Long acting medicines are convenient and can improve compliance with therapy as they do not need to be taken as often as shorter acting ones. However, long acting medicines do take some time (days to weeks) to reach effective levels in the body. They also take a similar time to leave the body completely once the medicine is stopped. A loading dose is an initial higher dose of a medicine given at the beginning of a course of treatment before dropping down to a lower maintenance dose. Loading doses can achieve a therapeutic effect more quickly and are used in the prevention and management of various conditions, including serious infections, heart failure and blood clots.
Mefloquine is long acting. Taken weekly it takes several weeks to reach effective anti-malarial levels. In order to achieve malaria protection quickly, three daily doses of mefloquine may be given in the week before deployment or travel (loading dose) with weekly doses continued thereafter (maintenance). This is particularly important for malaria prevention on short notice deployments.
This loading dose can be critical in the prevention of malaria, as was demonstrated by the experience of a unit of US Marines in Somalia in the early 1990s. During their deployment the US Marines were switched directly from daily doxycycline to weekly mefloquine without a loading dose and as a result some of the Marines developed malaria infections within two weeks after the switch. Around that same time loading doses of mefloquine were being used in the Dutch Marines who deployed into Cambodia as part of a United Nations force in 1992 and in the Indonesian Army in Irian Jaya in 1994.
How well an individual tolerates a medicine often depends on the dose. Higher doses generally involve more side-effects, although there is a lot of variation from person to person. Serious adverse events were not reported as common in either Dutch Marines or Indonesian Army members who used a loading dose of mefloquine. Possible adverse events were carefully examined in another US Marine unit and SwissAir trainee pilots who were not exposed to malaria, but who were observed during a study to determine the tolerability of the loading doses of mefloquine. Some adverse events such as sleep disturbances and dizziness were noted in both groups when receiving the loading doses of mefloquine. None were reported as serious and all resolved as the participants continued to take weekly medication.
When mefloquine is used to treat malaria, it is given in higher doses than those used for loading before a deployment. The loading dose is one tablet per day for three days, where as the treatment dose is three tablets at once followed by two more tablets several hours later (five tablets in one day). More adverse events are seen when using treatment rather than prophylactic doses of mefloquine, but it can be difficult to distinguish these from the symptoms of malaria in a person who is already ill with malaria.
It has been ADF policy since 1994 to use a loading dose of mefloquine for ADF members who are deploying to a highly malarious area and are unable to take other anti-malarial medications. This policy position was based on the operational need to have member protected against malaria on arrival in the malarious area and the evidence that showed that loading doses were effective and well tolerated. Otherwise, deploying troops who cannot take other antimalarials would need to start taking mefloquine 2 months before deployment.
By 2000-2002, when mefloquine was used with a loading dose in the ADF anti-malarial studies in East Timor, the efficacy and tolerability of a loading dose had already been carefully studied in similar groups and adopted as standard practice in providing immediate protection to troops deploying to highly malarious areas.
Pharmaceutical companies are responsible for developing the product information for their medications, which is then approved by the regulatory authority in each country where the medications are marketed.
The Lariam™ product information in Australia does not specifically recommend a loading dose of mefloquine. It notes that a weekly dose will achieve maximum steady blood levels in 7-10 weeks. It also states that prophylaxis of malaria with Lariam should be initiated one week before arrival in a malarious area, and gives a dosage schedule as a guide. The Lariam consumer medicine information advises that the directions given by the doctor and pharmacist should be followed carefully, and that these may differ from the information contained in the consumer medicine information.
In contrast, the Lariam product information distributed in other countries, such as New Zealand, specifically recommends a loading dose for “last-minute” travellers.
