage in Pediatric Patients

A 3-day treatment schedule with a total of 6 doses is recommended as below:

5 kg to less than 15 kg bodyweight: One tablet as an initial dose, 1 tablet again after 8 hours and then 1 tablet twice-daily for the following 2 days (total course of 6 tablets).

15 kg to less than 25 kg bodyweight: Two tablets as an initial dose, 2 tablets again after 8 hours and then 2 tablets twice-daily (morning and evening) for the following 2 days (total course of 12 tablets).

25 kg to less than 35 kg bodyweight: Three tablets as an initial dose, 3 tablets again after 8 hours and then 3 tablets twice-daily (morning and evening) for the following 2 days (total course of 18 tablets).

35 kg bodyweight and above: Four tablets as a single initial dose, 4 tablets again after 8 hours and then 4 tablets twice-daily (morning and evening) for the following 2 days (total course of 24 tablets).

2.4 Dosage in 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, Coartem and dihydroartemisinin (DHA) in healthy volunteers and while clinical experience in this population is limited, no dose adjustment is recommended.

Caution should be exercised when administering Coartem Tablets in patients with severe hepatic or renal impairment .

3 DOSAGE FORMS AND STRENGTHS

Coartem Tablets contain 20 mg of Coartem and 120 mg of lumefantrine. Coartem Tablets are supplied as yellow, round, flat tablets with beveled edges and scored on one side. Tablets are imprinted with N/C on one side and CG on the other side.

Tablets are scored and contain 20 mg Coartem and 120 mg lumefantrine. (3)

4 CONTRAINDICATIONS

Hypersensitivity


Strong CYP3A4 Inducers

5 WARNINGS AND PRECAUTIONS

5.1 Prolongation of the QT Interval

Some antimalarials (e.g., halofantrine, quinine, quinidine) including Coartem Tablets have been associated with prolongation of the QT interval on the electrocardiogram.

Coartem Tablets should be avoided in patients:

5.2 Use of QT Prolonging Drugs and Other Antimalarials

Halofantrine and Coartem Tablets should not be administered within 1 month of each other due to the long elimination half-life of lumefantrine and potential additive effects on the QT interval [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Antimalarials should not be given concomitantly with Coartem 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 Coartem 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 Warnings and Precautions (5.1), Drug Interactions (7.7), and Clinical Pharmacology (12.3)].

If mefloquine is administered immediately prior to Coartem Tablets 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 Coartem Tablets [see Dosage and Administration (2.1), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].

5.3 Drug Interactions with CYP3A4

When Coartem Tablets are coadministered with substrates of CYP3A4 it may result in decreased concentrations of the substrate and potential loss of substrate efficacy. When Coartem Tablets are coadministered with an inhibitor of CYP3A4, including grapefruit juice it may result in increased concentrations of Coartem and/or lumefantrine and potentiate QT prolongation. When Coartem Tablets are coadministered with inducers of CYP3A4 it may result in decreased concentrations of Coartem and/or lumefantrine and loss of antimalarial efficacy .

Drugs that have a mixed effect on CYP3A4, especially antiretroviral 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 Coartem Tablets .

Coartem Tablets may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control .

5.4 Drug Interactions with CYP2D6

Administration of Coartem Tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the coadministered 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 Coartem Tablets due to the potential additive effect on the QT interval .

5.5 Recrudescence

Food enhances absorption of Coartem and lumefantrine following administration of Coartem 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 Coartem Tablets, patients should be treated with a different antimalarial drug.

5.6 Hepatic and Renal Impairment

Coartem Tablets have not been studied for efficacy and safety in patients with severe hepatic and/or renal impairment .

5.7 Plasmodium vivax Infection

Coartem Tablets have been shown in limited data (43 patients) to be effective in treating the erythrocytic stage of P. vivax infection. However, relapsing malaria caused by P. vivax requires additional treatment with other antimalarial agents to achieve radical cure i.e., eradicate any hypnozoites forms that may remain dormant in the liver.

6 ADVERSE REACTIONS

The most common adverse reactions in adults are headache, anorexia, dizziness, asthenia, arthralgia and myalgia. The most common adverse reactions in children (>12%) are pyrexia, cough, vomiting, anorexia, and headache. (6.2)


To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Serious Adverse Reactions

The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling:

6.2 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 Coartem Tablets in 1,979 patients including 647 adults and 1,332 children (16 years and younger). For the 6-dose regimen, Coartem Tablets was studied in active-controlled (366 patients) and non-controlled, open-label trials (1,613 patients). The 6-dose Coartem Tablets population was patients with malaria between ages 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 pediatric populations, respectively. The majority of adult patients were enrolled in studies in Thailand, while the majority of pediatric 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 Coartem 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 Coartem Tablets appeared similar to that of another antimalarial regimen.

Discontinuation of Coartem 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.

