chapter
Other diabetic drugs
Pages 20

Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of sulphonylureas are often required for adequate glycaemic control

SULPHONYLUREAS SYMPATHOMIMETICS – EPINEPHRINE

May ≠ antidiabetic therapy requirement

Epinephrine causes the release of glucose from the liver and is an important defence/homeostatic mechanism. Hyperglycaemia due to antagonistic effect

Larger doses of antidiabetic therapy may be needed during the period of epinephrine use, which is usually in the short term or in emergency situations

SULPHONYLUREAS TESTOSTERONE ≠ hypoglycaemic effect and ≠ of hypoglycaemic episodes

Exact mechanism is uncertain. Low testosterone levels are associated with type II diabetes. Experimental work has suggested that testosterone may play a role in glucose efflux from cells

SULPHONYLUREAS THYROID HORMONES ↓ hypoglycaemic effect of sulphonylureas

Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of sulphonylureas are often required for adequate glycaemic control

OTHER ANTIDIABETIC DRUGS

ACARBOSE

ACARBOSE ALCOHOL Tends to mask signs of hypoglycaemia and ≠ risk of hypoglycaemic episodes

Inhibits glucose production and release from many sources, including the liver

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NEOMYCIN

≠ gastrointestinal effects as a result of concurrent use of acarbose and neomycin

Neomycin is known to cause a drop in blood glucose levels after meals; when used concomitantly with acarbose this ↓ may be ≠. Neomycin also exacerbates the adverse gastrointestinal effects caused by acarbose

Blood glucose levels should be closely monitored; if gastrointestinal signs are severe, the dose of acarbose should be ↓

ACARBOSE QUINOLONES – CIPROFLOXACIN, NORFLOXACIN, OFLOXACIN

≠ risk of hypoglycaemic episodes Mechanism uncertain. Ciprofloxacin is a potent inhibitor of CYP1A2. Norfloxacin is a weak inhibitor of CYP1A2, but these drugs may inhibit other CYP isoenzymes to varying degrees

ACARBOSE ANTIDEPRESSANTS

ACARBOSE SSRIs Fluctuations in blood sugar are very likely, with both hypoglycaemic and hyperglycaemic events being reported in diabetics receiving hypoglycaemic treatment. ≠ plasma concentrations of sulphonylureas (e.g. tolbutamide) may occur

Brain serotonin and corticotropinreleasing hormone systems participate in the control of blood sugar levels. ≠ (usually acute) in brain serotonergic activity induces a hyperglycaemic response. Fluvoxamine is a potent inhibitor and fluoxetine a less potent inhibitor of CYP2C9, which metabolizes sulphonylureas

Both hyper-and hypoglycaemic responses have been reported with SSRIs; there is a need to monitor blood glucose closely prior to, during and after discontinuing SSRI treatment ➣ For signs and symptoms of hypoglycaemia and hpyerglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia, Hpyerglycaemia

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ANTIDIABETIC DRUGS OTHER ANTIDIABETIC DRUGS Acarbose

TCAs may ≠ serum glucose levels by up to 150%, ≠ appetite (particularly carbohydrate craving) and ↓ metabolic rate

Be aware and monitor blood sugar weekly until stable. They are generally considered safe unless diabetes is poorly controlled or is associated with significant cardiac or renal disease. Amitriptyline, imipramine and citalopram are also used to treat painful diabetic neuropathy

ACARBOSE ANTIDIABETIC DRUGS ≠ risk of hypoglycaemic episodes Due to additive effects by similar or differing mechanisms to lower blood sugar

Combinations are often used and useful. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

ACARBOSE ANTIEPILEPTICS – VALPROATE

Case of ↓ valproate levels Uncertain Monitor valproate levels

ACARBOSE ANTIHYPERTENSIVES AND HEART FAILURE DRUGS – ADRENERGIC NEURONE BLOCKERS

≠ hypoglycaemic effect Catecholamines are diabetogenic; guanethidine blocks the release of catecholamines from nerve endings

Monitor blood glucose closely

ACARBOSE ANTIOBESITY DRUGS – ORLISTAT, RIMONABANT, SIBUTRAMINE

Tendency for blood glucose levels to fluctuate

These agents change dietary intake of carbohydrates and other foods, and the risk of fluctuations in blood glucose is greater if there is a concurrent dietary regimen. A side-effect of orlistat is hypoglycaemia

These agents are used often in patients with type II diabetes who are on hypoglycaemic therapy. Need to monitor blood sugars twice weekly until stable. Advise self-monitoring. Watch for and warn patients about symptoms of hypoglycaemia. Avoid co-administration of acarbose and orlistat ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

