Drug Interaction Report
1 drug interaction and 28 additional warnings found for the following 2 drugs:
- calcium carbonate
- Valrelease (diazepam)
Drug interactions
Minor drug interactions
Minor:diazePAM calcium carbonate
Applies to: Valrelease (diazepam), calcium carbonate
A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.
The information above is from our professional interaction data. Consumer information is not available for this interaction.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:Food/Lifestyle diazePAM
Applies to: Valrelease (diazepam)
Grapefruit and grapefruit juice may interact with diazePAM and lead to potentially dangerous side effects.
Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
Do not drink alcohol while taking diazePAM. This medication can increase the effects of alcohol. You may feel more drowsy, dizzy, or tired if you take diazePAM with alcohol.
Talk to your doctor or pharmacist if you have any questions or concerns.
Moderate:Food/Lifestyle calcium carbonate
Applies to: calcium carbonate
Calcium absorption may be increased by taking it with food. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.
Calcium may be taken with food to increase absorption. Consider spacing calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.
Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Minor food/lifestyle interactions
Minor:Caffeine diazePAM
Applies to: Valrelease (diazepam)
One study has reported a 22% reduction in diazepam plasma levels when coadministered with caffeine. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that changes to caffeine consumption habits may impact the efficacy of diazepam therapy.
The information above is from our professional interaction data. Consumer information is not available for this interaction.
Disease interactions
25 potential interactionsApplies to: 21 conditions, including Depression, Weight Loss, Seizures, Arrhythmia, and Psychosis.
Achlorhydria
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Achlorhydria.
Calcium is absorbed from the intestinal tract by active transport and passive diffusion. Malabsorption syndromes (celiac disease, GI resection), deficiency of vitamin D, parathyroid hormone, or calcitonin, or an alkaline gastric pH (achlorhydria, carbonate or phosphate salts) can decrease the absorption of oral formulations of calcium. Calcium is available in oral and parenteral formulations.
Acute Alcohol Intoxication
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Acute Alcohol Intoxication.
The use of benzodiazepines with alcohol is not recommended. Patients with acute alcohol intoxication exhibit depressed vital signs. The central nervous system depressant effects of benzodiazepines may be additive with those of alcohol, and severe respiratory depression and death may occur. Therapy with benzodiazepines should be administered cautiously in patients who might be prone to acute alcohol intake.
Altered Consciousness
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Altered Consciousness.
Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.
Arrhythmia
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Arrhythmia.
Calcium is involved in cardiac muscle contraction and electrical impulse conduction. Therapy with calcium salt formulations (particularly IV) should be administered cautiously to patients with cardiac disease. Patients receiving cardiac glycosides and concomitant IV calcium may experience arrhythmias. Therapy with IV calcium should be administered slowly and at reduced dosages in patients with cardiac disease.
Asphyxia
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Asphyxia.
Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.
Depression
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Depression.
Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Drug Dependence
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Drug Dependence.
Benzodiazepines have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use and/or excessive dosages. However, abrupt cessation following continual use of as few as 6 weeks at therapeutic levels has occasionally precipitated withdrawal symptoms. Addiction- prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance when treated with benzodiazepines. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of benzodiazepine therapy should be undertaken gradually using a dosage- tapering schedule. If withdrawal symptoms occur, temporary reinstitution of benzodiazepines may be necessary.
Glaucoma/Intraocular Hypertension
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Glaucoma/Intraocular Hypertension.
The manufacturers consider the use of benzodiazepines to be contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma. These agents do not possess anticholinergic activity but have very rarely been associated with increased intraocular pressure.
Hyperkinetic Syndrome of Childhood
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.
Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.
Liver Disease
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Liver Disease.
The use of diazepam is considered by the manufacturer to be contraindicated in patients with clinical or biochemical evidence of significant liver disease. Diazepam is primarily metabolized by the liver, and the metabolites are eliminated by the kidney. Due to the possibility of excess accumulation of metabolites and the unknown effects of such accumulation, therapy with diazepam should also be administered cautiously in patients with renal impairment. Monitoring renal function during treatment is recommended.
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Liver Disease.
