chapter
Minerals
Pages 9

Separate doses by at least 2 hours

CALCIUM ANTICANCER AND IMMUNOMODULATING DRUGS

CALCIUM CORTICOSTEROIDS ↓ calcium levels ↓ intestinal absorption and ≠ excretion

Separate doses as much as possible

CALCIUM AND DAIRY PRODUCTS

ESTRAMUSTINE ↓ plasma concentrations of estramustine and risk of poor therapeutic response

Due to ↓ absorption of estramustine due to the formation of a calcium phosphate complex

Administer estramustine 1 hour before or 2 hours after dairy products or calcium supplements

CALCIUM ANTIEPILEPTIC DRUGS ↓ plasma/body concentrations of calcium

A direct ↓ effect on absorption and also by ↓ vitamin D

Be aware

CALCIUM BISPHOSPHONATES ↓ bisphosphonate levels ↓ absorption Separate doses by at least 30 minutes CALCIUM CARDIAC GLYCOSIDES –

DIGOXIN Risk of cardiac arrhythmias with large intravenous doses of calcium

Uncertain. It is known that calcium levels directly correlate with the action of digoxin; therefore, high levels, even if transient, may increase the chance of toxicity

It is recommended that the parenteral administration of calcium should be avoided in patients taking digoxin. If this is not possible, administer calcium slowly and in small aliquots

CALCIUM DIURETICS – THIAZIDES Risk of hypercalcaemia with high-dose calcium

↓ renal excretion of calcium by thiazides

Monitor calcium levels closely

CALCIUM FLUORIDE ↓ efficacy of fluoride ↓ absorption Separate doses by 2-3 hours

↓ absorption. These two minerals compete for absorption

Separate doses as much as possible; monitor FBC closely. Monitor plasma calcium levels

CALCIUM COMPOUNDS SYMPATHOMIMETICS Parenteral calcium administration may ↓ positive inotropic effects of epinephrine and dobutamine

Uncertain; postulated that calcium modulates signal transmission from the receptor

Monitor BP closely; watch for poor response to these inotropes

CALCIUM THYROID HORMONES – LEVOTHYROXINE

↓ levothyroxine levels ↓ absorption due to formation of unabsorbable chelates

Separate doses by at least 4 hours. Monitor TFTs regularly and consider ≠ dose of levothyroxine

CALCIUM ZINC ↓ efficacy of zinc Unknown Separate doses by 2-3 hours CINACALCET

CINACALCET BUPROPION ≠ plasma concentrations of these substrates, with risk of toxic effects

Bupropion and its metabolite hydroxybupropion inhibit CYP2D6

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)

FLUORIDE

FLUORIDE CALCIUM ↓ efficacy of fluoride ↓ absorption Separate doses by 2-3 hours MAGNESIUM MAGNESIUM (PARENTERAL)

ANAESTHETICS – LOCAL – PROCAINE SOLUTIONS

Precipitation of drugs, which may not be immediately apparent

A pharmaceutical interaction Do not mix in the same infusion or syringe

MAGNESIUM ANALGESICS – ASPIRIN May ↓ effects of magnesium in the body

Attributed to an antagonistic effect; mechanism is uncertain

Be aware

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MISCELLANEOUS MINERALS Polystyrene sulphonate resins

parenteral magnesium

Both drugs inhibit calcium influx across cell membranes, and magnesium promotes the movement of calcium into the sarcoplasmic reticulum; this results in muscular paralysis

Do not administer calcium channel blockers during parenteral magnesium therapy

MAGNESIUM (PARENTERAL)

MUSCLE RELAXANTS – DEPOLARIZING, NONDEPOLARIZING

≠ efficacy of these muscle relaxants, with risk of prolonged neuromuscular blockade

Additive effect; magnesium inhibits ACh release and ↓ postsynaptic receptor sensitivity

Monitor nerve blockade closely

MAGNESIUM HORMONE REPLACEMENT THERAPY

May cause magnesium depletion

Mg levels tend to ↓ during menopause. Risk-benefit ratios need to be considered on an individual basis as there are suggestions that magnesium can counteract the alleged ≠ risk of heart attacks and strokes in patients on hormone replacement therapy

Be aware

MAGNESIUM ORAL CONTRACEPTIVES May cause magnesium depletion

Oral contraceptives tend to increase copper levels, which when high results in ↓ magnesium levels

Be aware

MAGNESIUM PENICILLAMINE May cause magnesium depletion

Penicillamine ↓ absorption of several minerals, including magnesium

Be aware and separate the oral intake. Parenteral magnesium is unlikely to be affected

POLYSTYRENE SULPHONATE RESINS

SODIUM POLYSTYRENE SULPHONATE

ANTACIDS – MAGNESIUMCONTAINING

Cases of metabolic alkalosis Uncertain; possibly ≠ absorption of bicarbonate due to its abnormal neutralization in the stomach

Consider an alternative antacid or administer sodium polystyrene sulphonate as an enema. If both need to be co-administered orally, monitor U&Es and blood gases closely

