Laridox Sulfadoxine & Pyrimethamine Tablets USP/Suspension/Injection
Description, Composition, Clinical pharmacology mechanism of actions, Pharmacokinetics, Indications, Dosage and administration, Overdosage, Adverse drug reactions, Precautions and warnings, Drug interactions, Contraindications, Storage, Presentation and Maker of Laridox Tablet, Suspension, Injection Medicine for Malaria.
Laridox is an antimalarial agent combining 2 drugs, sulfadoxine and pyrimethamine. Sulfadoxine is an ultra-long-acting sulphonamide. Pyrimethamine, an aminopyrimidine derivative, is an antimalarial agent that is structurally related to trimethoprim. Chemically,sulfadoxine is N1 (5,6-dimethoxypyrimidin-4-y1)-sulphailamide whereas pyrimethamine is 5-(4-chloropheny1)- 6-ethylpyrimidine-2,4-diyldiamine.
Each tablet contains:
Sulfadoxine USP 500mg
Pyrimethamine USP 25mg
Each 5ml contains:
Sulfadoxine USP 250mg
Pyrimethamine USP 12.5mg
Each 2.5ml contains:
Sulfadoxine USP 500mg
Pyrimethamine USP 25mg
CLINICAL PHARMACOLOGY MECHANISM OF ACTION
Sulfadoxine and pyrimethamine combination is an antimalarial agent, which acts by reciprocal potentiation of its two components, achieved by a sequential blockade of two enzymes involved in the biosynthesis of folinic acid within the parasites.
Sulfadoxine, like other sulphonamides, is a structural analog of para-aminobenzoic acid (PABA) and competitively inhibits dihydrofolic acid synthesis by inhibiting dihydropteroate synthetase, which is necessary for the acid.
Pyrimethamine is a folic acid antagonist and has a mechanism of action similar to that of trimethoprim. It interferes with the synthesis of tetrahydrofolic acid in malarial parasites at a point immediately succeeding that where sulphonamides act. By binding to and reversibly inhibiting dihydrofolate reductase, pyrimethamine inhibits the reduction of dihydrofolate acid to tetrahydrofolic acid (folinic acid). The combination of sulfadoxine and pyrimethamine results in a synergistic action against susceptible plasmodia.
Sulfadoxine and Pyrimethamine are blood schizonticidal agents and are active against the asexual erythrocytic forms of susceptible plasmodia.
It is effective against certain strains of plasmodium flaciparum that are resistant to chloroquine.
Both sulfadoxine and pyrimethamine are well absorbed from the GI tract Like other sulphonamides, sulfadoxine is widely distributed in the body. Pyrimethamine is distributed mainly to the kidneys, lungs, liver and spleen. Plasma protine binding is about 90% for both pyrimethamine and sulfadoxine. About 5% of sulfadoxine appears in the blood as acetylated matabolite, about 2-3% as the glucuronide. Pyrimethamine is transformed to several metabolites. Both sulfadoxine and pyrimethamine are excreted mainly by the kidneys. The apparent elimination halt life of sulfadoxine ranged from 100 to 231 hours with a mean of 169 hours, whereas pyrimethamine half lives ranged from 54 to 148 hours with a mean of 111 hours.
Laridox is indicated for intermittent preventive treatment of malaria in pregnancy (IPT)
DOSAGE AND ADMINISTRATION
One full treatment dose during the 2nd and 3rd trimesters. The last dose should be given not later than one month before the expected date. Second trimester starts from sixteen weeks or when the pregnant woman notices the kicking of the baby.
Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation. If anorexia or vomiting occurs during the therapy, these adverse effects may be minimized by taking the drug with meals. Instruct the patient to seek medical attention and discontinue prophylactic therapy if sore throat, fever, arthralgia cough, shortness of breath, pallor purpura, jaundice or glossitis develop.
Sulfadoxine-pyrimethamine dosage should be based on the weight of the patient. In situations where weight cannot be obtained, dosage should at least be based on age.
Acute intoxication may be manifested by anorexia vomiting and CNS stimulation (including convulsions), followed by megaloblastic anemia, leukopenia, thrombocytopenia, glossitis and crystalluria.
In acute intoxication, emesis and gastric lavage followed by purges may be of benefit. Adequately hydrate the patient to prevent renal damage. Monitor the renal and hematopoietic system for > 1 month after overdosage. If the patient is having convulsions, the use of a parenteral barbiturate is indicated. Administer folinic acid (leucovorin) 5 to 15mg IM daily for >3 days for depressed platelet or white blood cell counts.
