Hydroxychloroquine metabolism

On the basis of these data for chloroquine and cimetidine, the manufacturer of hydroxychloroquine states that, even though specific reports have not appeared, cimetidine might inhibit hydroxychloroquine metabolism. ... 

The drug is approximately 70% absorbed after oral administration (see Chapter 54). It is metabolized to a less active hydroxylated metabolite, and both the parent compound and the metabolite are polyglutamated within cells, where they stay for prolonged periods. Methotrexate s serum half-life is usually only 6-9 hours, although it may be as long as 24 hours in some individuals. Methotrexate s concentration is increased in the presence of hydroxychloroquine, which can reduce the clearance or increase the tubular reabsorption of methotrexate. This drug is excreted principally in the urine, but up to 30% may be excreted in bile. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

CIMETIDINE CHLOROQUINE, HYDROXYCHLOROQUINE t efficacy and adverse effects of chloroquine Inhibition of metabolism and excretion Consider ranitidine as alternative or take cimetidine at least 2 hours after chloroquine... 

Keratopathy due to Fabry s disease is another important condition in the differential diagnosis. The verticillate corneal findings are quite similar to those induced by chloroquine or hydroxychloroquine, but the systemic implications in this metabolic disease warrant consultation with an internist. 

Hydroxychloroquine (and also chloroquine, see Ch. 14) in addition to their antimalarial actions exert anti-inflammatory and immunomodulating effects that are useful in rheumatoid disease. Hydroxychloroquine accumulates within lymphocytes, macrophages, polymorphs and fibroblasts, and inhibits phagocyte function but its exact mode of action is unknown. Its action is terminated both by metabolism and renal elimination (t/ 18 days). 

The pharmacokinetics of hydroxychloroquine are poorly understood. It is well absorbed orally and widely distributed to body tissues. Hydroxychloroquine is partially metabolized in the liver and is excreted by the kidney. The onset of action of hydroxychloroquine may... 

As a rule, metabolic hydroxylation of an active compound represents a detoxication mechanism. It results generally from a first pass effect and can be followed or not by a conjugation reaction (see Chapters 30 and 31). Classical examples of drugs detoxified through hydroxylation are paracetamol, oxyphenbutazone and hydroxychloroquine. Other important reactions of hydroxy compounds, whether... 

Allopurinol is the only drug listed that decreases production of uric acid. Probenecid increases uric acid excretion. Colchicine and hydroxychloroquine do not affect uric acid metabolism. Aspirin actually slows renal secretion of uric acid and raises uric acid blood levels. It should not be used in gout. The answer is (A). 

Cimetldlne reduces the metabolism and clearance of chloroquine, but the clinical importance of this is uncertain. Hydroxychloroquine is predicted to interact in the same way as chloroquine. Ranitidine appears not to interact with chloroquine. 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

---