System Organ Class Preferred Term Adults*

N=647 (%)

Nervous system disorders Headache 360 (56)
Dizziness 253 (39)
Metabolism and nutrition disorders Anorexia 260 (40)
General disorders and administration site conditions Asthenia 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 Pruritus 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

System Organ Class Preferred Term Children*

N=1,332 (%)

General disorders and administration site conditions Pyrexia 381 (29)
Chills 72 (5)
Asthenia 63 (5)
Fatigue 46 (3)
Respiratory, thoracic and mediastinal disorders Cough 302 (23)
Gastrointestinal disorders Vomiting 242 (18)
Abdominal pain 112 (8)
Diarrhea 100 (8)
Nausea 61 (5)
Infections and infestations Plasmodium falciparum infection 224 (17)
Rhinitis 51 (4)
Metabolism and nutrition disorders Anorexia 175 (13)
Nervous system disorders Headache 168 (13)
Dizziness 56 (4)
Blood and lymphatic system disorders Splenomegaly 124 (9)
Anemia 115 (9)
Hepatobiliary disorders Hepatomegaly 75 (6)
Investigations Aspartate aminotransferase increased 51 (4)
Musculoskeletal and connective tissue disorders Arthralgia 39 (3)
Myalgia 39 (3)
Skin and subcutaneous tissue disorders Rash 38 (3)

* Children defined as patients ≤16 years of age

Clinically significant adverse reactions reported in adults and/or children treated with the 6-dose regimen of Coartem Tablets which occurred in clinical studies at <3% regardless of causality are listed below:

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, hematocrit

decreased, lymphocyte morphology abnormal, platelet count decreased, platelet count increased, white

blood cell count decreased, white blood cell count increased

Metabolism and nutrition disorders: hypokalemia

Musculoskeletal and connective tissue disorders: back pain

Nervous system disorders: ataxia, clonus, fine motor delay, hyperreflexia, hypoesthesia, nystagmus,

tremor

Psychiatric disorders: agitation, mood swings

Renal and urinary disorders: hematuria, proteinuria

Respiratory, thoracic and mediastinal disorders: asthma, pharyngo-laryngeal pain

Skin and subcutaneous tissue disorders: urticaria

6.3 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Coartem 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.

7 DRUG INTERACTIONS

7.1 Rifampin

Oral administration of rifampin, a strong CYP3A4 inducer, with Coartem Tablets resulted in significant decreases in exposure to Coartem, dihydroartemisinin (DHA, metabolite of Coartem) and lumefantrine by 89%, 85% and 68%, respectively, when compared to exposure values after Coartem Tablets alone. Concomitant use of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin, and St. John’s wort is contraindicated with Coartem Tablets [see Contraindications (4) and Clinical Pharmacology (12.3)].

7.2 Ketoconazole

Concurrent oral administration of ketoconazole, a potent CYP3A4 inhibitor, with a single dose of Coartem Tablets resulted in a moderate increase in exposure to Coartem, DHA, and lumefantrine in a study of 15 healthy subjects. No dose adjustment of Coartem 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, Coartem Tablets should be used cautiously with drugs that inhibit CYP3A4 [see Warnings and Precautions and Clinical Pharmacology (12.3)].

7.3 Antiretroviral Drugs

Both Coartem 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 Coartem, DHA, and lumefantrine are also variable . Coartem Tablets should be used cautiously in patients on antiretroviral drugs because decreased Coartem, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of Coartem Tablets, and increased lumefantrine concentrations may cause QT prolongation .

7.4 Prior Use of Mefloquine

Administration of 3 doses of mefloquine followed 12 hours later by a 6-dose regimen of Coartem Tablets in 14 healthy volunteers demonstrated no effect of mefloquine on plasma concentrations of Coartem 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 administration of Coartem Tablets [see Warnings and Precautions and Clinical Pharmacology (12.3)].

7.5 Hormonal Contraceptives

In vitro, the metabolism of ethinyl estradiol and levonorgestrel was not induced by Coartem, DHA, or lumefantrine. However, Coartem has been reported to weakly induce, in humans, the activity of CYP2C19, CYP2B6, and CYP3A. Therefore, Coartem Tablets may potentially reduce the effectiveness of hormonal contraceptives. Patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

7.6 CYP2D6 Substrates

Lumefantrine inhibits CYP2D6 in vitro. Administration of Coartem Tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the coadministered 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 Coartem Tablets due to the potential additive effect on the QT interval [see Warnings and Precautions (5.1, 5.4) and Clinical Pharmacology (12.3)].

7.7 Sequential Use of Quinine

A single dose of intravenous quinine (10 mg/kg bodyweight) concurrent with the final dose of a 6-dose regimen of Coartem Tablets demonstrated no effect of intravenous quinine on the systemic exposure of DHA or lumefantrine. Quinine exposure was also not altered. Exposure to Coartem was decreased. This decrease in Coartem 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 Coartem 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 (5.2) and Clinical Pharmacology (12.3)].