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with antidiabetic drugs

Additive effect; aspirin has a hypoglycaemic effect

Avoid high-dose aspirin

ACARBOSE ANTIPROTOZOALS – PENTAMIDINE

May alter acarbose requirements due altered glycaemic control

Attributed to pancreatic beta cell toxicity

Need to monitor blood sugar until stable and following withdrawal of pentamidine

ACARBOSE CARDIAC GLYCOSIDES Acarbose may ↓ plasma levels of digoxin

Uncertain; possibly ↓ absorption of digoxin

Monitor digoxin levels; watch for ↓ levels

ACARBOSE H2 RECEPTOR BLOCKERS – RANITIDINE

↓ blood levels of ranitidine Possibly due to ↓ absorption of ranitidine

Be aware

ACARBOSE LIPID-LOWERING DRUGS – ANION EXCHANGE RESINS

≠ hypoglycaemic effect of acarbose Uncertain Monitor blood glucose during co-administration and after discontinuation of concurrent therapy

ACARBOSE MUSCLE RELAXANTS – BACLOFEN

↓ hypoglycaemic effect Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of antidiabetic drugs are often required for adequate glycaemic control

ACARBOSE NANDROLONE ≠ effect of antidiabetic drugs Uncertain Monitor blood sugar closely ACARBOSE NIACIN ↓ hypoglycaemic effect Due to these drugs causing

hyperglycaemia, the mechanism being uncertain at present

≠ doses of antidiabetic drugs are often required for adequate glycaemic control

ACARBOSE NICOTINE ↓ hypoglycaemic effect Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of antidiabetic drugs are often required for adequate glycaemic control

ACARBOSE OESTROGENS Altered glycaemic control Uncertain at present Monitor blood glucose closely

ACARBOSE PANCREATIN Theoretical risk of ↓ efficacy of acarbose

↓ absorption Watch for poor response to acarbose; monitor capillary blood glucose closely

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ANTIDIABETIC DRUGS OTHER ANTIDIABETIC DRUGS Meglitinide derivatives

Uncertain at present Monitor blood glucose closely

Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of antidiabetic drugs are often required for adequate glycaemic control

ACARBOSE THYROID HORMONES ↓ hypoglycaemic effect Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present

≠ doses of antidiabetic drugs are often required for adequate glycaemic control

MEGLITINIDE DERIVATIVES – NATEGLINIDE, REPAGLINIDE

NATEGLINIDE, REPAGLINIDE

ALCOHOL Tends to mask signs of hypoglycaemia and ≠ risk of hypoglycaemic episodes

Inhibits glucose production and release from many sources, including the liver and release

NATEGLINIDE, REPAGLINIDE

ANTIARRHYTHMICS – DISOPYRAMIDE

≠ risk of hypoglycaemic episodes – particularly in patients with impaired renal function. Hypoglycaemic attacks may occur even when plasma levels of disopyramide are within the normal range (attacks occurring with plasma disopyramide levels of 1-4 ng/mL)

Disopyramide and its metabolite mono-isopropyl disopyramide ≠ secretion of insulin (considered to be due to inhibition of potassium-ATP channels). Suggestion that disopyramide causes an impairment of the counterregulatory (homeostatic) mechanisms that follow hypoglycaemia

In patients receiving antidiabetic drugs, start with the lowest dose of disopyramide if there is no alternative. Measure creatinine clearance. If creatinine clearance is 40 mL/min or less, the dose of disopyramide should not exceed 100 mg and should be administered once daily if creatinine clearance is 15 ml/min. Watch for and warn patients about symptoms of hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

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NATEGLINIDE, REPAGLINIDE

ISONIAZID ↓ efficacy of antidiabetic drugs Isoniazid causes hyperglycaemia, the mechanism being uncertain at present

Monitor capillary blood glucose closely; ≠ doses of antidiabetic drugs may be needed

REPAGLINIDE MACROLIDES – ERYTHROMYCIN, CLARITHROMYCIN, TELITHROMYCIN

Likely to ≠ plasma concentrations of repaglinide and ≠ risk of hypoglycaemic episodes. ≠ risk of gastrointestinal side-effects with clarithromycin

Due to inhibition of CYP3A4 isoenzymes, which metabolize repaglinide. These drugs vary in potency as inhibitors (clarithromycin is a potent inhibitor), and ≠ plasma concentrations will vary. Clarithromycin ≠ plasma concentrations by 60% However, the alternative pathway – CYP2C8 – is unaffected by these inhibitors

