Qualaquin (Page 6 of 7)
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:
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- 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%.
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- 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%.
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- Cure was defined as initial clearing of parasitemia within 7 days without recrudescence by day 28 after treatment initiation.
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- 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
QUALAQUIN® (quinine sulfate) Capsules, USP, 324 mg are available as clear/clear capsules imprinted AR 102:
- Bottles of 30 NDC 49708-153-07
Storage
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container as defined in the USP.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide)
Important Administration Instructions
Instruct patients to:
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- Take all of the medication as directed.
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- Take no more of the medication than the amount prescribed.
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- 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 trademarks are property of their respective owners.
Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512
Rev 04, June 2019
MEDICATION GUIDE
QUALAQUIN® (kwol-a-kwin) (quinine sulfate) capsules, for oral use |
Read the Medication Guide that comes with QUALAQUIN before you start taking it 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 QUALAQUIN when you start taking it and at regular checkups. QUALAQUIN is not approved for the prevention or treatment of night-time leg cramps. |
What is the most important information I should know about QUALAQUIN? QUALAQUIN used to treat or prevent leg cramps may cause serious side effects or even death. QUALAQUIN may cause:
Call your healthcare provider right away if you have: QUALAQUIN can have other serious side effects. See “What are the possible side effects of QUALAQUIN? ” |
What is QUALAQUIN? QUALAQUIN is a prescription medicine used to treat uncomplicated malaria caused by the parasite Plasmodium falciparum. QUALAQUIN is not approved to:
It is not known if QUALAQUIN is safe and effective in children under 16 years of age. |
Who should not take QUALAQUIN? Do not take QUALAQUIN if you have:
|
What should I tell my healthcare provider before taking QUALAQUIN? Before taking QUALAQUIN, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. QUALAQUIN and other medicines may affect each other causing serious side effects. Certain medicines can cause the blood levels of QUALAQUIN 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 QUALAQUIN and cause serious side effects or death. |
How should I take QUALAQUIN?
|
What are the possible side effects of QUALAQUIN? QUALAQUIN may cause serious side effects, including:
The most common side effects of QUALAQUIN include: 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 QUALAQUIN. 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 QUALAQUIN?
Keep QUALAQUIN and all medicines out of the reach of children. |
General information about the safe and effective use of QUALAQUIN. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use QUALAQUIN for a condition for which it was not prescribed. Do not give QUALAQUIN to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about QUALAQUIN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about QUALAQUIN that is written for health professionals. |
What are the ingredients in QUALAQUIN? Active Ingredients: quinine sulfate, USP Inactive Ingredients: corn starch, magnesium stearate, talc All trademarks are property of their respective owners. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 For more information about QUALAQUIN, call 1-800-406-7984. |
- This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 6/2019
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