Quinine works by killing the parasite or preventing it from growing. This medicine may be used alone or given together with one or more medicines for malaria. Quinine should not be used to treat or prevent night time leg cramps. This medicine may cause very serious unwanted effects and should only be used for patients with malaria. In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make.
For this medicine, the following should be considered:. Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully. Appropriate studies have not been performed on the relationship of age to the effects of quinine in children younger than 16 years of age.
Safety and efficacy have not been established. Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of quinine in the elderly. Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary.
When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive. Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines. Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco. The presence of other medical problems may affect the use of this medicine.
Make sure you tell your doctor if you have any other medical problems, especially:. Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for unwanted effects. This medicine comes with a Medication Guide. Read and follow the instructions carefully.
Ask your doctor if you have any questions. Several trials and meta-analyses comparing intramuscular artemether with intravenous quinine have consistently shown no benefit of treatment with artemether over quinine in children with severe malaria in sub-Saharan Africa [ 73 — 75 ] Table 2. These observations recently led to a change in WHO recommendations, with intravenous artesunate now advocated in preference to quinine for the management of severe malaria in children.
The most critical issues that will need to be addressed, however, are the availability of intravenous artesunate for the patients who need it, especially in resource-limited settings, and its effectiveness in real-life settings. Until recently, the available formulations of injectable artesunate that have been used in several clinical trials were not produced according to Good Manufacturing Practices GMP and this could be a problem for African countries relying on donors who do not permit purchase of non-GMP artesunate.
WHO recently pre-qualified intravenous artesunate manufactured by Guilin Pharmaceuticals in China and this may resolve problems of procurement of GMP artesunate. However, it is unclear whether supplies will be sufficient for the thousands of patients in need. Until these procurement and supplies issues are resolved, intravenous quinine may remain the only readily available drug for treating severe malaria in sub-Saharan Africa and other resource-limited settings. Furthermore, there are several health systems challenges related to the management of severe malaria in resource limited settings that impact on treatment outcomes, independent of the parenteral anti-malarial drugs used.
Consequently, changes in treatment policies, in this case from quinine to artesunate, may not offer improvements without considering drug availability as well as additional measures to strengthen health systems.
Another important aspect of severe malaria case management is pre-referral treatment, which is treatment given to a patient with severe malaria before they are referred to a health facility. This is critical, as most malaria deaths, especially in Africa, occur outside hospitals, either in the communities or at lower levels of care.
Studies evaluating the role of rectal artesunate and artemether as pre-referral treatment have found these options to be highly efficacious [ 76 , 77 ]. However, the biggest challenge faced in resource limited settings has been the non-availability of these preparations in health facilities. A feasible alternative is rectal quinine, which has been found to have comparable efficacy with intravenous quinine in the management of severe malaria in children [ 79 — 84 ] Table 2 and could play a more significant role than currently acknowledged as pre-referral treatment for severe malaria.
More recent studies in Senegal and Mali provide additional support for the efficacy and feasibility of this route and also show that a pre-referral kit of rectal quinine was acceptable to both caretakers and health workers [ 85 , 86 ]. Following successful administration of parenteral treatment for severe malaria, it is recommended to continue with an oral anti-malarial drug once a patient is able to tolerate oral therapy.
The current practice is to continue the same medicine orally as given parenterally to complete a full treatment course [ 23 ]. The options for oral continuation therapy that are available in many African settings would therefore include oral quinine or an ACT.
In non-pregnant adults, doxycyline would also be added to either of these drugs and given twice daily for 7 days. Where available, clindamycin may be substituted in children, since doxycyline is contraindicated in this age group [ 23 ].
The choice of oral continuation therapy following initial parenteral treatment of severe malaria may also have an impact on clinical outcomes, particularly on parasite clearance, fever clearance and potentially the risk of recurrent parasitaemia. In this regard completing intravenous quinine treatment with an ACT instead of oral quinine may improve the overall treatment outcome of parenteral quinine therapy. Studies evaluating this approach to therapy are limited.
Additional studies should explore other options, in particular ACT, for improving therapeutic outcomes with intravenous quinine treatment. Parasite drug resistance is probably the greatest problem faced by malaria control programs worldwide and is an important public health concern. Over the years, malaria parasites have developed resistance to a number of commonly used anti-malarial drugs.
However the development of resistance to quinine has been slow. Although its use started in the 17 th century, resistance to quinine was first reported in [ 88 ]. In comparison, resistance to chloroquine and proguanil emerged within only 12 [ 89 ] and 1 year [ 88 , 90 ] of their introduction, respectively.
Resistance to quinine is usually low grade, with the drug retaining some activity but having its action delayed or diminished. Diminished sensitivity of P. A recent study from Thailand showed significant reductions in efficacy of quinine, artemisinin and mefloquine when compared to previous reports from the same area, suggesting further increase in drug resistance in this region [ 97 ].
No convincing evidence of high grade quinine resistance in the treatment of severe malaria has been reported. Findings from a recent systematic review of about clinical trials published between and showed that the recrudescence rates for quinine reported over these past 30 years remained roughly constant [ 98 ].
