Anti-malarial / blood schizonticide.
Each 5ml when reconstituted contains 15mg Artemether and 90mg Lumefantrine.
Tap bottle to disloge powder. Add 42ml of freshly boiled and cooled water. Shake well until all powder is dispersed.
Artemether is a sesquiterpene lactone derived from the naturally occurring substance artemisinin.
Lumefantrine is a synthetic racemic fluorene mixture.
COMAX DPS comprises a fixed ratio of 1:6 parts of Artemether and Lumefantrine, respectively. The site of anti-parasitic action of both components is the food vacuole of the malaria 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. Lumefantrine is thought to interfere with the polymerization 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 of inhibition of nucleic acid and protein synthesis within the malarial parasite. Data from in-vitro and in-vivo studies show that the combination of Artemether and Lumefantrine did not induce resistance, and that the anti-malarial activity is greater than that of either substance alone. In patients in whom gametocytes were present, the median time for gametocyte clearance is 96 hours.
Artemether is absorbed fairly rapidly with peak plasma concentrations about 2 hours after administration. For Lumefantrine, a highly lipophilic compound, there is a lag-time of up to 2 hours with peak concentrations at about 6-8 hours after administration. Food enhances absorption of both Artemether and Lumefantrine. Patients should therefore be encouraged to take COMAX DPS with a normal diet as soon as food can be tolerated.
Artemether and Lumefantrine are both highly bound to human serum proteins in-vitro, 95.4% and 99.7% respectively. Dihydroartemisinin is also bound to serum proteins (45-76%). Protein binding to human plasma proteins is linear.
Artemether is rapidly and extensively metabolized with substantial first-pass metabolism by liver microsomes to the biologically active dihydroartemisinin (demethylation), mostly through enzyme CYP3A4/5.
The Artemether/ Diihydroartemisinin ratio is 1.2 after a single dose and 0.3 after 6 doses given over 3 days. Lumefantrine is N-debutylated mainly by CYP3A4 in liver microsomes. In-vitro, Lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations.
Artemether and Dihydroartemisinin are rapidly cleared from plasma with an elimination half-life of about 2hours. Lumefantrine is eliminated slowly with terminal half-life of 2-3 days in healthy volunteers and 4-6 days in falciparum malaria patients. Sex and weight appear to have no clinically relevant effects on the pharmacokinetics of Co-Max. No urinary excretion data are available for humans. In rats and dogs, metabolites of Artemether are found in both faeces and urine while excretion of Lumefantrine is primarily in faeces, most of it as the parent drug.
It is indicated for treatment of adults and children with acute, uncomplicated infections due to Plasmodium falciparum or mixed infections including P. falciparum. Because COMAX DPS is effective against both drug-sensitive and drug-resistant P. falciparum, it is also recommended for malaria infections acquired in areas where the parasites may be resistant to other anti-malarials.
For travelers (non-immune subjects), prescribers are advised to issue COMAX DPS for self-administration with guidance regarding the appropriate use.
COMAX DPS is contraindicated in:
Patients hypersensitive to the active substances or any of the excipients.
Patients with severe malaria according to WHO definition.
Patients with a family history of congenital elongation of QTc interval , cardiac arrhythmias, clinically relevant bradycardia or with severe cardiac disease and in known disturbances of electrolyte balance e.g. hypokalaemia or hypomagnesaemia.
Patients taking any drug which is metabolized by the cytochrome enzyme CYP2D6 e.g. Fleicanide, Metoprolol, Imipramine, Amitryptiline, Clomipramine.
Patients taking drugs that prolong QT interval such as anti-arrhythmics of classes
IA and III , neuroleptics, antidepressant agents, certain antibiotics including ; macrolides, fluoroquinolones, imidazole and triazole antifungal agents, certain non-sedating anti-histaminics(terfenadine,astemizole), cisapride.
First trimester of pregnancy where other suitable and effective anti-malarials are available. PRECAUTIONS:
COMAX DPS has not been indicated for prophylaxis, treatment of cerebral malaria or other manifestations of severe malaria including pulmonary oedema or renal failure. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence is greater.
COMAX DPS is not indicated for the treatment of malaria due to P. vivax, P. malariae or P.ovale. Data on safety and efficacy are limited when COMAX DPS is given concurrently with anti-malarials other than Mefloquine or Quinine. COMAX DPS should be administered at least one month after the last Halofantrine dose.
The long elimination half-life of Lumefantrine must be taken into account when administering Quinine in patients previously treated with COMAX DPS.
Sequential treatment with Primaquine should be used to achieve hypnozoite eradication in case of co-infection with P.vivax.
Caution is recommended when combining COMAX DPS with substrates, inhibitors or inducers of CYP3A4.
Dizziness or fatigue / asthenia might occur in which case patients should not drive or operate machinery.
Although the likelihood of COMAX DPS interactions with other drugs is minimal in view of its short duration of administration and wide therapeutic index, three interactions have been noted. Ketoconazole leads to a modest increase in Artemether, Dihydroartemisinin and Lumefantrine exposure but is not associated with increased side effects or changes in electrocardiographic parameters. Hence dose adjustment of the combination is considered unnecessary. If COMAX DPS is given sequentially to Mefloquine or Quinine, close monitoring of food intake (for Mefloquine) or ECG (for Quinine) is necessary. Patients are encouraged to eat during dosing times to increase bioavailability.
COMAX DPS is generally very well tolerated by children, with most adverse events being of mild to moderate severity and duration. Many of the reported events are likely to be related to the underlying malaria and / or to an unsatisfactory response to the treatment, concomitant drugs or infections rather than to COMAX DPS.
Common side effects are palpitations, abdominal pain, anorexia, arthralgia, myalgia, headache, dizziness, sleep disorders, cough, pruritus, asthenia and fatigue. Rarely hypersensitivity, somnolence, involuntary muscle contractions, paraesthesia, ataxia may occur. Asymptomatic QT prolongation has reported in adults and children but no causal relationship with COMAX DPS could be confirmed.
DOSAGE AND ADMINISTRATION:
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 COMAX DPS. In the event of vomiting within 1 hour of administration, a repeat dose should be taken.
The dose depends on the severity of the case and clinical situation of the patient. In general: 4mg artemether / kg body weight in combination with a 6 fold of that dose for lumefantrine per day, administered as a single dose.
For each patient it will be calculated how many mililitres should be administered. It is recommended to round off the dosage to the nearest subdivision. However, it should be remarked that this is an average dosing scheme. Depending on the severity of the case and clinical situation of the patient the dose may be increased.
Packs of 60ml in amber colored bottles.
Do not store above 30OC. Store in a dry place. Protect from direct sunlight. Keep out of reach of children. After reconstitution the solution should be stored below 30OC and should be used within 14 days.
LEGAL CATEGORY :
Prescription only medicine.