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Interactions between Insulin isophane and Lithium

1 drug interaction and 31 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

lithium insulin isophane (NPH)

Applies to: lithium and insulin isophane
Monitor

Lithium may interfere with the therapeutic effects of insulin and other antidiabetic agents. In one study, 10 psychiatric patients treated with lithium carbonate for two weeks demonstrated elevated blood glucose levels and impaired glucose tolerance tests. There have also been isolated case reports of hyperglycemia, impaired glucose tolerance, or diabetes mellitus in patients receiving lithium therapy, although a causal relationship has not been established. According to the labeling for several insulin products, lithium can either potentiate or weaken the blood glucose-lowering effect of insulin. The mechanism by which lithium may induce these changes is not understood.

Management

Blood glucose should be monitored more closely following initiation or discontinuation of lithium in patients receiving insulin or other antidiabetic agents. If hypo- or hyperglycemia occur during lithium therapy, patients should initiate appropriate remedial therapy immediately and contact their physician. Dosage adjustments may be required if an interaction is suspected.

References (5)
  1. Shopsin B, Stern S, Gershon S (1972) "Altered carbohydrate metabolism during treatment with lithium carbonate." Arch Gen Psychiatry, 26, p. 566-71
  2. (2001) "Product Information. Lantus (insulin glargine)." Aventis Pharmaceuticals
  3. (2022) "Product Information. NovoLOG Mix 70/30 FlexPen (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc
  4. (2004) "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals
  5. (2026) "Product Information. Awiqli FlexTouch (insulin icodec)." Novo Nordisk Pharmaceuticals Inc

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

lithium Food/Lifestyle

Applies to: lithium
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:

insulin isophane (NPH) Food/Lifestyle

Applies to: insulin isophane
Generally avoid

Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

Management

Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References (11)
  1. Jerntorp P, Almer LO (1981) "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand, 656, p. 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. (1983) "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol, 24, p. 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. (1983) "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia, 24, p. 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A (1987) "Interaction of ethanol and glipizide in humans." Diabetes Care, 10, p. 683-6
  5. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  6. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM (1981) "The pharmacology of sulfonylureas." Am J Med, 70, p. 361-72
  9. (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  11. (2026) "Product Information. Awiqli FlexTouch (insulin icodec)." Novo Nordisk Pharmaceuticals Inc
Moderate:

lithium Caffeine

Applies to: lithium
Monitor

One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

Management

When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

References (1)
  1. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A (1995) "Caffeine withdrawal increases lithium blood levels." Biol Psychiatry, 37, p. 348-50

Disease interactions

28 potential interactions Applies to: 24 conditions, including Underactive Thyroid, Diarrhea, Breast Cancer, Hypokalemia, and Fever.

Adrenal Insufficiency

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Adrenal Insufficiency.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Alcoholism

Major:

lithium

Lithium has a major potential interaction with Alcoholism.

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

Anorexia/Feeding Problems

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Anorexia/Feeding Problems.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Autonomic Neuropathy

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Autonomic Neuropathy.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Breast Cancer

Moderate:

lithium

Lithium has a moderate potential interaction with Breast Cancer.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

Cardiovascular Conditions and Disorders

Major:

lithium

Lithium has a major potential interaction with Cardiovascular Conditions and Disorders.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

Central Nervous System Disorders

Major:

lithium

Lithium has a major potential interaction with Central Nervous System Disorders.

Antipsychotics can lower the seizure threshold and trigger seizures in a dose-dependent manner. Seizures have been reported in patients receiving antipsychotic therapy and may occur in epileptic patients even with maintenance of routine anticonvulsant treatment. Therapy with antipsychotics should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. High dosages should be avoided if possible.

Dehydration

Major:

lithium

Lithium has a major potential interaction with Dehydration.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Dementia

Major:

lithium

Lithium has a major potential interaction with Dementia.

Antipsychotic drugs are not approved for the treatment of patients with dementia-related psychosis. Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo.

Diarrhea

Major:

lithium

Lithium has a major potential interaction with Diarrhea.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Major:

lithium

Lithium has a major potential interaction with Diarrhea.

The risk for lithium toxicity may be increased in patients with diarrhea and excessive sweating. Dehydration and sodium depletion may occur in these patients leading to lithium retention and toxicity. The use of lithium may need to be reduced or suspended until the condition resolves. Supplemental fluid and salt may need to be administered. Monitoring serum lithium levels is recommended.

Fever

Major:

lithium

Lithium has a major potential interaction with Fever.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Moderate:

lithium

Lithium has a moderate potential interaction with Fever.

Patients with fever may have a lower tolerance to lithium due to increased fluid and sodium loss. Lithium dosage may need to be reduced or suspended in such patients. Monitoring lithium serum levels is recommended.

Hyperhidrosis

Major:

lithium

Lithium has a major potential interaction with Hyperhidrosis.

Lithium reduces the ability of the kidney to concentrate urine and produces a mild diabetes insipidus and polyuria. Therefore, patients with preexisting dehydration are more prone to lithium retention and toxicity. Therapy with lithium should be administered cautiously in dehydrated patients and may need to be discontinued until improvement in hydration status. Careful monitoring of lithium levels are recommended. Patients with sweating, diarrhea or concomitant infection with fever may need a temporary reduction or cessation of medication.

