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2017 HCHB_digital

OTC Medicines:

OTC Medicines: Interactions OTC Medicines: Interactions Drug/drug group Interacting substance Details Antacids cont… Antidiarrhoeals – loperamide Antifungals – clotrimazole vaginal cream Antifungals – fluconazole (Fluconazole inhibits CYP2C9 and 3A4 but to a lesser extent than ketoconazole) Antifungals – miconazole oral gel Antihistamines – sedating (eg, brompheniramine, chlorpheniramine, cyclizine, diphenhydramine, promethazine, triprolidine, meclozine) Antihistamines – non-sedating (eg, cetirizine, loratadine) Quinolone antibiotics (eg, ciprofloxacin, norfloxacin) Zinc supplements Clozapine Desmopressin Ergotamine or related compounds Latex condoms Warfarin Benzodiazepines (eg, midazolam, triazolam) Carbamazepine Celecoxib Cyclosporin Ergotamine or related compounds Phenytoin Quetiapine QT-interval prolonging drugs (eg, quinolones, salmeterol, tricyclic antidepressants) SSRI antidepressants Statins Sulphonylureas and possibly thiazolidinediones Warfarin Zidovudine Warfarin Antihypertensive medicines CNS depressants (eg, anxiolytics, hypnotics, sedatives, alcohol, opiate analgesics, antipsychotics) Other agents with anticholinergic/ antimuscarinic effects (eg, amantadine, benztropine, bromocriptine, disopyramide, levodopa, selegiline, pergolide, procyclidine, sedating antihistamines, phenothiazines, tricyclic antidepressants, orphenadrine) Phenytoin Topiramate Amiodarone Nefazodone May decrease the solubility of fluoroquinolones in the urine and increase the risk of crystalluria Reduction in the amount of zinc absorbed with calcium containing antacids. Separate administration by 2–3 hours One fatal report. Possible increased risk of toxic megacolon Increased GI absorption of desmopressin caused by reduction in GI motility caused by loperamide. Monitor for increased adverse effects (eg, hyponatraemia) Although systemic absorption is limited, azole antifungals may inhibit the metabolism of ergot derivatives resulting in increased adverse effects. Avoid if possible Some intravaginal clotrimazole products may damage latex condoms causing contraceptive failure Potential to interact (rare reports) Inhibits metabolism of benzodiazepines metabolised by CYP3A4 (eg, midazolam, triazolam) resulting in increased risk of toxicity. Use lowest dose or change to benzodiazepine metabolised by glucuronidation (eg, temazepam, lorazepam) Decreases carbamazepine metabolism causing a possible increase in carbamazepine levels. Monitor Inhibits celecoxib metabolism and can increase celecoxib levels up to two-fold. Initiate celecoxib at lowest recommended dose Inhibits cyclosporin metabolism, increasing cyclosporin levels and risk of toxicity. Avoid combination or closely monitor Inhibits metabolism resulting in increased adverse effects of ergot alkaloids (risk of vasospasm and serious/ life-threatening ischaemia increased). Avoid Inhibits metabolism resulting in increased phenytoin levels and possible toxicity. Avoid combination or closely monitor Possible increased levels quetiapine through inhibition of metabolism Increased risk of QT prolongation although combination may often be used. Monitor Fluconazole also inhibits CYP2C19 so may increase serum concentrations of citalopram and escitalopram. Increased risk of serotonin syndrome Some reports of serious or life-threatening musculoskeletal toxicity associated with increased plasma levels of statins. Generally avoid with atorvastatin or simvastatin. Pravastatin may be safer as not metabolised by CYP450 3A4 Inhibits metabolism resulting in increased serum concentrations and possible hypoglycaemia. Monitor and reduce dosage of oral hypoglycaemic agent if necessary Inhibits metabolism resulting in increased prothrombin time/INRs and increased risk of bleeding events. Single doses of fluconazole may also potentiate warfarin effects Increased serum concentrations and half-life of zidovudine. Increased risk of adverse effects Inhibits metabolism resulting in increased prothrombin time/INRs and increased risk of bleeding events May potentiate hypotensive effect. Monitor closely Additive CNS depressant effects may occur (eg, sedation) Additive cholinergic adverse effects (eg, dry mouth, urine retention, constipation, confusion in elderly) Some reports of increased phenytoin levels. Monitor May potentiate the risk of oligohydrosis and hyperthermia associated occasionally with topiramate, especially in pediatric patients or those exposed to hot weather Possible increased risk of QT prolongation Possible increased risk of QT prolongation with higher doses of loratadine (20mg/day) Page 186 HEALTHCARE HANDBOOK 2017-2018 References Charts

