Interactions between Mephobarbital and Nata Komplete
1 drug interaction and 20 additional warnings found for the following 2 drugs:
- mephobarbital
- Nata Komplete (multivitamin, prenatal)
Drug interactions
Moderate drug interactions
Moderate:
mephobarbital multivitamins, prenatal
Applies to: mephobarbital and Nata Komplete (multivitamin, prenatal)
Monitor
Anticonvulsants including, but not limited to, carbamazepine, lamotrigine, phenobarbital, phenytoin, primidone, and valproic acid have been shown to impair folate absorption and increase the metabolism of circulating folate. The precise mechanism of interaction has not been established.
Monitor
Coadministration with folate therapy may reduce the anticonvulsant effects of phenytoin, phenobarbital, primidone, and succinimides. The exact mechanism of interaction is unknown. Available data pertain primarily to phenytoin. Some investigators suggest that folic acid may serve as a cofactor in the metabolism of phenytoin, thus clearance is increased in the presence of folic acid. In one study, administration of folic acid for 14 days reduced the serum levels of phenytoin in normal subjects without significantly altering the bound fraction. Urinary excretion of phenytoin and its metabolite, meta-hydroxydiphenylhydantoin, was increased. In another study, three of four folate-deficient male patients receiving phenytoin monotherapy for epilepsy demonstrated a 7.5% to 47.6% decrease in total phenytoin plasma concentration following the addition of folic acid 1 mg/day for 180 or 300 days. Ratios of urinary metabolites to parent drug increased in these patients, suggesting an increase in phenytoin oxidative metabolism. The interaction is further supported by case reports describing subtherapeutic phenytoin levels and/or breakthrough seizures following the addition of folate therapy, including one case involving folinic acid (leucovorin). Limited data are available for phenobarbital and primidone. In one study, the addition of folic acid 15 mg/day increased the frequency and severity of seizures in 13 of 26 folate-deficient epileptic patients receiving two or more anticonvulsant drugs, including phenytoin, phenobarbital, and primidone. Nine of them required discontinuation of folic acid therapy. No data are available for other hydantoins.
Management
Caution is advised when folate therapy is coadministered with anticonvulsants. Close monitoring for clinical and laboratory evidence of diminished therapeutic response to both treatments is recommended. Patients should be advised to notify their physician if they experience loss of seizure control.
References (22)
- Furlanut M, Benetello P, Avogaro A, Dainese R (1978) "Effects of folic acid on phenytoin kinetics in healthy subjects." Clin Pharmacol Ther, 24, p. 294-7
- Carl GF, Smith ML (1992) "Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin." Epilepsia, 33, p. 372-5
- Berg MJ, Fincham RW, Ebert BE, Schottelius DD (1992) "Phenytoin pharmacokinetics: before and after folic acid administration." Epilepsia, 33, p. 712-20
- MacCosbe PE, Toomey K (1983) "Interaction of phenytoin and folic acid." Clin Pharm, 2, p. 362-9
- Robenberg IH (1972) "Drugs and folic acid absorption." Gastroenterology, 63, p. 353-7
- Ch'ien LT, Krumdieck CL, Scott CW Jr, Butterworth CE Jr (1975) "Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug- treated epileptics." Am J Clin Nutr, 28, p. 51-8
- Katz M (1973) "Potential danger of self-medication with folic acid." N Engl J Med, 289, p. 1095
- Yuen GJ (1984) "Interaction of phenytoin and folic acid: an alternative explanation." Clin Pharm, 3, 116,119
- Berg MJ, Rivey MP, Vern BA, Fischer LJ, Schottelius DD (1983) "Phenytoin and folic acid: individualized drug-drug interaction." Ther Drug Monit, 5, p. 395-9
- Berg MJ, Fischer LJ, Rivey MP, Vern BA, Lantz RK, Schottelius DD (1983) "Phenytoin and folic acid interaction: a preliminary report." Ther Drug Monit, 5, p. 389-94
- Berg MJ, Stumbo PJ, Chenard CA, Fincham RW, Schneider PJ, Schottelius D (1995) "Folic acid improves phenytoin pharmacokinetics." J Am Diet Assoc, 95, p. 352-6
- Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ (1995) "Phenytoin-folic acid interaction." Ann Pharmacother, 29, p. 726-35
- "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
- Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M (1999) "Phenytoin-folic acid interaction: A lesson to be learned." Clin Neuropharmacol, 22, p. 268-72
- Veldhorst-Janssen NM, Boersma HH, de Krom MC, van Rijswijk RE (2004) "Oral tegafur/folinic acid chemotherapy decreases phenytoin efficacy." Br J Cancer, 90, p. 745
- Steinweg DL, Bentley ML (2005) "Seizures following reduction in phenytoin level after orally administered folic acid." Neurology, 64, p. 1982
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2008) "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical
- Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
- (2018) "Product Information. L-Methylfolate Calcium (l-methylfolate)." Virtus Pharmaceuticals LLC
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
mephobarbital Alcohol (Ethanol)
Applies to: mephobarbital
Generally avoid
Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.
Management
The combination of ethanol and barbiturates should be avoided.
References (5)
- Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
- Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
- Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
- Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
- Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
Moderate food/lifestyle interactions
Moderate:
multivitamins, prenatal Food/Lifestyle
Applies to: Nata Komplete (multivitamin, prenatal)
Adjust dosing interval
Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa. Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.