Major:

lithium

Lithium has a major potential interaction with Hyperhidrosis.

The risk for lithium toxicity may be increased in patients with diarrhea and excessive sweating. Dehydration and sodium depletion may occur in these patients leading to lithium retention and toxicity. The use of lithium may need to be reduced or suspended until the condition resolves. Supplemental fluid and salt may need to be administered. Monitoring serum lithium levels is recommended.

Hyperprolactinemia

Moderate:

lithium

Lithium has a moderate potential interaction with Hyperprolactinemia.

Antipsychotic drugs can elevate serum prolactin concentrations, and this elevation persists during chronic administration. This should be considered if therapy will be prescribed in patients with previously detected breast cancer as one-third of human breast cancers are prolactin-dependent in vitro. Associated disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Appropriate laboratory testing and follow-up is advised.

Hypokalemia

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Hypokalemia.

Hypokalemia may commonly occur during treatment with insulin. Use with caution in patients who may be particularly at risk of developing hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).

Hyponatremia

Major:

lithium

Lithium has a major potential interaction with Hyponatremia.

Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therapy with lithium should be administered cautiously in patients with preexisting sodium depletion as the risk of lithium toxicity is increased. Lower dosages may be required. Patients should maintain a normal diet, including salt, and an adequate fluid intake. Monitoring lithium serum concentrations is recommended.

Liver Disease

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Liver Disease.

Insulin requirements may be diminished in patients with renal or hepatic impairment due to reduced insulin metabolism and, in the latter case, also to reduced capacity for gluconeogenesis. Lower initial dosages may be appropriate, with careful monitoring of plasma glucose levels and dosing adjustments.

Malnourishment

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Malnourishment.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Neuroleptic Malignant Syndrome

Major:

lithium

Lithium has a major potential interaction with Neuroleptic Malignant Syndrome.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with the use of antipsychotic drugs. The diagnostic evaluation is complicated and the management requires immediate discontinuation of the antipsychotic therapy and intensive symptomatic treatment and medical monitoring. If a patient that has recovered from NMS requires antipsychotic drug treatment again, the reintroduction of therapy should be carefully considered as NMS recurrences have been reported.

Neutropenia

Moderate:

lithium

Lithium has a moderate potential interaction with Neutropenia.

The use of antipsychotics has been associated with events of leukopenia, neutropenia and agranulocytosis. Possible risk factors include preexisting low white blood cell count, and history of drug induced leukopenia/neutropenia. Patients with these risk factors should have complete blood count monitored frequently during the first few months of therapy. Patients should also be monitored for any signs or symptoms of infection. Treatment should be discontinued in any patient who develops a sore throat, fever, stomatitis, or other signs of infection along with a low WBC count or severe neutropenia (ANC < 1000/mm3).

Panhypopituitarism

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Panhypopituitarism.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Renal Dysfunction

Major:

lithium

Lithium has a major potential interaction with Renal Dysfunction.

Lithium is primarily eliminated by the kidneys and should generally not be administered to patients with significant renal dysfunction. Additionally, morphological changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy, although the association has not been clearly established. Kidney function should be assessed in patients prior to starting therapy, during and thereafter and routine urinalysis and renal function tests are recommended. Progressive or sudden changes in renal function indicate the need for reevaluation of treatment. Monitoring lithium serum levels is also recommended.

Moderate:

insulin isophane

The insulin isophane (NPH) in insulin isophane has a moderate potential interaction with Renal Dysfunction.

Insulin requirements may be diminished in patients with renal or hepatic impairment due to reduced insulin metabolism and, in the latter case, also to reduced capacity for gluconeogenesis. Lower initial dosages may be appropriate, with careful monitoring of plasma glucose levels and dosing adjustments.

Syncope

Major:

lithium

Lithium has a major potential interaction with Syncope.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

Tachyarrhythmia

Major:

lithium

Lithium has a major potential interaction with Tachyarrhythmia.

Lithium should generally not be given to patients with significant cardiovascular disease since the risk of lithium toxicity is high in these patients. Additionally, there have been postmarketing reports of a possible association between lithium therapy and the unmasking of Brugada Syndrome, a disorder characterized by abnormal EKG findings and a risk of sudden death. Lithium should be avoided in patients with this diagnosis or suspicion of it, or that have risk factors, which include unexplained syncope, family history of this syndrome, or family history of unexplained sudden death before the age of 45 years.
Therapy with lithium should be administered with extreme caution in patients with preexisting cardiac disease. Consultation with a cardiologist is highly recommended and cardiac monitoring should be completed before and during treatment.

Underactive Thyroid

Major:

lithium

Lithium has a major potential interaction with Underactive Thyroid.

The use of lithium has been associated with hypothyroidism in 5% to 15% of patient as it blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin. Therapy with lithium should be administered cautiously in patients with preexisting hypothyroidism. Careful monitoring of the thyroid function is recommended and supplemental thyroid treatment may be required.

More resources

insulin isophane

A total of 458 drugs are known to interact with insulin isophane.

lithium

A total of 750 drugs are known to interact with lithium.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.