OTC Medicines: Interactions Drug/drug group Interacting substance Details Antimuscarinics (eg, hyoscine [scopolamine], atropine. Alcohol, other CNS depressants Metoclopramide Nitrates Other agents with antimuscarinic effects (eg, amantadine, benztropine, bromocriptine, disopyramide, levodopa, selegiline, pergolide, procyclidine, sedating antihistamines, phenothiazines, tricyclic antidepressants, orphenadrine) Potassium salts (solid-dose formulations) Additive sedative effects Possible reduction in prokinetic effect of metoclopramide Possible reduced effect of sublingual nitrates (failure to dissolve under tongue due to dry mouth) Increased adverse effects (eg, dry mouth, urine retention, constipation, confusion in elderly) Antimuscarinic action may slow transit time. Severe GI injury reported due to high localised concentration of potassium salts. Avoid if possible Chloramphenicol (ocular) Bone marrow depressant medications Although concerns around aplastic anaemia occurring with ocular chloramphenicol have been largely discounted, literature recommends avoiding concomittant use Phenytoin Theoretically may increase plasma phenytoin levels. Avoid or monitor closely Warfarin Some case reports available which document an increased INR with concomitant warfarin and ocular chloramphenicol use. Monitor Dextromethorphan (Dextromethorphan is primarily metabolised by CYP2D6 and also has serotonergic effects) Diptheria/ tetanus/ pertussis (Tdap) CNS depressants (eg, alcohol, sedatives) CYP2D6 inhibitors (eg, amiodarone, bupropion, fluoxetine, quinidine) SSRIs (eg, fluoxetine, paroxetine), venlafaxine MAOIs – irreversible (eg, phenelzine, tranylcypromine) MAOIs – reversible (eg, moclobemide) Selegiline Other injectable vaccines or immunoglobulin Possible enhanced sedative and hypotensive effect Increased adverse effects of dextromethorphan (eg, GI upset, sedation) Some reports of serotonin syndrome. Monitor Many reports of serotonin syndrome, including fatalities. Avoid concurrent use Significantly reduced metabolism of dextromethorphan. Adverse effects increased. Avoid combination Reports of serotonin syndrome. Avoid combination if possible Administer at different sites Dukoral Food/ drink Vaccine is acid labile so separate administration from food or drink by one hour as food and drink may increase acid production in stomach Typhoid vaccine (oral) Take at least eight hours apart Probenecid Probenecid may increase the serum concentrations of famciclovir and its active metabolite, penciclovir, through competitive inhibition of renal tubular secretion. Monitor H2-antagonists (Ranitidine) Iodine supplements (oral) Antacids Antifungals Atazanavir Cefuroxime axetil (oral) Enteric-coated formulations Amiodarone Anti-thyroid medicines (eg, propylthiouracil, iodide) Lithium Potassium-sparing medicines (eg, ACE inhibitors, angiotensin II receptor antagonists, spironolactone) Warfarin Antacids Antibacterials – quinolones (eg, ciprofloxacin, norfloxacin) Antibacterials – tetracyclines (eg, doxycycline, minocycline) Biphosphonates (eg, alendronate, etidronate) Significant reductions in ranitidine bioavailability demonstrated with co-administration of aluminium or magnesium containing antacids. Administer 1–2 hours apart Reduced absorption of itraconazole and ketoconazole. Avoid concomitant use Reduced absorption of atazanavir since H2- antagonists reduce gastric pH. Separate administration (give either 2 hours before or 10 hours after H2-receptor agonists) Bioavailability may be reduced resulting in lower cefuroxime concentrations May increase dissolution rate of enteric-coated formulations. Generally avoid or separate administration by 2–3 hours Additive effect as amiodarone contains iodine. Avoid combination except on medical advice Potentiation of hypothyroid effect. Avoid combination unless under medical advice Combination can cause hypothyroidism Most iodine supplements contain potassium.Some medicines reduce the excretion of potassium by the kidneys and the combination can increase potassium levels in the body. Avoid combination unless under medical advice Anticoagulant effect of warfarin may be decreased Some studies show significant reductions in amount of iron absorbed. Separate administration by 2–3 hours Decreases absorption and may reduce plasma concentrations of quinolone antibiotics to subtherapeutic levels. Separate administration by at least 2–3 hours. Monitor response Insoluble chelate formed which decreases absorption of tetracyclines. Separate administration by at least 2–3 hours. Monitor patient for reduced response Reduced absorption of bisphosphonates. Separate administration by at least 30 minutes to 2 hours depending on biphosphonate used Carbidopa and levodopa Reduced absorption may be clinically significant in some patients. Separate administration by at least 2–3 hours. Monitor patient for reduced response Cholestyramine Reduced absorption of iron Page 187

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