Avoidance of Unwanted Effects by Regarding the Maximal Daily Dose

To prevent unwanted effects, especially retinopathy, it was recommended that the cumulative total dose of chloroquine be limited to a maximum of 100-300 g, that the duration of therapy be limited to 1 year, or that patients be treated only intermittently. These recommendations severely restricted the use of chloroquine. Chloroquine is undoubtedly able to induce retinal changes. The incidence, however, depends on neither the duration nor the cumulative dose. It is only related to the maximal daily dose of 3.5 (to 4) mg/kg ideal body weight for chloroquine and 6 (to 6.5) mg/kg ideal body weight for hydroxychloroquine.

Chloroquine has to be given according to the ideal body weight (calculation for daily routine: males, [body length (in centimeters) -100] -10%; females, [body length (in centimeters) -15%]), as the substance is not stored in fatty tissues.

Several publications demonstrate that even continuous prolonged therapy for years does not induce retinopathy if these daily doses are not exceeded (Mackenzie 1983, Maksymowych and Russell 1987, Scherbel et al. 1965, Levy et al. 1997). This also holds true for children (Laaksonen et al. 1974). Mackenzie did not observe retinal damage in 900 patients who received chloroquine for a mean of 7 years (cumulative dose, ~608 g). A retinopathy developed only if daily doses 4mg/kg for chloroquine or 6.5 mg/kg for hydroxychloroquine were given (Mackenzie 1983). Levy et al. did not find evidence of maculopathy in 1207 patients treated with hydroxychloroquine at doses less than 6.5 mg/kg ideal body weight. The authors found one case of retinopa-thy in a patient treated with high doses (average, 6.98 mg/kg daily) for more than 7 years (Levy et al. 1997). These maximal daily doses should not be exceeded over prolonged periods.

The routine daily dose of one tablet of chloroquine (250 mg) or two tablets of hydroxychloroquine (400 mg) leads to an overdose if the ideal or actual body weight is < 63 kg (Mackenzie 1983; see Table 26.3 and Fig. 26.1). Patients with ideal body weights between 63 and 72 kg receive 3.5-4mg/kg chloroquine. Only body weights greater than 72 kg pose no problems with a daily dose of one tablet (Tables 26.3,26.4). Care has to be taken when patients with an actual or ideal body weight less than 63 kg are treated. This concerns small and light persons, mainly women and corpulent short people (Fig. 26.1). If kidney or liver functions are impaired, the doses given in Table 26.3 have to be lowered further.

The maximal daily dose of quinacrine is 100 mg. The higher doses given formerly significantly increased the rate of side effects.

Table 26.3. Recommended daily dose according to ideal body weight (I-bw) for chloroquine and hydroxychloroquine3

I-bw (kg)

Chloroquine 3.5 mg/kg I-bw

4 mg/kg I-bw

Hydroxychloroquine 6 mg/kg I-bw 6.5 mg/kg I-bw

I-bw (kg)

Chloroquine 3.5 kg/kg I-bw

4 mg/kg I-bw

Hydroxychloroquine 6 mg/kg I-bw 6.5 mg/kg I-bw

30

105

120

180

195

60

210

240

360

390

31

108.5

124

186

201.5

61

213.5

244

366

396.5

32

112

128

192

208

62

217

248

372

403

33

115.5

132

198

214.5

63

220.5

252

378

409.5

34

119

136

204

221

64

224

256

384

416

35

122.5

140

210

227.5

65

227.5

260

390

422.5

36

126

144

216

234

66

231

264

396

429

37

129.5

148

222

240.5

67

234.5

268

402

435.5

38

133

152

228

247

68

238

272

408

442

39

136.5

156

234

253.5

69

241.5

276

414

448.5

40

140

160

240

260

70

245

280

420

455

41

143.5

164

246

266.5

71

248.5

284

426

461.5

42

147

168

252

273

72

252

288

432

468

43

150.5

172

258

279.5

73

255.5

292

438

474.5

44

154

176

264

286

74

259

296

444

481

45

157.5

180

270

292.5

75

262.5

300

450

487.5

46

161

184

276

299

76

266

304

456

494

47

164.5

188

282

305.5

77

269.5

308

462

500.5

48

168

192

288

312

78

273

312

468

507

49

171.5

196

294

318.5

79

276.5

316

474

513.5

50

175

200

300

325

80

280

320

480

520

51

178.5

204

306

331.5

81

283.5

324

486

526.5

52

182

208

312

338

82

287

328

492

533

53

185.5

212

318

344.5

83

290.5

332

498

539.5

54

189

216

324

351

84

294

336

504

546

55

192.5

220

330

357.5

85

297.5

340

510

552.5

56

196

224

336

364

86

301

344

516

559

57

199.5

228

342

370.5

87

304.5

348

522

565.5

58

203

232

348

377

88

308

352

528

572

59

206.5

236

354

383.5

89

311.5

356

534

578.5

a Data are given in milligrams. In the case of liver or kidney insufficiency, the doses have to be lowered.

a Data are given in milligrams. In the case of liver or kidney insufficiency, the doses have to be lowered.

Table 26.4. Recommendations for the practical management of the maximal daily dose of chloroquine (3.5-4mg/kg ideal body weight)a

Chloroquine as a tablet Chloroquine as a syrup

Table 26.4. Recommendations for the practical management of the maximal daily dose of chloroquine (3.5-4mg/kg ideal body weight)a

Chloroquine as a tablet Chloroquine as a syrup

Ideal body

250 mg

+

81 mg

(ml)

Measuring

Chloroquine

weight (kg)

(Junior)

spoonb

dose (mg)

32-35

1/2

-

5.4

1

125

36-41

1/4

+

1

6.2

1

144

42-46

-

2

7.0

2

162

47-53

3/4

-

8.1

2

188

54-59

1/2

+

1

8.9

2

206

60-65

3/4

+

1/2

9.8

2

228

66-70

-

3

10.5

3

243

>71

1

-

10.8

3 1/10

250

a Within the weight classes, the chloroquine dose approximates 4mg/kg with lighter weights and 3.5mg/kg with heavier weights. The lowest possible dose should be used. With syrup, an individual dose is possible. Caution is necessary in patients with hepatic or renal disease, in whom a dose reduction may be necessary. b One measuring spoon (3.5 ml)=81 mg chloroquine; the maximal daily dose = 4mg/kg ideal body weight corresponds to 0.17 ml/kg.

a Within the weight classes, the chloroquine dose approximates 4mg/kg with lighter weights and 3.5mg/kg with heavier weights. The lowest possible dose should be used. With syrup, an individual dose is possible. Caution is necessary in patients with hepatic or renal disease, in whom a dose reduction may be necessary. b One measuring spoon (3.5 ml)=81 mg chloroquine; the maximal daily dose = 4mg/kg ideal body weight corresponds to 0.17 ml/kg.

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