INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo MALATEQ FILM-COATED TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

MALATEQ FILM-COATED TABLETS

COMPOSITION:
Each film-coated tablet contains 250 mg
atovaquone and 100 mg proguanil hydrochloride.
Inactive ingredients:
Colloidal silicon dioxide, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, opadry brown (ferric oxide, hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide), poloxamer 188, povidone and sodium starch glycolate.

PHARMACOLOGICAL CLASSIFICATION:
A 20.2.6 Medicines against protozoa

PHARMACOLOGICAL ACTION:
Pharmacodynamics
:
Atovaquone and proguanil hydrochloride, interfere with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. The mechanism of action of atovaquone against P. falciparum is at mitochondrial level, via inhibition of mitochondrial electron transport at the level of the cytochrome bc
1 complex, and collapse of mitochondrial membrane potential. One mechanism of action of proguanil hydrochloride, via its metabolite cycloguanil, is inhibition of dihydrofolatereductase, which disrupts deoxythymidylate synthesis. This causes the inhibition of DNA synthesis. Pharmacokinetics:
Absorption:
The pharmacokinetics of atovaquone is comparable between healthy subjects and HIV-infected patients. Although there are no atovaquone bioavailability data in healthy subjects, in HIV-infected patients the absolute bioavailability of a 750 mg single dose of atovaquone tablets taken with food is 21% (90% CI: 17- 27%). Dietary fat taken with atovaquone increases the rate and extent of absorption, increasing AUC 2-3 times and Cmax 5 times over fasting.
Proguanil hydrochloride is well and extensively absorbed regardless of food intake.
Distribution:
Atovaquone is highly protein bound (>99%) but does not displace other highly protein bound medicines in vitro, indicating significant interactions arising from displacement are unlikely. The volume of distribution of atovaquone is 0,62 + 0,19L/kg. Proguanil hydrochloride is 75% protein bound. In human plasma, the binding of atovaquone and proguanil hydrochloride were unaffected by the presence of the other.
Metabolism:
There is no evidence that atovaquone is metabolised, and only trace amounts appear in the urine with parent substance being predominantly (>90%) eliminated unchanged in faeces. Proguanil hydrochloride is partially metabolised with less than 40% being excreted unchanged in the urine. Its metabolites cycloguanil and 4chlorophenylbiguanide are also excreted in the urine.
Pharmacokinetics in the elderly:
There is no clinically significant change in the average rate or extent of absorption of atovaquone or proguanil hydrochloride between elderly and young patients. Systemic availability of cycloguanil is higher in the elderly compared to young patients, but there is no change in its elimination half-life (see: “DOSAGE AND DIRECTIONS FOR USE”).
Pharmacokinetics in hepatic impairment:
In patients with mild to moderate hepatic impairment there is no clinically significant change in exposure to atovaquone when compared to healthy patients. In patients with mild to moderate hepatic impairment there is an increase in proguanil AUC with no change in its elimination half-life and there is a decrease in C
max and AUC for cycloguanil. No data is available in patients with severe hepatic impairment (see: “DOSAGE AND DIRECTIONS FOR USE”).
Pharmacokinetics in renal impairment:
In patients with mild to moderate renal impairment, oral clearance and/or AUC data for atovaquone, proguanil hydrochloride and cycloguanil are within the range of values observed in patients with normal renal function. Atovaquone C and AUC
max are reduced in patients with severe renal impairment. The elimination half-lives for proguanil hydrochloride and cycloguanil are prolonged in patients with severe renal impairment with corresponding increases in AUC, resulting in the potential of accumulation with repeated dosing (see: “DOSAGE AND DIRECTIONS FOR USE” and “WARNINGS AND SPECIAL PRECAUTIONS”).

INDICATIONS:
MALATEQ
is indicated for the prophylaxis of drug-sensitive and drug-resistant Plasmodium falciparum malaria. Official guidelines and local information on the prevalence of resistance to antimalarial medicines should be taken into consideration.

CONTRA-INDICATIONS:
MALATEQ
is contra-indicated in known hypersensitivity to atovaquone or proguanil hydrochloride or any of the other inactive ingredients.
MALATEQ is contra-indicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min).