These findings are encouraging and may suggest that efficacy of quinine has been preserved. Treatment failures with quinine could also be explained by varying pharmacokinetic profiles of the drug. It is known that quinine pharmacokinetic properties and therapeutic responses vary with age, pregnancy, immunity and disease severity [ 99 ].
Also, as patients recover from malaria, there is usually an expansion of the volume of distribution and an increase in systemic clearance of quinine resulting in a decline in the average concentration of quinine in plasma [ ]. These variations may lead to drug levels that may be inadequate to completely clear infection. The possibility that pharmacokinetic factors may explain quinine treatment failure was initially raised about 20 years ago when a Thai patient who had fatal severe malaria and apparent RIII resistance was found to have abnormally low levels of quinine despite adequate dosing [ ].
Additional evidence for the impact of unusual quinine pharmacokinetics on treatment outcomes was provided by a more recent study describing early treatment failure in a patient with severe malaria with an abnormally high volume of distribution and increased quinine clearance, resulting in abnormally low quinine concentrations [ ].
A few studies have proposed that an increase in the quinine dosage after the third day could compensate for declines in plasma drug levels during recovery, especially in areas with resistant P. However, this is not routinely practiced. Despite these anecdotal observations, there is little evidence for large variations in quinine pharmacokinetics [ ] and the exact role that variations in drug levels play in quinine treatment responses is unclear.
The quality of quinine used in routine care could play a key role in clinical outcomes. Poor quality drugs remain a problem worldwide and are a serious public health threat. Several other studies have also described varying problems with quinine drug quality in different settings [ , ]. Ideally, branded anti-malarial drugs should be used, but unfortunately, branded quinine products are not universally available in Africa and other malaria endemic settings. In addition, national drug regulators need to strengthen their roles in the monitoring of anti-malarial drug quality.
Another potential explanation for quinine treatment failures may be poor compliance. Quinine's prolonged treatment course and significant tolerability problems may lead to poor compliance, and hence poor therapeutic outcomes [ 32 , 45 , 59 ]. In this aspect, ACT has an advantage over quinine since it is administered once or twice daily over three days. A recent study in Uganda showed comparable compliance on day 3 of treatment in patients taking either quinine or artemether-lumefantrine. Promotion of shorter courses of quinine, especially in combination with antibiotics, should improve compliance as well as treatment outcomes [ 39 , ].
In the near future, quinine will continue to play a significant role in the management of malaria, particularly in resource limited settings. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but this remains a promising intervention given the limited availability of rectal artemisinin preparations in resource limited settings.
Quinine continues to play a critical role in the management of malaria in the first trimester of pregnancy, and will remain so until safer alternatives become available. The continued use of quinine in the management of uncomplicated malaria is a concern. Clearly, the seven day duration of therapy and thrice daily administration of quinine present a major challenge to completion of therapy, leading to sub-optimal treatment outcomes.
In these situations, ACT is a better option given the simplicity of dosing and shorter treatment duration. However, because of the frequent ACT stock outs, the rapid withdrawal of quinine as a treatment option for uncomplicated malaria cases is risky.
The best approach would be, besides improving the supply system, to maintain quinine as a fall-back drug in case of ACT stock-outs. How Was Quinine Discovered?. Google Scholar. Cinchona bark. Dobson SMaM: The history of antimalarial drugs. Edited by: PJ R. Chemical News. Salako LA, Sowunmi A: Disposition of quinine in plasma, red blood cells and saliva after oral and intravenous administration to healthy adult Africans.
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Malar J. Yeka A, Achan J, D'Alessandro U, Talisuna AO: Quinine monotherapy for treating uncomplicated malaria in the era of artemisinin-based combination therapy: an appropriate public health policy?. Lancet Infect Dis. A qualitative study of factors affecting the prescription of artemether-lumefantrine. Bull World Health Organ. Am J Trop Med Hyg. Antimicrob Agents Chemother. Acta Trop. Harinasuta TBD: Drug resistant malaria with special reference to chemotherapy.
Mosquito-Borne Diseases Bulletin. Rogier C, Brau R, Tall A, Cisse B, Trape JF: Reducing the oral quinine-quinidine-cinchonin Quinimax treatment of uncomplicated malaria to three days does not increase the recurrence of attacks among children living in a highly endemic area of Senegal. J Infect Dis. Ann Trop Med Parasitol. Clin Infect Dis. East Mediterr Health J. Clin Pharmacol Ther. J Infect. A prospective, longitudinal cohort study of children.
J Pharm Pharmacol. J Acquir Immune Defic Syndr. Lesi A, Meremikwu M: High first dose quinine regimen for treating severe malaria. Cochrane Database Syst Rev. Nowadays the quinine content of tonic water is minimal, and more effective antimalarial drugs have been developed, but a close relative of quinine, quinidine , is still commonly used as an antiarrhythmic drug to treat irregular heart rhythms.
The two compounds only differ in the position of one of their chemical groups: quinine features an OH group that points in one direction, while in quinidine it points in the opposite direction. This small switch is enough to change the function of the drug from antimalarial to antiarrhythmic. Enter your keywords. Sign-Up Here. First came the tonic as treatment , then came the gin for flavour!
Ada McVean B.
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