Label: Information for the User

Daraprim 25 mg Tablets

Pirimetamina

Read this label carefully before taking this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again. If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Daraprim contains pyrimethamine, which belongs to a group of medicines called antimalarials. It is indicated for adults and children for the treatment of uncomplicated malaria caused by sensitive strains ofPlasmodium falciparum.

Daraprim in combination with a sulfonamide is indicated for the treatment of congenital and acquired toxoplasmosis.

Pyrimethamine should not be used as monotherapy for the treatment of malaria and toxoplasmosis.

Do not take Daraprim

• If you are allergic to the active ingredient or any of the other components of this medication listed in section 6.

Warnings and precautions

• If you have a type of anemia called megaloblastic anemia or symptoms of malnutrition, as pyrimethamine may intensify the folate deficiency associated with this type of anemia. In accordance with this, these individuals should receive a folinic acid supplement.
• If you have a history of seizures; in these patients, high initial doses of pyrimethamine should be avoided.

When pyrimethamine is administered with a sulfonamide, general precautions applicable to sulfonamides should be taken into account. In any case, adequate liquid intake should be ensured to minimize the risk of crystalluria.

Use of Daraprim with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Especially pyrimethamine may modify the effect of the following medications: antibiotics such as cotrimoxazole or trimethoprim, antimalarials such as proguanil, antivirals such as zidovudine, or cytostatic agents (such as, for example, methotrexate). Concomitant administration with a trimethoprim/sulfamethoxazole combination may develop megaloblastic anemia.

Concomitant administration of lorazepam (benzodiazepine) and pyrimethamine may induce mild liver damage.

Cases of total or partial disappearance of cells normally found in the bone marrow (fatal aplastic anemia of the bone marrow) have been associated with the administration of the antibiotic daunorubicin and pyrimethamine to individuals suffering from a type of leukemia known as acute myeloid leukemia.

Antacids and the antidiarrheal agent kaolin reduce the absorption of pyrimethamine.

Pyrimethamine may affect the efficacy or toxicity of medications such as quinine or antimalarials or anticoagulants such as warfarin if administered concomitantly.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Daraprim is only recommended for combination therapy with sulfamethoxazole during the second and third trimesters of pregnancy. In the first trimester, an alternative therapy is recommended.

Administration of folinic acid calcium is recommended if Daraprim is administered during pregnancy.

Pyrimethamine passes into breast milk, so its use is not recommended during breastfeeding, unless your doctor considers it necessary.

Driving and operating machinery

No effect on the ability to drive vehicles and use machines has been observed with Daraprim.

Daraprim 25 mg tablets contain lactose and sodium

This medication contains lactose. If your doctor has indicated that you have an intolerance to certain sugars, consult with them before taking this medication.

This medication contains less than 23 mg of sodium (1 mmol) per tablet; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Remember to take your medication.

Your doctor will indicate if you should increase or decrease the medication dose during the treatment period, as well as the duration of the treatment.

Daraprim is an oral tablet. It should be taken in the morning or at night, with or without food. The tablets should be swallowed without chewing with the help of a little liquid (a glass of water).

All patients receiving pyrimethamine must receive a folinic acid supplement to reduce the risk of bone marrow damage.

Treatment of malaria:

Daraprim should be administered in a single dose concomitantly with sulfadiazine and another antimalarial.

Adults:

A single dose of two to three Daraprim tablets (50 to 75 mg of pyrimethamine), along with 1,000 mg to 1,500 mg of sulfadiazine.

Generally, a dose higher than that for adults should be administered in patients with a weight of more than 60 kg.

Use in children:

Pyrimethamine can be used orally with sulfadoxine/sulfadiazine in children from 2 months of age.

The following dosage guidelines are recommended based on body weight:

• Children weighing 5 to 10 kg: 12.5 mg of pyrimethamine in a single dose.
• Children weighing 11 to 20 kg: 25 mg of pyrimethamine in a single dose.
• Children weighing 21 to 30 kg: 37.5 mg of pyrimethamine in a single dose.
• Children weighing 31 to 45 kg: 50 mg of pyrimethamine in a single dose.
• Children weighing more than 45 kg: use the same dose as for adults.

Use in elderly patients:

No information is available on the effect of Daraprim in elderly patients. At the recommended doses for malaria, it is unlikely that pyrimethamine will have adverse effects in elderly patients.

Treatment of toxoplasmosis

Daraprim should be administered concomitantly with sulfadiazine or clindamycin. The use of an alternative sulfonamide may require a dose adjustment.

Adult immunocompetent patients:

Pyrimethamine: An initial dose of four tablets (100 mg of pyrimethamine) followed by a daily dose of one to two tablets (25-50 mg of pyrimethamine).

Adult immunocompromised patients:

Daraprim should be administered concomitantly with sulfadiazine or clindamycin

• <60>
• ≥60 kg: pyrimethamine 200 mg orally as a loading dose, followed by 75 mg daily.

Subsequently, the secondary prophylaxis regimen should be administered.

