Quinine Sulfate: Package Insert and Label Information (Page 3 of 3)

12.4 Microbiology

Mechanism of Action

Quinine inhibits nucleic acid synthesis, protein synthesis, and glycolysis in P. falciparum and can bind with hemazoin in parasitized erythrocytes. However, the precise mechanism of the antimalarial activity of quinine sulfate is not completely understood.

Antimicrobial Activity

Quinine sulfate acts primarily on the blood schizont form of P. falciparum. It is not gametocidal and has little effect on the sporozoite or pre-erythrocytic forms.

Resistance

Strains of P. falciparum with decreased sensitivity to quinine can be selected in vivo. P. falciparum malaria that is clinically resistant to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies of quinine have not been conducted.

Mutagenesis

Genotoxicity studies of quinine were positive in the Ames bacterial mutation assay with metabolic activation and in the sister chromatid exchange assay in mice. The sex-linked recessive lethal test performed in Drosophila , the in vivo mouse micronucleus assay, and the chromosomal aberration assay in mice and Chinese hamsters were negative.

Impairment of Fertility

In published studies, quinine produced testicular toxicity in mice at a single intraperitoneal dose of 300 mg/kg corresponding to a dose of approximately 0.75 times the maximum recommended human dose (MRHD; 32 mg/kg/day) and in rats at an intramuscular dose of 10 mg/kg/day, 5 days/week, for 8 weeks corresponding to a daily dose of approximately 0.05 times the MRHD based on body surface area (BSA) comparisons. The findings include atrophy or degeneration of the seminiferous tubules, decreased sperm count and motility, and decreased testosterone levels in the serum and testes. There were no changes in testes weight or testicular histopathology in studies of oral doses of up to 500 mg/kg/day in mice and 700 mg/kg/day in rats (approximately 1.2 and 3.5 times the MRHD respectively based on BSA comparisons).

14 CLINICAL STUDIES

Quinine has been used worldwide for hundreds of years in the treatment of malaria. Thorough searches of the published literature identified over 1300 references to the treatment of malaria with quinine, and from these, 21 randomized, active-controlled studies were identified which evaluated oral quinine monotherapy or combination therapy for treatment of uncomplicated P. falciparum malaria. Over 2900 patients from malaria-endemic areas were enrolled in these studies, and more than 1400 patients received oral quinine. The following conclusions were drawn from review of these studies:

In areas where multi-drug resistance of P. falciparum is increasing, such as Southeast Asia, cure rates with 7 days of oral quinine monotherapy were at least 80%; while cure rates for 7 days of oral quinine combined with an antimicrobial agent (tetracycline or clindamycin) were greater than 90%. In areas where multi-drug resistance of the parasite was not as widespread, cure rates with 7 days of quinine monotherapy ranged from 86 to 100%. Cure was defined as initial clearing of parasitemia within 7 days without recrudescence by day 28 after treatment initiation. P. falciparum malaria that is clinically resistant to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh, and quinine may not be as effective in those areas.

Completion of a 7 day oral quinine treatment regimen may be limited by drug intolerance, and shorter courses (3 days) of quinine combination therapy have been used. However, the published data from randomized, controlled clinical trials for shorter regimens of oral quinine in conjunction with tetracycline, doxycycline, or clindamycin for treatment of uncomplicated P. falciparum malaria is limited, and these shorter course combination regimens may not be as effective as the longer regimens.

15 REFERENCES

  1. Looareesuwan S et al (1985). Quinine and severe falciparum malaria in late pregnancy. Lancet. 2(8445):4-8.
  2. Kovacs SD et al (2015). Treating severe malaria in pregnancy: a review of the evidence. Drug Saf. 38(2):165-81.
  3. Clark RL (2017). Animal embryotoxicity studies of key non-artemisinin antimalarials and use in women in the first trimester. Birth Defects Res. 109(14):1075-1126.
  4. Tanimura T (1972). The use of non-human primates in research on human reproduction. WHO research and Training Centre on Human Reproduction. Karolinska Institutet (Symposium), Stockholm, 293-308.
  5. Ejebe DE et al. (2008). Effects of anti-malarial alkaloids on the sperm properties and blood levels of reproductive hormones of adult men. Afr J Biotech. 7: 3395-3400.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Quinine Sulfate Capsules USP, 324 mg are available as opaque white hard gelatin capsules, imprinted in black “93” over “3002” on the cap portion and “93” over “3002” on the body portion of the capsule, in bottles of 30 (NDC 0093-3002-56).