↓ absorption Monitor TFTs regularly, and consider ≠ dose of levothyroxine

POTASSIUM

Warn patients to avoid salt substitutes that contain potassium. OTC preparations of minerals and vitamins are unlikely to contain a potentially harmful content of potassium. However, a quarter of a teaspoon of salt substitute with potassium may contain 650 mg of potassium, compared with a prescription potassium tablet of 20 mEq, which contains 750 mg

POTASSIUM ALISKIREN Risk of hyperkalaemia Additive effect Avoid co-administration

POTASSIUM ANALGESICS

POTASSIUM ASPIRIN Risk of hypokalaemia Aspirin is considered to ≠ excretion of potassium

Be aware, particularly in people on long-term aspirin therapy, although it is uncertain whether 75-100 mg doses of aspirin cause significant effects

POTASSIUM NSAIDs ≠ risk of hyperkalaemia Additive effect ➣ For signs and symptoms of hyperkalaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperkalaemia

POTASSIUM CITRATE ANTIBIOTICS – METHENAMINE

↓ methenamine levels Citrate alkalinizes the urine, which ≠ excretion of methenamine

Avoid co-administration

POTASSIUM ANTICANCER AND IMMUNOMODULATING DRUGS

POTASSIUM CICLOSPORIN ≠ risk of hyperkalaemia Additive effect ➣ For signs and symptoms of hyperkalaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperkalaemia

POTASSIUM CORTICOSTEROIDS Risk of hypokalaemia Most corticosteroids (cortisone, prednisone) ≠ loss of potassium

Be aware and monitor serum potassium levels, particularly in patients on long-term therapy with steroids

POTASSIUM TACROLIMUS Risk of hyperkalaemia Additive effect Monitor potassium levels closely

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MISCELLANEOUS MINERALS Vitamins

ANGIOTENSIN II RECEPTOR ANTAGONISTS

Retention of potassium by ACE inhibitors and additional intake of potassium

Monitor serum potassium daily

POTASSIUM DIURETICS – POTASSIUMSPARING

Risk of hyperkalaemia Additive effect Monitor potassium levels closely

POTASSIUM LAXATIVES Long-term use of laxatives may cause hypokalaemia. Laxatives may cause ↓ plasma/body concentrations of several minerals

Due to ≠ intestinal loss of potassium. Long-term use may cause ↓ absorption of several minerals

Be aware

SEVELAMER

SEVELAMER ANTIBIOTICS – CIPROFLOXACIN

↓ plasma concentrations of ciprofloxacin

↓ absorption Separate the doses as much as possible

SEVELAMER MYCOPHENOLATE ↓ plasma concentrations of mycophenolate

Attributed to binding of mycophenolate to calcium free phosphate binders

Separate administration by at least 2 hours

VITAMINS

VITAMIN A RETINOIDS Risk of vitamin A toxicity Additive effect; tretinoin is a form of vitamin A

Avoid co-administration

VITAMIN B6 ANTIEPILEPTICS – PHENOBARBITONE, PHENYTOIN

↓ plasma concentrations of these antiepileptics

Uncertain Watch for poor response to these antiepileptics if large doses of vitamin B6 are given

inhibitor)

A derivative of vitamin B6 is a co-factor in the peripheral conversion of levodopa to dopamine, which ↓ amount available for conversion in the CNS. Dopa decarboxylase inhibitors inhibit this peripheral reaction

Avoid co-administration of levodopa with vitamin B6; co-administration of vitamin B6 with co-beneldopa or co-careldopa is acceptable

VITAMIN B12 ANTIBIOTICS – CHLORAMPHENICOL

↓ efficacy of hydroxycobalamin Chloramphenicol depresses the bone marrow; this opposes the action of vitamin B12

Be aware; monitor FBC and vitamin B12 levels closely

VITAMIN C ANTACIDS CONTAINING ALUMINIUM

≠ aluminium levels, with risk of encephalopathy in patients with renal failure

Uncertain; possibly ≠ absorption due to the ascorbic acid in the presence of ↓ renal excretion

Avoid co-ingestion in patients with renal failure

VITAMIN C ASPIRIN May ↓ vitamin C levels Attributed to aspirin ‘blocking’ the absorption of vitamin C. Aspirin has been found to ≠ elimination of vitamin C and all B vitamins

Be aware

VITAMIN D ANTIEPILEPTICS – PHENYTOIN, CARBAMAZEPINE, PRIMIDONE , BARBITURATES

↓ efficacy of vitamin D Attributed to induction of vitamin D metabolism

Be aware; consider ≠ dose of vitamin D

VITAMIN D DIURETICS – THIAZIDES Risk of hypercalcaemia with vitamin D

↓ renal excretion of calcium by thiazides

Monitor calcium levels closely

VITAMIN D MAGNESIUM ≠ plasma concentrations of magnesium

Due to ≠ absorption Be aware

VITAMIN E ANTICOAGULANTS – ORAL Case of ≠ anticoagulant effect Uncertain Monitor INR closely for 1-2 weeks after starting and stopping vitamin E

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MISCELLANEOUS MINERALS Other drug-mineral interactions