7.8 Interaction with Drugs that are Known to Prolong the QT Interval

Coartem Tablets are to be used with caution when coadministered with drugs that may cause prolonged QT interval such as antiarrhythmics of classes IA and III, neuroleptics and antidepressant agents, certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents .

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Safety data from an observational pregnancy study of approximately 500 pregnant women who were exposed to Coartem 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 background rate.

The efficacy of Coartem Tablets in the treatment of acute, uncomplicated malaria in pregnant women has not been established.

Coartem Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnant rats dosed during the period of organogenesis at or higher than a dose of about half the highest clinical dose of 1120 mg artemether-lumefantrine per day (based on body surface area comparisons), showed increases in fetal loss, early resorptions and post implantation loss. No adverse effects were observed in animals dosed at about one-third the highest clinical dose. Similarly, dosing in pregnant rabbits at about 3 times the clinical dose (based on body surface area comparisons) resulted in abortions, preimplantation loss, post implantation loss and decreases in the number of live fetuses. No adverse reproductive effects were detected in rabbits at 2 times the clinical dose. Embryo-fetal loss is a significant reproductive toxicity. Other artemisinins are known to be embryotoxic in animals. However, because metabolic profiles in animals and humans are dissimilar, Coartem exposures in animals may not be predictive of human exposures . These data cannot rule out an increased risk for early pregnancy loss or fetal defects in humans.

8.3 Nursing Mothers

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

8.4 Pediatric Use

The safety and effectiveness of Coartem Tablets have been established for the treatment of acute, uncomplicated malaria in studies involving pediatric patients weighing 5 kg or more . The safety and efficacy have not been established in pediatric patients who weigh less than 5 kg. Children from non-endemic countries were not included in clinical trials.

8.5 Geriatric Use

Clinical studies of Coartem Tablets did not include sufficient numbers of subjects aged 65 years and over to determine 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 Coartem Tablets.

8.6 Hepatic and Renal Impairment

No specific pharmacokinetic studies have been performed in patients with either hepatic or renal impairment. Coartem Tablets have not been studied for efficacy and safety in patients with severe hepatic and/or renal impairment. Based on the pharmacokinetic data in 16 healthy subjects showing no or insignificant renal excretion of lumefantrine, Coartem and DHA, no dose adjustment for the use of Coartem Tablets in patients with renal impairment is advised. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment .

10 OVERDOSAGE

There is no information on overdoses of Coartem Tablets higher than the doses recommended for treatment.

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

11 DESCRIPTION

Coartem Tablets contain a fixed combination of 2 antimalarial active ingredients, Coartem, an artemisinin derivative, and lumefantrine. Both components are blood schizontocides. The chemical name of Coartem is (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepine. Coartem is a white, crystalline powder that is freely soluble in acetone, soluble in methanol and ethanol, and practically insoluble in water. It has the empirical formula C16H26O5 with a molecular weight of 298.4, and the following structural formula:

The chemical name of lumefantrine is (1RS)-2-(dibutylamino)-1-{(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylene]-9H-fluorene-4-yl}ethanol. Lumefantrine is a yellow, crystalline powder that is freely soluble in N,N-dimethylformamide, chloroform, and ethyl acetate; soluble in dichloromethane; slightly soluble in ethanol and methanol; and insoluble in water. It has the empirical formula C30H32Cl3NO with a molecular weight of 528.9, and the following structural formula:


Coartem Tablets are for oral administration. Each Coartem Tablet contains 20 mg of Coartem and 120 mg lumefantrine. The inactive ingredients are colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, and polysorbate 80.

Coartem structural formula Lumefantrine structural formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Coartem Tablets, a fixed dose combination of Coartem and lumefantrine in the ratio of 1:6, is an antimalarial agent .

12.3 Pharmacokinetics

Absorption

Following administration of Coartem Tablets to healthy volunteers and patients with malaria, Coartem is absorbed with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with peak plasma concentrations about 6 to 8 hours after administration. The single dose (4 tablets) pharmacokinetic parameters for Coartem, dihydroartemisinin (DHA), an active antimalarial metabolite of Coartem, and lumefantrine in adult Caucasian healthy volunteers are given in Table 3. Multiple dose data after the 6-dose regimen of Coartem Tablets in adult malaria patients are given in Table 4.

Study 2102

(n=50)

Study 2104

(n=48)

Coartem
Cmax (ng/mL) 60.0 ± 32.5 83.8 ± 59.7
tmax (h) 1.50 2.00
AUClast (ng·h/mL) 146 ± 72.2 259 ± 150
t½ (h) 1.6 ± 0.7 2.2 ± 1.9
DHA
Cmax (ng/mL) 104 ± 35.3 90.4 ± 48.9
tmax (h) 1.76 2.00
AUClast (ng·h/mL) 284 ± 83.8 285 ± 98.0
t½ (h) 1.6 ± 0.6 2.2 ± 1.5
Lumefantrine
Cmax (µg/mL) 7.38 ± 3.19 9.80 ± 4.20
tmax (h) 6.01 8.00
AUClast (µg·h/mL) 158 ± 70.1 243 ± 117
t½ (h) 101 ± 35.6 119 ± 51.0

aMean ± SD Cmax, AUClast, t½ and Median tmax

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

Distribution

Coartem 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% to 76%). Protein binding to human plasma proteins is linear.