Use in children

The following dosage guidelines are recommended for the treatment of toxoplasmosis:

• Children less than 3 months (congenital toxoplasmosis): For the treatment of congenital toxoplasmosis, it is recommended that newborns receive pyrimethamine 2 mg/kg/day for 2 days; 1 mg/kg/day for 2-6 months, and then 1 mg/kg/day three times a week until completion of 12 months of treatment.

• Children 3 to 9 months: 6.25 mg daily of pyrimethamine along with sulfadiazine: 100 mg/kg body weight (maximum 1 g) per day in four divided doses.
• Children 10 months to 2 years: 1 mg/kg body weight/day of pyrimethamine along with 150 mg/kg body weight of sulfadiazine (maximum 1.5 g) per day in four divided doses.
• Children 3 to 6 years: A loading dose of pyrimethamine 2 mg/kg body weight (up to a maximum of 50 mg) followed by a daily dose of 1 mg/kg (maximum 25 mg); along with 150 mg/kg body weight of sulfadiazine (maximum 2 g) per day in four divided doses.
• Children over 6 years: Same as for adults.

In immunocompromised children, the dosage guidelines are not defined. As a general guide, refer to the dosage guidelines indicated for children with toxoplasmosis infections.

Use in elderly patients:

No information is available on the effect of Daraprim in elderly patients. In theory, it is possible that these patients under treatment for toxoplasmosis may be more susceptible to bone marrow damage caused by folate deficiency associated with daily administration of Daraprim.

Use during pregnancy:

25 mg daily until delivery.

If you take more Daraprim than you should

If you have taken more Daraprim than you should, consult your doctor or pharmacist immediately. The most common symptoms in cases of acute overdose are: vomiting and convulsions. Ataxia, tremor, and respiratory depression may also occur.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Daraprim

Do not take a double dose to compensate for the missed doses. Take the next dose when it is due.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Symptoms to be aware of

Bone marrow damage(bone marrow failure to produce blood cells)

This increases the risk of bleeding andreduces your ability tofight off infections. Symptoms include:

• unexplained bleeding or bruising
• fever
• sore throat
• mouth ulcers
• extreme paleness or weakness

Inform your doctor as soon as possibleif you experience any of these symptoms – whether they are new or worsen.

Observed side effects are classified according to their frequency of occurrence as: very frequent (may affect more than 1 in 10 people), frequent (may affect up to 1 in 10 people), infrequent (may affect up to 1 in 100 people), rare (may affect up to 1 in 1,000 people), very rare (may affect up to 1 in 10,000 people):

Very frequent side effects

May affectmore than 1 in 10patients:

• headaches (headache)
• vomiting, nausea, diarrhea
• skin rash

Very frequent side effects that may appear in blood tests:

• anemia (decrease in the number of red blood cells)

Frequent side effects

May affectup to 1 in 10patients:

• dizziness

Frequent side effects that may appear in blood tests are:

• leucopenia (decrease in the number of white blood cells)
• trombocytopenia (decrease in the number of platelets)

Daily therapeutic doses of pyrimethamine have shown to depress hematopoiesis (blood cell formation) in 25 – 50% of patients. The probability of inducing leucopenia, anemia, or thrombocytopenia is reduced by concomitant administration of calcium folinate.

Infrequent side effects

May affectup to 1 in 100patients:

• fever
• abnormal skin pigmentation

Very rare side effects

May affectup to 1 in 10,000patients:

• colic
• convulsions

Convulsions have been observed predominantly in patients treated for toxoplasmosis

• mouth ulcers
• cellular and eosinophilic pneumonia

Observed when pyrimethamine is administered once a week in association with sulfadoxine

• dermatitis.

Very rare side effects that may appear in blood tests are:

• pancytopenia (decrease in the number of all types of blood cells)

Pancytopenia, in response to folates, has been observed in patients with a probable pre-existing folate deficiency. Deaths have occurred in the absence of folate treatment.

If you consider that any of the side effects you experience are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not appearing in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:http://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above 25°C. Store protected from light.

Do not use this medication after the expiration date (EXP) that appears on the packaging. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of containers and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Daraprim

• The active ingredient is pyrimethamine. Each tablet contains 25 mg of pyrimethamine.
• The other components (excipients) are: lactose monohydrate, cornstarch, hydrolyzed cornstarch, sodium docusate, and magnesium stearate.

Appearance of the product and contents of the packaging

Daraprim are white, biconvex, scored, and engraved tablets with an identifying code. They are presented in packaging with 30 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

SmithKline Beecham Farma, S.A.

P.T.M. C/ Severo Ochoa, 2

28760 Tres Cantos (Madrid)

Tel: +34 900 202 700

[email protected]

Responsible for manufacturing

GlaxoSmithKline Trading Services Limited

12 Riverwalk

Citywest Business Campus

Dublín 24

Irlanda

Last review date of this prospectus:October 2020.

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

Daraprim is packaged in child-resistant blister packaging.

How to remove a tablet

1.Separate a tablet:pull along the pre-scored line to separate a compartment from the blister.

2.Remove the outer sheet:starting from the corner, lift and remove the outer sheet from the compartment.

3.Press to remove the tablet:press from one side of the tablet to remove the tablet from the aluminum sheet.