WARNINGS AND SPECIAL PRECAUTIONS:
Safety and efficacy of MALATEQ for the prophylaxis of malaria in patients who weigh less than 40 kg has not been established. A repeat dose of MALATEQ should be taken if vomiting occurs within 1 hour of dosing. In the event of recrudescent infections due to P. falciparum or failure of chemoprophylaxis, patients should be treated with a different blood schizonticide. If diarrhoea occurs, normal dosing should be continued. Absorption of atovaquone may be reduced in patients with diarrhoea or vomiting, but diarrhoea or vomiting was not associated with reduced efficacy for malaria prophylaxis.
However, patients with diarrhoea or vomiting should be advised to continue to comply with personal protection measures (repellents, bed nets). It is not recommended that mothers receiving MALATEQ breastfeed their babies.
Patients are advised to continue to use normal preventative measures i.e. mosquito repellents, window and bed nets when visiting areas known or suspected to be malaria infected.
The concomitant administration of MALATEQ and rifampicin or rifabutin is not recommended (see: “INTERACTIONS”).

Effects on ability to drive or use machines:
No studies have been done to investigate the effect of MALATEQ on driving performance or the ability to operate machinery. A prediction on detrimental effect on such activities cannot be made on the pharmacology of the ingredients of MALATEQ.

INTERACTIONS:
Concomitant use of tetracycline, metoclopramide, rifampicin and rifabutin may result in decrease in plasma-atovaquone concentrations (see: “WARNINGS AND SPECIAL PRECAUTIONS”). Concomitant administration of atovaquone and indinavir results in a decrease in the C
max of indinavir (23% decrease; min 90% CI: 8 - 35%). Caution should be exercised in prescribing atovaquone with indinavir due to the decrease in trough levels of indinavir. Atovaquone is highly protein bound (>99%) but does not displace other highly protein bound medicines in vitro, indicating that significant interactions arising from displacement are unlikely.

PREGNANCY AND LACTATION:
The safety of MALATEQ when administered concurrently in human pregnancy and lactation has not been established
.

DOSAGE AND DIRECTIONS FOR USE:
The daily dose should be taken with food or milk at the same time each day. Should vomiting occur within 1 hour of dosing, a repeat dose should be taken.
Prophylaxis:
Prophylaxis should start 1 to 2 days before entering a malaria-endemic area, and be continued daily until 7 days after leaving the area.
Dosage in adults:
One MALATEQ tablet daily.
Dosage in the elderly:
No dosage adjustments are needed in the elderly (see: “Pharmacokinetics”).
Dosage in hepatic impairment:
No dosage adjustments are needed in patients with mild to moderate hepatic impairment. No studies have been conducted in patients with severe hepatic impairment.
Dosage in renal impairment:
No dosage adjustments are needed in patients with mild to moderate renal impairment. For prophylaxis of P. falciparum malaria in patients with severe renal impairment see “CONTRA-INDICATIONS”.

SIDE EFFECTS:
MALATEQ
contains atovaquone and proguanil hydrochloride, therefore, the adverse events associated with each of these compounds may be expected with MALATEQ. At the doses employed for prophylaxis of malaria, adverse events are generally mild and of limited duration. There is no evidence of added toxicity following concurrent administration of atovaquone and proguanil hydrochloride.
Blood & lymphatic system disorders:
Less frequent
: Anaemia, neutropenia, pancytopenia
Immune system disorder:
Less frequent: angioedema
Endocrine disorder:
Less frequent: hyponatraemia
Gastrointestinal disorder:
Frequent: Abdominal pain, nausea, vomiting, diarrhoea, gastric intolerance, oral ulceration, stomatitis
Hepatobiliary disorders:
Less frequent: Elevated liver enzymes, elevated amylase levels
Metabolism and nutrition disorders:
Frequency unknown: Anorexia
Nervous system disorders:
Frequent: Headache, insomnia
General disorders and administrative site conditions:
Frequent
: Fever
The following adverse events have been reported, the frequency is unknown:
Respiratory, thoracic and mediastinal disorders:
Cough
Skin and subcutaneous tissue disorders:
Rash (including urticaria), hair loss

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In case of suspected overdose, treatment is symptomatic and supportive, given as appropriate.

IDENTIFICATION:
MALATEQ
Tablets: Pinkish brown to brown coloured, circular, biconvex bevelled edge film-coated tablets with ‘404’debossed on one side and ‘G’debossed on the other side.