Biotransformation

In human liver microsomes and recombinant CYP450 enzymes, the metabolism of Coartem was catalyzed predominantly by CYP3A4/5. Dihydroartemisinin (DHA) is an active metabolite of Coartem. The metabolism of Coartem was also catalyzed to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. In vitro studies with Coartem at therapeutic concentrations revealed no significant inhibition of the metabolic activities of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and CYP4A9/11. In vitro studies with Coartem, DHA, and lumefantrine at therapeutic concentrations revealed no significant induction of the metabolic activities of CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, or CYP3A5.

During repeated administration of Coartem Tablets, systemic exposure of Coartem decreased significantly, while concentrations of DHA increased, although not to a statistically significant degree. The artemether/DHA AUC ratio is 1.2 after a single dose and 0.3 after 6 doses given over 3 days. This suggests that there was induction of enzymes responsible for the metabolism of Coartem.

In human liver microsomes and in recombinant CYP450 enzymes, lumefantrine was metabolized mainly by CYP3A4 to desbutyl-lumefantrine. The systemic exposure to the metabolite desbutyl-lumefantrine 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 Coartem Tablets with substrates, inhibitors, or inducers of CYP3A4, especially antiretroviral drugs and those that prolong the QT interval (e.g., macrolide antibiotics, pimozide) [see Contraindications (4), Warnings and Precautions (5.1, 5.2, 5.3), and Drug Interactions (7)].

Coadministration of Coartem 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 Coartem Tablets due to the potential additive effect on the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine) [see Warnings and Precautions (5.1, 5.4) and Drug Interactions (7.6)].

Elimination

Coartem and DHA are cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated more slowly, with an elimination 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 Coartem and lumefantrine.

In 16 healthy volunteers, neither lumefantrine nor Coartem was found in the urine after administration of Coartem Tablets, and urinary excretion of DHA amounted to less than 0.01% of the Coartem 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, Coartem and DHA in healthy volunteers and while clinical experience in this population is limited, no dose adjustment in renal impairment is recommended .

Pediatric Patients

The PK of Coartem, DHA, and lumefantrine were obtained in 2 pediatric studies by sparse sampling using a population-based approach. PK estimates derived from a composite plasma concentration profile for Coartem, DHA, and lumefantrine are provided in Table 4.

Systemic exposure to Coartem, DHA, and lumefantrine, when dosed on a mg/kg body weight basis in pediatric patients (≥5 to <35 kg body weight), is comparable to that of the recommended dosing regimen in adult patients.

Adults1 Pediatric patients (body weight, kg) 2
Drug 5 to <15 15 to <25 25 to <35
Lumefantrine
Mean Cmax, range (mcg/mL) 5.60 - 9.0 4.71 – 12.6 Not Available
Mean AUClast, range (mcg·h/mL) 410 - 561 372 – 699 Not Available
Coartem
Mean Cmax ± SD (ng/mL) 186 ± 125 223 ± 309 198 ± 179 174 ± 145
Dihydroartemisinin
Mean Cmax ± SD (ng/mL) 101 ± 58 54.7 ± 58.9 79.8 ± 80.5 65.3 ± 23.6
1 There are a total of 181 adults for lumefantrine pharmacokinetic parameters and a total of 25 adults for Coartem and dihydroartemisinin pharmacokinetic parameters.

2 There are 477 children for the lumefantrine pharmacokinetic parameters; for Coartem and dihydroartemisinin pharmacokinetic parameters there are 55, 29, and 8 children

for the 5 to <15, 15 to <25 and the 25 to <35 kg groups, respectively.

Geriatric Patients

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

Drug Interactions

Rifampin (strong CYP3A4 inducer)

Oral administration of rifampin (600 mg daily), a strong CYP3A4 inducer, with Coartem Tablets (6-dose regimen over 3 days) in 6 HIV-1 and tuberculosis co-infected adults without malaria resulted in significant decreases in exposure, in terms of AUC, to Coartem, DHA and lumefantrine by 89%, 85% and 68%, respectively, when compared to exposure values after Coartem Tablets alone. Concomitant use of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin, and St. John’s wort is contraindicated with Coartem Tablets .