ADVERSE DRUG REACTIONS
Sulfadoxine and Pyrimethamine generally is well tolerated.
CNS – Headache, peripheral neuritis, mental depression, convulsions, ataxia, hallucinations, tinnitus, vertigo, insomnia, apathy, fatigue, muscle weakness, nervousness and polyneuritis.
GI – Glossitis, stomatitis, nausea, emesis, abdominal pains, hepatitis, hepatocellular necrosis, diarrhoea, pancreatitis, feeling of fullness and transient rise of liver enzymes.
Hematologic – Agranulocytosis, aplastic anemia, thrombocytopenia, leucopenia, hemolytic anemia, purpura, hypoprothrombinemia, methemoglobinemia, eocinophilia.
Hypersensivity – Erythema multiforme, stevens-johnson syndrome, generalized skin eruptions, toxic epidermal necrolysis, urticaria, serum sickness, pruritus, exfoliative dermatitis, anaphylactoid reactions, periorbital edema, conjunctival and scleral injection, photosensitization, arthralgia, allergic myocarditis, slight hair loss, Lyell’s syndrome and allergic pericarditis.
Hepatic – Adverse hepatic effects, possibly secondary to sulphonamide hypersensitivity, have been reported in patients receiving sulfadoxine and pyrimethamine. In some patients adverse hepatic effects have been associated with severe cutaneous reactions to the combination. Abnormal liver function tests, jaundice, hepatomegaly, and hepatitis which can be fatal, have been reported with the combination.
Miscellaneous – Pulmonary infiltrates, drug fever, chills, renal failure, interstitial nephritis, BUN and serum creatinine elevations, toxic nephrosis with oliguria and anuria, crystalluria, periarteritis nodosa, LE phenomenon.
PRECAUTIONS AND WARNINGS
Sulfadoxine-pyrimethamine must not be used in the first trimester.
Oral sulfadoxines-pyrimethamine have not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria, including hyperparasitaemia, pulmonary edema or renal failure. Patients with severe malaria are not candidates for oral therapy. Excessive exposure to the sun must be strictly avoided. Administer with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency including patients with malabsorption syndrome, alcoholism and to those with severe allergy or bronchial asthma. As with some sulphonamide drugs, in glucose-6-phosphate dehydrogenase-deficient individuals, hemolysis may occur. Perform a urinalysis with microscopic examination and renal function test during therapy for patients who have impaired renal function.
Because sulfadoxine and pyrimethamine contains a sulphonamide, the drug shares the toxic potentials of the sulfonamides, and the usual precautions and contraindications to sulphonamide therapy should be observed, including maintenance of an adequate fluid intake to prevent crystalluria. Patients who develop signs suggestive of sulphonamide or pyrimethamine sensitivity should never receive drugs containing these substances again. These signs including skin rashes, evidence of haemolyis including dark urine and purpura and presumptive signs of bone marrow depression such as sore throat and mouth ulcers.
1. Laridox has not been reported to interfere with antidiabetic agent.
2. Laridox is compatible with Quinine and with antibiotics.
However, antibiotic drugs such as sulfonamides or Trimethoprim-Sulfamethoxazole combinations should not be used while patients is receiving Laridox for antimalarial prophylaxis.
Sulfadoxine and Pyrimethamine tablet belongs to the antifoliate group of antimalarials. There is evidence that folic acid administered concurrently with Sulphanamide-pyrimethamine combinátion can antagonize sulfadoxine action, Therefore, folic, acid supplement should be delayed for one week after S/P use to avoid an inhibitory effect on anti malarial efficacy.
The drug is contraindicated in patients with severe renal insufficiency, marked liver parenchymal damage or blood dyscrasias, hypersensitivity to pyrimethamine or sulphonamides, patients with documented megaloblastic anernia due to folate deficiency.
Store below 30oC in a dry place, away from light
KEEP ALL MEDICINES AWAY FROM CHILDREN
Tablets: Blister strip of 3 tablets
Injection: Ampoule of 2.5 ml
Suspension: 10 ml Bottle
Made in India by
Ipca Laboratories Ltd.
Regd. Off.: 48, Kandivli Ind. Estate,
Mumbai 400 067