62 - Adverse effects, Precautions and Contraindications of Chloroquine

Toxicity and Side Effects: 

Taken in proper doses, chloroquine is an extraordinarily safe drug; however, its safety margin is narrow, and a single dose of 30 mg/kg may be fatal (Taylor and White, 2004). Acute chloroquine toxicity is encountered most frequently when therapeutic or high doses are administered too rapidly by parenteral routes. Toxic manifestations relate primarily to the cardiovascular system and the CNS. Cardiovascular effects include hypotension, vasodilation, suppressed myocardial function, cardiac arrhythmias, and eventual cardiac arrest. Confusion, convulsions, and coma indicate CNS dysfunction. Chloroquine doses of more than 5 g given parenterally usually are fatal. Prompt treatment with mechanical ventilation, epinephrine, and diazepam may be lifesaving.

Doses of chloroquine used for oral therapy of the acute malarial attack may cause GI upset, headache, visual disturbances, and urticaria. Pruritus also occurs, most commonly among dark-skinned persons. Prolonged medication with suppressive doses occasionally causes side effects such as headache, blurring of vision, diplopia, confusion, convulsions, lichenoid skin eruptions, bleaching of hair, widening of the QRS interval, and T-wave abnormalities. These complications usually disappear soon after the drug is withheld. Rare instances of hemolysis and blood dyscrasias have been reported. Chloroquine may cause discoloration of nail beds and mucous membranes. Chloroquine can interfere with the immunogenicity of certain vaccines (Horowitz and Carbonaro, 1992; Pappaioanou et al., 1986).

Irreversible retinopathy and ototoxicity can result from high daily doses (>250 mg) of chloroquine or hydroxychloroquine that lead to cumulative total doses of more than 1 g of base per kilogram body weight, such as those used for treatment of diseases other than malaria. Retinopathy presumably is related to drug accumulation in melanin-rich tissues and can be avoided if the daily dose is 250 mg or less (see Rennie, 1993). Prolonged therapy with high doses of 4-aminoquinoline also can cause toxic myopathy, cardiopathy, and peripheral neuropathy; these reactions improve if the drug is withdrawn promptly (Estes et al., 1987). Rarely, neuropsychiatric disturbances, including suicide, may be related to overdose.

Precautions and Contraindications :

This topic has been reviewed by Taylor and White (2004). Chloroquine is not recommended for treating individuals with epilepsy or myasthenia gravis. The drug should be used cautiously if at all in the presence of hepatic disease or severe gastrointestinal, neurological, or blood disorders. The dose must be adjusted in renal failure. In rare cases, chloroquine can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (see Primaquine below). Concomitant use of gold or phenylbutazone (no longer available in the United States) with chloroquine should be avoided because of the tendency of all three agents to produce dermatitis. Chloroquine should not be prescribed for patients with psoriasis or other exfoliative skin conditions because it causes severe reactions. It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease . Chloroquine is an inhibitor of CYP2D6 and interacts with a variety of different agents. It should not be given with mefloquine because of increased risk of seizures. Most important, this antimalarial opposes the action of anticonvulsants and increases the risk of ventricular arrhythmias from coadministration with amiodarone or halofantrine. By increasing plasma levels of digoxin and cyclosporine, chloroquine also can increase the risk of toxicity from these agents. For patients receiving long-term, high-dose therapy, ophthalmological and neurological evaluations are recommended every 3 to 6 months.

61 - Drugs potentially harmful in Porphyria

1. BARBITURATES : The effect of barbiturates on ALA synthetase can cause dangerous disease exacerbations in persons with intermittent porphyria.Because barbiturates enhance porphyrin synthesis, they are absolutely contraindicated in patients with acute intermittent porphyria or porphyria variegata.
2. ETHCHLORVYNOL: Ethchlorvynol may enhance the hepatic metabolism of other drugs such as oral anticoagulants, and it is contraindicated in patients with intermittent porphyria.
3. CHLOROQUINE : It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease.

Documented Porphyrinogenic  Carbamazepine Carisoprodol Chloramphenicol Clindamycin Dextropropoxyphene Dihydralazine Dihydroergotamine Drospirenone + estrogen Dydrogesterone Etonogestrel Fosphenytoin sodium Hydralazine Hydroxyzine Indinavir Ketamine Ketoconazole Lidocaine Lynestrenol Lynestrenol + estrogen Mecillinam Medroxyprogesterone Megestrol Methylergometrine Methyldopa Mifepristone Nicotinic acid/meclozine/hydroxyzine Nitrofurantoin Norethisterone Norgestimate + estrogen Orphenadrine Phenobarbital Phenytoin Pivampicillin Pivmecillinam Primidone Rifampicin Ritonavir Spironolactone Sulfadiazine + trimethoprim Tamoxifen Testosterone, inj. Thiopental Trimethoprim Valproic acid