Ketoconazole (potent CYP3A4 inhibitor)

Concurrent oral administration of ketoconazole (400 mg on day 1 followed by 200 mg on days 2, 3, 4 and 5) with Coartem Tablets (single dose of 4 tablets of 20 mg artemether/120 mg lumefantrine per tablet) with a meal led to an increase in exposure, in terms of area under the curve (AUC), of Coartem (2.3-fold), DHA (1.5-fold), and lumefantrine (1.6-fold) in 13 healthy subjects. The pharmacokinetics of ketoconazole was not evaluated. Based on this study, dose adjustment of Coartem Tablets is considered unnecessary when administered with ketoconazole or other CYP3A4 inhibitors. However, due to the potential for increased concentrations of lumefantrine which could lead to QT prolongation, Coartem Tablets should be used cautiously with other drugs that inhibit CYP3A4 (e.g., antiretroviral drugs, macrolide antibiotics, antidepressants, imidazole antifungal agents) .

Antimalarials

The oral administration of mefloquine in 14 healthy volunteers administered as 3 doses of 500 mg, 250 mg and 250 mg, followed 12 hours later by Coartem Tablets (6 doses of 4 tablets of 20 mg artemether/120 mg lumefantrine per tablet), had no effect on plasma concentrations of Coartem or the artemether/DHA ratio. In the same study, there was a 30% reduction in Cmax and 40% reduction in AUC of lumefantrine, possibly due to lower absorption secondary to a mefloquine-induced decrease in bile production.

Intravenous administration of a single dose of quinine (10 mg/kg bodyweight) concurrent with the last dose of a 6-dose regimen of Coartem Tablets had no effect on systemic exposure of DHA, lumefantrine or quinine in 14 healthy volunteers. Mean AUC of Coartem were 46% lower when administered with quinine compared to Coartem Tablets alone. This decrease in Coartem exposure is not thought to be clinically significant. However, quinine should be used cautiously in patients following treatment with Coartem Tablets due to the long elimination half-life of lumefantrine and the potential for additive effects on the QT interval; ECG monitoring is advised if use of quinine is medically required .

Antiretroviral Drugs

The oral administration of lopinavir/ritonavir (400 mg/100 mg twice daily for 26 days) in 10 healthy volunteers coadministered with Coartem Tablets (6-dose regimen over 3 days), resulted in a decrease in systemic exposures, in terms of AUC, to Coartem and DHA by approximately 40%, but an increase in exposure to lumefantrine by approximately 2.3-fold. The oral administration of efavirenz (600 mg once daily for 26 days) in 12 healthy volunteers coadministered with Coartem Tablets (6-dose regimen over 3 days), resulted in a decrease in exposures to Coartem, DHA, and lumefantrine by approximately 50%, 45%, and 20%, respectively. Exposures to lopinavir/ritonavir and efavirenz were not significantly affected by concomitant use of Coartem Tablets. Coartem Tablets should be used cautiously in patients on antiretroviral drugs such as HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors because decreased Coartem, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of Coartem Tablets, and increased lumefantrine concentrations may cause QT prolongation [see Warnings and Precautions (5.3) and Drug Interactions (7.3)].

Hormonal Contraceptives

No clinical drug-drug interaction studies between Coartem Tablets and hormonal contraceptives have been performed. In vitro studies revealed that the metabolism of ethinyl estradiol and levonorgestrel was not induced by Coartem, DHA or lumefantrine. However, Coartem has been reported to weakly induce, in humans, the activity of CYP2C19, CYP2B6, and CYP3A. Therefore, coadministration of Coartem Tablets may potentially reduce the effectiveness of hormonal contraceptives [see Warnings and Precautions (5.3) and Drug Interactions (7.5)].

12.4 Microbiology

Mechanism of Action

Coartem Tablets, a fixed ratio of 1:6 parts of Coartem and lumefantrine, respectively, is an antimalarial agent. Coartem is rapidly metabolized into an active metabolite dihydroartemisinin. The antimalarial activity of Coartem and DHA has been attributed to endoperoxide moiety. The exact mechanism by which lumefantrine exerts its antimalarial effect is not well defined. Available data suggest lumefantrine inhibits the formation of β-hematin by forming a complex with hemin. Both Coartem and lumefantrine were shown to inhibit nucleic acid and protein synthesis.

Activity In Vitro and In Vivo

Coartem and lumefantrine are active against the erythrocytic stages of Plasmodium falciparum.

Drug Resistance

Strains of P. falciparum with a moderate decrease in susceptibility to Coartem or lumefantrine alone can be selected in vitro or in vivo, but not maintained in the case of Coartem. The clinical relevance of such an effect is not known.

12.6 Effects on the Electrocardiogram

In a healthy adult volunteer parallel-group study including a placebo and moxifloxacin control-group (n=42 per group), the administration of the 6-dose regimen of Coartem Tablets was associated with prolongation of QTcF (Fridericia). Following administration of a 6-dose regimen of Coartem Tablets consisting of 4 tablets per dose (total of 4 tablets of 80 mg artemether/480 mg lumefantrine) taken with food, the maximum mean change from baseline and placebo adjusted QTcF was 7.5 msec (1-sided 95% Upper CI: 11 msec). There was a concentration-dependent increase in QTcF for lumefantrine.