The use of some benzodiazepines such as clonazepam and diazepam (oral tablets), is considered by the manufacturer to be contraindicated in patients with clinical or biochemical evidence of significant liver disease. These drugs are primarily metabolized by the liver and there is a risk of excess accumulation. Although all benzodiazepines may worsen hepatic encephalopathy, the manufacturer specifically recommends that lorazepam should be avoided in these patients.
Malabsorption Syndrome
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Malabsorption Syndrome.
Calcium is absorbed from the intestinal tract by active transport and passive diffusion. Malabsorption syndromes (celiac disease, GI resection), deficiency of vitamin D, parathyroid hormone, or calcitonin, or an alkaline gastric pH (achlorhydria, carbonate or phosphate salts) can decrease the absorption of oral formulations of calcium. Calcium is available in oral and parenteral formulations.
Myasthenia Gravis
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Myasthenia Gravis.
The use of diazepam is contraindicated in patients with myasthenia gravis.
Phosphate Imbalance
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Phosphate Imbalance.
Elevated serum concentrations of calcium and phosphate can exceed the solubility level and result in calcium- phosphate precipitates that deposit in vascular and renal systems as well as other soft tissues of the body. Therapy with calcium should be administered with extreme caution in patients with hyperphosphatemia (hypoparathyroidism or severe renal impairment). Administration of oral calcium acetate or calcium carbonate, in addition to providing calcium, complexes phosphates within the GI tract. These complexes are eliminated in the feces. Clinical monitoring of serum calcium and phosphate concentrations is necessary.
Psychosis
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Psychosis.
Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Psychosis.
Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.
Pulmonary Impairment
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Pulmonary Impairment.
Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.
Renal Dysfunction
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Renal Dysfunction.
Absorption of oral calcium formulations may be altered and elimination of calcium by the kidney decreased with renal impairment. Hyperphosphatemia occurs during renal failure. Calcium acetate or calcium carbonate, in addition to providing calcium, complexes phosphates within the GI tract. Calcium carbonate can partially correct metabolic acidosis associated with chronic renal failure. Clinical monitoring of renal function and serum calcium and phosphate concentrations is necessary.
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Renal Dysfunction.
The use of diazepam is considered by the manufacturer to be contraindicated in patients with clinical or biochemical evidence of significant liver disease. Diazepam is primarily metabolized by the liver, and the metabolites are eliminated by the kidney. Due to the possibility of excess accumulation of metabolites and the unknown effects of such accumulation, therapy with diazepam should also be administered cautiously in patients with renal impairment. Monitoring renal function during treatment is recommended.
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Renal Dysfunction.
Benzodiazepines are excreted by the kidneys and should be used with caution in patients with impaired renal function and end-stage kidney disease.
Respiratory Arrest
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Respiratory Arrest.
Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.
Sarcoidosis
Major:calcium carbonate
Calcium carbonate has a major potential interaction with Sarcoidosis.
Hypercalciuria, with or without hypercalcemia, may occasionally occur in patients with sarcoidosis. Elevated calcium levels may result from increased intestinal absorption of calcium, which is related to the extrarenal production of vitamin D by mononuclear phagocytes present within the sarcoid granuloma. Therapy with calcium salts should be administered cautiously and only if necessary in patients with sarcoidosis.
Seizures
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Seizures.
The use of benzodiazepines in patients with seizure disorders may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). Appropriate anticonvulsant medication might need to be initiated or the dosage increased. Abrupt cessation of benzodiazepine therapy may precipitate seizures and other withdrawal symptoms, particularly after prolonged use and/or excessive dosages. Status epilepticus may occur in patients with a history of seizures withdrawn rapidly from benzodiazepine therapy. Following chronic administration, cessation of benzodiazepine therapy should occur gradually with incrementally reduced dosages. Patients should be advised not to discontinue medication without first consulting with the physician.
Shock
Major:Valrelease
The diazePAM in Valrelease has a major potential interaction with Shock.
Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.
Weight Loss
Moderate:Valrelease
The diazePAM in Valrelease has a moderate potential interaction with Weight Loss.
The plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam. Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
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Further information
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