TETRACYCLINES

tetracyclines

↓ absorption Separate doses by at least 2 hours

ZINC ANTICANCER AND IMMUNOMODULATING DRUGS – PENICILLAMINE

↓ penicillamine and zinc levels Mutual ↓ absorption Avoid co-administration

ZINC CALCIUM ↓ efficacy of zinc Unknown Separate doses by 2-3 hours ZINC IRON – ORAL ↓ iron levels when iron is given

orally ↓ absorption Separate doses as much as

possible – monitor FBC closely

ZINC TRIENTINE ↓ zinc and trientine levels Mutually ↓ absorption Separate doses by at least 2 hours OTHER DRUG-MINERAL INTERACTIONS

ALLOPURINOL COPPER ↓ plasma concentration of copper Allopurinol chelates copper Be aware and separate oral intake by at least 2 hours

ANTACIDS

ANTACIDS COPPER ↓ plasma concentration of copper Most antacids will ↓ absorption of copper

If antacids are used in the long term, consider copper supplements of 1-2 mg/day

H2 ANTAGONISTS COPPER AND IRON ↓ plasma and body concentrations of copper, iron, zinc and calcium

As a class, H2 antagonists act as free radical scavengers and cause depletion of calcium, iron and zinc. Cimetidine in particular binds to copper and iron, and these minerals are not made available for free radical production

Be aware and separate oral intake by 2 hours

ANTIBIOTICS

AZITHROMYCIN MAGNESIUM ↓ plasma/body concentrations of magnesium

Due to ↓ absorption Be aware

COPPER

↓ absorption due to formation of unabsorbable chelates

Separate oral intake by at least 2 hours

OFLOXACIN MINERALS – CALCIUM, MAGNESIUM, IRON, ZINC

↓ absorption of iron and zinc Due to formation of unabsorbable chelates

Separate oral intake by at least 2 hours

LEVOFLOXACIN MAGNESIUM, IRON ↓ plasma/body levels of magnesium and iron

↓ absorption due to formation of unabsorbable chelates

Separate oral intake by at least 2 hours

NITROFURANTOIN MAGNESIUM ↓ plasma/body concentrations of magnesium

Due to ↓ absorption Be aware

TETRACYCLINES MINERALS – CALCIUM, MAGNESIUM, IRON, ZINC

↓ plasma/body levels of calcium, magnesium, iron and zinc

↓ absorption due to formation of unabsorbable chelates

Separate oral intake by at least 2 hours

ANTIDIABETIC DRUGS

GLIPIZIDE MAGNESIUM ↓ plasma/body concentrations of magnesium

Due to ↓ absorption Be aware

HYPOGLYCAEMIC DRUGS CHROMIUM Chromium supplements may ≠ risk of hypoglycaemia

Chromium is necessary for the production of insulin

Be aware

ANTIEPILEPTICS

CARBAMAZEPINE PHENYTOIN BARBITURATES PRIMIDONE

COPPER AND ZINC ↓ plasma concentrations of copper and zinc

Attributed to ↓ absorption Be aware

VALPROIC ACID SELENIUM ↓ selenium levels Uncertain Be aware ANTIPSYCHOTIC DRUGS – CLOZAPINE

SELENIUM ↓ selenium levels Uncertain Be aware

COLESTYRAMINE, COLESTIPOL

IRON ↓ plasma/body concentrations of iron

Due to ↓ absorption Be aware and do an FBC at least 2-weekly if on long-term therapy. Separate oral intake by 2 hours

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MISCELLANEOUS MINERALS Other drug-mineral interactions

Attributed to ≠ loss of selenium and chromium

Be aware

PREDNISONE, CORTISONE ZINC, CALCIUM, CHROMIUM, MAGNESIUM, SELENIUM

↓ plasma/body concentrations of these minerals

Attributed to ≠ loss and/or ↓ absorption

Be aware and monitor plasma concentrations of these minerals; provide supplements

ETHAMBUTOL COPPER ↓ plasma concentration of copper Ethambutol binds to copper Be aware and separate oral intake by at least 2 hours

LEVODOPA, METHYLDOPA

IRON-CONTAINING COMPOUNDS

↓ plasma concentrations of methyldopa (peak levels ↓ by 55%) and levodopa, with risk of therapeutic failure

Iron preparations impair the absorption of methyldopa and levodopa

Be aware and separate oral intake by at least 2 hours

PENICILLAMINE ZINC, IRON AND OTHER MINERALS

↓ plasma concentrations of several minerals

Due to formation of unabsorbable chelates

Separate oral intake by at least 2 hours

PROTON PUMP INHIBITORS

IRON ↓ plasma concentrations of iron Proton pump inhibitors inhibit the absorption of iron

Consider use of parenteral iron in patients on proton pump inhibitors treatment

WARFARIN MAGNESIUM, IRON, ZINC ↓ plasma/body concentrations of magnesium, iron and zinc

Due to ↓ absorption Be aware

ZIDOVUDINE ZINC ↓ plasma/body concentrations of zinc

Due to ↓ absorption Be aware