In clinical trials conducted in children, no patient had QTcF >500 msec. Over 5% of patients had an increase in QTcF of over 60 msec.

In clinical trials conducted in adults, QTcF prolongation of >500 msec was reported in 3 (0.3%) patients. Over 6% of adults had a QTcF increase of over 60 msec from baseline.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies were not conducted.

Mutagenesis

No evidence of mutagenicity was detected. The Coartem: lumefantrine combination was evaluated using the Salmonella and Escherichia/mammalian-microsome mutagenicity test, the gene mutation test with Chinese hamster cells V79, the cytogenetic test on Chinese hamster cells in vitro, and the rat micronucleus test, in vivo.

Impairment of Fertility

Pregnancy rates were reduced by about one-half in female rats dosed for 2 to 4 weeks with the artemether-lumefantrine combination at 1000 mg/kg. Male rats dosed for 70 days showed increases in abnormal sperm (87% abnormal) and increased testes weights at 30 mg/kg doses (about one-third the clinical dose). Higher doses (about 9 times the clinical dose) resulted in decreased sperm motility and 100% abnormal sperm cells.

13.2 Animal Toxicology and/or Pharmacology

Neonatal rats (7 to 21 days old) were more sensitive to the toxic effects of Coartem (a component of Coartem Tablets) than older juvenile rats or adults. Mortality and severe clinical signs were observed in neonatal rats at doses which were well tolerated in pups above 22 days old.

14 CLINICAL STUDIES

14.1 Treatment of Acute, Uncomplicated P. falciparum Malaria

The efficacy of Coartem Tablets was evaluated for the treatment of acute, uncomplicated malaria caused by P. falciparum in HIV negative patients in 8 clinical studies. Uncomplicated malaria was defined as symptomatic P. falciparum malaria without signs and symptoms of severe malaria or evidence of vital organ dysfunction. Baseline parasite density ranged from 500/mcL to 200,000/mcL (0.01% to 4% parasitemia) in the majority of patients. Studies were conducted in partially immune and non-immune adults and children (≥5kg body weight) with uncomplicated malaria in China, Thailand, sub-Saharan Africa, Europe, and South America. Patients who had clinical features of severe malaria, severe cardiac, renal, or hepatic impairment were excluded.

The studies include two 4-dose studies assessing the efficacy of the components of the regimen, a study comparing a 4-dose versus a 6-dose regimen, and 5 additional 6-dose regimen studies.

Coartem Tablets were administered at 0, 8, 24, and 48 hours in the 4-dose regimen, and at 0, 8, 24, 36, 48, and 60 hours in the 6-dose regimen. Efficacy endpoints consisted of:


The modified intent to treat (mITT) population includes all patients with malaria diagnosis confirmation who received at least 1 dose of study drug. Evaluable patients generally are all patients who had a day 7 and a day 28 parasitological assessment or experienced treatment failure by day 28.

Studies 1 and 2: The 2 studies which assessed the efficacy of Coartem Tablets (4 doses of 4 tablets of 20 mg artemether/120 mg lumefantrine) compared to each component alone were randomized, double-blind, comparative, single center, conducted in China. The efficacy results (Table 5) support that the combination of Coartem and lumefantrine in Coartem Tablets had a significantly higher 28-day cure rate compared to Coartem and had a significantly faster parasite clearance time (PCT) and fever clearance time (FCT) compared to lumefantrine.

Study No.

Region/patient ages

28-day cure rate 2

n/N (%) patients

 Median FCT 3

[25th,75th percentile]

 Median PCT

[25th,75th percentile]
Study 1

China, ages 13 to 57 years
Coartem Tablets 50/51 (98.0) 24 hours [9, 48] 30 hours [24, 36]
Coartem4 24/52 (46.2) 21 hours [12, 30] 30 hours [24, 33]
Lumefantrine5 47/52 (90.4) 60 hours [36, 78] 54 hours [45, 66]
Study 2

China, ages 12 to 65 years
Coartem Tablets 50/52 (96.2) 21 hours [6, 33] 30 hours [24, 36]
Lumefantrine 6 45/51 (88.2) 36 hours [12, 60] 48 hours [42, 60]
1In mITT analysis, patients whose status was uncertain were classified as treatment failures.

2Efficacy cure rate based on blood smear microscopy.

3For patients who had a body temperature >37.5°C at baseline only

495% CI (Coartem Tablets – Coartem) on 28-day cure rate: 37.8%, 66.0%

5P-value comparing Coartem Tablets to lumefantrine on parasite clearance time (PCT) and fever clearance time (FCT): <0.001

6P-value comparing Coartem Tablets to lumefantrine on parasite clearance time (PCT): <0.001 and on fever clearance time (FCT): <0.05

Results of 4-dose studies conducted in areas with high resistance such as Thailand during 1995-96 showed lower efficacy results than the above studies. Therefore, Study 3 was conducted.

