Mepron

Atovaquone comes as a suspension (liquid) to take by mouth. When atovaquone is used to treat pneumonia, it is usually taken with meals twice a day for 21 days. When atovaquone is used to prevent pneumonia, it is usually taken with a meal once a day. Take atovaquone at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take atovaquone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If your medication comes in a bottle, shake the bottle gently before each use to mix the medication evenly. Use a dose measuring spoon or a cup to measure the correct amount of liquid for each dose, not a regular household spoon.

If your medication comes in a packet, you may drink the medication directly from the packet or pour the medication into a dosing spoon or cup.

Take this medication until you finish the prescription. Do not stop taking the medication early even if you are taking it to treat pneumonia and you feel better. If you stop taking atovaquone too soon or skip doses, your infection may not be completely treated or you may not be protected from future infections.

If you have PCP, you may also have other types of lung infections. Atovaquone will not treat these infections. Your doctor may prescribe other antibiotics for you to take along with this medication.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze this medication. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take atovaquone with a meal for best results.

Shake the liquid medicine bottle well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

If you are taking a pre-measured atovaquone dose from a foil pouch, tear open the pouch along the perforated line and take all of the medicine in the pouch. You may drink it directly from the pouch or pour it into a spoon or cup before taking.

Take this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated.

Store atovaquone at cool room temperature away from moisture and heat. Do not allow the medicine to freeze.

Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of an atovaquone overdose are not known.

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

The following adverse reactions are discussed in other sections of the labeling:

• Hepatotoxicity [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Additionally, because many subjects who participated in clinical trials with MEPRON had complications of advanced human immunodeficiency virus (HIV) disease, it was often difficult to distinguish adverse reactions caused by MEPRON from those caused by underlying medical conditions.

PCP Prevention Trials

In two clinical trials, MEPRON suspension was compared with dapsone or aerosolized pentamidine in HIV-1-infected adolescent (13 to 18 years) and adult subjects at risk of PCP (CD4 count < 200 cells/mm³ or a prior episode of PCP) and unable to tolerate TMP-SMX.

Dapsone Comparative Trial: In the dapsone comparative trial (n = 1,057), the majority of subjects were white (64%), male (88%), and receiving prophylaxis for PCP at randomization (73%); the mean age was 38 years. Subjects received MEPRON suspension 1,500 mg once daily (n = 536) or dapsone 100 mg once daily (n = 521); median durations of exposure were 6.7 and 6.5 months, respectively. Adverse reaction data were collected only for adverse reactions requiring discontinuation of treatment, which occurred at similar frequencies in subjects treated with MEPRON suspension or dapsone (Table 1). Among subjects taking neither dapsone nor atovaquone at enrollment (n = 487), adverse reactions requiring discontinuation of treatment occurred in 43% of subjects treated with dapsone and 20% of subjects treated with MEPRON suspension. Gastrointestinal adverse reactions (nausea, diarrhea, and vomiting) were more frequently reported in subjects treated with MEPRON suspension (Table 1).

Table 1: Percentage ( > 2%) of Subjects with Selected Adverse Reactions Requiring Discontinuation of Treatment in the Dapsone Comparative PCP Prevention Trial

Aerosolized Pentamidine Comparative Trial: In the aerosolized pentamidine comparative trial (n = 549), the majority of subjects were white (79%), male (92%), and were primary prophylaxis patients at enrollment (58%); the mean age was 38 years. Subjects received MEPRON suspension once daily at a dose of 750 mg (n = 188) or 1,500 mg (n = 175) or received aerosolized pentamidine 300 mg every 4 weeks (n = 186); the median durations of exposure were 6.2, 6.0, and 7.8 months, respectively. Table 2 summarizes the clinical adverse reactions reported by ≥ 20% of the subjects receiving either the 1,500-mg dose of MEPRON suspension or aerosolized pentamidine.

