Quinine is a popular product known all over the world. From the bottled quinine water used as a mixer in alcoholic drinks to the lifesaving elixir in the movies depicting malaria outbreaks in the jungles of Africa, quinine has been a staple in medicine for centuries—so much so that until a few years ago, it was commercially available as an OTC remedy.

Quinine is a bitter-tasting, white, crystalline compound made from the bark of the cinchona tree, an evergreen that grows on the eastern slopes of the Andes Mountains. The Quechua Indians of Peru and Bolivia are credited with discovering this product’s medicinal properties.

In the early 17th century, the native Indians and the Jesuits learned that the racking chills and fevers associated with malaria were vastly reduced when cinchona bark was brewed into a liquid and ingested. This information spread rapidly, and the overharvesting of the cinchona trees almost brought them to extinction before commercial interests intervened and a controlled usage began.1

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Malaria is estimated to claim between 1.5 and 2.7 million lives annually, with the majority of these being children.1 The exact mechanism of quinine against malaria is not completely understood, but researchers attribute its effectiveness to an ability to disturb the acid/base balance and aggregate heme molecules within the parasitic cell, causing cell death.2 Additional properties attributed to quinine are those of a smooth-muscle relaxant. This quality is what is thought to calm the shivering that occurs during malarial rigors.

Even though the original crude quinine extract has been refined many times over into sophisticated prescription medications, it is not uniformly available around the world, even in the United States.3 Because of the FDA’s concerns about side effects and drug interactions, the only form of antimalarial quinine for use in life-threatening emergencies is often not even stocked in hospital pharmacies.3 However, with the increase in global travel, cases of acute malarial attacks in community emergency departments are becoming more common, and the tragic consequences of unavailable therapy are noteworthy. In 2009, the FDA approved a new quinine combination medication for treatment of “uncomplicated” malaria.4

OTC quinine and quinine sulfate have historically been used for muscle cramps, particularly nocturnal leg cramps. Leg cramps strike an estimated 70% of people and are especially common among the elderly.5 Because of the associated significant sleep disturbance and increased risks of such comorbidities as falling, this seemingly benign ailment can be seriously disabling. The mechanism of action of quinine in mitigating leg cramps is unclear; however, the proposed action is the reduced excitability of the motor end plate, thereby diminishing muscle contractility.5 In one study, 27 men with reports of at least six leg cramps per month were randomized to either quinine or placebo. After a four-week period, the report of cramps in the treatment group fell by 50%.5

Other data supporting this claim, however, are loose and poorly structured. In addition, the severity of a cramp is very subjective, as is the reported benefit of any remedy. From 1969 to 1992, the FDA received more than 157 reports of adverse reactions related to quinine use, including 23 deaths.6 Consequently, the FDA banned all OTC sales of quinine in 1994. Prescription quinine formulations are still available but are highly regulated. The only form of quinine currently available without prescription is the small amount found in tonic water.6

Safety, drug interactions

One of the major concerns surrounding the use of unregulated quinine is that one of the compounds released during metabolism is the cardio-active quinidine. Overuse is directly cardiotoxic, triggering lethal, irreversible arrhythmias. Other side effects include blood dyscrasias, hypersensitivity reactions, severe GI disturbances, vision problems, and deafness.7

Quinine potentiates the action of warfarin and some antiepileptic drugs, including carba­mazepine (Tegretol) and phenobarbital.7 Quinine also has an inhibitory effect on proton pump inhibitors and H2 blocking agents, attributable to its action of increasing stomach acid.7

Except in cases of verified malaria, quinine should not be used in women who are pregnant or nursing or in young children.7

Dose, how supplied

Although nonprescription quinine is not available in the United States, many sources on the Internet advertise quinine sulfate, the popular consumer formulation. In some instances, the actual cinchona tree bark is marketed, making the potential for toxicity very real. In controlled situations, the standard quinine dose is 600- to 650-mg capsules every eight hours for at least three days to treat malaria.8 For leg cramps, one to two 325-mg capsules of quinine sulfate taken at bedtime is recommended.8


With its large burden of potential lethal toxicities and drug interactions, quinine should only be used by prescription. In verified cases of malaria or in refractory nocturnal leg cramps that impair daily function, prescription quinine is definitely indicated. Close follow-up and observation for side effects is mandatory. n


1. Chemical & Engineering News. Quinine. Available at pubs.acs.org/cen/coverstory/83/8325/8325quinine.html.

2. Reyburn H, Mtove G, Hendriksen I, von Seidlein L. Oral quinine for the treatment of uncomplicated malaria. BMJ. 2009;339:b2066.

3. Magill A, Panosian C. Making antimalarial agents available in the United States. N Engl J Med. 2005;353:335-337.

4. Thompson CA. First artemisinin-based antimalarial combination approved for U.S. market. Am J Health Syst Pharm. 2009;66:880.

5. Mandal AK, Abernathy T, Nelluri SN, Stitzel V. Is quinine effective and safe in leg cramps? J Clin Pharmacol. 1995;35:588-593.

6. U.S. Food and Drug Administration. Questions and answers about FDA’s enforcement action against unapproved quinine products. Available at www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/electedEnforcementActionsonUnapprovedDrugs/ucm119653.pdf.

7. Katzberg HD, Khan AH, So YT. Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 2010;74:691-696. Available at www.neurology.org/cgi/content/full/74/8/691.

8. Mayo Clinic. Quinine (oral route). Available at www.mayoclinic.com/health/drug-information/DR601187/.

All electronic documents accessed September 15, 2010.

By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the VA Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.