Study 3: Study 3 was a randomized, double-blind, 2-center study conducted in Thailand in adults and children (aged ≥2 years), which compared the 4-dose regimen (administered over 48 hours) of Coartem Tablets to a 6-dose regimen (administered over 60 hours). Twenty-eight day cure rate in mITT subjects was 81% (96/118) for the Coartem Tablets 6-dose arm as compared to 71% (85/120) in the 4-dose arm.

Studies 4, 5, 6, 7, and 8: In these studies, Coartem Tablets were administered as the 6-dose regimen.

In study 4, a total of 150 adults and children aged ≥2 years received Coartem Tablets. In study 5, a total 164 adults and children ≥12 years received Coartem Tablets. Both studies were conducted in Thailand.

Study 6 was a study of 165 non-immune adults residing in regions non-endemic for malaria (Europe and Colombia) who contracted acute uncomplicated falciparum malaria when traveling in endemic regions.

Study 7 was conducted in Africa in 310 infants and children aged 2 months to 9 years, weighing 5 kg to 25 kg, with an axillary temperature ≥37.5ºC.

Study 8 was conducted in Africa in 452 infants and children, aged 3 months to 12 years, weighing 5 kg to <35 kg, with fever (≥37.5°C axillary or ≥38°C rectally) or history of fever in the preceding 24 hours.

Results of 28-day cure rate, median parasite clearance time (PCT), and fever clearance time (FCT) for Studies 3 to 8 are reported in Table 6.

Study No. Region/ages 28-day cure rate 1 n/N (%) patients Median FCT 2

[25th, 75th percentile]

 Median PCT

[25th, 75th percentile]
mITT 3 Evaluable
Study 3 Thailand, ages 3 – 62 years 96/118 (81.4) 93/96 (96.9) 35 hours

[20, 46]

 44 hours

[22, 47]
Early failure4 0 0
Late failure5 4 (3.4) 3 (3.1)
Lost to follow-up 18 (15.3)
Other6 0
Study 4 Thailand, ages 2 – 63 years 130/149 (87.2) 130/134 (97.0) 22 hours

[19, 44]

 NA
Early failure4 0 0
Late failure5 4 (2.7) 4 (3.0)
Lost to follow-up 13 (8.7)
Other6 2 (1.3)
Study 5 Thailand, ages 12 – 71 years 148/164 (90.2) 148/155 (95.5) 29 hours

[8, 51]

 29 hours

[18, 40]
Early failure4 0 0
Late failure5 7 (4.3) 7 (4.5)
Lost to follow-up 9 (5.5)
Other6 0
Study 6

Europe/Columbia, ages 16 – 66 years

120/162 (74.1) 119/124 (96.0) 37 hours

[18, 44]

 42 hours

[34, 63]
Early failure4 6 (3.7) 1 (0.8)
Late failure5 3 (1.9) 3 (2.4)
Lost to follow-up 17 (10.5)
Other6 16 (9.9) 1 (0.8)
Study 7 Africa, ages 2 months – 9 years 268/310 (86.5) 267/300 (89.0) 8 hours

[8, 24]

 24 hours

[24, 36]
Early failure4 2 (0.6) 0
Late failure5 34 (11.0) 33 (11.0)
Lost to follow-up 2 (0.6)
Other6 4 (1.3)
Study 8 Africa, ages 3 months – 12 years 374/452 (82.7) 370/419 (88.3) 8 hours

[8, 23]

 35 hours

[24, 36]
Early failure4 13 (2.9) 0
Late failure5 49 (10.8) 49 (11.7)
Lost to follow-up 6 (1.3)
Other6 10 (2.2)
1 Efficacy cure rate based on blood smear microscopy

2 For patients who had a body temperature >37.5°C at baseline only

3 In mITT analysis, patients whose status was uncertain were classified as treatment failures.

4 Early failures were usually defined as patients withdrawn for unsatisfactory therapeutic effect within the first 7 days or because they received another antimalarial medication within the first 7 days

5 Late failures were defined as patients achieving parasite clearance within 7 days but having parasite reappearance including recrudescence or new infection during the 28-day follow-up period

6 Other includes withdrawn due to protocol violation or non-compliance, received additional medication after day 7, withdrew consent, missing day 7 or 28 assessment

In all studies, patients’ signs and symptoms of malaria resolved when parasites were cleared.

In studies conducted in areas with high transmission rates, such as Africa, reappearance of P. falciparum parasites may be due to recrudescence or a new infection.

The efficacy by body weight category for studies 7 and 8 is summarized in Table 7.

Study No.