Probably Porphyrinogenic  Altretamine Lidocaine Aminophylline Lopinavir Amiodarone Lutropin alfa Amitriptyline Lymecycline Amlodipine Meclozine Amprenavir Medroxyprogesterone + estrogen Aprepitant Atorvastatin Metoclopramide Azathioprine Metronidazole Bosentan Metyrapone Bromocriptine Moxonidine Buspirone Nandrolone Busulfan Nefazodone Butylscopolamine Nelfinavir Cabergoline Nevirapine Ceftriaxone + lidocaine Nifedipine Cerivastatin Nimodipine Cetirizine Nitrazepam Cholinetheophyllinate Norethisterone Clarithromycin Nortriptyline Clemastine Oxcarbazepine Clonidine Oxytetracycline Cyclizine Paclitaxel Cyproterone Paroxetine Danazol Phenazone + caffeine Delavirdine Pioglitazone Desogestrel + estrogen Probenecid Diazepam Progesterone, vaginal gel Dienogest + estrogen Quinidine Diclofenac Rabeprazole Diltiazem Raloxiphene Diphenhydramine Rifabutin Disopyramide Riluzole Disulfiram Risperidone Drospirenone + estrogen Rosiglitazone Dydrogesterone Saquinavir Ergoloid mesylate Selegiline Erythromycin Simvastatin Estramustine Sulfasalazine Ethosuximide Telithromycin Etoposide Terbinafine Exemestane Terfenadine Felbamate Testosterone, transdermal patch Felodipine Tetracycline Fluconazole Theophylline Flunitrazepam Thiamazole Fluvastatin Tibolone Glibenclamide Ticlopidine Halothane Tinidazole Hyoscyamine Thiotepa Imipramine Topiramate Irinotecan Topotecan Isoniazid Toremifene Isradipine Tramadol Itraconazole Trimegestone + estrogen Lamivudine +zidovudine Verapamil Lansoprazole Voriconazole Lercanidipine Zidovudine/AZT Levonorgestrel

Possibly Porphyrinogenic  Aceclofenac Gramicidin Phenylpropanolamine + cinnarizine Acitretin Guaifenesin Pizotifen Acrivastine Hydrocortisone Polidocanol Alfuzosin Hydroxycarbamide Polyestradiol phosphate Anastrozole Hydroxychloroquine Potassium canrenoate Auranofin Ibutilide Pravastatin Azelastine Imatinib Prednisolone Benzatropine Indomethacin Prilocaine Benzydamine Ketobemidone + DDBA Proguanil Betaxolol Ketorolac Propafenone Bicalutamide Lamotrigine Pseudoephedrine + dexbrompheniramine Biperiden Letrozole Quillaia extract Bupropion Levodopa + benserazide Quinagolide Carvedilol Levonorgestrel intrauterine Quinine Chlorambucil Levosimendan Quinupristin + dalfopristin Chlorcyclizine + guaifenesin Linezolid ReBoxetine Chloroquine Lofepramine Repaglinide Chlorprothixene Lomustine Rizatriptan Chlorzoxazone Malathion Rofecoxib Chorionic gonadotrophin Maprotiline Ropinirole Ciclosporin Mebendazole Ropivacaine Cisapride Mefloquine Roxithromycin Citalopram Melperone Sertraline Clomethiazole Melphalan Sevoflurane Clomiphene Mepenzolate Sibutramine Clomipramine Mepivacaine Sildenafil Clopidogrel Mercaptopurine Sirolimus Clotrimazole Methadone Sodium aurothiomalate Cortisone Methylprednisolone Sodium oleate + chlorocymol Cyclandelate Metixene Stavudine Metolazone Cyclophosphamide Sulindac Cyproheptadine Metronidazole Sumatriptan Dacarbazine Mexiletine Tacrolimus Daunorubicin Mianserin Tadalafil Desogestrel Midazolam Tegafur + uracil Dichlorobenzyl alcohol Minoxidil Telmisartan Dithranol Mirtazapine Thioridazine Docetaxel Mitomycin Thioguanine Donepezil Mitoxantrone Tolphenamic acid Doxycycline Moclobemide Tolterodine Ebastine Montelukast Torsemide Econazole Morphine + scopolamine Triamcinolone Efavirenz Multivitamins Trihexyphenidyl Escitalopram Mupirocin Trimipramine Esomeprazole Nabumetone Valerian Estradiol/tablets Nafarelin Venlafaxine Estriol/tablets Naltrexone Vinblastine Estrio/vainal crème, tablet Nateglinide Vincristine Ifosfamide Nilutamide Vindesine Estrogen, conjug. Noscapine Vinorelbine Finasteride Omeprazole Xylometazoline Flecainide Oxybutynin Zaleplon Flucloxacillin Oxycodone Ziprasidone Fluoxetine Pantoprazole Zolmitriptan Flupentixol Papaverine Zolpidem Flutamide Parecoxib Zuclopenthixol Fluvoxamine Pentifylline Follitropin alfa and beta Pentoxyverine Galantamine Glimepiride Glipizide Gonadorelin