NATEGLINIDE, REPAGLINIDE

QUINOLONES – CIPROFLOXACIN, LEVOFLOXACIN, NORFLOXACIN, OFLOXACIN

≠ risk of hypoglycaemic episodes Mechanism uncertain. Ciprofloxacin is a potent inhibitor of CYP1A2. Norfloxacin is a weak inhibitor of CYP1A2, but these drugs may inhibit other CYP isoenzymes to varying degrees

REPAGLINIDE RIFAMPICIN ↓ plasma concentrations of repaglinide likely. Rifampicin ↓ AUC of repaglinide by 25%

Due to inducing CYP3A4 isoenzymes, which metabolize repaglinide. However, the alternative pathway – CYP2C8 – is unaffected by these inducers except by rifampicin

The interaction is likely to be most severe with rifampicin. Be aware and monitor for hyperglycaemia ➣ For signs and symptoms of hyperglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperglycaemia

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ANTIDIABETIC DRUGS OTHER ANTIDIABETIC DRUGS Meglitinide derivatives

Hepatic metabolism inhibited Manufacturers do not recommend concurrent use

REPAGLINIDE

REPAGLINIDE IMATINIB Likely to ≠ plasma concentrations of repaglinide and ≠ risk of hypoglycaemic episodes

Due to inhibition of CYP3A4 isoenzymes, which metabolize repaglinide

REPAGLINIDE ANASTRAZOLE Risk of hypoglycaemia Mechanism unknown Watch for and warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

NATEGLINIDE, REPAGLINIDE

LANREOTIDE, OCTREOTIDE Likely to alter antidiabetic requirements

Octreotide and lanreotide suppress pancreatic insulin and counterregulatory hormones (glucagon, growth hormone) and delay or ↓ absorption of glucose from the intestine

Essential to monitor blood sugar at least twice a week after initiating concurrent treatment until blood sugar levels are stable. Advise self-monitoring. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

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≠ risk of hypoglycaemia

Hepatic metabolism inhibited Watch for and warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

NATEGLINIDE, REPAGLINIDE

ANTIDEPRESSANTS

NATEGLINIDE, REPAGLINIDE

SSRIs Fluctuations in blood sugar are very likely, with both hypoglycaemic and hyperglycaemic events being reported in diabetics receiving hypoglycaemic treatment. ≠ plasma concentrations of sulphonylureas (e.g. tolbutamide) may occur

Brain serotonin and corticotropinreleasing hormone systems participate in the control of blood sugar levels. ≠ (usually acute) in brain serotonergic activity induces a hyperglycaemic response. Fluvoxamine is a potent inhibitor and fluoxetine a less potent inhibitor of CYP2C9, which metabolizes sulphonylureas

Both hyper-and hypoglycaemic responses have been reported with SSRIs; there is a need to monitor blood glucose closely prior to, during and after discontinuing SSRI treatment ➣ For signs and symptoms of hypoglycaemia and hpyerglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia, Hyperglycaemia

REPAGLINIDE ST JOHN’S WORT ↓ plasma concentrations of repaglinide likely

Due to inducing CYP3A4 isoenzymes, which metabolize repaglinide. However, the alternative pathway – CYP2C8 – is unaffected by these inducers

NATEGLINIDE, REPAGLINIDE

TCAs Likely to impair control of diabetes

TCAs may ≠ serum glucose levels by up to 150%, ≠ appetite (particularly carbohydrate craving) and ↓ metabolic rate

Be aware and monitor blood sugar weekly until stable. They are generally considered safe unless diabetes is poorly controlled or is associated with significant cardiac or renal disease. Amitriptyline, imipramine and citalopram are also used to treat painful diabetic neuropathy

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ANTIDIABETIC DRUGS OTHER ANTIDIABETIC DRUGS Meglitinide derivatives

Due to additive effects by similar or differing mechanisms to lower blood sugar

REPAGLINIDE ANTIEPILEPTICS – CARBAMAZEPINE, PHENOBARBITONE, HYDANTOINS

↓ plasma concentrations of repaglinide likely

Due to inducing CYP3A4 isoenzymes, which metabolize repaglinide. However, the alternative pathway – CYP2C8 – is unaffected by these inducers

NATEGLINIDE, REPAGLINIDE

ANTIFUNGALS

NATEGLINIDE, REPAGLINIDE

AZOLES – KETOCONAZOLE, FLUCONAZOLE, ITRACONAZOLE, VORICONAZOLE

Likely to ≠ plasma concentrations of repaglinide and ≠ risk of hypoglycaemic episodes.