Rash occurred more often in subjects treated with MEPRON suspension (46%) than in subjects treated with aerosolized pentamidine (28%). Treatment-limiting adverse reactions occurred in 25% of subjects treated with MEPRON suspension 1,500 mg once daily and in 7% of subjects treated with aerosolized pentamidine. The most frequent adverse reactions requiring discontinuation of dosing in the group receiving MEPRON suspension 1,500 mg once daily were rash (6%), diarrhea (4%), and nausea (3%). The most frequent adverse reaction requiring discontinuation of dosing in the group receiving aerosolized pentamidine was bronchospasm (2%).

Table 2: Percentage ( ≥ 20%) of Subjects with Selected Adverse Reactions in the Aerosolized Pentamidine Comparative PCP Prevention Trial

Other reactions occurring in ≥ 10% of subjects receiving the recommended dose of MEPRON suspension (1,500 mg once daily) included vomiting, sweating, flu syndrome, sinusitis, pruritus, insomnia, depression, and myalgia.

PCP Treatment Trials

Safety information is presented from 2 clinical efficacy trials of the MEPRON tablet formulation: 1) a randomized, double-blind trial comparing MEPRON tablets with TMP-SMX in subjects with acquired immunodeficiency syndrome (AIDS) and mild-to-moderate PCP [(A-a)DO2] ≤ 45 mm Hg and PaO2 ≥ 60 mm Hg on room air; 2) a randomized, open-label trial comparing MEPRON tablets with intravenous (IV) pentamidine isethionate in subjects with mild-to-moderate PCP who could not tolerate trimethoprim or sulfa antimicrobials.

TMP-SMX Comparative Trial: In the TMP-SMX comparative trial (n = 408), the majority of subjects were white (66%) and male (95%); the mean age was 36 years. Subjects received MEPRON 750 mg (three 250-mg tablets) 3 times daily for 21 days or TMP 320 mg plus SMX 1,600 mg 3 times daily for 21 days; median durations of exposure were 21 and 15 days, respectively.

Table 3 summarizes all clinical adverse reactions reported by ≥ 10% of the trial population regardless of attribution. Nine percent of subjects who received MEPRON and 24% of subjects who received TMP-SMX discontinued therapy due to an adverse reaction. Among the subjects who discontinued, 4% of subjects receiving MEPRON and 8% of subjects in the TMP-SMX group discontinued therapy due to rash.

The incidence of adverse reactions with MEPRON suspension at the recommended dose (750 mg twice daily) was similar to that seen with the tablet formulation.

Table 3: Percentage ( ≥ 10%) of Subjects with Selected Adverse Reactions in the TMP-SMX Comparative PCP Treatment Trial

Two percent of subjects treated with MEPRON and 7% of subjects treated with TMP-SMX had therapy prematurely discontinued due to elevations in ALT/AST.

Pentamidine Comparative Trial: In the pentamidine comparative trial (n = 174), the majority of subjects in the primary therapy trial population (n = 145) were white (72%) and male (97%); the mean age was 37 years. Subjects received MEPRON 750 mg (three 250-mg tablets) 3 times daily for 21 days or a 3-to 4-mg/kg single pentamidine isethionate IV infusion daily for 21 days; the median durations of exposure were 21 and 14 days, respectively.

Table 4 summarizes the clinical adverse reactions reported by ≥ 10% of the primary therapy trial population regardless of attribution. Fewer subjects who received MEPRON reported adverse reactions than subjects who received pentamidine (63% vs. 72%). However, only 7% of subjects discontinued treatment with MEPRON due to adverse reactions, while 41% of subjects who received pentamidine discontinued treatment for this reason. Of the 5 subjects who discontinued therapy with MEPRON, 3 reported rash (4%). Rash was not severe in any subject. The most frequently cited reasons for discontinuation of pentamidine therapy were hypoglycemia (11%) and vomiting (9%).

Table 4: Percentage ( ≥ 10%) of Subjects with Selected Adverse Reactions in the Pentamidine Comparative PCP Treatment Trial (Primary Therapy Group)

Laboratory abnormality was reported as the reason for discontinuation of treatment in 2 of 73 subjects (3%) who received MEPRON, and in 14 of 71 subjects (20%) who received pentamidine. One subject (1%) receiving MEPRON had elevated creatinine and BUN levels and 1 subject (1%) had elevated amylase levels. In this trial, elevated levels of amylase occurred in subjects (8% versus 4%) receiving MEPRON tablets or pentamidine, respectively.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of MEPRON suspension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Methemoglobinemia, thrombocytopenia.