PRESENTATION:
MALATEQ
Tablets are packed in white HDPE containers with white caps containing 100 tablets.
MALATEQ Tablets are packed in PVC/PVDC (Clear) paper backed with push through Aluminium Foil blister containing 12 tablets.

STORAGE INSTRUCTIONS:
Store at or below 25ºC.
Keep out of reach of children.

REGISTRATION NUMBER:
A47/20.2.6/1015

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
Glenmark Pharmaceuticals South Africa (Pty) Ltd
Unit 7/8 York House, Tybalt Place,185 Howick Close, Waterfall Office Park, Bekker Street, Vorna Valley, MIDRAND, 1686

MARKETED BY:
Lamar International (Pty) Ltd
13 Pasita Street, Rosen Heights, Rosen Park, Bellville, 7530

DATE OF PUBLICATION OF THE PACKAGE INSERT:
November 2014

PATIENT INFORMATION

Read all of this leaflet carefully before you start taking MALATEQ Film-coated Tablets:
• Keep this leaflet. You may need to read it again.
• If you have further questions, please ask your doctor or your pharmacist.
MALATEQ has been prescribed for you personally and you should not share your medicine with other people. It may harm them, even if their symptoms are the same as yours.

1. WHAT MALATEQ FILM-COATED TABLETS CONTAIN:
The active substances in each MALATEQ tablet are 250 mg atovaquone and 100 mg proguanil hydrochloride. The other (inactive) ingredients are colloidal silicone dioxide (Aerosil 200), low substituted hydroxypropyl cellulose (L-HPC LH-21), magnesium stearate, microcrystalline cellulose (Apical PH 101), microcrystalline cellulose (Apical PH 102), opadry brown 03C86943, poloxamer 188 (Lutrol F68), povidone (Kollidon 30), purified water and sodium starch glycolate (Primojel).
2. WHAT MALATEQ TABLETS ARE USED FOR:
MALATEQ
is indicated for the prevention of Plasmodium falciparum malaria. It belongs to a group of medicines called antimalarials. MALATEQ is used to reduce the risk of contracting malaria caused by Plasmodium falciparum, a parasite. MALATEQ contains two active ingredients which kill the malaria parasites in your body to reduce the risk of contracting malaria.
3. BEFORE YOU TAKE MALATEQ TABLETS:
Do not take MALATEQ tablets
• If you are allergic to atovaquone, proguanil hydrochloride or any of the other ingredients of MALATEQ.
• If you have severe kidney impairment.
Tell your doctor, pharmacist or healthcare professional before taking MALATEQ if:
• you weigh less than 40 kilograms;
• you have diarrhoea or are vomiting;
• you are taking any medicines containing rifampicin, rifabutin, tetracycline or metoclopramide;
• you are taking medicine containing indinavir;
• you have problems with your kidneys;
• you are pregnant or likely to become pregnant soon; and
• you are breastfeeding.

Taking MALATEQ tablets with food and drink:
       
MALATEQ tablets should be taken with food or milk

Pregnancy and Breastfeeding:
        Before taking MALATEQ, tell your doctor if you are breastfeeding, pregnant or likely to become pregnant soon.
If you are pregnant or breastfeeding your baby while taking MALATEQ, please consult your doctor, pharmacist or other healthcare professional for advice.
Safety during pregnancy and breastfeeding has not been established. Women breastfeeding their infants should not receive MALATEQ.
Driving and using machinery:
        No studies have been done to investigate the effect of MALATEQ on driving performance or the ability to operate machinery.
Taking other medicines with MALATEQ tablets:
        If you are using medicines on a regular basis, including complementary or traditional medicines, the use of MALATEQ with these medicines may cause undesirable interactions. Please consult your doctor, pharmacist or other healthcare professionals for advice.
Make sure your doctor knows what other medicines you are taking, including those that you have bought yourself.
Before taking MALATEQ, tell your doctor if:
• you are taking any medicines containing rifampicin, rifabutin, tetracycline or metoclopramide; or
• you are taking medicine containing indinavir.
4. HOW TO TAKE MALATEQ TABLETS:
        Do not share medicines prescribed for you with any other person.
Always take MALATEQ exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.
Prevention of malaria:
        The usual dose is:
Adults: One MALATEQ tablet daily. In order to prevent malaria, it is important that you take your MALATEQ tablet every day. Start taking 1 or 2 days before travelling to an area, or a country (or countries) where malaria is transmitted. Continue daily dosing while you are there, and for 7 days after returning. MALATEQ tablets should be swallowed whole with a drink. Take the tablets with food or milk, as the active ingredients are then absorbed better from the stomach.
For prevention of malaria, MALATEQ should be taken at the same time each day. In the event of vomiting within one hour of taking a dose, a repeat dose should be taken. In the event of diarrhoea, normal dosing should be continued and personal protection should be used (e.g., repellents, bednets). Your doctor may decide to give you other medicines as well. Please read any instruction leaflet carefully.
Your doctor will tell you how long your treatment with MALATEQ will last. Do not stop treatment because you may increase the risk of contracting malaria. If you have the impression that the effect of MALATEQ is too strong or too weak, tell your doctor or pharmacist.
If you take more MALATEQ tablets than you should:
        It is important to take only the dose of MALATEQ prescribed by your doctor.
        In the event of overdosage, consult your doctor or pharmacist. If neither is available, seek help at the nearest hospital or poison control centre.