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

Important Administration Instructions

Instruct patients to:

  • Take all of the medication as directed.
  • Take no more of the medication than the amount prescribed.
  • Take with food to minimize possible gastrointestinal irritation.

Missed Doses

Advise patients that if a dose is missed, patients should not double the next dose. If more than 4 hours has elapsed since the missed dose, the patient should wait and take the next dose as previously scheduled.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

Manufactured In Canada By:
Teva Canada Limited
Toronto, Canada M1B 2K9

Manufactured For:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454

Rev. H 1/2020

MEDICATION GUIDE

Quinine Sulfate (kwye’ nine sul’ fate)

C apsules, for oral use

Read the Medication Guide that comes with quinine sulfate capsules before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about quinine sulfate capsules when you start taking them and at regular checkups. Quinine sulfate capsules are not approved for the prevention or treatment of night-time leg cramps.

What is the most important information I should know about quinine sulfate capsules?

Quinine sulfate capsules used to treat or prevent leg cramps may cause serious side effects or even death.

Quinine sulfate capsules may cause:

  • your blood cell (platelet) count to drop causing serious bleeding problems. In some people, serious kidney problems can happen.
  • problems with your heart rhythm that can lead to death.
  • serious allergic reactions.

Call your healthcare provider right away if you have:

  • easy bruising
  • severe nose bleed
  • blood in urine or stool
  • bleeding gums
  • unusual purple, brown or red spots on your skin (bleeding under your skin)
  • rash
  • hives
  • severe itching
  • severe flushing
  • swelling of your face
  • trouble breathing
  • chest pain
  • rapid heartbeat
  • irregular heart rhythm
  • weakness
  • sweating
  • ·nervousness

Quinine sulfate capsules can have other serious side effects. See “What are the possible side effects of quinine sulfate capsules?

What are quinine sulfate capsules?

Quinine sulfate capsules are a prescription medicine used to treat uncomplicated malaria caused by the parasite Plasmodium falciparum.

Quinine sulfate capsules are not approved to:

  • Prevent malaria
  • Treat severe or complicated Plasmodium falciparum malaria
  • Prevent or treat night-time leg cramps

It is not known if quinine sulfate capsules are safe and effective in children under 16 years of age.

Who should not take quinine sulfate capsules?

Do not take quinine sulfate capsules if you have:

  • changes in the electrical activity of your heart called QT prolongation
  • had allergic reactions to quinine (the active ingredient in quinine sulfate capsules), such as low platelets, which are necessary for your blood to clot.
  • had allergic reactions to mefloquine (Lariam) or quinidine.
  • an autoimmune disease (myasthenia gravis) that leads to muscle weakness.
  • an inflammation of the nerve important for vision (optic neuritis).

What should I tell my healthcare provider before taking quinine sulfate capsules?

Before taking quinine sulfate capsules, tell your healthcare provider about all of your medical conditions, including if you:

  • have heart problems.
  • have kidney problems.
  • have liver problems.
  • are pregnant or plan to become pregnant. Treatment of malaria is important because it can be a serious disease for a pregnant woman and her unborn baby. Talk to your healthcare provider about the benefits and risks of taking quinine sulfate capsules during pregnancy. Low blood sugar (hypoglycemia) can happen in pregnant women while taking quinine sulfate capsules. Signs and symptoms of low blood sugar can include sweating, weakness, nausea, vomiting, and confusion. You and your healthcare provider can decide if quinine sulfate capsules are right for you.
  • are breastfeeding or plan to breastfeed. Quinine sulfate can pass into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while taking quinine sulfate capsules.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Quinine sulfate capsules and other medicines may affect each other causing serious side effects. Certain medicines can cause the blood levels of quinine sulfate capsules to be too high or too low in your body. Do not start taking a new medicine without telling your healthcare provider or pharmacist. Even medicines that you may take for a short period of time, such as antibiotics, can mix in your blood with quinine sulfate and cause serious side effects or death.