Hypersensitivity reactions including angioedema, bronchospasm, throat tightness, and urticaria.

Vortex keratopathy.

Pancreatitis.

Hepatitis, fatal liver failure.

Erythema multiforme, Stevens-Johnson syndrome, and skin desquamation.

Acute renal impairment.

Mepron is part of the drug class:

• Other agents against amoebiasis and other protozoal diseases

Serious side effects have been reported with Mepron. See "Mepron Precautions" section.

Common side effects of Mepron include:

• Rash
• Diarrhea
• Nausea
• Headache
• Vomiting
• Fever
• Trouble falling or staying asleep
• Cough
• Sweating

This is not a complete list of Mepron side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Antiprotozoal; hydroxynaphthoquinone derivative.1 7 8 10 15 17

In the U.S.

• Mepron

Available Dosage Forms:

• Tablet
• Suspension

Therapeutic Class: Antiprotozoal

Chemical Class: Ubiquinone

• It is used to prevent Pneumocystis jirovecii pneumonia.
• It is used to treat Pneumocystis jirovecii pneumonia.
• It may be given to you for other reasons. Talk with the doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

All products:

• To gain the most benefit, do not miss doses.
• Keep taking Mepron as you have been told by your doctor or other health care provider, even if you feel well.
• Shake well before use.
• Take this medicine with food.
• If you have trouble taking Mepron with food, talk with your doctor.

Unit-dose:

• Open pouch. Take contents by mouth. Can be put into a dosing spoon, a cup, or right in the mouth.

Bottle:

• Measure liquid doses carefully. Use the measuring device that comes with this medicine. If there is none, ask the pharmacist for a device to measure Mepron.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it, with a meal.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Prevention of Pneumocystis jiroveci Pneumonia

Mepron suspension is indicated for the prevention of Pneumocystis jiroveci pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX).

Treatment of Mild-to-Moderate Pneumocystis jiroveci Pneumonia

Mepron suspension is indicated for the acute oral treatment of mild-to-moderate PCP in adults and adolescents (aged 13 years and older) who cannot tolerate TMP-SMX.

Limitations of Use

Clinical experience with Mepron for the treatment of PCP has been limited to subjects with mild-to-moderate PCP (alveolar-arterial oxygen diffusion gradient [(A-a)DO2] ≤45 mm Hg). Treatment of more severe episodes of PCP with Mepron has not been studied. The efficacy of Mepron in subjects who are failing therapy with TMP-SMX has also not been studied.

Administration Instructions

Instruct patients to:

Mepron is a registered trademark of the GSK group of companies.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2017 the GSK group of companies. All rights reserved.

MPR:6PI

PRINCIPAL DISPLAY PANEL

NDC 0173-0665-18

Mepron®

(atovaquone)

SUSPENSION

750mg/5mL

Each 5 mL (1 teaspoonful) contains 750 mg atovaquone.

Rx only

210 mL

See accompanying prescribing information for Dosage and Administration.

Store at 15o to 25oC (59o to 77oF).

DO NOT FREEZE. Dispense in a tight container as defined in USP.

SHAKE GENTLY BEFORE USING.

Do not use if shrinkband on bottle is broken or missing.

GlaxoSmithKline

Research Triangle Park, NC 27709

Made in Canada

PRINCIPAL DISPLAY PANEL

NDC 0173-0547-00

Mepron®

(atovaquone)

SUSPENSION

750 mg/ 5mL

Each 5 mL sachet (1 teaspoonful) contains 750 mg atovaquone.

Store at 15o to 25oC (59o to 77oF). DO NOT FREEZE.

See accompanying prescribing information for Dosage and Administration.

5 mL

Rx only

Contains 42 sachets of 5 mL each

©2015, the GSK group of companies