If you forget to take MALATEQ tablets:
        If you forget to take a dose, take another as soon as possible. Then go on as before. Do not take a double dose to make up for forgotten individual doses.

5. POSSIBLE SIDE EFFECTS:
        MALATEQ can have side effects.
Not all side effects reported for MALATEQ are included in this leaflet. Should your general health worsen while taking MALATEQ, please consult your doctor, pharmacist or other healthcare professional for advice.
If any of the following happen, stop taking MALATEQ and tell your doctor immediately or go to the casualty department at your nearest hospital:
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing;
• rash or itching.
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to MALATEQ. You may need urgent medical attention or hospitalisation. All of these very serious side effects usually occur less frequently.
Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:
• fever
This is a serious side effect. You may need urgent medical attention. Serious side effects usually occur less frequently.
Tell your doctor as soon as possible, if you notice any of the following:
• Loss of appetite, feeling sick (nausea) and/or being sick (vomiting), stomach pain, diarrhoea.
• Mouth inflammation (swelling, redness, pain) and mouth ulcers.
• Allergic reactions including rash, itching and swelling.
• Headache, difficulty in sleeping, raised body temperature, hair loss, coughing.
MALATEQ may cause changes to the body’s normal blood levels of certain cells or chemicals or lead to other blood abnormalities. If you are having a blood test for any reason, tell the person who is taking your blood sample that you are receiving MALATEQ, as it may affect your result. While taking MALATEQ, if you feel unwell or have any unusual symptoms, even those that are not mentioned in this leaflet, seek the advice of your doctor or pharmacist.

6. STORING AND DISPOSING OF MALATEQ TABLETS:
        Keep MALATEQ tablets in a safe place where children cannot see or reach it. Your medicine could harm them.
• Keep the medicine in its original container.
• Store at or below 25ºC.
• Check the use before date shown on the carton at the time of receipt. Do not use it if out of date.
• Keep all medicines out of the reach and sight of children. It may harm them.
• Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).
• Do not share medicines prescribed for you with others.

7. PRESENTATION OF MALATEQ TABLETS:
        MALATEQ tablets are packed in white HDPE containers with white caps containing 100 tablets.
MALATEQ tablets are packed in PVC/PVDC (Clear) paper backed with push through Aluminium Foil blister containing 12 tablets.

8. IDENTIFICATION OF MALATEQ TABLETS:
        MALATEQ tablets: Pinkish brown to brown coloured, circular, biconvex bevelled edge film-coated tablets with ‘404’debossed on one side and ‘G’debossed on the other side.

9. REGISTRATION NUMBER:
        A47/20.2.6/1015

10. NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
        Glenmark Pharmaceuticals South Africa (Pty) Ltd
Unit 7/8 York House, Tybalt Place
185 Howick Close, Waterfall Office Park,
Bekker Street, Vorna Valley,
MIDRAND, 1686

11. MARKETED BY:
        Lamar International (Pty) Ltd
13 Pasita Street
Rosen Heights
Rosen Park
Bellville, 7530

12. DATE OF PUBLICATION:
        November 2014
LI0041/15A

New addition to this site: December 2016
Source: Pharmaceutical Industry

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