Management
Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.
References (2)
- "Product Information. Feosol (ferrous sulfate)." SmithKline Beecham
- (2021) "Product Information. Accrufer (ferric maltol)." Shield Therapeutics
Disease interactions
18 potential interactions Applies to: 17 conditions, including Depression, Vitamin D Deficiency, Psychosis, Adrenal Insufficiency, and Liver Disease.
Acute Alcohol Intoxication
Major:
mephobarbital
Mephobarbital has a major potential interaction with Acute Alcohol Intoxication.
The use of barbiturates is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of barbiturates may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with barbiturates should be administered cautiously in patients who might be prone to acute alcohol intake.
Adrenal Insufficiency
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Adrenal Insufficiency.
Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.
Alcoholism
Major:
mephobarbital
Mephobarbital has a major potential interaction with Alcoholism.
Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. 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 barbiturates should be undertaken gradually using a dosage-tapering schedule.
Asphyxia
Major:
mephobarbital
Mephobarbital has a major potential interaction with Asphyxia.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Bone Marrow Depression/Low Blood Counts
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Hematologic toxicity, including agranulocytosis, thrombocytopenic purpura and megaloblastic anemia, has been reported rarely during use of barbiturates. Therapy with barbiturates should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Blood counts are recommended prior to and periodically during long-term therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, easy bruising, petechiae, bleeding, pallor, dizziness, or jaundice. Barbiturate therapy should be discontinued if blood dyscrasias occur.
Depression
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Depression.
Barbiturates depress the central nervous system and may cause or exacerbate mental depression. Therapy with barbiturates should be administered cautiously in patients with a history of depression or suicidal tendencies. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Depression.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Dermatitis, Drug-Induced
Major:
mephobarbital
Mephobarbital has a major potential interaction with Dermatitis, Drug-Induced.
Skin eruptions may precede rare but potentially fatal barbiturate-induced reactions such as systemic lupus erythematosus and exfoliative dermatitis, the latter of which may be accompanied by hepatitis and jaundice. Therapy with barbiturates should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to barbiturates. Barbiturate therapy should be withdrawn promptly at the first sign of a dermatologic adverse effect. However, cutaneous reactions may proceed to an irreversible stage even after cessation of medication due to the slow rate of metabolism and excretion of barbiturates. Patients should be advised to promptly report signs that may indicate impending development of barbiturate-related cutaneous lesions, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Rashes may be more likely to occur with phenobarbital and mephobarbital.
Drug Dependence
Major:
mephobarbital
Mephobarbital has a major potential interaction with Drug Dependence.
Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. 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 barbiturates should be undertaken gradually using a dosage-tapering schedule.
Hyperkinetic Syndrome of Childhood
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.
Paradoxical reactions characterized by excitability and restlessness may occur in pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with barbiturates.
Liver Disease
Major:
mephobarbital
Mephobarbital has a major potential interaction with Liver Disease.
Barbiturates are extensively metabolized by the liver. The plasma clearance of barbiturates may be decreased and the half-lives prolonged in patients with impaired hepatic function. Therapy with barbiturates should be administered cautiously and initiated at reduced dosages in patients with liver disease. Barbiturates are not recommended for use in patients with cirrhosis, hepatic failure, hepatic coma, or other severe hepatic impairment.
Panhypopituitarism
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Panhypopituitarism.
Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.
Porphyria
Major:
mephobarbital
Mephobarbital has a major potential interaction with Porphyria.
The use of barbiturates is contraindicated in patients with a history of porphyria. Barbiturates may exacerbate acute intermittent porphyria or porphyria variegata by inducing the enzymes responsible for porphyrin synthesis.
Psychosis
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Psychosis.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Pulmonary Impairment
Major:
mephobarbital
Mephobarbital has a major potential interaction with Pulmonary Impairment.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Renal Dysfunction
Major:
mephobarbital
Mephobarbital has a major potential interaction with Renal Dysfunction.
The long-acting barbiturate, phenobarbital, is partially eliminated by the kidney. The plasma clearance of phenobarbital may be decreased and the half-life prolonged in patients with impaired renal function. Therapy with phenobarbital should be administered cautiously and initiated at reduced dosages in patients with renal impairment. Since approximately 75% of a mephobarbital dose is metabolized to phenobarbital, the same precaution should be observed with mephobarbital. The remaining barbiturates, which are short- and intermediate-acting, are all negligibly excreted in the urine and may be appropriate alternatives in these patients.
Respiratory Arrest
Major:
mephobarbital
Mephobarbital has a major potential interaction with Respiratory Arrest.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Vitamin D Deficiency
Moderate:
mephobarbital
Mephobarbital has a moderate potential interaction with Vitamin D Deficiency.
Rickets and osteomalacia have rarely been reported following prolonged use of barbiturates, possibly due to increased metabolism of vitamin D as a result of enzyme induction by barbiturates. Long-term therapy with barbiturates should be administered cautiously in patients with vitamin D deficiency.
More resources
mephobarbital
A total of 592 drugs are known to interact with mephobarbital.
- Mephobarbital is in the following drug classes: barbiturate anticonvulsants, barbiturates.
- Mephobarbital is used to treat the following conditions:
Nata Komplete
A total of 172 drugs are known to interact with Nata Komplete.
- Nata komplete is used to treat Vitamin/Mineral Supplementation during Pregnancy/Lactation.
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. |
Further information
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