Pyrimethamine

Brands of Pyrimethamine in kenya

Xoprim, Cosmos Limited1PPB Drugs Retention Register


Pyrimethamine in Kenya
Pyrimethamine Chemical Structure

MODE OF ACTION

The antiparasitic action of pyrimethamine is due to its specific activity on folic acid metabolism in the Plasmodium and Toxoplasma parasites. In this respect it competitively inhibits the dihydrofolate reductase enzyme with an affinity far greater for the protozoal than for the human enzyme.2Rollo, I. M. “The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum.” British journal of pharmacology and chemotherapy 10.2 (1955): 208.

INDICATIONS

For the treatment of:

Toxoplasmosis, including ocular infections, proven foetal infection following maternal infection during pregnancy, and toxoplasmosis in immune-deficient patients (for the treatment of toxoplasmosis pyrimethamine must always be used in combination with a synergistic agent e.g. sulphadiazine).

Treatment is not normally required for asymtomatic or mild toxoplasma infection.

DOSAGE AND ADMINISTRATION

Toxoplasmosis (including ocular infections)

Pyrimethamine should be given concurrently with sulphadiazine or another appropriate antibiotic.

In the treatment of toxoplasmosis, all patients receiving Pyrimethamine should be given a folinic acid supplement (calcium folinate) to reduce the risk of bone marrow depression.

Pyrimethamine treatment should generally be given for 3 to 6 weeks and not less than six weeks in immunosuppressed patients. If further therapy is indicated, a period of two weeks should elapse between treatments.

There have been no dose response studies of pyrimethamine in the treatment of toxoplasmosis. The following recommendations are therefore for guidance only.

Adults

A loading dose of Pyrimethamine 100 mg should be given for the first 1 to 2 days, followed by 25 mg to 50 mg daily. This should be given together with 2 g to 4 g of sulphadiazine daily in divided doses.

• Foetal toxoplasmosis during pregnancy

Pyrimethamine 50 mg every 12 hours for 2 days, followed by 50 mg daily. This should be given together with an initial dose of sulfadiazine 75 mg/kg, followed by 50 mg/kg every 12 hours (to a maximum of 4 g daily).

Immune-deficient adults and adolescents

Guidelines for the treatment of opportunistic infections in HIV-infected adults and adolescents consider pyrimethamine plus sulfadiazine to be the initial therapy of choice for Toxoplasma gondii encephalitis and recommend the following doses, based on body-weight, be given for at least 6 weeks:

– less than 60 kg – pyrimethamine 200 mg orally, followed by 50 mg daily plus sulfadiazine 1 g orally every 6 hours

– 60 kg or more – pyrimethamine 200 mg orally, followed by 75 mg daily plus sulfadiazine 1.5 g orally every 6 hours.

Paediatric Population

Children over 6 years

A loading dose of Pyrimethamine 100 mg should be given for the first 1 to 2 days, followed by 25 mg to 50 mg daily. This should be given together with 2 g to 4 g of sulphadiazine daily in divided doses.

Children aged 5 to 6 years

An initial dose of Pyrimethamine 2 mg/kg bodyweight (to a maximum of 50 mg) followed by 1 mg/kg bodyweight/day (to a maximum of 25 mg); combined with sulphadiazine 150 mg/kg bodyweight (maximum 2 g) daily in four divided doses.

Immune-deficient children

Dosage regimens for immune-deficient children are not defined.

Children under 5 years

There is insufficient data to provide specific dose recommendations in children. This formulation is not suitable for children under 5 years.

Elderly

There is no definitive information on the effect of Daraprim on elderly individuals. It is theoretically possible that elderly patients might be more susceptible to folate depression associated with the daily administration of Pyrimethamine in the treatment of toxoplasmosis, and supplementation of folinic acid is therefore essential.

Patients with renal impairment

Pyrimethamine should be given with caution to patients with renal impairment. Since Pyrimethamine is co-administered with a sulphonamide care should be taken to avoid accumulation of the sulphonamide in patients with renal impairment.