Age category

Coartem Tablets 6-dose Regimen
mITT population 1 Evaluable population
Median PCT

[25 th ,75 th percentile]

28-day cure rate 2

n/N (%) patients

28-day cure rate 2

n/N (%) patients

Study 7
5 to <10 kg 24 [24, 36] 133/154 (86.4) 133/149 (89.3)
10 to <15 kg 35 [24, 36] 94/110 (85.5) 94/107 (87.9)
15 to 25 kg 24 [24, 36] 41/46 (89.1) 40/44 (90.9)
Study 8 3
5 to <10 kg 36 [24, 36] 61/83 (73.5) 61/69 (88.4)
10 to <15 kg 35 [24, 36] 160/190 (84.2) 157/179 (87.7)
15 to <25 kg 35 [24, 36] 123/145 (84.8) 123/140 (87.9)
25 to <35 kg 26 [24, 36] 30/34 (88.2) 29/31 (93.5)
1 In mITT analysis, patients whose status was uncertain were classified as treatment failures.

2 Efficacy cure rate based on blood smear microscopy

3 Coartem Tablets administered as crushed tablets

The efficacy of Coartem Tablets for the treatment P. falciparum infections mixed with P. vivax was assessed in a small number of patients. Coartem Tablets are only active against the erythrocytic phase of P. vivax malaria. Of the 43 patients with mixed infections at baseline, all cleared their parasitemia within 48 hours. However, parasite relapse occurred commonly (14/43; 33%). Relapsing malaria caused by P. vivax requires additional treatment with other antimalarial agents to achieve radical cure i.e., eradicate any hypnozoite forms that may remain dormant in the liver.

16 HOW SUPPLIED/STORAGE AND HANDLING

Coartem (artemether/lumefantrine) Tablets

20 mg/120 mg Tablets - yellow, round flat tablets with beveled edges and scored on one side. Tablets are imprinted with N/C on one side and CG on the other.

Bottle of 24 NDC 0078-0568-45

Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

Dispense in tight container (USP).

17 PATIENT COUNSELING INFORMATION

Advise patients to read the FDA-Approved Patient Labeling.

Information for Safe Use


T2015-44

March 2015

FDA-Approved Patient Labeling

Patient Information

Coartem®

(co-AR-tem)

(artemether and lumefantrine)

Tablets

Read this patient information before you start taking Coartem. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is Coartem?

Coartem is a prescription medicine used to treat uncomplicated malaria in adults and children who weigh at least 11 pounds (5 kg).

Who should not take Coartem?

Do not take Coartem if you are allergic to any of the ingredients. See the end of this leaflet for a complete list of ingredients in Coartem.

Do not take Coartem if you are taking rifampin (medicine to treat leprosy or tuberculosis), certain medicines used to treat epilepsy (such as carbamazepine, phenytoin), or St. John’s wort (Hypericum perforatum, a medicinal plant or extract of this medicinal plant).

What should I tell my healthcare provider before taking Coartem?

Before you take Coartem, tell your healthcare provider about all your medical conditions including if you:


Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Coartem and other medicines may affect each other causing side effects. Coartem may affect the way other medicines work and other medicines may affect how Coartem works.

Especially tell your doctor if you take:


Ask your healthcare provider if you are not sure if your medicine is 1 that is listed above. Know the medicines you take. Keep a list of your medicines with you to show your healthcare providers when you get a new medicine.

How should I take Coartem?


Take Coartem for 3 days even if you are feeling better.


Tell your healthcare provider right away if:


What are the possible side effects of Coartem?

Coartem can cause serious side effects including:


The most common side effects in adults are:


The most common side effects in children are:


These are not all the possible side effects of Coartem. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Coartem?

Store Coartem between 59ºF to 86ºF (15ºC to 30ºC).

Keep Coartem and all medicines out of the reach of children.

General information about the safe and effective use of Coartem.

Medicines are sometimes prescribed for purposes other than those listed in patient information leaflets. Do not use Coartem for a condition for which it was not prescribed. Do not give Coartem to other people, even if they have the same symptoms that you have. It may harm them.

This patient information leaflet summarizes the most important information about Coartem. If you would like more information about Coartem talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Coartem that is written for health professionals. For more information call 1-855-262-7836.

What are the ingredients in Coartem?

Active ingredients include: Coartem, lumefantrine

Inactive ingredients include: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polysorbate 80

Distributed by:

Novartis Pharmaceuticals Corporation

East Hanover, New Jersey 07936

© Novartis

T2015-45

March 2015

Coartem pharmaceutical active ingredients containing related brand and generic drugs:


Coartem available forms, composition, doses:


Coartem destination | category:


Coartem Anatomical Therapeutic Chemical codes:


Coartem pharmaceutical companies:


References

  1. Dailymed."LUMEFANTRINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."ARTEMETHER; LUMEFANTRINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "Artemether". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Coartem?

Depending on the reaction of the Coartem after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Coartem not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Coartem addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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sdrugs.com conducted a study on Coartem, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Coartem consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology


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