How should I take quinine sulfate capsules?

  • Take quinine sulfate capsules exactly as your healthcare provider tells you to take it.
  • Your healthcare provider will tell you how many quinine sulfate capsules to take and when to take them.
  • Take quinine sulfate capsules with food to lower your chance of having an upset stomach
  • Do not skip any doses or stop taking quinine sulfate capsules without first talking to your healthcare provider, even if you feel better.
  • Do not take more quinine sulfate capsules than prescribed.
  • If you miss a dose of quinine sulfate capsules, do not double the next dose to make up for a missed dose. If it has been more than 4 hours since the missed dose, take your next dose at the next scheduled time. Call your healthcare provider if you are not sure what to do.
  • If you take too many quinine sulfate capsules, call your healthcare provider or go to the nearest emergency room right away.

What are the possible side effects of quinine sulfate capsules?

Quinine sulfate capsules may cause serious side effects, including:

  • See “What is the most important information I should know about quinine sulfate capsules? ” section.
  • Heart rhythm problems (atrial fibrillation and atrial flutter).
  • Low blood sugar (hypoglycemia). Signs and symptoms of low blood sugar can include sweating, weakness, nausea, vomiting, and confusion.

The most common side effects of quinine sulfate capsules include:

  • headache
  • sweating
  • flushing
  • ·nausea
  • ringing in your ears
  • diarrhea
  • deafness
  • problems with heart rhythm or conduction
  • hearing loss
  • dizziness (vertigo)
  • blurred vision
  • changes in how you see color
  • ·vomiting
  • stomach pain
  • blindness

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

These are not all of the possible side effects of quinine sulfate capsules. For more information, ask your healthcare provider or pharmacist.

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

How should I store quinine sulfate capsules?

  • Keep the capsules in a tightly closed container.
  • Store quinine sulfate capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep quinine sulfate capsules and all medicines out of the reach of children.

General information about the safe and effective use of quinine sulfate capsules

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use quinine sulfate capsules for a condition for which they were not prescribed. Do not give quinine sulfate capsules to other people, even if they have the same symptoms that you have. They may harm them.

This Medication Guide summarizes the most important information about quinine sulfate capsules. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about quinine sulfate capsules that is written for health professionals.

What are the ingredients in quinine sulfate capsules?

Active Ingredients: quinine sulfate

Inactive Ingredients: colloidal silicon dioxide, gelatin, iron oxide black, magnesium stearate, pregelatinized corn starch, propylene glycol, shellac, sodium lauryl sulfate, and titanium dioxide. The imprinting ink may contain potassium hydroxide.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

Manufactured In Canada By:
Teva Canada Limited
Toronto, Canada M1B 2K9

Manufactured For:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454

For more information, call 1-888-838-2872.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. G 1/2020

Package/Label Display Panel

image
(click image for full-size original)

Quinine Sulfate Capsules USP 324 mg 30s Label Text

NDC 0093-3002- 56

Quinine Sulfate
Capsules USP
324 mg

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx only

30 CAPSULES

TEVA

QUININE SULFATE
quinine sulfate capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0093-3002
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
QUININE SULFATE (QUININE) QUININE SULFATE 324 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE
GELATIN
FERROSOFERRIC OXIDE
MAGNESIUM STEARATE
STARCH, CORN
PROPYLENE GLYCOL
SHELLAC
SODIUM LAURYL SULFATE
TITANIUM DIOXIDE
POTASSIUM HYDROXIDE
Product Characteristics
Color WHITE Score no score
Shape CAPSULE Size 22mm
Flavor Imprint Code 93;3002;93;3002
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0093-3002-56 30 CAPSULE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091661 09/28/2012
Labeler — Teva Pharmaceuticals USA, Inc. (001627975)

Revised: 02/2020 Teva Pharmaceuticals USA, Inc.

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