Patients with hepatic impairment

Pyrimethamine should be given with caution to patients with hepatic impairment. There are no general recommendations for dosage reductions for liver-impaired states but consideration should be given to dose adjustments for individual cases

CONTRAINDICATIONS

Pyrimethamine is contraindicated in:

Hypersensitivity to pyrimethamine or to any of the excipients of this medicinal product.

Pyrimethamine should not generally be used during the first trimester of pregnancy.

Since Pyrimethamine is to be taken in conjunction with another drug for the indications listed, the relevant prescribing information for the synergistic agent should also be considered.

Breast-feeding should be avoided during toxoplasmosis treatment.3Cook, G. C. “Use of antiprotozoan and anthelmintic drugs during pregnancy: side-effects and contra-indications.” Journal of Infection 25.1 (1992): 1-9.

DRUG INTERACTIONS

Folate inhibitors, agents associated with myelosuppression

Pyrimethamine , by its mode of action, may further depress folate metabolism in patients receiving treatment with other folate inhibitors, or agents associated with myelosuppression, including cotrimoxazole, trimethoprim, proguanil, zidovudine, or cytostatic agents (e.g. methotrexate).

Cases of fatal bone marrow aplasia have been associated with the administration of daunorubicin, cytosine arabinoside and pyrimethamine to individuals suffering from acute myeloid leukaemia.

Megaloblastic anaemia has been reported occasionally in individuals who took pyrimethamine concurrently with a trimethoprim/sulphonamide combination.

Methotrexate

Convulsions have occurred after concurrent administration of methotrexate and pyrimethamine to children with central nervous system leukaemia.

Other antimalarial drugs

Seizures have occasionally been reported when pyrimethamine was used in combination with other antimalarial drugs.

Lorazepam

The concurrent administration of lorazepam and Pyrimethamine may induce hepatotoxicity.

Antacid salts, kaolin

In vitro data suggest that antacid salts and the anti-diarrhoeal agent kaolin reduce the absorption of pyrimethamine.

Highly protein bound compounds

The high protein binding exhibited by pyrimethamine may prevent protein binding by other compounds (eg. quinine or warfarin). This could affect the efficacy or toxicity of the concomitant drug depending on the levels of unbound drug.

DRUG ADVERSE EFFECTS

Blood and lymphatic system disorders
Very common:
Anaemia
Common:
Leucopenia, thromboctopenia
Very rare:
Pancytopenia
Nervous system disorders
Very common:
Headache
Common:
Dizziness
Very rare:
Convulsions
Respiratory, thoracic and mediastinal Disorders
Very rare:
Pneumonia with cellular and eosinophilic pulmonary infiltration (observed when pyrimethamine was administered once weekly in association with sulfadoxine)
Gastrointestinal disorders
Very common:
Vomiting, nausea, diarrhoea
Very rare:
Colic, buccal ulceration
Skin and subcutaneous tissue disorders
Very common:
Rash
Uncommon:
Abnormal skin pigmentation
Very rare:
Dermatitis
General disorders and administrative site conditions
Uncommon:
Fever

Reporting of suspected adverse reactions:

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting, and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorization of the medicinal product are important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients are encouraged to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:


Pyrimethamine in Kenya
Pyrimethamine in Kenya
Pyrimethamine in Kenya
Pyrimethamine in Kenya
Pyrimethamine in Kenya

Clinical | Pharmacokinetic data


Pregnancy Category: C (Risk not ruled out)
Routes of Administration: Oral
Bioavailability: Not Available
Protein Binding: Not Available
Metabolosim: Not Available
Onset of Action: N/A
Elimination Half life: Not Available
Excretion: Not Available

Legal Status | Dosage forms & Strengths


Prescription Category:
Prescription only Medicine (POM) , ℞-only
Narcotic Drugs and Psychotropic Substances (Control ) Act Schedule:
This drug is not a controlled substance under Narcotic Drugs and Psychotropic Substances (Control ) Act
Dosage Forms | Strengths:


Drug Indentifiers:

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Drug Images

References/ Citation:

  1. Rollo, I. M. “The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum.” British journal of pharmacology and chemotherapy 10.2 (1955): 208.
  2. PPB Drugs Retention Register



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