Description and Composition of Grimal
Table of Contents
Grimal is an ethyl ether derivative of Fontether indicated for the treatment of severe and resistant Plasmodium falciparium malaria. It contains alpha, beta Arteether as its active pharmaceutical ingredient. Grimal is a fast acting blood schizonticide. It is sourced from Artemisia annua plant.
Pharmacology of Grimal
How does Grimal work?
α/β Arteether is a fast acting blood schizonticidal agent for P. falciparum malaria at the erythrocytic stage. Arteether is concentrated in parasitized erythrocytes. The functional group responsible for antimalarial activity of α/β Arteether is “endoperoxide bridge. Researchers believe that iron from the digested haemoglobin of the parasite’s victim reduces this bridge releasing a highly reactive free radical iron (IV) oxo species which rips apart the parasitic cells. It is proposed that α/β Arteether inhibits the protein synthesis and alter the ribosomal organisation and endoplasmic reticulum. α/β Arteether also acts on the membranes of the parasites through lipid peroxidation
Pharmacokinetics of Grimal
The main metabolite of α/β Arteether is Dihydroartemisinin. The half life of Dihydroartemisinin is more than 20 hours. The elimination of the drug is through hepatic metabolism and gets eliminated at a low rate as compared to other artemisinin derivatives.
Clinical Data of Grimal
In multicentric clinical evaluation of α/β Arteether in complicated and uncomplicated P falciparum malaria, a total of 267 patients of uncomplicated P. falciparum malaria having fever with chilli rigor and 221 patients with complicated P. falciparum malaria having fever, headache, vomiting, diarrhoea, convulsions, renal impairment, severe anaemia, splenomegaly, hypotension and coma were treated with a-B Arteether. Most of the cases became afebrile within 36 hours without the use of antipyretic drugs and parasite free within 72 hours. The cure rate in uncomplicated malaria was nearly 100% and in complicated P falciparum malaria about 90%. Recrudescence was less than 7%.
α/β Arteether is more lipophillic and has the advantage of greater accumulation in brain tissue, hence a potential drug for the treatment of cerebral malaria.
a-B Arteether, also exhibits gametocytocidal action on P. falciparum which will be an added advantage in cutting down the transmission of P. falciparum malaria.
a-B Arteether is well tolerated and compliance is very good with virtually no drug related side effects.
Indications and Uses of Grimal
What is Grimal used for?
Grimal is indicated for use in severe Plasmodium falciparum malaria including cerebral malaria and as a second line treatment in chloroquine resistant malaria.
Contraindication of Grimal
Grimal is contraindicated in patients hypersensitive to artemisinin derivatives.
Dosage and Administration of Grimal
150 mg once daily for 3 consecutive days or as directed by the physician
3 mg/kg per day administered by intramuscular injection over a 3 day period or as directed by the physician.
α/β Arteether, the active ingredient of this injection is for intramuscular use only.
The injection must be given in aseptic conditions, deep intramuscularly in the upper-external quadrant of the buttock
No other drug should be mixed in the same syringe
Overdosage of Grimal
The pre-clinical studies of α/β Arteether have shown that the median lethal dose value, LD₅₀, is more than 1000 mg/kg, whereas the maximum dose injected in adult is about 2.5 mg/kg per day. This confirms that the safety window for the dose administered is very wide. Hence this study concludes that α/β Arteether is well tolerated even when an overdose is administered.
Since no clinical data is available for the use of α/β Arteether during pregnancy, it should be used with caution in pregnant women, if the potential benefits outweighs the potential risk to the foetus
It is not known whether α/β Arteether is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised while using α/β Arteether by breastfeeding women.
Grimal (α/β Arteether) does not interfere with the action of other commonly used drugs for treatment of P. falciparum malaria, example, Quinine and can be administered along with these drugs for the treatment of severe form of malaria. However, it should not be used together with other Artemisinin derivatives (ACTs) like Artesunate and Artemether.
Adverse Effects of Grimal
Neurotoxicity is the common side effect associated with all artemisinin compounds in high doses.
Neurotoxicity manifests as gait disturbances, loss of spinal cord pain responses, incoordination, respiratory depression, convulsions and cardio respiratory arrest. Other side effects are nausea, dizziness and depressed GIT activity.
Clinical, neurological, electro-cardiographic and biochemical abnormality were seen. In the multi centric trials of a-B Arteether involving 478 patients suffering from P. falciparum malaria, no significant side effects were observed.
Storage of Grimal
Store below 30°C. Protect from light. Keep all medicines out of the reach of children.