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Garydox

Agary Pharmaceutical Limited
Plot C39A, Amuwo Odofin Commercial Scheme, Along Alakoso Avenue, Amuwo Odofin, Lagos.
Email: agarypharm@gmail.com
Tel: 0809-275-6424, 0809-275-6425, 0808-745-4848.
Website: http://agarypharm.com/

Brand Name

Garydox

Manufacturer

Agary Pharmaceutical Limited
Plot C39A Amuwo Odofin Comm. Scheme, Along Alakoso Avenue, Amuwo Odofin, Lagos.

Therapeutic Class

Antimalarial drugs

Dosage Form, Composition & NAFDAC Registration Number (NRN)

Tablet (NRN: B4-1781): Sulfamethoxazole 500 mg and Pyrimethamine 25 mg; white scored tablets marked “AGARY”

Pack Size: 525 mg - 3’s (in blisters)

Garydox new

Pharmacology

Pharmacodynanics

Sulfadoxine and Pyrimethamine as an antimalarial combination, acts by reciprocal potentiation of its components, achieved by sequential blockade of two enzymes involved in the biosynthesis of folinic acid within the parasites. The bacteriostatic action of sulphonamides occur through competitive antagonism of para-aminobenzoic acid, an essential component of folic acid synthesis.

Pyrimethamine inhibits the enzyme dihydrofolate reductase which catalyses the reduction of dihydrofolate to tetrahydrofolate and is important for cellular biosynthesis of purines, pyrimidines and some amino acids. By virtue of this marked synergistic action the combination is effective against Plasmodium falciparum strains that are resistant to chloroquine.

Pharmacokinetics:

Sulfadoxine and Pyrimethamine are well absorbed orally. Following oral absorption, the peak levels of Sulfadoxine occur at 2.5 to 6 hours. Sulfadoxine has a long half life ranging from 100 to 231 hours. Peak plasma concentration of pyrimethamine occurs in 1.5 to 8 hours. The apparent half life of pyrimethamine is 54 to 148 hours. Excretion is mainly by the kidneys. Both drugs appear in the breast milk of nursing mothers.

Garydox is an antimalarial agent which acts by reciprocal potentiation of its two components (Sulfadoxine and Pyrimethamine) achieved by a sequential blockade of two enzymes involved in the biosynthesis of folinic acid within the parasites.

Pyrimethamine is a dihydrofolate reductase inhibitor and Sulfadoxine is a dihydropteroate synthase inhibitor. The combination has blood schizonticidal activity against P. falciparum and P. vivax. Garydox is effective against certain strains of P. falciparum that are resistant to Chloroquine.

Pharmacokinetics:

Both Sulfadoxine and Pyrimethamine are well absorbed from the GI tract. Following oral administration, peak serum concentrations of Pyrimethamine reportedly occur within 2-6 hours of administration. Pyrimethamine is distributed mainly in the kidneys, lung, liver and spleen and has an apparent volume of distribution of about 13 L/kg in adults. Like other sulfonamides, Sulfadoxine is widely distributed in the body.

Pyrimethamine is approximately 80-87% bound in plasma proteins. Pyrimethamine and Sulfadoxine are both distributed into milk. Pyrimethamine reportedly has an average plasma half life of 111 hours (range 54-148 hours). The plasma half life of Sulfadoxine reportedly averages 169 hours (range 100-231 hours). Pyrimethamine and several unidentified metabolites of the drug are excreted in urine. Sulfadoxine is excreted mainly in urine.

Indications

It is indicated for the treatment of Plasmodium falciparum malaria for those patients in whom Chloroquine-resistance is suspected. Although, a single dose of Garydox may be effective when used alone for uncomplicated attacks of chloroquine-resistant P. falciparum malaria, oral Quinine is usually used concomitantly, particularly for the treatment of more severe infections and when a rapid reduction in parasitaemia is desirable.

Garydox should not be used alone for the treatment of malaria caused by other Plasmodium, specially P. vivax, since the drug may be ineffective in these infections.

Contra-indications

This combination should not be used in premature or newborn infants in the first two months of life because of the immaturity of their enzyme systems.

Pyrimethamine has been reported to cause aplastic anaemia if used between courses of antineoplastic agents. This should be borne in mind when using Sulfadoxine-Pyrimethamine combination. This combination is contraindicated in patients with renal or hepatic failure, or with blood dyscrasias.

Precautions/Warnings

Long acting sulfonamides have been reported to cause erythema multiforme.

This combination contains Sulfadoxine, a long-acting sulfonamide. Because of the long half-lives of Sulfadoxine and Pyrimethamine, the possiblity of accumulation should be borne in mind. Care should be exercised in patients with hepatic and particularly renal impairment and dosage adjustments made if necessary.

Laboratory Tests:

Regular blood counts are indicated whenever this combination is administered for more than three months. Urinalysis with microscopic examination and renal function tests should be performed during therapy of those patients who have impaired renal function.

Excessive exposure to the sun must be strictly avoided. Caution should be exercised in patients with folate deficiency and to those with severe allergy or bronchial asthma. As with some sulfonamide drugs, in glucose-6-phosphate dehydrogenase deficient individuals, haemolysis may occur.

Fatalities associated with the administration of sulfonamides although rare have occurred due to severe reactions including fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias.

Carcinogenesis, mutagenesis and impairment of fertility:

Pyrimethamine was not found carcinogenetic in female mice or in male and female rats. Pyrimethamine was found to be mutagenic in laboratory animals and also in human marrow follwing 3 or 4 consecutive daily doses totalling 200 to 300 mg. Fertility of male rats and the ability of male and female rats to mate were not adversely affected at dosages upto 210 mg/kg/day of Garydox.

Pregnancy:

Category C-
Risk cannot be ruled out. Human studies are lacking and animal studies are either positive for fetal risk or lacking. However, potential benefits may justify the potential risks. Women of child bearing potential who are traveling to areas malaria is endemic should be advised against becoming pregnant.

In addition, they should be advised to practice contraception during treatment with and for three months after the last dose. Pyrimethamine may interfere with Folic acid metabolism and if Pyrimethamine is given during pregnancy, Folic acid supplementation may be required. Sulfadoxine may cause kernicterus in babies during the first month of life by displacing bilirubin from plasma albumin. Sulfadoxine should therefore be avoided during the last month of pregnancy.

Use in lactation:

Pyrimethamine is excreted in breast milk. There is no information on the excretion of Sulfadoxine or the combination in breast milk, hence, it should not be given to nursing mothers. If administration is considered essential, alternate arrangements should be made for feeding the infant.

Paediatric precautions:

Sulfadoxine and Pyrimethamine are contraindicated in children younger than 2 months of age. Patients should be warned to keep Pyrimethamine out of the reach of children, since children are extremely susceptible to adverse effects from an overdosage of Pyrimethamine and accidental ingestion of the drug has been fatal in children.

Advice to Patients

Patients should be advised that sore throat, fever, cough, dyspnoea or purpura may be the first signs of serious side effects. The intake of Sulfadoxine-Pyrimethamine must be stopped immediately at the first signs of skin eruptions, a significant decrease of blood cells, or a bacterial or fungal superinfection.

Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias. Garydox (sulfadoxine and pyrimethamine) prophylactic regimen has been reported to cause leukopenia during a treatment of 2 months or longer. This leukopenia is generally mild and reversible.

Interactions

There have been reports which may indicate an increase in incidence and severity of adverse reactions when chloroquine is used with Garydox (sulfadoxine and pyrimethamine) as compared to the use of Garydox (sulfadoxine and pyrimethamine) alone.

No information is available at present concerning interactions between Sulfadoxine-Pyrimethamine combination and other drugs. However, the individual components of this combination interact with drugs as follows:

The hypoglycaemic effect of some sulfonylureas is enhanced by sulphonamides. Long acting sulfonamides may displace protein bound drugs such as Phenytoin, Coumarin derivatives etc, and thus, enhance their toxicity. The urinary excretion of sulfonamides is pH dependent and can significantly influence their plasma half life. Drugs containing the para-aminobenzoic acid nucleus (e.g. some local anaesthetics competitively antagonize the effects of sulfonamides.

Garydox (sulfadoxine and pyrimethamine) is compatible with quinine and with antibiotics. It can potentiate the effects of folic acid anatagonists e.g. Methotrexate, sulfonamides, trimethoprim, or trimethoprim-sulfamethoxazole combinations; they should not be used while the patient is receiving Garydox (sulfadoxine and pyrimethamine) for antimalarial prophylaxis.

If signs of folic acid deficiency develop, Garydox (sulfadoxine and pyrimethamine) should be discontinued. When recovery of depressed platelets or white blood cell counts in patients with drug-induced folic acid deficiency is too slow, folinic acid (leucovorin) may be administered in doses of 5 to 15 mg intramuscularly daily for 3 days or longer.

Concomitant adminstration of Sulfadoxine-Pyrimethamine and Trimethoprim or Trimethoprim-Sulfonamide combinations may intensify the impairment of folic acid metabolism and the related haematological side effects, and should therefore be avoided.

Adverse Effects

Given the recommended doses, Sulfadoxine-Pyrimethamine combination is generally very well tolerated. It is however, potentially capable of producing all the adverse effects known for sulfonamides and for Pyrimethamine. Skin reactions or gastrointestinal disorders may occasionally occur.

Hepatic reactions: 

There have been isolated reports of a transient rise of liver enzymes as well as hepatitis.

Haematological changes: 

In infrequent cases, thrombocytopenia, megaloblastic anaemia and leucopenia have been observed, though these usually have been asymptomatic. In isolated cases they take form of agranulocytosis or purpura. As a rule, all these changes regress after withdrawal of the drug.

Other side effects: 

Fatigue, headache, dizziness, fever and polyneuritis may occassionally occur. Pulmonary infiltrates resembling eosinophilic or allergic alveolitis have been reported in isolated instances. If symptoms such as cough or shortness of breath should occur, treatment with this combination should be discontinued. Isolated cases of serum sickness as well as allergic pericarditis have also been reported.

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist with these agents. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides, and long-term administration has produced thyroid malignancies in the species.

Given the recommended doses, Sulfadoxine-Pyrimethamine combination is generally very well tolerated. It is however, potentially capable of producing all the adverse effects known for sulfonamides and for Pyrimethamine. Skin reactions or gastrointestinal disorders may occasionally occur.

Dosage & Administration

Curative treatment with a single dose of Garydox:

Age   Dose
 2 months - 2 years ½ tablet 
 2 - 6 years  One tablet 
 6 - 12 years  Two tablets 
 12 years and above Three tablets

OVERDOSAGE

The symptoms of overdosage are likely to be those due to the individual components. These include headache, anorexia, nausea, vomiting, skin rashes, pruritus, symptoms of folic acid deficiency, signs of excitation, and haematological changes (megaloblastic anaemia, leucopenia, thrombocytopenia).

Convulsions and respiratory and failure may occur. Symptomatic treatment should be instituted as necessary. Elimination may be facilitated by gastric lavage, increased fluid intake (if renal function is normal) and administration of alkalinizers. Haemodialysis may be of use. Folinic acid may be administered to treat the folic acid deprivation

Storage/Handling Recommendations

Store below 25oC in a dry place.

Protect from light. Keep all medicines out of the reach of children.

Review Date

2017-09-14 05:17:05